Adiponectin and its receptors in patients with chronic hepatitis C

Background/Aims: There is increasing interest in the influence of excess body weight and associated metabolic factors on the liver. In patients with non-alcoholic steatohepatitis, lower levels of adiponectin were associated with higher grades of hepatic steatosis and necroinflammatory activity, suggesting a pathophysiological role for this adipokine in liver disease. Methods: We studied 194 consecutive patients with untreated chronic HCV, to assess the relationship between adiponectin and its receptors and hepatic steatosis, fibrosis and inflammation. Results: Significant negative correlations between serum adiponectin and male gender, body mass index and serum insulin were observed. However, there was no association between serum adiponectin and stage of fibrosis and lower levels of serum adiponectin were associated with the presence of steatosis in males only. In contrast, there was a significant increase in serum adiponectin and hepatic adiponectin immunoreactivity with increasing inflammation. The hepatic mRNA expression of the adiponectin receptors, AdipoR1 and AdipoR2, displayed significant but opposite associations with phosphoenolpyruvate carboxykinase (PEPCK) gene expression, a substitute marker of hepatic insulin sensitivity. Conclusions: In patients with chronic HCV, adiponectin was associated with steatosis only in males and was paradoxically increased with inflammation. Our results suggest that the role of adiponectin in chronic liver diseases may be linked to gender and etiology. (c) 2005 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

The stability and formulation of topical analgesics

High-performance liquid chromatographic methods are developed for the simultaneous determination of various salicylates, their p-hydroxy isomers and nicotinic acid esters. The method is sensitive enough to detect trace amounts (~µM/L)of the product generated from cross reactivity between the drugs and the vehicle. The developed method also allows analysis of various topical products containing salicylate and nicotinate esters in their formulations. Applying this method, the degradation profiles of salicylates, nicotinates, p-hydroxy benzoate, o-methoxy benzoate and aspirin prodrugs in alkaline media are determined. The profile for alkyl salicylate degradation is found to be first order (A---? B) When the alcoholic radical is similar to that of the ester. In alcohol having a radical different from that of the ester function, the degradation is found to proceed through competitive transesterification and hydrolysis. The intermediates are identified following synthesis and isolation. The rate and extent of transesterification depends on the proportion of alcohol present in the system. Equations are presented to model the time profiles of reactant and product concentration. The reactions are base catalysed and the predominant pathway involves a concerted solvent attack upon the salicylate anion. Competitive hydrolysis of both ester components also follows this mechanism at moderate pH values but rates increase under strongly alkaline conditions as direct hydroxide attack becomes significant. In contrast, transesterification is independent of base concentration once full ionization is accomplished. The competitive hydrolysis is modelled using equations involving the dielectric constant of the medium. A range of other esters are also shown to undergo base-catalysed transesterification. In non-alcoholic solution phenyl salicylate undergoes a concentration-dependent oligomerisation which yields salsalate among the products. Competitive transesterification and hydrolysis also occur in products for topical use which have vehicles based upon alcohol, glycol or glycol polymers. Such reactions may compromise stability assessments, pharmaceutical integrity and delivery profiles.

