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SummaryBackgroundAddressing childhood obesity in Latin America requires a package of multisectoral, evidence‐based policies that enable environments conducive to healthy lifestyles.ObjectiveIdentify and examine key elements to translating research into effective obesity policies in Latin America.MethodsWe examined obesity prevention policies through case studies developed with an expert in the specific policy. Policies were selected based on their level of implementation, visibility and potential impact to reduce childhood obesity. They include: (i) excise taxes on sugar sweetened beverages and energy‐dense foods; (ii) front‐of‐package food label legislation; (iii) trans fatty acids removal from processed foods; and (iv) Ciclovías recreativas or ‘open streets’. Case studies were coded to identify components that explained successful implementation and sustainability using the Complex Adaptive Health Systems framework.ResultsThe analysis identified key elements for effective and sustainable policy, including evidence justifying policy; evidence‐based advocacy by civil society; political will; and legislation and skillful negotiations across government, academia, the private sector and civil society. Scientific evidence and evaluation played an important role in achieving tipping points for policies' launch and sustain effective implementation.ConclusionsWell‐coordinated, intersectoral partnerships are needed to successfully implement evidence‐based anti‐obesity policies. Prospective policy research may be useful for advancing knowledge translation.

A mixture of 0.05 N HCl and methanol is capable of completely inhibiting thionin and azure A metachromasia of intestinal mucin, cartilage and mast cell granules after treatment for 2 hours at 58°C. or 48 hours at room temperature. Slight reduction is noted after 2 weeks at 3°C. Cytoplasmic basophilia is completely destroyed after 4 hours of methylation at 58°C. or 48 hours at room temperature. Pancreatic acinar cell cytoplasm appears more resistant, requiring 8 hours at 58°C. and longer than 9 days at room temperature. Methylation at 3°C. is ineffective in inhibiting this basophilia even after 2 weeks. Nuclear and nucleolar basophilia with aniline dyes (azure A and thionin) requires 24 hours of methylation at 58°C. or 14 days at room temperature before there is complete destruction. There is no effect produced by methylation at 3°C. for 2 weeks. Alum hematoxylin staining of these structures is unaffected by the methylation procedure, indicating the different nature of action of this dye complex from the aniline dyes used. Reversal of the methylation procedure or demethylation can be accomplished with 0.5% KMnO4 for ½ hour at room temperature provided the methylation has not been too prolonged. Other oxidants such as periodic, peracetic and chromic acids as well as aqueous HCl and alkali (borax solution) fail to reverse the blockade. The substitution of 0.1 N HCl for the usual 0.05 N HCl in the methylation procedure brings about effective blockade in approximately ½ the time required by the 0.05 H NCl methanol. Despite the removal of cytoplasmic and nuclear basophilia by this method sections treated concomitantly and stained with the Feulgen nucleal procedure demonstrate strong Feulgen reactions indicating selectivity for the acid portion of the nucleic acid involved. Methylation after fixation of tissue in a chromate containing fixative (Zenker acetic) requires more prolonged treatment to inhibit cytoplasmic basophilia than is required after Formalin or 95% alcohol fixation. Otherwise the reactions occur similarly after either of the three fixatives. The positive periodic acid-Schiff reaction of colonic mucin, mixed tumor stroma and cartilage is completely inhibited by prior methylation for 96 hours at 58°C. and the reaction of gastric and small intestine mucins is only moderately reduced at this period. At room temperature no alteration is observed after methylation for 21 days. The positive reaction of human mast cell granules is abolished after 72 hours of treatment at 58°C. and is only moderately affected after treatment for 21 days at room temperature.

Alcohol (ethanol) and 3,4-methylenedioxymethamphetamine (MDMA, ecstasy) are frequently co-abused, but recent findings indicate a harmful drug interaction between these two agents. In our previous study, we showed that MDMA exposure inhibits the activity of the acetaldehyde (ACH) metabolizing enzyme, aldehyde dehydrogenase2 (ALDH2). Based on this finding, we hypothesized that the co-administration of MDMA and ethanol would reduce the metabolism of ACH and result in increased accumulation of ACH. Rats were treated with MDMA or vehicle and then administered a single dose of ethanol. Liver ALDH2 activity decreased by 35% in the MDMA-treated rats compared to control rats. The peak concentration and the area under the concentration versus time curve of plasma ACH were 31% and 59% higher, respectively, in the MDMA-ethanol group compared to the ethanol-only group. In addition, the MDMA-ethanol group had 80% higher plasma transaminase levels than the ethanol-only group, indicating greater hepatocellular damage. Our results not only support a drug interaction between MDMA and ethanol but a novel underlying mechanism for the interaction.

