The attractive female body weight and female body dissatisfaction in 26 countries across 10 world regions : results of the international body project 1

This study reports results from the first International Body Project (IBP-I), which surveyed 7,434 individuals in 10 major world regions about body weight ideals and body dissatisfaction. Participants completed the female Contour Drawing Figure Rating Scale (CDFRS) and self-reported their exposure to Western and local media. Results indicated there were significant cross-regional differences in the ideal female figure and body dissatisfaction, but effect sizes were small across highsocioeconomic-status (SES) sites. Within cultures, heavier bodies were preferred in low-SES sites compared to high-SES sites in Malaysia and South Africa (ds = 1.94-2.49) but not in Austria. Participant age, body mass index (BMI), and Western media exposure predicted body weight ideals. BMI and Western media exposure predicted body dissatisfaction among women. Our results show that body dissatisfaction and desire for thinness is commonplace in high-SES settings across world regions, highlighting the need for international attention to this problem.

Hydrogen sulfide attenuates carbon tetrachloride-induced hepatotoxicity, liver cirrhosis and portal hypertension in rats

BACKGROUND : Hydrogen sulfide (H(2)S) displays vasodilative, anti-oxidative, anti-inflammatory and cytoprotective activities. Impaired production of H(2)S contributes to the increased intrahepatic resistance in cirrhotic livers. The study aimed to investigate the roles of H(2)S in carbon tetrachloride (CCl(4))-induced hepatotoxicity, cirrhosis and portal hypertension.

METHODS AND FINDINGS : Sodium hydrosulfide (NaHS), a donor of H(2)S, and DL-propargylglycine (PAG), an irreversible inhibitor of cystathionine γ-lyase (CSE), were applied to the rats to investigate the effects of H(2)S on CCl(4)-induced acute hepatotoxicity, cirrhosis and portal hypertension by measuring serum levels of H(2)S, hepatic H(2)S producing activity and CSE expression, liver function, activity of cytochrome P450 (CYP) 2E1, oxidative and inflammatory parameters, liver fibrosis and portal pressure. CCl(4) significantly reduced serum levels of H(2)S, hepatic H(2)S production and CSE expression. NaHS attenuated CCl(4)-induced acute hepatotoxicity by supplementing exogenous H(2)S, which displayed anti-oxidative activities and inhibited the CYP2E1 activity. NaHS protected liver function, attenuated liver fibrosis, inhibited inflammation, and reduced the portal pressure, evidenced by the alterations of serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), hyaluronic acid (HA), albumin, tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6 and soluble intercellular adhesion molecule (ICAM)-1, liver histology, hepatic hydroxyproline content and α-smooth muscle actin (SMA) expression. PAG showed opposing effects to NaHS on most of the above parameters.

CONCLUSIONS :  Exogenous H2S attenuates CCl4-induced hepatotoxicity, liver cirrhosis and portal hypertension by its multiple functions including anti-oxidation, anti-inflammation, cytoprotection and anti-fibrosis, indicating that targeting H2S may present a promising approach, particularly for its prophylactic effects, against liver cirrhosis and portal hypertension.

School based education programme to reduce salt intake in children and their families (School-EduSalt): cluster randomised controlled trial

Objective To determine whether an education programme targeted at schoolchildren could lower salt intake in children and their families. Design Cluster randomised controlled trial, with schools randomly assigned to either the intervention or control group. Setting 28 primary schools in urban Changzhi, northern China. Participants 279 children in grade 5 of primary school, with mean age of 10.1; 553 adult family members (mean age 43.8). Intervention Children in the intervention group were educated on the harmful effects of salt and how to reduce salt intake within the schools' usual health education lessons. Children then delivered the salt reduction message to their families. The intervention lasted for one school term (about 3.5 months). Main outcome measures The primary outcome was the difference between the groups in the change in salt intake (as measured by 24 hour urinary sodium excretion) from baseline to the end of the trial. The secondary outcome was the difference between the two groups in the change in blood pressure. Results At baseline, the mean salt intake in children was 7.3 (SE 0.3) g/day in the intervention group and 6.8 (SE 0.3) g/day in the control group. In adult family members the salt intakes were 12.6 (SE 0.4) and 11.3 (SE 0.4) g/day, respectively. During the study there was a reduction in salt intake in the intervention group, whereas in the control group salt intake increased. The mean effect on salt intake for intervention versus control group was -1.9 g/day (95% confidence interval -2.6 to -1.3 g/day; P<0.001) in children and -2.9 g/day (-3.7 to -2.2 g/ day; P<0.001) in adults. The mean effect on systolic blood pressure was -0.8 mm Hg (-3.0 to 1.5 mm Hg; P=0.51) in children and -2.3 mm Hg (-4.5 to -0.04 mm Hg; P<0.05) in adults. Conclusions An education programme delivered to primary school children as part of the usual curriculum is effective in lowering salt intake in children and their families. This offers a novel and important approach to reducing salt intake in a population in which most of the salt in the diet is added by consumers.

