Search

We applied density-functional theory (DFT) with the projector-augmented-wave method (PAW) to investigate systematically the energetics of C-N coupling reactions on Pt(111) and Ni(111)surfaces. Our approach includes several steps: the adsorption of reactants and products (CHx, NHy and CHxNHy, x = 0-3, y = 0-2), movement of molecular fragments on the surface, and then C-N coupling. According to our calculations, the energies (ignoring the conventional negative sign) of adsorption of CHx and NHy on Pt(111)/Ni(111) surfaces decrease in the order C > CH > CH2 > CH3 and N > NH > NH2, with values 7.41/6.91, 6.97/6.52, 4.58/4.39, 2.19/2.01 eV and 5.10/5.49, 4.12/4.79, 2.75/2.87 eV, respectively. Regarding the adsorption energies among CHxNHy, the adsorption energy of CNH2 species is the highest on the Pt(111) surface, whereas on the Ni(111) surface CH3N is the most stable. The C-N coupling barriers differ on the two metallic surfaces despite the structures of initial, transition and final states being similar. On the Pt(111) surface, the coupling reaction of CH2 + NH2 has the smallest barrier, whereas CH + NH2 is the most favorable on the Ni(111) surface. The detailed local density of states (LDOS) and electron-localization functions (ELF) were investigated to rationalize the calculated outcomes.

Human endothelial nitric oxide synthase (eNOS) mRNA is highly stable in endothelial cells (ECs). Posttranscriptional regulation of eNOS mRNA stability is an important component of eNOS regulation, especially under hypoxic conditions. Here, we show that the human eNOS 3' untranslated region (3' UTR) contains multiple, evolutionarily conserved pyrimidine (C and CU)-rich sequence elements that are both necessary and sufficient for mRNA stabilization. Importantly, RNA immunoprecipitations and RNA electrophoretic mobility shift assays (EMSAs) revealed the formation of heterogeneous nuclear ribonucleoprotein E1 (hnRNP E1)-containing RNP complexes at these 3'-UTR elements. Knockdown of hnRNP E1 decreased eNOS mRNA half-life, mRNA levels, and protein expression. Significantly, these stabilizing RNP complexes protect eNOS mRNA from the inhibitory effects of its antisense transcript sONE and 3'-UTR-targeting small interfering RNAs (siRNAs), as well as microRNAs, specifically, hsa-miR-765, which targets eNOS mRNA stability determinants. Hypoxia disrupts hnRNP E1/eNOS 3'-UTR interactions via increased Akt-mediated serine phosphorylation (including serine 43) and increased nuclear localization of hnRNP E1. These mechanisms account, at least in part, for the decrease in eNOS mRNA stability under hypoxic conditions. Thus, the stabilization of human eNOS mRNA by hnRNP E1-containing RNP complexes serves as a key protective mechanism against the posttranscriptional inhibitory effects of antisense RNA and microRNAs under basal conditions but is disrupted under hypoxic conditions.

Background: About 5% of schoolchildren have a specific learning disorder, defined as an unexpected failure to acquire adequate abilities in reading, writing or mathematic skills not as a result of reduced intellectual ability, inadequate teaching or social deprivation. Of these, 80% are reading disorders. Polyunsaturated fatty acids (PUFAs), in particular omega-3 and omega-6 fatty acids, which are found abundantly in the brain and retina are important for learning. Some children with specific learning disorders have been found to be deficient in these PUFAs, and it is argued that supplementation of PUFAs may help these children improve their learning abilities., Objectives: To assess the effects of polyunsaturated fatty acids (PUFAs) supplementation for children with specific learning disorders, on learning outcomes., Search Methods: We searched the following databases in April 2012: CENTRAL (2012, Issue 4), MEDLINE (1948 to April Week 2 2012), EMBASE (1980 to 2012 Week 16), PsycINFO (1806 to April 2012), ERIC (1966 to April 2012), Science Citation Index (1970 to 20 April 2012), Social Science Citation Index (1970 to 20 April 2012), Conference Proceedings Citation Index-Science (1970 to 20 April 2012), Conference Proceedings Citation Index-Social Sciences and Humanites (1970 to 20 April 2012), Cochrane Database of Systematic Reviews (2012, Issue 4), DARE (2012, Issue 2) , ZETOC (24 April 2012) and WorldCat (24 April 2012). We searched the WHO International Clinical Trials Registry Platform and ClinicalTrials.gov on 24 April 2012. We also searched the reference lists of relevant articles identified by the searches., Selection Criteria: Randomised or quasi-randomised controlled trials comparing polyunsaturated fatty acids (PUFAs) with placebo or no treatment in children aged below 18 years with specific learning disabilities diagnosed using DSM-IV, ICD-10 or equivalent criteria. We intended to include participants with co-existing developmental disorders such as attention deficit hyperactivity disorder (ADHD) or autism., Data Collection and Analysis: Two authors (ML and KH) independently screened the titles and abstracts of the search results and eliminated all studies that did not meet the inclusion criteria. Authors were contacted for missing information and clarifications when needed., Main Results: We did not find any studies suitable for inclusion in the review. One study is awaiting classification as we were unable to get any information from the study author., Authors' Conclusions: There is insufficient evidence to draw any conclusion about the use of PUFAs for children with specific learning disorders. There is a need for well designed randomised studies to support or refute the use of PUFAs in this group of children.

Sulfur, a pollutant known to poison fuel-cell electrodes, generally comes from S-containing species such as hydrogen sulfide (H(2)S). The S-containing species become adsorbed on a metal electrode and leave atomic S strongly bound to the metal surface. This surface sulfur is completely removed typically by oxidation with O(2) into gaseous SO(2). According to our DFT calculations, the oxidation of sulfur at 0.25 ML surface sulfur coverage on pure Pt(111) and Ni(111) metal surfaces is exothermic. The barriers to the formation of SO(2) are 0.41 and 1.07 eV, respectively. Various metals combined to form bimetallic surfaces are reported to tune the catalytic capabilities toward some reactions. Our results show that it is more difficult to remove surface sulfur from a Ni@Pt(111) surface with reaction barrier 1.86 eV for SO(2) formation than from a Pt@Ni(111) surface (0.13 eV). This result is in good agreement with the statement that bimetallic surfaces could demonstrate more or less activity than to pure metal surfaces by comparing electronic and structural effects. Furthermore, by calculating the reaction free energies we found that the sulfur oxidation reaction on the Pt@Ni(111) surface exhibits the best spontaneity of SO(2) desorption at either room temperature or high temperatures., (Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Background: Breastfeeding (BF) is well recognised as the best food for infants. The impact of antenatal BF education on the duration of BF has not been evaluated., Objectives: To evaluate the effectiveness of antenatal BF education for increasing BF initiation and duration., Search Methods: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (2 December 2011), CENTRAL (The Cochrane Library 2011, Issue 11), MEDLINE (1966 to 30 November 2011) and Scopus (January 1985 to 30 November 2011). We contacted experts and searched reference lists of retrieved articles., Selection Criteria: All identified published, unpublished and ongoing randomised controlled trials (RCTs) assessing the effect of formal antenatal BF education or comparing two different methods of formal antenatal BF education, on duration of BF. We excluded RCTs that also included intrapartum or postpartum BF education., Data Collection and Analysis: We assessed all potential studies identified as a result of the search strategy. Two review authors extracted data from each included study using the agreed form and assessed risk of bias. We resolved discrepancies through discussion., Main Results: We included 19 studies with 8506 women in the review and 16 studies involving 8262 women contributed data to the analyses. We did not carry out any meta-analysis because there was only one study for each comparison.Five studies compared a single method of BF education with routine care. Peer counselling significantly increased BF initiation.Three studies compared one form of BF education versus another. No intervention was significantly more effective than another intervention in increasing initiation or duration of BF.Seven studies compared multiple methods versus a single method of BF education. Combined BF educational interventions were not significantly better than a single intervention in initiating or increasing BF duration. However, in one trial a combined BF education significantly reduced nipple pain and trauma.One study compared different combinations of interventions. There was a marginally significant increase in exclusive BF at six months in women receiving a booklet plus video plus lactation consultation (LC) compared with the booklet plus video only.Two studies compared multiple methods of BF education versus routine care. The combination of BF booklet plus video plus LC was significantly better than routine care for exclusive BF at three months., Authors' Conclusions: Because there were significant methodological limitations and the observed effect sizes were small, it is not appropriate to recommend any specific antenatal BF education.There is an urgent need to conduct RCTs with adequate power to evaluate the effectiveness of antenatal BF education.