IntroductionHeavy alcohol use and alcohol use disorder (AUD) continues to rise as a public health problem and increases the risk for disease. Elevated rates of anxiety, depression, sleep disruption and stress are associated with alcohol use. Symptoms may progress to diagnosed neurophysiological conditions and increase risk for relapse if abstinence is attempted. Research on mechanisms connecting the gastrointestinal microbiome to neuropsychological disorders through the gut-brain axis is well-established. Less is known how the oral microbiome and oral microbial-associated biomarkers may signal to the brain. Therefore, a synthesis of research studying relationships between alcohol intake, alcohol-associated neurophysiological symptoms and the oral microbiome is needed to understand the state of the current science. In this paper, we outline our protocol to collect, evaluate and synthesise research focused on associations between alcohol intake and AUD-related neuropsychological disorders with the oral microbiome.Methods and analysisThe search strategy was developed and will be executed in collaboration with a medical research librarian. Studies will be screened by two independent investigators according to the aim of the scoping review, along with the outlined exclusion and inclusion criteria. After screening, data will be extracted and synthesised from the included papers according to predefined demographic, clinical and microbiome methodology metrics.Ethics and disseminationA scoping review of primary sources is needed to synthesise the data on relationships between alcohol use, neuropsychological conditions associated with AUD and the oral microbiome. The proposed scoping review is based on the data from publicly available databases and does not require ethical approval. We expect the results of this synthesis will identify gaps in the growing literature and highlight potential mechanisms linking the oral-brain axis to addiction and other associated neuropsychological conditions. The study findings and results will be disseminated through journals and conferences related to psychology, neuroscience, dentistry and the microbiome.

Aldehyde dehydrogenase 2 (ALDH2) is the major enzyme that metabolizes acetaldehyde produced from alcohol metabolism. Approximately 40-50% of East Asians carry an inactive ALDH2 gene and exhibit acetaldehyde accumulation after alcohol consumption. However, the role of ALDH2 deficiency in the pathogenesis of alcoholic liver injury remains obscure. In the present study, wild-type and ALDH2−/− mice were subjected to ethanol feeding and/or carbon tetrachloride (CCl4) treatment, and liver injury was assessed. Compared with wild-type mice, ethanol-fed ALDH2−/− mice had higher levels of malondialdehyde-acetaldehyde (MAA) adduct and greater hepatic inflammation, with higher hepatic interleukin (IL)-6 expression but surprisingly lower levels of steatosis and serum alanine aminotransferase (ALT). Higher IL-6 levels were also detected in ethanol-treated precision-cut liver slices from ALDH2−/− mice and in Kupffer cells isolated from ethanol-fed ALDH2−/− mice than those levels in wild-type mice. In vitro incubation with MAA enhanced the lipopolysaccharide (LPS)-mediated stimulation of IL-6 production in Kupffer cells. In agreement with these findings, hepatic activation of the major IL-6 downstream signaling molecule signal transducer and activator of transcription 3 (STAT3) was higher in ethanol-fed ALDH2−/− mice than in wild-type mice. An additional deletion of hepatic STAT3 increased steatosis and hepatocellular damage in ALDH2−/− mice. Finally, ethanol-fed ALDH2−/− mice were more prone to CCl4-induced liver inflammation and fibrosis than ethanol-fed wild-type mice. Conclusion : ALDH2−/− mice are resistant to ethanol-induced steatosis but prone to inflammation and fibrosis by way of MAA-mediated paracrine activation of IL-6 in Kupffer cells. These findings suggest that alcohol, by way of acetaldehyde and its associated adducts, stimulates hepatic inflammation and fibrosis independent from causing hepatocyte death, and that ALDH2-deficient individuals may be resistant to steatosis and blood ALT elevation, but are prone to liver inflammation and fibrosis following alcohol consumption. (Hepatology 2014;60:146–157)