Enhancement of the antifouling properties and filtration performance of poly(ethersulfone) ultrafiltration membranes by incorporation of nanoporous titania nanoparticles

Nanoporous titania nanoparticles (NTNs) were synthesized and used as an additive at a low concentration of 0.1-1 wt % in the fabrication of poly(ethersulfone) (PES) ultrafiltration membranes via non-solvent-induced phase separation. The structure and properties of nanoparticles were characterized using nitrogen sorption, X-ray diffraction, scanning electron microscopy, and transmission electron microscopy. The NTNs have a size distribution with a particle size of mainly <100 nm and have a Brunauer, Emmett, and Teller surface area of ∼100 m2 g-1. The modified membranes were fabricated and investigated in terms of their pure water flux, solute rejection, and fouling resistance. The water permeability and molecular weight cutoffs (MWCOs) of membranes were determined under constant-pressure filtration in dead-end mode at 100 kPa. The membrane fouling resistance was characterized under constant flux operation using bovine serum albumin as a model foulant. The membranes were characterized in terms of morphology, porosity, pore size distribution, energy-dispersive X-ray spectroscopy, contact angle goniometry, surface free energy, and viscosity of the dope solution. Overall, the modified membrane showed increased wettability and reduced surface free energy and pore size. The modified UF membrane with 0.5 wt % NTN loading exhibited improved fouling resistance (fouling rate of 0.58 kPa/min compared to a rate of 0.70 kPa/min for the control membrane) with ∼80% water flux recovery. The same membrane showed an ∼20% increase in water flux, an improvement in MWCO, and a narrower pore size distribution.

The Global Paleomonsoon as seen through speleothem records from Asia and the Americas

The regional monsoons of the world have long been viewed as seasonal atmospheric circulation reversal-analogous to a thermally-driven land-sea breeze on a continental scale. This conventional view of monsoons is now being integrated at a global scale and accordingly, a new paradigm has emerged which considers regional monsoons to be manifestations of global-scale seasonal changes in response to overturning of atmospheric circulation in the tropics and subtropics, and henceforth, interactive components of a singular Global Monsoon (GM) system. The paleoclimate community, however, tends to view 'paleomonsoon' (PM), largely in terms of regional circulation phenomena. In the past decade, many high-quality speleothem oxygen isotope (delta O-18) records have been established from the Asian Monsoon and the South American Monsoon regions that primarily reflect changes in the integrated intensities of monsoons on orbital-to-decadal timescales. With the emergence of these high-resolution and absolute-dated records from both sides of the Equator, it is now possible to test a concept of the 'Global-Paleo-Monsoon' (GPM) on a wide-range of timescales. Here we present a comprehensive synthesis of globally-distributed speleothem delta O-18 records and highlight three aspects of the GPM that are comparable to the modern GM: (1) the GPM intensity swings on different timescales; (2) their global extent; and (3) an anti-phased inter-hemispheric relationship between the Asian and South American monsoon systems on a wide range of timescales.

Deletion of CD39 on natural killer cells attenuates hepatic ischemia/reperfusion injury in mice

Natural killer (NK) cells play crucial roles in innate immunity and express CD39 (Ecto-nucleoside triphosphate diphosphohydrolase 1 [E-NTPD1]), a rate-limiting ectonucleotidase in the phosphohydrolysis of extracellular nucleotides to adenosine. We have studied the effects of CD39 gene deletion on NK cells in dictating outcomes after partial hepatic ischemia/reperfusion injury (IRI). We show in mice that gene deletion of CD39 is associated with marked decreases in phosphohydrolysis of adenosine triphosphate (ATP) and adenosine diphosphate to adenosine monophosphate on NK cells, thereby modulating the type-2 purinergic (P2) receptors demonstrated on these cells. We note that CD39-null mice are protected from acute vascular injury after single-lobe warm IRI, and, relative to control wild-type mice, display significantly less elevation of aminotransferases with less pronounced histopathological changes associated with IRI. Selective adoptive transfers of immune cells into Rag2/common gamma null mice (deficient in T cells, B cells, and NK/NKT cells) suggest that it is CD39 deletion on NK cells that provides end-organ protection, which is comparable to that seen in the absence of interferon gamma. Indeed, NK effector mechanisms such as interferon gamma secretion are inhibited by P2 receptor activation in vitro. Specifically, ATPgammaS (a nonhydrolyzable ATP analog) inhibits secretion of interferon gamma by NK cells in response to interleukin-12 and interleukin-18, providing a mechanistic link between CD39 deletion and altered cytokine secretion. CONCLUSION: We propose that CD39 deficiency and changes in P2 receptor activation abrogate secretion of interferon gamma by NK cells in response to inflammatory mediators, thereby limiting tissue damage mediated by these innate immune cells during IRI.