Background: Separate care for a new mother and infant may affect the duration of breastfeeding, breastfeeding behaviour and may have an adverse effect on neonatal and maternal outcomes., Objectives: To assess the effect of mother-infant separation versus rooming-in on the duration of breastfeeding (exclusive and total duration of breastfeeding)., Search Methods: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (30 June 2012)., Selection Criteria: Randomised or quasi-randomised controlled trials (RCTs) investigating the effect of separate mother-infant care versus rooming-in after hospital birth or at home on the duration of breastfeeding, proportion of breastfeeding at six months and adverse neonatal and maternal outcomes., Data Collection and Analysis: Two review authors independently assessed the studies for inclusion and assessed trial quality. Two review authors extracted data. Data were checked for accuracy., Main Results: There were 23 reports from 19 potential trials identified. After assessment, one trial (involving 176 women) met our inclusion criteria.One trial reported an overall median duration of any breastfeeding of four months. Exclusive breastfeeding before discharge from hospital (at day four postpartum) was significantly lower in the separate care group compared with the rooming-in group (risk ratio (RR) 0.58; 95% CI 0.42 to 0.81; one trial, 141 women). , Authors' Conclusions: We found little evidence to support or refute the practice of mother-infant separation versus rooming-in. Therefore, we see no reason to practise it. We recommend a well designed RCT to investigate full mother-infant rooming-in versus partial rooming-in or separate care on all of the primary and secondary outcomes suggested.

The processes by which cells sense and respond to ambient oxygen concentration are fundamental to cell survival and function, and they commonly target gene regulatory events. To date, however, little is known about the link between the microRNA pathway and hypoxia signaling. Here, we show in vitro and in vivo that chronic hypoxia impairs Dicer (DICER1) expression and activity, resulting in global consequences on microRNA biogenesis. We show that von Hippel-Lindau-dependent down-regulation of Dicer is key to the expression and function of hypoxia-inducible factor α (HIF-α) subunits. Specifically, we show that EPAS1/HIF-2α is regulated by the Dicer-dependent microRNA miR-185, which is down-regulated by hypoxia. Full expression of hypoxia-responsive/HIF target genes in chronic hypoxia (e.g. VEGFA, FLT1/VEGFR1, KDR/VEGFR2, BNIP3L, and SLC2A1/GLUT1), the function of which is to regulate various adaptive responses to compromised oxygen availability, is also dependent on hypoxia-mediated down-regulation of Dicer function and changes in post-transcriptional gene regulation. Therefore, functional deficiency of Dicer in chronic hypoxia is relevant to both HIF-α isoforms and hypoxia-responsive/HIF target genes, especially in the vascular endothelium. These findings have relevance to emerging therapies given that we show that the efficacy of RNA interference under chronic hypoxia, but not normal oxygen availability, is Dicer-dependent. Collectively, these findings show that the down-regulation of Dicer under chronic hypoxia is an adaptive mechanism that serves to maintain the cellular hypoxic response through HIF-α- and microRNA-dependent mechanisms, thereby providing an essential mechanistic insight into the oxygen-dependent microRNA regulatory pathway.

Background: Symphysis fundal height (SFH) measurement is commonly practiced primarily to detect fetal intrauterine growth restriction (IUGR). Undiagnosed IUGR may lead to fetal death as well as increase perinatal mortality and morbidity., Objectives: The objective of this review is to compare SFH measurement with serial ultrasound measurement of fetal parameters or clinical palpation to detect abnormal fetal growth (IUGR and large-for-gestational age), and improving perinatal outcome., Search Methods: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (20 January 2012) and reference lists of retrieved articles., Selection Criteria: Randomised controlled trials including quasi-randomised and cluster-randomised trials involving pregnant women with singleton fetuses at 20 weeks' gestation and above comparing tape measurement of SFH with serial ultrasound measurement of fetal parameters or clinical palpation using anatomical landmarks., Data Collection and Analysis: Two review authors independently assessed trials for inclusion, trial quality and extracted data. Data were checked for accuracy., Main Results: One trial involving 1639 women was included. It compared SFH measurement with clinical abdominal palpation.There was no difference in the two reported primary outcomes of incidence of small-for-gestational age (risk ratio (RR) 1.32; 95% confidence interval (CI) 0.92 to 1.90) or perinatal death. There was no difference in the reported secondary outcomes of neonatal hypoglycaemia, admission to neonatal nursery, admission to the neonatal nursery for IUGR, induction of labour and caesarean section., Authors' Conclusions: There is insufficient evidence to determine whether SFH measurement is effective in detecting IUGR. We cannot therefore recommended any change of current practice. Further trials are needed.

Background: To successfully initiate and maintain breastfeeding for a longer duration, the World Health Organization's Ten Steps to Successful Breastfeeding recommends total avoidance of artificial teats or pacifiers for breastfeeding infants. Offering the pacifier instead of the breast to calm the infant may lead to less frequent episodes of breastfeeding and as a consequence may reduce breast milk production and shorten duration of breastfeeding; however, this remains unclear., Objectives: To assess the effect of unrestricted versus restricted pacifier use in healthy full-term newborns whose mothers have initiated breastfeeding and intend to exclusively breastfeed, on the duration of breastfeeding, other breastfeeding outcomes and infant health., Search Methods: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (14 March 2012)., Selection Criteria: Randomised and quasi-randomised controlled trials comparing unrestricted versus restricted pacifier use in healthy full-term newborns who have initiated breastfeeding regardless of whether they were born at home or in the hospital., Data Collection and Analysis: Two authors independently assessed the studies for inclusion, assessed risk of bias and carried out data extraction. Data were checked for accuracy., Main Results: We found three trials (involving 1915 babies) for inclusion in the review but have included only two trials (involving 1302 healthy full-term breastfeeding infants) in the analysis. Meta-analysis of the two combined studies showed that pacifier use in healthy breastfeeding infants had no significant effect on the proportion of infants exclusively breastfed at three months (risk ratio (RR) 0.99; 95% confidence interval (CI) 0.93 to 1.05), and at four months of age (RR 0.99; 95% CI 0.92 to 1.06) and also had no effect on the proportion of infants partially breastfed at three months (RR 1.00; 95% CI 0.98 to 1.13), and at 4 months of age (RR 1.01; 95% CI 0.98 to 1.03)., Authors' Conclusions: Pacifier use in healthy term breastfeeding infants, started from birth or after lactation is established, did not significantly affect the prevalence or duration of exclusive and partial breastfeeding up to four months of age. However, evidence to assess the short-term breastfeeding difficulties faced by mothers and long-term effect of pacifiers on infants' health is lacking.