Glutamic acid is a commonly used linker to form dimeric peptides with enhanced binding affinity than their corresponding monomeric counterparts. We have previously labeled NOTA-Bn-NCS-PEG3-E[c(RGDyK)]2 (NOTA-PRGD2) [1] with [(18)F]AlF and (68)Ga for imaging tumor angiogenesis. The p-SCN-Bn-NOTA was attached to E[c(RGDyK)]2 [2] through a mini-PEG with a thiourea linkage, and the product [1] was stable at radiolabeling condition of 100 °C and pH 4.0 acetate buffer. However, when the same p-SCN-Bn-NOTA was directly attached to the α-amine of E[c(RGDfK)]2 [3], the product NOTA-Bn-NCS-E[c(RGDfK)]2 [4] became unstable under similar conditions and the release of monomeric c(RGDfK) [5] was observed. The purpose of this work was to use HPLC and LC-MS to monitor the decomposition of glutamic acid linked dimeric peptides and their NOTA derivatives. A c(RGDyK) [6] and bombesin (BBN) [7] heterodimer c(RGDyK)-E-BBN [8], and a dimeric bombesin E(BBN)2 [9], both with a glutamic acid as the linker, along with a model compound PhSCN-E[c(RGDfK)] [10] were also studied. All the compounds were dissolved in 0.5 M pH 4.0 acetate buffer at the concentration of 1 mg/mL, and 0.1 mL of each sample was heated at 100 °C for 10 min and the more stable compounds were heated for another 30 min. The samples at both time points were analyzed with analytical HPLC to monitor the decomposition of the heated samples. The samples with decomposition were further analyzed by LC-MS to determine the mass of products from the decomposition for possible structure elucidation. After 10 min heating, the obvious release of c(RGDfK) [5] was observed for NOTA-Bn-NCS-E[c(RGDfK)]2 [4] and Ph-SCN-E[c(RGDfK)] [10]. Little or no release of monomers was observed for the remaining samples at this time point. After further heating, the release of monomers was clearly observed for E[c(RGDyK)]2 [2], E[c(RGDfK)]2 [3], c(RGDyK)-E-BBN [8], and E(BBN)2 [9]. No decomposition or little decomposition was observed for NOTA-Bn-NCS-PEG3-E[c(RGDyK)]2 [1], PEG3-E[c(RGDyK)]2 [11], NOTA-E[c(RGDyK)]2 [12], and NOTA-PEG3-E[c(RGDyK)]2 [13]. The glutamic acid linked dimeric peptides with a free α-amine are labile due to the neighboring amine participation in the hydrolysis. The stability of peptides could be increased by converting the free amine into amide. The instability of thiourea derivatives formed from α-amine was caused by participation of thiol group derived from thiourea.

This report is a summary of Ron Thurman Symposium on the Mechanisms of Alcohol-Induced Hepatic Fibrosis which was organized by The National Institutes of Health in Santa Barbara, California, June 25, 2005. The Symposium and this report highlight the unique aspects by which drinking alcoholic beverages may result in hepatic fibrosis. Acetaldehyde, the first metabolite of ethanol, can upregulate transcription of collagen I directly as well as indirectly by upregulating the synthesis of transforming growth factor-beta 1 (TGF-beta1). Reactive oxygen species (ROS) generated in hepatocytes by alcohol metabolism can activate collagen production in hepatic stellate cells (HSCs) in a paracrine manner. Alcohol-induced hepatocyte apoptotic bodies can be phagocytosed by HSCs and Kupffer cells and result in increased expression of TGF-beta1 and subsequent HSC activation. Kupffer cells may contribute to the activation of HSCs by releasing ROS and TGF- beta1. Innate immunity may suppress hepatic fibrosis by killing activated HSCs and blocking TGF-beta1 signaling. In patients infected with hepatitis C virus (HCV), alcohol may promote hepatic fibrosis by suppressing innate immunity. HCV core and non-structural proteins contribute to HCV-induced hepatic fibrosis. Alcohol and HCV together may promote hepatic fibrosis through increased oxidative stress and upregulation of fibrogenic cytokines. The inactive aldehyde dehydrogenase (ALDH2) and the super-active alcohol dehydrogenase (ADH2) alleles may promote hepatic fibrosis through increased accumulation of acetaldehyde in the liver. Hepatic fibrosis can be reversed by inducing selective apoptosis or necrosis of activated HSCs, or by reverse trans-differentiation of activated HSCs into the quiescent phenotype.

ObjectiveCirculating albumin is negatively associated with adiposity but whether it is associated with increased energy intake, lower energy expenditure or weight gain has not been examined.MethodsIn study 1 (n=238; 146 men), we evaluated whether fasting albumin concentration was associated with 24-h energy expenditure and ad libitum energy intake. In study 2 (n=325;167 men), we evaluated the association between plasma albumin and change in weight and body composition.ResultsAfter adjustment for known determinants of energy intake lower plasma albumin concentration was associated with greater total daily energy intake (β= 89.8 kcal/day per 0.1 g/dl difference in plasma albumin, p=0.0047). No associations were observed between plasma albumin concentrations and 24-h energy expenditure or 24-h respiratory quotient (p>0.2). Over 6 years, volunteers gained on average 7.5 ± 11.7 kg (p<0.0001). Lower albumin concentrations were associated with greater weight [β=3.53 kg, p=0.039 (adjusted for age, sex, follow up time), CI 0.16 to 6.21 per 1 g/dl difference albumin concentration] and fat mass (β=2.3 kg, p=0.022), respectively, but not with changes in fat free mass (p=0.06).ConclusionsLower albumin concentrations were associated with increased ad libitum food intake and weight gain, indicating albumin as a marker of energy intake regulation.Clinical Trial RegistrationClinicalTrials.gov, identifiers NCT00340132, NCT00342732.