Adult Alternatives for Social Drinking: A Direction

In their survey/study - Adult Alternatives for Social Drinking: A Direction - by John Dienhart and Sandra Strick, Assistant Professors, Department of Restaurant, Hotel and Institutional Management, Purdue University, Dienhart and Strick begin with: “Changes in consumer habits have brought about a change in the business of selling alcoholic drinks and have impacted upon hotel food and beverage operations. The authors surveyed a sample of hotel corporate food and beverage directors to ascertain how they are handling this challenge.” Dienhart and Strick declare that the alcoholic beverage market, sale and consumption thereof, has taken a bit of a hit in contemporary society. “Even to the casual observer, it's obvious that the bar and beverage industry has undergone a great deal of change in the past few years,” say the authors. “Observations include a change in the types of drinks people are ordering, as well as a decrease in the number of drinks being sold,” they qualify. Dienhart and Strick allude to an increase in the federal excise tax, attacks from alcohol awareness groups, the diminished capacity of bars and restaurants to offer happy hours, increased liability insurance premiums as well as third-party liability issues, and people’s awareness of their own mortality as some of the reasons for the change. To quantify some empirical data on beverage consumption the Restaurant, Hotel, and Institutional Management Department of Purdue University conducted a study “… to determine if observed trends could be documented with hard data.” In regards to the subject, the study asks and answers a lot of interesting questions with the results presented to concerned followers via percentages. Typical of the results are: “When asked whether the corporation experienced a change in alcoholic sales in the past year, 67 percent reported a decrease in the amount of alcohol sold.” “Sixty-two percent of the respondents reported an increase in non-alcoholic sales over the past year. The average size of the increase was 8 percent. What Dienhart and Strick observe is that the decrease in alcoholic beverage consumption has resulted in a net increase for non-alcoholic beverage consumption. What are termed specialty drinks are gaining a foothold in the market, say the authors. “These include traditional cocktails made with alcohol-free products, as well as creative new juice based drinks, cream based drinks, carbonated beverages, and heated drinks,” say Dienhart and Strick by way of citation . Another result of the non-alcoholic consumption trend is the emergence of some novel marketing approaches by beer, wine, and spirits producers, including price increases on their alcohol based beverages as well as the introduction of faux alcoholic drinks like non-alcoholic beer and wine. Who or what is the big winner in all of this? That distinction might go to bottled water!

Exercise Training Reduces Liver Fat and Increases Rates of VLDL Clearance, but not VLDL Production in NAFLD

Context Randomised controlled trials in non-alcoholic fatty liver disease (NAFLD) have shown that regular exercise, even without calorie restriction, reduces liver steatosis. A previous study has shown that 16 weeks supervised exercise training in NAFLD did not affect total VLDL kinetics. Objective To determine the effect of exercise training on intrahepatocellular fat (IHCL) and the kinetics of large triglyceride-(TG)-rich VLDL1 and smaller denser VLDL2 which has a lower TG content. Design A 16 week randomised controlled trial. Patients 27 sedentary patients with NAFLD. Intervention Supervised exercise with moderate-intensity aerobic exercise or conventional lifestyle advice (control). Main outcome Very low density lipoprotein1 (VLDL1) and VLDL2-TG and apolipoproteinB (apoB) kinetics investigated using stable isotopes before and after the intervention. Results In the exercise group VO2max increased by 31±6% (mean±SEM) and IHCL decreased from 19.6% (14.8, 30.0) to 8.9% (5.4, 17.3) (median (IQR)) with no significant change in VO2max or IHCL in the control group (change between groups p<0.001 and p=0.02, respectively). Exercise training increased VLDL1-TG and apoB fractional catabolic rates, a measure of clearance, (change between groups p=0.02 and p=0.01, respectively), and VLDL1-apoB production rate (change between groups p=0.006), with no change in VLDL1 -TG production rate. Plasma TG did not change in either group. Conclusion An increased clearance of VLDL1 may contribute to the significant decrease in liver fat following 16 weeks of exercise in NAFLD. A longer duration or higher intensity exercise interventions may be needed to lower plasma TG and VLDL production rate.

The cost of a minimum essential food basket in the Republic of Ireland: Study for six household types.