We have disclosed a new mode of a chemically regioselective switch for C-H bond functionalization of benzimidazole derivatives via a cooperative effect invoked by Ni-Al bimetallic catalysis to create a steric requirement for obtaining the linear product of styrene insertion. Yet, excluding the AlMe(3) cocatalyst switches the reaction toward branch selectivity., (© 2012 American Chemical Society)

Pluripotency is a central, well-studied feature of embryonic development, but the role of pluripotent cell regulation in somatic tissue regeneration remains poorly understood. In planarians, regeneration of entire animals from tissue fragments is promoted by the activity of adult pluripotent stem cells (cNeoblasts). We utilized transcriptional profiling to identify planarian genes expressed in adult proliferating, regenerative cells (neoblasts). We also developed quantitative clonal analysis methods for expansion and differentiation of cNeoblast descendants that, together with RNAi, revealed gene roles in stem cell biology. Genes encoding two zinc finger proteins, Vasa, a LIM domain protein, Sox and Jun-like transcription factors, two candidate RNA-binding proteins, a Setd8-like protein, and PRC2 (Polycomb) were required for proliferative expansion and/or differentiation of cNeoblast-derived clones. These findings suggest that planarian stem cells utilize molecular mechanisms found in germ cells and other pluripotent cell types and identify genetic regulators of the planarian stem cell system., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Endothelial-derived nitric oxide (NO) is classically viewed as a regulator of vasomotor tone. NO plays an important role in regulating O(2) delivery through paracrine control of vasomotor tone locally and cardiovascular and respiratory responses centrally. Very soon after the cloning and functional characterization of the endothelial nitric oxide synthase (eNOS), studies on the interaction between O(2) and NO made the paradoxical finding that hypoxia led to decreases in eNOS expression and function. Why would decreases in O(2) content in tissues elicit a loss of a potent endothelial-derived vasodilator? We now know that restricting our view of NO as a regulator of vasomotor tone or blood pressure limited deeper levels of mechanistic insight. Exciting new studies indicate that functional interactions between NO and O(2) exhibit profound complexity and are relevant to diseases states, especially those associated with hypoxia in tissues. NOS isoforms catalytically require O(2). Hypoxia regulates steady-state expression of the mRNA and protein abundance of the NOS enzymes. Animals genetically deficient in NOS isoforms have perturbations in their ability to adapt to changes in O(2) supply or demand. Most interestingly, the intracellular pathways for O(2) sensing that evolved to ensure an appropriate balance of O(2) delivery and utilization intersect with NO signaling networks. Recent studies demonstrate that hypoxia-inducible factor (HIF) stabilization and transcriptional activity is achieved through two parallel pathways: (1) a decrease in O(2)-dependent prolyl hydroxylation of HIF and (2) S-nitrosylation of HIF pathway components. Recent findings support a role for S-nitrosothiols as hypoxia-mimetics in certain biological and/or disease settings, such as living at high altitude, exposure to small molecules that can bind NO, or anemia.

Hemolytic uremic syndrome (HUS) is a potentially life-threatening condition. It often occurs after gastrointestinal infection with E. coli O157:H7, which produces Shiga toxins (Stx) that cause hemolytic anemia, thrombocytopenia, and renal injury. Stx-mediated changes in endothelial phenotype have been linked to the pathogenesis of HUS. Here we report our studies investigating Stx-induced changes in gene expression and their contribution to the pathogenesis of HUS. Stx function by inactivating host ribosomes but can also alter gene expression at concentrations that minimally affect global protein synthesis. Gene expression profiling of human microvascular endothelium treated with Stx implicated a role for activation of CXCR4 and CXCR7 by their shared cognate chemokine ligand (stromal cell-derived factor-1 [SDF-1]) in Stx-mediated pathophysiology. The changes in gene expression required a catalytically active Stx A subunit and were mediated by enhanced transcription and mRNA stability. Stx also enhanced the association of CXCR4, CXCR7, and SDF1 mRNAs with ribosomes. In a mouse model of Stx-mediated pathology, we noted changes in plasma and tissue content of CXCR4, CXCR7, and SDF-1 after Stx exposure. Furthermore, inhibition of the CXCR4/SDF-1 interaction decreased endothelial activation and organ injury and improved animal survival. Finally, in children infected with E. coli O157:H7, plasma SDF-1 levels were elevated in individuals who progressed to HUS. Collectively, these data implicate the CXCR4/CXCR7/SDF-1 pathway in Stx-mediated pathogenesis and suggest novel therapeutic strategies for prevention and/or treatment of complications associated with E. coli O157:H7 infection.

The Cu/TiO(2)(110) surface displays a great catalytic activity toward the water-gas shift reaction (WGSR), for which Cu is considered to be the most active metal on a TiO(2)(110)-supported surface. Experiments revealed that Cu nanoparticles bind preferentially to the terrace and steps of the TiO(2)(110) surface, which would not only affect the growth mode of the surface cluster but also enhance the catalytic activity, unlike Au nanoparticles for which occupancy of surface vacancies is favored, resulting in poorer catalytic performance than Cu. With density-functional theory we calculated some possible potential-energy surfaces for the carboxyl and redox mechanisms of the WGSR at the interface between the Cu cluster and the TiO(2) support. Our results show that the redox mechanism would be the dominant path; the resident Cu clusters greatly diminish the barrier for CO oxidation (22.49 and 108.68 kJ mol(-1), with and without Cu clusters, respectively). When adsorbed CO is catalytically oxidized by the bridging oxygen of the Cu/TiO(2)(110) surface to form CO(2), the release of CO(2) from the surface would result in the formation of an oxygen vacancy on the surface to facilitate the ensuing water splitting (barrier 34.90 vs. 50.49 kJ mol(-1), with and without the aid of a surface vacancy).

Background: Breastfeeding (BF) is well recognised as the best food for infants. The impact of antenatal BF education on the duration of BF has not been evaluated., Objectives: To evaluate the effectiveness of antenatal BF education for increasing BF initiation and duration., Search Methods: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (21 April 2010), CENTRAL (The Cochrane Library 2010, Issue 2), MEDLINE (1966 to April 2010) and SCOPUS (January 1985 to April 2010). We contacted experts and searched reference lists of retrieved articles. We updated the search of the Pregnancy and Childbirth Group's Trials Register on 28 September 2011 and added the results to the awaiting classification section of the review., Selection Criteria: All identified published, unpublished and ongoing randomised controlled trials (RCTs) assessing the effect of formal antenatal BF education or comparing two different methods of formal antenatal BF education, on duration of BF. We excluded RCTs that also included intrapartum or postpartum BF education., Data Collection and Analysis: We assessed all potential studies identified as a result of the search strategy. Two review authors extracted data from each included study using the agreed form and assessed risk of bias. We resolved discrepancies through discussion., Main Results: We included 17 studies with 7131 women in the review and 14 studies involving 6932 women contributed data to the analyses. We did not do any meta-analysis because there was only one study for each comparison.Five studies compared a single method of BF education with routine care. Peer counselling significantly increased BF initiation.Three studies compared one form of BF education versus another. No intervention was significantly more effective than another intervention in increasing initiation or duration of BF.Seven studies compared multiple methods versus a single method of BF education. Combined BF educational interventions were not significantly better than a single intervention in initiating or increasing BF duration. However, in one trial a combined BF education significantly reduced nipple pain and trauma.One study compared different combinations of interventions. There was a marginally significant increase in exclusive BF at six months in women receiving a booklet plus video plus lactation consultation (LC) compared with the booklet plus video only.Two studies compared multiple methods of BF education versus routine care. The combination of BF booklet plus video plus LC was significantly better than routine care for exclusive BF at three months., Authors' Conclusions: Because there were significant methodological limitations and the observed effect sizes were small, it is not appropriate to recommend any antenatal BF education.There is an urgent need to conduct RCTs study with adequate power to evaluate the effectiveness of antenatal BF education.