Analysis of N1-acetyl-N2-formyl-5-methoxykynuramine/N1-acetyl-5-methoxy-kynuramine formation from melatonin in mice

The interactions of melatonin, a potent endogenous antioxidant, with reactive oxygen species generate several products that include N(1)-acetyl-N(2)-formyl-5-methoxykynuramine (AFMK) and N(1)-acetyl-5-methoxy-kynuramine (AMK). The physiological or pathological significance of AFMK/AMK formation during the process of melatonin metabolism in mammals has not been clarified. Using a metabolomic approach in the current study, the AFMK/AMK pathway was thoroughly investigated both in mice and humans. Unexpectedly, AFMK and AMK were not identified in the urine of humans nor in the urine, feces or tissues (including liver, brain, and eyes) in mice under the current experimental conditions. Metabolomic analysis did identify novel metabolites of AMK, i.e. hydroxy-AMK and glucuronide-conjugated hydroxy-AMK. These two newly identified metabolites were, however, not found in the urine of humans. In addition, oxidative stress induced by acetaminophen in the mouse model did not boost AFMK/AMK formation. These data suggest that AFMK/AMK formation is not a significant pathway of melatonin disposition in mice, even under conditions of oxidative stress.

First-principle studies of intermolecular and intramolecular catalysis of protonated cocaine

We have performed a series of first-principles electronic structure calculations to examine the reaction pathways and the corresponding free energy barriers for the ester hydrolysis of protonated cocaine in its chair and boat conformations. The calculated free energy barriers for the benzoyl ester hydrolysis of protonated chair cocaine are close to the corresponding barriers calculated for the benzoyl ester hydrolysis of neutral cocaine. However, the free energy barrier calculated for the methyl ester hydrolysis of protonated cocaine in its chair conformation is significantly lower than for the methyl ester hydrolysis of neutral cocaine and for the dominant pathway of the benzoyl ester hydrolysis of protonated cocaine. The significant decrease of the free energy barrier, ∼4 kcal/mol, is attributed to the intramolecular acid catalysis of the methyl ester hydrolysis of protonated cocaine, because the transition state structure is stabilized by the strong hydrogen bond between the carbonyl oxygen of the methyl ester moiety and the protonated tropane N. The relative magnitudes of the free energy barriers calculated for different pathways of the ester hydrolysis of protonated chair cocaine are consistent with the experimental kinetic data for cocaine hydrolysis under physiologic conditions. Similar intramolecular acid catalysis also occurs for the benzoyl ester hydrolysis of (protonated) boat cocaine in the physiologic condition, although the contribution of the intramolecular hydrogen bonding to transition state stabilization is negligible. Nonetheless, the predictability of the intramolecular hydrogen bonding could be useful in generating antibody-based catalysts that recruit cocaine to the boat conformation and an analog that elicited antibodies to approximate the protonated tropane N and the benzoyl O more closely than the natural boat conformer might increase the contribution from hydrogen bonding. Such a stable analog of the transition state for intramolecular catalysis of cocaine benzoyl-ester hydrolysis was synthesized and used to successfully elicit a number of anticocaine catalytic antibodies.