Somatic reprogramming induced by defined transcription factors is a low-efficiency process that is enhanced by p53 deficiency. So far, p21 is the only p53 target shown to contribute to p53 repression of iPSC (induced pluripotent stem cell) generation, indicating that additional p53 targets may regulate this process. Here, we demonstrate that miR-34 microRNAs (miRNAs), particularly miR-34a, exhibit p53-dependent induction during reprogramming. Mir34a deficiency in mice significantly increased reprogramming efficiency and kinetics, with miR-34a and p21 cooperatively regulating somatic reprogramming downstream of p53. Unlike p53 deficiency, which enhances reprogramming at the expense of iPSC pluripotency, genetic ablation of Mir34a promoted iPSC generation without compromising self-renewal or differentiation. Suppression of reprogramming by miR-34a was due, at least in part, to repression of pluripotency genes, including Nanog, Sox2 and Mycn (also known as N-Myc). This post-transcriptional gene repression by miR-34a also regulated iPSC differentiation kinetics. miR-34b and c similarly repressed reprogramming; and all three miR-34 miRNAs acted cooperatively in this process. Taken together, our findings identified miR-34 miRNAs as p53 targets that play an essential role in restraining somatic reprogramming.

Cells sense and respond to changes in oxygen concentration through gene regulatory processes that are fundamental to survival. Surprisingly, little is known about how anemia affects hypoxia signaling. Because nitric oxide synthases (NOSs) figure prominently in the cellular responses to acute hypoxia, we defined the effects of NOS deficiency in acute anemia. In contrast to endothelial NOS or inducible NOS deficiency, neuronal NOS (nNOS)(-/-) mice demonstrated increased mortality during anemia. Unlike wild-type (WT) animals, anemia did not increase cardiac output (CO) or reduce systemic vascular resistance (SVR) in nNOS(-/-) mice. At the cellular level, anemia increased expression of HIF-1α protein and HIF-responsive mRNA levels (EPO, VEGF, GLUT1, PDK1) in the brain of WT, but not nNOS(-/-) mice, despite comparable reductions in tissue PO(2). Paradoxically, nNOS(-/-) mice survived longer during hypoxia, retained the ability to regulate CO and SVR, and increased brain HIF-α protein levels and HIF-responsive mRNA transcripts. Real-time imaging of transgenic animals expressing a reporter HIF-α(ODD)-luciferase chimeric protein confirmed that nNOS was essential for anemia-mediated increases in HIF-α protein stability in vivo. S-nitrosylation effects the functional interaction between HIF and pVHL. We found that anemia led to nNOS-dependent S-nitrosylation of pVHL in vivo and, of interest, led to decreased expression of GSNO reductase. These findings identify nNOS effects on the HIF/pVHL signaling pathway as critically important in the physiological responses to anemia in vivo and provide essential mechanistic insight into the differences between anemia and hypoxia.

We conducted a before and after study to determine whether an educational intervention to build capacity in the understanding and implementation of evidence could result in improved outcomes for mothers and babies in obstetric and neonatal units of two Malaysian hospitals. Twelve practices and thirteen associated outcomes were selected based on clear evidence from the Cochrane Library. There were significant improvements in most practices with little change in outcomes. In the short term a targeted intervention to build capacity in the understanding and implementation of evidence results in an improved process of care without adverse outcomes.

Background: To successfully initiate and maintain breastfeeding for a longer duration, the World Health Organization's Ten Steps to Successful Breastfeeding recommends total avoidance of artificial teats or pacifiers for breastfeeding infants. Offering the pacifier instead of the breast to calm the infant may lead to less frequent episodes of breastfeeding and as a consequence may reduce breast milk production and shorten duration of breastfeeding; however, this remains unclear., Objectives: To assess the effect of pacifier use versus no pacifier use in healthy full-term newborns whose mothers have initiated breastfeeding and intend to exclusively breastfeed, on the duration of breastfeeding, other breastfeeding outcomes and infant health., Search Strategy: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (31 December 2010)., Selection Criteria: Randomised and quasi-randomised controlled trials comparing pacifier use versus no pacifier use in healthy full-term newborns who have initiated breastfeeding regardless of whether they were born at home or in the hospital., Data Collection and Analysis: Two authors independently assessed the studies for inclusion, assessed risk of bias and carried out data extraction., Main Results: We found three trials (involving 1915 babies) for inclusion in the review but have included only two trials (involving 1302 healthy full-term breastfeeding infants) in the analysis. Meta-analysis of the two combined studies showed that pacifier use in healthy breastfeeding infants had no significant effect on the proportion of infants exclusively breastfed at three months (risk ratio (RR) 1.00; 95% confidence interval (CI) 0.95 to 1.06), and at four months of age (RR 0.99; 95% CI 0.92 to 1.06) and also had no effect on the proportion of infants partially breastfed at three months (RR 1.00; 95% CI 0.97 to 1.02), and at 4 months of age (RR 1.01; 95% CI 0.98 to 1.03)., Authors' Conclusions: Pacifier use in healthy term breastfeeding infants, started from birth or after lactation is established, did not significantly affect the prevalence or duration of exclusive and partial breastfeeding up to four months of age. However, evidence to assess the short-term breastfeeding difficulties faced by mothers and long-term effect of pacifiers on infants' health is lacking.

Objective: To investigate the morbidity and distribution of 35 inherited metabolic diseases in high risk children by LC-MS/MS in northern China., Methods: The dry blood on filter papers, collected from 2760 children clinically suspected to have inherited metabolic diseases from more than sixty hospitals in north China, was tested by LC-MS/MS. The specimen was extracted out of the dry blood on filter paper, derivatized before being injected into LCMS/MS. The LC-MS/MS methodology used in the study was transferred from Pediatrix Medical Group (1301 Concord Terrace, Sunrise, FL 33323), validated in our lab and further compared with United States CDC standard. The positive results were further confirmed by gas chromatography-mass, other laboratory tests and clinical symptoms., Results: 249 of the 2760 children (9%) were diagnosed with one or more of twenty-one disorders. Out of 249 patients, there are 41 (16.5%) fatty acid disorders, 71 (28.5%) amino acid diseases, and 137 (55%) organic acidemias. 48 of the 249 patients (19.3%) were neonates, including 11 (22.9%) with fatty acid disorders, 15 (31.3%) with amino acid diseases, and 22 (45.8%) with organic acidemias. 201 of the 249 patients were elder than 28 days, and was composed of 30 (14.9%) with fatty acid disorders, 56 (27.9%) with amino acid diseases, 115 (57.2%) with organic acidemias., Conclusions: The LC-MS/MS technology can be used to detect over 30 inherited metabolic disorders for Chinese pediatric clinic in a single collection of blood. The morbidity of IMD (9%) is relatively high among high risk children, thus we highly suggest that we shall provide initial screening of over 30 IMDs for the high risk children in China using the technology of LC-MS/MS.

We applied periodic density-functional theory to investigate the interaction of NO(x) on Ni(111) surface for small and large coverages. For a small coverage, adsorbed species, such as NO, N(2)O and NO(2), tend to dissociate to form atomic N and atomic O on the surface, but a large barrier, 2.34 eV, hinders the recombination of adsorbed N to form N(2). At a large coverage, the recombination of N and NO to form N(2)O is favorable; this species might either desorb or break the N-O bond to form N(2). Our calculated results agree satisfactorily with experimental observations. The formation of N(2)via paths that vary with coverage is analyzed and discussed.

Objective: To examine episiotomy practices before and after a multi-component intervention designed to support the use and generation of research evidence in maternal and neonatal health care., Methods: Set in 9 centers across 4 Southeast Asian countries, a retrospective survey was performed for 12 recommended pregnancy/childbirth practices and 13 outcomes of women in each center before and after intervention. Qualitative interviews were conducted to assess staff awareness and experience in evidence-based practice., Results: There were significant decreases in the rate of episiotomy, from 64.1% to 60.1% (risk difference [RD] -4.0; 95% confidence interval [CI], -5.8 to -2.2) for all women and from 92.2% to 80.7% (RD -11.5; 95% CI, -13.4 to -9.6) for nulliparous women. Severe trauma decreased from 3.9% to 1.9% (RD -2.0; 95% CI, -2.7 to -1.4) for all women and from 6.7% to 3.0% (RD -3.7; 95% CI, -4.9 to -2.5) for nulliparous women. The frequency of intact perineum increased from 12.4% to 15.6% (RD 3.2; 95% CI, 1.9-4.6) for all women and from 1.7% to 8.0% (RD 6.3; 95% CI, 5.0-7.5) for nulliparous women., Conclusion: An intervention based on understanding and using the best available evidence can result in significant improvements in care and health outcomes., (Crown Copyright © 2010. Published by Elsevier Ireland Ltd. All rights reserved.)

Background: Thromboembolic complications are much higher in pregnancy due to procoagulant changes. Heparin does not cross the placenta and the use of unfractionated heparin (UFH) is the current established practice in prophylaxis and treatment for thromboembolism in pregnancy., Objectives: To compare the effectiveness of anticoagulant therapies for the treatment of deep vein thrombosis in pregnancy. The anticoagulant drugs included are UFH, low molecular weight heparin (LMWH) and warfarin., Search Strategy: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (March 2010) and reference lists of retrieved studies., Selection Criteria: Randomised controlled trials comparing any combination of warfarin, UFH, LMWH and placebo in pregnant women., Data Collection and Analysis: We used methods described in the Cochrane Handbooks for Systemic Reviews of Interventions for assessing the eligibility of studies identified by the search strategy. A minimum of two review authors independently assessed each study., Main Results: We did not identify any eligible studies for inclusion in the review.We identified three potential studies; after assessing eligibility, we excluded all three as they did not meet the prespecified inclusion criteria. One study compared LMWH and UFH in pregnant women with previous thromboembolic events and, for most of these women, anticoagulants were used as thromboprophylaxis. There were only three women who had a thromboembolic event during the current pregnancy and it was unclear whether the anticoagulant was used as therapy or prophylaxis. We excluded one study because it included only women undergoing caesarean birth. The third study was not a randomised trial., Authors' Conclusions: There is no evidence from randomised controlled trials on the effectiveness of anticoagulation for deep vein thrombosis in pregnancy. Further studies are required.

Objective: To investigate the feasibility of analyzing acylcarnitine in dry filter-paper blood spots by liquid chromatography-tandem mass spectrometry (LC-MS/MS) which could be applied to detect inborn errors of metabolism in neonates., Methods: We obtained filter-paper blood from 26 dead infants from a neonatal intensive care unit (NICU) between October 1, 2008 and September 30, 2009. Acylcarnitine and amino acid profiles were obtained with LC-MS/MS. Four infants underwent routine autopsy. The postmortem blood specimens were compared with newborn blood specimens, and with specimens obtained from older infants with metabolic disorders., Results: Of all the 26 patients, 5 (19.2%) were diagnosed as having different kinds of diseases: 3 with methylmalonic acidemia (the concentration of C3, and the ratio of C3/C16, C3/C2 increased), 1 with maple syrup urine disease (the concentration of leucine and isoleucine increased), and 1 with isovaleric acidemia (the concentration of C5 increased)., Conclusions: Postmortem metabolic test can explain infant deaths and provide estimates of deaths attributable to inborn errors of metabolism in NICU. LC-MS/MS is suitable for analysis of postmortem specimens and can be considered for routine application in NICU autopsy.

Spin-polarized density functional theory calculation was carried out to characterize the adsorption and dissociation of CO(2) molecule on the Fe(111) surface. It was shown that the barriers for the stepwise CO(2) dissociation reaction, CO(2(g)) --> C(a) + 2O(a), are 21.73 kcal/mol (for OC-O bond activation) and 23.87 kcal/mol (for C-O bond activation), and the entire process is 35.73 kcal/mol exothermic. The rate constants for the dissociative adsorption of CO(2) have been predicted with variational RRKM theory, and the predicted rate constants, k(CO(2)) (in units of cm(3) molecule(-1) s(-1)), can be represented by the equations 2.12 x 10(-8)T(-0.842) exp(-0.258 kcal mol(-1)/RT) at T = 100-1000 K. To gain insights into high catalytic activity of the Fe(111) surface, the interaction nature between adsorbate and substrate is also analyzed by the detailed electronic analysis.

Hypoxia elicits endothelial dysfunction, in part, through reduced expression of endothelial nitric-oxide synthase (eNOS). Here we present evidence that hypoxia causes a rapid decrease in the transcription of the eNOS/NOS3 gene, accompanied by decreased acetylation and lysine 4 (histone H3) methylation of eNOS proximal promoter histones. Surprisingly, we demonstrate that histones are rapidly evicted from the eNOS proximal promoter during hypoxia. We also demonstrate endothelium-specific H2A.Z incorporation at the eNOS promoter and find that H2A.Z is also evicted by hypoxic stimulation. After longer durations of hypoxia, histones are reincorporated at the eNOS promoter, but these histones lack substantial histone acetylation. Additionally, we identify a key role for the chromatin remodeler, BRG1, in re-establishing eNOS expression following reoxygenation of hypoxic cells. We posit that post-translational histone modifications are required to maintain constitutive eNOS transcriptional activity and that histone eviction rapidly resets histone marks and is a proximal event in the hypoxic repression of eNOS. Although nucleosome eviction has been reported in models of transcriptional activation, the observation that eviction can also accompany transcriptional repression in hypoxic mammalian cells argues that eviction may be broadly relevant to both positive and negative changes in transcription.

We have developed a continuous SrF radical beam for the loading of helium buffer gas cooling. The SrF molecules are efficiently generated by high-temperature chemical reaction of the solid precursor SrF(2) with boron in a graphite oven. The beam properties are characterized with laser-induced fluorescence spectroscopic method. We obtain a molecular flux of up to 2.1x10(15) sr(-1) s(-1) at the detection region for all rotational states. The dependence of the flux on oven temperature suggests that even higher flux is possible if a higher temperature in the oven is achieved.

Background: Evidence-based practice (EBP) can provide appropriate care for women and their babies; however implementation of EBP requires health professionals to have access to knowledge, the ability to interpret health care information and then strategies to apply care. The aim of this survey was to assess current knowledge of evidence-based practice, information seeking practices, perceptions and potential enablers and barriers to clinical practice change among maternal and infant health practitioners in South East Asia., Methods: Questionnaires about IT access for health information and evidence-based practice were administered during August to December 2005 to health care professionals working at the nine hospitals participating in the South East Asia Optimising Reproductive and Child Health in Developing countries (SEA-ORCHID) project in Indonesia, Malaysia, Thailand and The Philippines., Results: The survey was completed by 660 staff from six health professional groups. Overall, easy IT access for health care information was available to 46% of participants. However, over a fifth reported no IT access was available and over half of nurses and midwives never used IT health information. Evidence-based practice had been heard of by 58% but the majority did not understand the concept. The most frequent sites accessed were Google and PubMed. The Cochrane Library had been heard of by 47% of whom 51% had access although the majority did not use it or used it less than monthly. Only 27% had heard of the WHO Reproductive Health Library and 35% had been involved in a clinical practice change and were able to identify enablers and barriers to change. Only a third of participants had been actively involved in practice change with wide variation between the countries. Willingness to participate in professional development workshops on evidence-based practice was high., Conclusion: This survey has identified the need to improve IT access to health care information and health professionals' knowledge of evidence-based health care to assist in employing evidence base practice effectively.

Introduction: A study was done between December 2005 and January 2006 to determine the prevalence of emotional disorders among medical students in a private medical school in Ipoh, Perak, Malaysia and to determine the demographical characteristics, contributing factors and the key person consulted for emotional problems., Methods: Medical students in the private medical school completed the 12-item English version of the General Health Questionnaire (GHQ-12) and a demographical questionnaire. A cut-off point of 3/4 for the GHQ was used to determine negative and positive scores for emotional disorders., Results: Out of 292 medical students, 86.6 percent completed the questionnaires. A total of 117 students (46.2 percent) were found to have emotional disorders. There was no significant association of ethnicity, gender, age group, number of examinations sat, examination performances, past medical conditions and relationships with parents, siblings, course-mates and lecturers with positive GHQ scores. A significant association, however, was found between positive GHQ scores for emotional disorders and the year of study, pressure faced due to examinations, and not having a love relationship. 39 percent of the students stated friends as their main preference for consultation of any emotional problem., Conclusion: The prevalence of emotional disorders among medical students was high. Further studies and diagnostic measures are recommended, including a more systematic screening and counselling programme by the medical school for early diagnosis and treatment to prevent complications.