Urinary metabolites and antioxidant products of exogenous melatonin in the mouse

Exogenous melatonin is widely used for sleep disorders and has potential value in neuroprotection, cardioprotection and as an antioxidant. Here, a novel method is described for the determination of melatonin and six metabolites in mouse urine by use of LC-MS/MS and GC-MS. LC-MS/MS is used for the measurement of melatonin, N1-acetyl-5-methoxykynuramine (AMK), N1-acetyl-N2-formyl-5-methoxykynuramine (AFMK) and 6-hydroxymelatonin (6-HMEL), while GC/MS is used for the determination of N-[2-(5-methoxy-2-oxo-2,3-dihydro-1H-indol-3-yl)-ethyl]-acetamide (2-OMEL) and cyclic 3-hydroxymelatonin (3-HMEL) with detection limits on column of 0.02-0.5 pmol, depending on the metabolite. Following oral administration of melatonin to mice, a 0-24 hr urine collection revealed the presence of melatonin (0.2% dose), 6-HMEL (37.1%) and NAS (3.1%) comprising >90% of the total metabolites; AMK and AFMK were also detected at 0.01% each; 2-OMEL was found at 2.2% of the dose, which is >100 times more than the AMK/AFMK pathway, and comprises >5% of the melatonin-related material detected in mouse urine. 3-HMEL was largely found as a sulfate conjugate. These studies establish sensitive assays for determination of six melatonin metabolites in mouse urine and confirm the potential for antioxidant activity of melatonin through the identification in vivo of AMK and AFMK, ring-opened metabolites with a high capacity for scavenging reactive oxygen species.

Quantitative Myocardial Contrast Echocardiography during Pharmacological Stress for Diagnosis of Coronary Artery Disease: A Systematic Review and Meta-analysis of Diagnostic Accuracy Studies

AIMS: We conducted a meta-analysis to evaluate the accuracy of quantitative stress myocardial contrast echocardiography (MCE) in coronary artery disease (CAD). METHODS AND RESULTS: Database search was performed through January 2008. We included studies evaluating accuracy of quantitative stress MCE for detection of CAD compared with coronary angiography or single-photon emission computed tomography (SPECT) and measuring reserve parameters of A, beta, and Abeta. Data from studies were verified and supplemented by the authors of each study. Using random effects meta-analysis, we estimated weighted mean difference (WMD), likelihood ratios (LRs), diagnostic odds ratios (DORs), and summary area under curve (AUC), all with 95% confidence interval (CI). Of 1443 studies, 13 including 627 patients (age range, 38-75 years) and comparing MCE with angiography (n = 10), SPECT (n = 1), or both (n = 2) were eligible. WMD (95% CI) were significantly less in CAD group than no-CAD group: 0.12 (0.06-0.18) (P < 0.001), 1.38 (1.28-1.52) (P < 0.001), and 1.47 (1.18-1.76) (P < 0.001) for A, beta, and Abeta reserves, respectively. Pooled LRs for positive test were 1.33 (1.13-1.57), 3.76 (2.43-5.80), and 3.64 (2.87-4.78) and LRs for negative test were 0.68 (0.55-0.83), 0.30 (0.24-0.38), and 0.27 (0.22-0.34) for A, beta, and Abeta reserves, respectively. Pooled DORs were 2.09 (1.42-3.07), 15.11 (7.90-28.91), and 14.73 (9.61-22.57) and AUCs were 0.637 (0.594-0.677), 0.851 (0.828-0.872), and 0.859 (0.842-0.750) for A, beta, and Abeta reserves, respectively. CONCLUSION: Evidence supports the use of quantitative MCE as a non-invasive test for detection of CAD. Standardizing MCE quantification analysis and adherence to reporting standards for diagnostic tests could enhance the quality of evidence in this field.

Multivalency effects in Pseudomonas aeruginosa biofilm inhibition and dispersal by glycopeptide dendrimers targeting lectin LecA

The galactose specific lectin LecA partly mediates the formation of antibiotic resistant biofilms by Pseudomonas aeruginosa, an opportunistic pathogen causing lethal airways infections in immunocompromised and cystic fibrosis patients, suggesting that preventing LecA binding to natural saccharides might provide new opportunities for treatment. Here 8-fold (G3) and 16-fold (G4) galactosylated analogs of GalAG2, a tetravalent G2 glycopeptide dendrimer LecA ligand and P. aeruginosa biofilm inhibitor, were obtained by convergent chloroacetyl thioether (ClAc) ligation between 4-fold or 8-fold chloroacetylated dendrimer cores and digalactosylated dendritic arms. Hemagglutination inhibition, isothermal titration calorimetry and biofilm inhibition assays showed that G3 dendrimers bind LecA slightly better than their parent G2 dendrimers and induce complete biofilm inhibition and dispersal of P. aeruginosa biofilms, while G4 dendrimers show reduced binding and no biofilm inhibition. A binding model accounting for the observed saturation of glycopeptide dendrimer galactosyl groups and LecA binding sites is proposed based on the crystal structure of a G3 dendrimer LecA complex.