Background: Disorders related to pregnancy and childbirth are a major health issue in South East Asia. They represent one of the biggest health risk differentials between the developed and developing world. Our broad research question is: Can the health of mothers and babies in Thailand, Indonesia, the Philippines and Malaysia be improved by increasing the local capacity for the synthesis of research, implementation of effective interventions, and identification of gaps in knowledge needing further research?, Methods/design: The project is a before-after study which planned to benefit from and extend existing regional and international networks. Over five years the project was designed to comprise five phases; pre-study, pre-intervention, intervention, outcome assessment and reporting/dissemination. The study was proposed to be conducted across seven project nodes: four in South East Asia and three in Australia. Each South East Asian study node was planned to be established within an existing department of obstetrics and gynaecology or neonatology and was intended to form the project coordinating centre and focus for evidence-based practice activities within that region. Nine hospitals in South East Asia planned to participate, representing a range of clinical settings. The three project nodes in Australia were intended to provide project support. The intervention was planned to consist of capacity-strengthening activities targeted at three groups: generators of evidence, users of evidence and teachers of evidence. The primary outcome was established as changes in adherence to recommended clinical practices from baseline to completion of the project and impact on health outcomes., Discussion: The SEA-ORCHID project was intended to improve care during pregnancy and the perinatal period of mothers and their babies in South East Asia. The possible benefits extend beyond this however, as at the end of this project there is hoped to be an existing network of South East Asian researchers and health care providers with the capacity to generalise this model to other health priority areas. It is anticipated that this project facilitate ongoing development of evidence-based practice and policy in South East Asia through attracting long-term funding, expansion into other hospitals and community-based care and the establishment of nodes in other countries.

Background: Over a 10-year period there was increasing involvement by clinicians in the generation and implementation of evidence-based practices in the neonatal intensive care unit (NICU). For two cohorts of very low birth weight (VLBW) babies admitted 10 years apart to a developing country, NICU were compared and changes occurring in process of care that might have contributed to any change in outcome were documented., Methods: Prospective data were collected on characteristics, management and complications of all VLBW infants admitted over the same 6-month period in 1993 and 2003 and examined for changes in evidence-based practices and outcome., Results: Compared to the first cohort of 69 babies, 60 babies in the second cohort were significantly more likely to have been inborn (p < 0.001), born by Caesarean section (p = 0.035), to have received antenatal corticosteroids (p < 0.001), to be intubated at birth (p < 0.001) and have a 5 min Apgar score above 6 (p = 0.034). They were also significantly lighter and of lower gestation (p = 0.005). They were significantly more likely to have received surfactant (p < 0.001), to have been ventilated and to have had double prong nasal continuous positive pressure either as a mode of ventilation or for weaning (p < 0.001). Hypothermia on admission was more common in the second cohort (p < 0.001). Survival increased from 62.3% to 81.6% (p = 0.015)., Conclusions: Although causality cannot be established, an increase in the use of evidence-based practices was associated with a significant improvement in outcomes. In spite of greater barriers to implementation there are evidence-based strategies that can be put into neonatal practice in developing countries.

Background: Persistent pulmonary hypertension of the newborn (PPHN) occurs in approximately 1.9 per 1000 newborns and may be more frequent in developing countries. There is strong evidence for the use of inhaled nitric oxide (iNO) and extra corporeal membrane oxygenation (ECMO) in the treatment of PPHN. However, many developing countries do not have access or the technical expertise required for these expensive therapies. Magnesium sulfate is a potent vasodilator and hence has the potential to reduce the high pulmonary arterial pressures associated with PPHN. If magnesium sulfate were found to be effective in the treatment of PPHN, this could be a cost effective and potentially life-saving therapy., Objectives: To evaluate the use of magnesium sulfate compared with placebo or standard ventilator management alone, sildenafil infusion, adenosine infusion, or inhaled nitric oxide on mortality or the use of backup iNO or ECMO in term and near-term newborns (> 34 weeks gestational age) with PPHN., Search Strategy: The standard search strategy of the Cochrane Neonatal Review Group (CNRG) was used. No language restrictions was applied. The Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 1, 2006) and MEDLINE (1966 to April 20, 2007) were searched for relevant randomized and quasi-randomized trials. In addition the reference lists of retrieved articles were reviewed and known experts were contacted to obtain unpublished data., Selection Criteria: All randomised or quasi-random studies were eligible where one of the treatment groups received magnesium sulfate for PPHN., Data Collection and Analysis: Standard methods of the Cochrane Collaboration and the CNRG were used, including independent assessment of trial quality and extraction of data by each author., Main Results: No eligible trials were found, Authors' Conclusions: On the basis of the current lack of evidence, the use of magnesium sulphate cannot be recommended in the treatment of PPHN. Randomised controlled trials are recommended.

Background: Ethnic differences in gastroesophageal reflux disease (GERD) and its complications as well as racial variations in the prevalence of Helicobacter pylori infection are well documented. Nevertheless, the association between reflux disease, H. pylori, and race has not been adequately explored., Aims: We estimated the strength of the association between H. pylori, ethnicity, and the gastroesophageal reflux disease (GERD) spectrum, including Barrett's esophagus, in Asian patients presenting for endoscopy in a tertiary referral center., Methods: Prospectively, we studied 188 consecutive patients with GERD, short- and long-segment Barrett's esophagus, and controls. All patients underwent gastroscopy with gastric biopsies to assess H. pylori, gastritis, and atrophy. CagA status and H. pylori infection were determined by immunoblot assay., Results: The overall prevalence of H. pylori infection was 52.1% (of which 77.6% were cagA(+)) and was lowest in the long-segment Barrett's esophagus group (36.7%) (p = .048). When Barrett's esophagus was present, the length of abnormality was 44.8% shorter in the presence of H. pylori (p = .015). Indians had the highest prevalence of H. pylori (75%) and Malays the lowest (19.6%) (p < .001). In Indians, increased prevalence of H. pylori and cagA-positive strains was associated with reduced severity of GERD (p < .004 and p < .001, respectively), a trend not apparent in the other races. Corpus atrophy, which was almost exclusively associated with H. pylori, was highest in Indians as compared to the other races (p = .013)., Conclusions: Presence of H. pylori was associated with a reduced severity of GERD spectrum disease in Asians, especially Indians. H. pylori infection may protect against complicated reflux disease via induction of corpus atrophy.

Calculations of the activation energy of cyclization of alpha-sulfenyl-, alpha-sulfinyl-, and alpha-sulfonyl-5-hexenyl radicals and their respective 5-methyl-5-hexenyl counterparts at the G3MP2B3 level agree quite well with experimental data. The alpha-sulfinyl-5-hexenyl radical exhibits unexpected regioselectivity (93.99:6.01) via the 5-exo mode, whereas the alpha-sulfenyl- and alpha-sulfonyl-5-hexenyl radicals show increasing branching ratios of the 6-endo product. In contrast, the cyclization of the alpha-sulfur-based 5-methyl-substituted counterparts yields essentially the 6-endo products in all cases; in particular, the alpha-SO2-5-CH3-5-hexenyl radical gives high regioselectivity (98.85:1.15) via the 6-endo mode. Several other 5-substituted moieties, including the electron-withdrawing (CN and NO2) or electron-donating substituents (NH2), also proceed preferentially to 6-endo closure. The alpha-sulfonyl-5-amine-5-hexenyl radical is calculated to proceed to exclusively the 6-endo product, a demonstration of the high synthetic value of this reactant.

Background: The extent of regional lymph node (LN) metastasis is the most important factor in the evaluation of resectability and prognosis of non-small cell lung cancer (NSCLC) to increase the chance of complete cure. The authors attempted to deduce a group of genes from the analysis of mRNA expression profiles of the tumor tissues of NSCLC patients with or without LN metastasis, and make a classification model for better prediction of LN metastasis., Methods: The authors analyzed mRNA expression profiles of 79 NSCLC patients with or without LN metastasis, and deduced the gene signature for the predictive model of LN metastasis in lung cancer. The authors evaluated the predictive accuracy of each of four algorithms by applying them to another set of 33 NSCLC patients. Each algorithm's accuracy was calculated by 10-fold cross-validation, and a combined model showed a level of accuracy that was higher than any one of the better three component algorithms (i.e., ANN, DT, or NB). Avadis, SAS, ArrayXPath, and R-package were the statistical analysis software packages used., Results: The authors selected 949 genes using a classical permutation t test (p < 0.01) and finally obtained a gene signature consisting of 31 genes by adjustment of multiple-hypothesis testing. The LN metastasis prediction model derived from the signature (31 genes) and their characteristic interactions provided a predictive accuracy of 84.85% when applied to a test set of 33 patients., Conclusions: The authors have demonstrated that their gene signature developed by the expression profiling of mRNAs from the primary tissue could predict the LN metastasis status of NSCLC.

This study assesses the loss of life expectancy and potential working life in Taiwan, between 1986 and 2000, from various types of occupational accidents resulting in mortality or permanent disability. The databases on occupational mortality and permanent disability were obtained from the Bureau of Labor Insurance, with this information then being linked to national death registry data to construct the survival function. A Monte Carlo simulation method was subsequently used to extrapolate the survival rate for up to 600 months, to derive the life expectancy for different types of occupational accidents leading to permanent disability (n=81,249). Based upon the life table for each calendar year, the life expectancy lost by age-gender cohort was also estimated for cases of mortality (n=20,001). In those cases resulting in permanent occupational disability, variations in the expected years of life lost (EYLL) were demonstrated by different occupational injuries, ranging from 7.4 to 13.6 years per case. The overall EYLL through permanent occupational disability is found to be almost identical to that of occupational mortality, with a ratio of 1.04:1. We conclude that permanent disability resulting from occupational injuries has a significant impact on society as a whole.

Background: Human leucocyte antigen (HLA) expression is altered in oesophageal carcinomas compared with normal tissue. It is unclear, however, whether this phenotype precedes malignant transformation or results as a consequence of it., Aim: To investigate HLA class I and II expression in Barrett's oesophagus and normal squamous oesophageal tissue., Methods: Asian patients with Barrett's oesophagus (n = 64) and a control group (n = 60) with a normal oesophagus but without reflux symptoms were recruited using endoscopic and histopathological criteria. Tissue samples were stained with monoclonal antibodies specific for HLA-ABC, HLA-DR alpha chain or HLA-DP/DQ/DR, and scored semiquantitatively. The results of immunohistochemical staining were correlated with clinical and histopathological characteristics of patients., Results: Marked expression of HLA-ABC was observed in 50% of Barrett's oesophagus sections as compared with 68.3% of controls (p = 0.038). HLA-DR staining was seen in 51.6% of Barrett's oesophagus samples versus 11.7% of controls (p<0.001). Expression of HLA-DP/DQ/DR was evident in 73.4% of oesophageal intestinal metaplasia tissue as opposed to 18.3% of controls (p<0.001). Importantly, a total loss of HLA-ABC and a concomitant gain of HLA-DP/DQ/DR expression were seen in 37.5% of patients with Barrett's oesophagus but in none of the controls (p<0.001). Interestingly, this phenotype was associated positively with dysplasia (adjusted p, p* = 0.031) but negatively with non-steroidal anti-inflammatory drug use (p* = 0.004)., Conclusions: HLA class I expression is down regulated and class II expression is up regulated in Barrett's oesophagus. As these changes predate malignant transformation, altered major histocompatibility complex expression may be a key event in disease progression, possibly in facilitating evasion from immune surveillance.

We applied periodic density-functional theory (DFT) to investigate the dehydrogenation of ethanol on a Rh/CeO2 (111) surface. Ethanol is calculated to have the greatest energy of adsorption when the oxygen atom of the molecule is adsorbed onto a Ce atom in the surface, relative to other surface atoms (Rh or O). Before forming a six-membered ring of an oxametallacyclic compound (Rh-CH2CH2O-Ce(a)), two hydrogen atoms from ethanol are first eliminated; the barriers for dissociation of the O-H and the beta-carbon (CH2-H) hydrogens are calculated to be 12.00 and 28.57 kcal/mol, respectively. The dehydrogenated H atom has the greatest adsorption energy (E(ads) = 101.59 kcal/mol) when it is adsorbed onto an oxygen atom of the surface. The dehydrogenation continues with the loss of two hydrogens from the alpha-carbon, forming an intermediate species Rh-CH2CO-Ce(a), for which the successive barriers are 34.26 and 40.84 kcal/mol. Scission of the C-C bond occurs at this stage with a dissociation barrier Ea = 49.54 kcal/mol, to form Rh-CH(2(a)) + 4H(a) + CO(g). At high temperatures, these adsorbates desorb to yield the final products CH(4(g)), H(2(g)), and CO(g).

The mechanisms of the reaction of H2XN (X = C, Si) with NO were studied at the level CCSD(T)/aug-cc-PVTZ//B3LYP/6-31++G(d,p). The results indicate that there are two most favorable reaction pathways in the reaction H2CN + NO that have similar energy barriers; these two pathways lead to the formation of HCN + HNO (P1) and H2CO + N2 (P3), with the calculated barriers 11.1 and 10.2 kcal/mol, respectively, with respect to the reactants (H2CN + NO). In the reaction H2SiN + NO the difference of the barriers in these two analogous pathways becomes large, and the preferable pathway shifts to the production of H2SiO + N2 (P3s), which has no barrier with respect to the reactants (H2SiN + NO). A direct reduction of NO into a stable and nontoxic nitrogen molecule with no energy input becomes possible. As a consequence, H2SiN might be an effective reagent to convert the reactive and toxic NO into a benign gas N2 in several NO-producing combustion systems. We offer a possible explanation of the differences between H2CN and H2SiN toward NO as well as the calculated potential energies for these reactions.

Hypothesis: Positron emission tomography can be useful in predicting response of esophageal cancer after preoperative chemo-radiation therapy (CRT). We evaluated the use of integrated computed tomography (CT)-PET among patients with esophageal cancer being considered for resection after CRT., Methods: Three reviewers blinded to clinical and pathologic staging retrospectively reviewed the CT-PET scans of patients with esophageal cancer after preoperative CRT who underwent esophagectomy. [F]-fluoro-2-deoxy-D-glucose uptake for residual malignancy was determined by visual analysis and semi-quantitatively when standardized uptake value (SUV) was > or =4., Results: Forty-two patients underwent esophageal resection. Using visual analysis, CT-PET had a sensitivity of 47% and specificity of 58% in detecting residual malignancy. Using semi-quantitative analysis, 19 patients had a SUV > or =4 in the region of the primary esophageal tumor and were interpreted as having residual malignancy (sensitivity 43%, specificity 50%). Of these 19, six had complete pathologic response to CRT. These false-positive results, due to therapy-induced ulceration detected at endoscopy, limit the use of CT-PET alone in detecting residual malignancy. Similarly, sensitivity (25%) and specificity (73%) of endoscopy/biopsy in detecting residual malignancy were poor. However, the accuracy of CT-PET in detecting residual malignancy was improved when combined with endoscopic findings. In the absence of ulceration at endoscopy, 8 of 8 patients with SUV > or =4 after chemo-radiation had residual malignancy at surgery., Conclusions: CRT-induced ulceration results in false-positive results on CT-PET and precludes accurate detection of residual esophageal tumor. However, CT-PET in combination with endoscopy is useful in identifying patients with a high risk of residual tumor post-CRT.

Objectives: This study attempts to estimate life expectancy and explore the determinants of survival for workers with permanent occupational disabilities., Methods: A database on permanent occupational disabilities occurring between 1986 and 2000 was linked with the national death registry database to construct the survival function. A method with Monte Carlo simulation was used to extrapolate survival for up to 600 months to derive the life expectancy for different disability grades (N=81249). A Cox (proportional hazard) regression was carried out to explore the determinants and to estimate the hazard ratios. Demographic variables, including age, gender, insured wage, severity of disability, injury causes, and organ-system disability, were included in the model as covariates., Results: The results indicate that the survival period for workers suffering permanent occupational disabilities is shorter than that of the general population, amounting to an estimated loss of life expectancy ranging from 5 to 19 years. After adjustment for age and gender, a higher severity of disability, impairment of vital organs or lower extremities, and a lower insured wage had a significant association with shorter survival. Injury types, including transportation incidents, being struck by sliding objects, or a trip, slip or stumble, and collapse injury, indicated hazard ratios of between 1.24 and 1.34, as compared with injuries such as being trapped or caught in machinery., Conclusions: The findings identify major determinants for predicting survival for workers with permanent occupational disabilities; these determinants may be of use in improving the equity of the compensation system for workers.

The optical properties and surface morphologies of sputtering films both without and with use of the ion-assisted deposition (IAD) technique are investigated and compared. Optimal antireflection (AR) coating films with SiO2/Nb2O5 layers, which are grown at 80 degrees C with a 15 cm distance between target and substrate, 55 SCCM oxygen flow (SCCM denotes cubic centimeters per minute at STP), and 1250 W magnetron sputtering power with use of the IAD technique, are used to study the optical performance. By using an atomic force microscope to investigate the surface of the sputtered Nb2O5 films, we find that the films' roughness is 0.185 nm. On a flexible hardness polycarbonate (HPC) substrate with the multilayer AR films, the peak transmittances measured in the visible range are 95.89% and 93.40%, respectively, for coatings with and without use of the IAD sputtering technology. These results are better than those measured with a bare HPC substrate (91.25%) and are well above the commercial liquid-crystal display standard (90%) and flexible application.

Background: Characteristic immune profiles have been demonstrated in gastro-oesophageal reflux disease. However, the genetic basis of gastro-oesophageal reflux disease remains unclear., Aim: To investigate whether certain human leucocyte antigen genes are associated with Barrett's oesophagus., Methods: Asian patients of Malay, Chinese and Indian descent with Barrett's oesophagus (n = 59) and those without reflux symptoms and a normal oesophagus (n =60) were recruited prospectively using endoscopic and histopathological criteria. Human leucocyte antigen class I and II typing was performed using a polymerase chain reaction sequence-specific primers method., Results: The HLA-B7 allele was present in 17% (10 of 59) of patients with Barrett's oesophagus when compared with 0% (zero of 60) of controls [P = 0.0006, corrected P = 0.0171, OR = 25.67]. Subgroup analysis revealed that the HLA-B7 allele was confined almost exclusively to Indians with Barrett's oesophagus, 43% (nine of 21) vs. 0% (zero of 19) Indian controls (P = 0.0014, corrected P = 0.0406, OR = 29.64). No class II associations, protective human leucocyte antigens or extended haplotypes for disease susceptibility were identified., Conclusions: Barrett's oesophagus in Asians, particularly Indians, is strongly positively associated with HLA-B7; reinforcing a genetic component to gastro-oesophageal reflux disease. A larger sample size and different ethnic populations should be genotyped to further confirm this association and identify possible additional risk factors in the human leucocyte antigen locus.

Within the process of calculating the true costs of illness, physical pain is a component of intangible, or human, costs. One method of estimating the monetary value of such costs is the 'contingent valuation method' (CVM), a stated preference method based upon the elicitation of levels of willingness to pay (WTP) facilitated through surveys. This study is amongst the first of its kind to apply CVM to the estimation of the cost of the removal of physical pain resulting from permanently disabling occupational injuries. We assume that a painkilling drug has been invented to mitigate physical pain with the advantages of validity and instantaneity, and without any side effects. The WTP of each of the respondents is determined by a two-step sequential-bidding process. The maximum WTP under log normal distribution was NT 1791 US dollars/day (65.1 US dollars), whilst under Weibull distribution it was NT 1913 US dollars/day (69.6 US dollars). Older respondents, those with higher household income, fall injuries, longer periods of hospitalization, or with a perceived demand for the painkilling drug in excess of one day, displayed a positive independent effect on the eliciting of their WTP. In addition, respondents with higher 'out-of-pocket' expenses, or where the interview took place 2 years or more after the injury occurred, responded with a lower WTP.

Quantum-chemical calculations were performed on the mechanisms of reaction of NCN with NO and NS. Possible mechanisms were classified according to four pathways yielding products in the following four possible groups: N2O/N2S + CN, N2 + NCO/NCS, N2 + CNO/CNS, and CNN + NO/NS, labeled in order from p1/p1s to p4/p4s. The local structures, transition structures, and potential-energy surfaces with respect to the reaction coordinates are calculated, and the barriers are compared. In the NCN + NO reaction, out of several adduct structures, only the nitroso adduct NCNNO lies lower in energy than the reactants, by 21.89 kcal/mol; that adduct undergoes rapid transformation into the products, in agreement with experimental observation. For the NS counterpart, both thionitroso NCNNS and thiazyl NCNSN adducts have energies much lower than those of the reactants, by 43 and 29 kcal/mol, respectively, and a five-membered-ring NCNNS (having an energy lower than those of the reactants by 36 kcal/mol) acts as a bridge in connecting these two adducts. The net energy barriers leading to product channels other than p4s are negative for the NS reaction, whereas those for the NO analogue are all positive. The channel leading to p1 (N2O + CN) has the lowest energy (3.81 kcal/mol), whereas the channels leading to p2 (N2 + NCO) and p2s (N2 + NCS) are the most exothermic (100.94 and 107.38 kcal/mol, respectively).

Birth defects are one of the leading causes of paediatric disability and mortality in developed and developing countries. Data on birth defects from population-based studies originating from developing countries are lacking. One of the objectives of this study was to determine the epidemiology of major birth defects in births during the perinatal period in Kinta district, Perak, Malaysia over a 14-month period, using a population-based birth defect register. There were 253 babies with major birth defects in 17,720 births, giving an incidence of 14.3/1000 births, a birth prevalence of 1 in 70. There were 80 babies with multiple birth defects and 173 with isolated birth defects. The exact syndromic diagnosis of the babies with multiple birth defects could not be identified in 18 (22.5%) babies. The main organ systems involved in the isolated birth defects were cardiovascular (13.8%), cleft lip and palate (11.9%), clubfeet (9.1%), central nervous system (CNS) (including neural tube defects) (7.9%), musculoskeletal (5.5%) and gastrointestinal systems (4.7%), and hydrops fetalis (4.3%). The babies with major birth defects were associated with lower birth weights, premature deliveries, higher Caesarean section rates, prolonged hospitalization and increased specialist care. Among the cohort of babies with major birth defects, the mortality rate was 25.2% during the perinatal period. Mothers with affected babies were associated with advanced maternal age, birth defects themselves or their relatives but not in their other offspring, and significantly higher rates of previous abortions. The consanguinity rate of 2.4% was twice that of the control population. It is concluded that a birth defects register is needed to monitor these developments and future interventional trials are needed to reduce birth defects in Malaysia.