A Minimum Essential Standard of Living (MESL) is derived from a negotiated consensus on what people believe is a minimum standard. It is a standard of living that meets an individual’s or a household’s physical, psychological and social needs. This is calculated by identifying the goods and services required by different household types in order to meet their needs. While an MESL is based on needs, not wants, it is a standard of living below which nobody should be expected to live. This report focuses on food, one of the 16 elements of the Minimum Essential Standard of Living (MESL) data. It is based on a methodology called Consensual Budget Standards (CBS). The report is presented in the context of increasing concerns about the issue of food poverty in the Republic of Ireland (ROI) and an increase in the number of people reporting that they do not have enough money to buy food. Recent data from The Organisation for Economic Co-operation and Development (OECD) have shown that the number of people believing they cannot afford food doubled from 4.2% in 2008 to 9% in 2014. Data from Eurostat show that in 2013, food and non-alcoholic beverage prices in Ireland were 17% higher than the EU average. Moreover, research by Carney and Maitre, using data from the Survey on Income and Living Conditions (SILC), found that one in ten people are living in food poverty in Ireland. Food poverty is defined as the inability to have an adequate and nutritious diet due to issues of affordability and access to food. This has related effects on health, culture and social participation. The 2013 data from the Survey on Income and Living Conditions (SILC) show that 1.4 million people, almost 31% of the population, suffer from deprivation. This means that they are unable to afford two items from a list of 11 very basic items (of which one is not being able to eat a meal with meat, chicken, fish or a vegetarian equivalent every second day). The highest levels of deprivation are experienced by lone parents (63%), unemployed people (55%) and people not at work because of illness or disability (53%). The experience of the Vincentian Partnership for Social Justice (VPSJ) is that expenditure on food tends to be one of the least important considerations when households are dealing with competing demands on an inadequate income. A Minimum Essential Standard of Living (MESL) is derived from a negotiated consensus on what people believe is a minimum standard. It is a standard of living that meets an individual’s or a household’s physical, psychological and social needs. This is calculated by identifying the goods and services required by different household types in order to meet their needs. While an MESL is based on needs, not wants, it is a standard of living below which nobody should be expected to live. This report focuses on food, one of the 16 elements of the Minimum Essential Standard of Living (MESL) data. It is based on a methodology called Consensual Budget Standards (CBS). The report is presented in the context of increasing concerns about the issue of food poverty in the Republic of Ireland (ROI) and an increase in the number of people reporting that they do not have enough money to buy food. Recent data from The Organisation for Economic Co-operation and Development (OECD) have shown that the number of people believing they cannot afford food doubled from 4.2% in 2008 to 9% in 2014. Data from Eurostat show that in 2013, food and non-alcoholic beverage prices in Ireland were 17% higher than the EU average. Moreover, research by Carney and Maitre, using data from the Survey on Income and Living Conditions (SILC), found that one in ten people are living in food poverty in Ireland. Food poverty is defined as the inability to have an adequate and nutritious diet due to issues of affordability and access to food. This has related effects on health, culture and social participation. The 2013 data from the Survey on Income and Living Conditions (SILC) show that 1.4 million people, almost 31% of the population, suffer from deprivation. This means that they are unable to afford two items from a list of 11 very basic items (of which one is not being able to eat a meal with meat, chicken, fish or a vegetarian equivalent every second day). The highest levels of deprivation are experienced by lone parents (63%), unemployed people (55%) and people not at work because of illness or disability (53%). The experience of the Vincentian Partnership for Social Justice (VPSJ) is that expenditure on food tends to be one of the least important considerations when households are dealing with competing demands on an inadequate income. - See more at: http://www.safefood.eu/Publications/Research-reports/The-cost-of-a-healthy-food-basket.aspx#sthash.RiBpj5no.dpuf A Minimum Essential Standard of Living (MESL) is derived from a negotiated consensus on what people believe is a minimum standard. It is a standard of living that meets an individual’s or a household’s physical, psychological and social needs. This is calculated by identifying the goods and services required by different household types in order to meet their needs. While an MESL is based on needs, not wants, it is a standard of living below which nobody should be expected to live. This report focuses on food, one of the 16 elements of the Minimum Essential Standard of Living (MESL) data. It is based on a methodology called Consensual Budget Standards (CBS). The report is presented in the context of increasing concerns about the issue of food poverty in the Republic of Ireland (ROI) and an increase in the number of people reporting that they do not have enough money to buy food. Recent data from The Organisation for Economic Co-operation and Development (OECD) have shown that the number of people believing they cannot afford food doubled from 4.2% in 2008 to 9% in 2014. Data from Eurostat show that in 2013, food and non-alcoholic beverage prices in Ireland were 17% higher than the EU average. Moreover, research by Carney and Maitre, using data from the Survey on Income and Living Conditions (SILC), found that one in ten people are living in food poverty in Ireland. Food poverty is defined as the inability to have an adequate and nutritious diet due to issues of affordability and access to food. This has related effects on health, culture and social participation. The 2013 data from the Survey on Income and Living Conditions (SILC) show that 1.4 million people, almost 31% of the population, suffer from deprivation. This means that they are unable to afford two items from a list of 11 very basic items (of which one is not being able to eat a meal with meat, chicken, fish or a vegetarian equivalent every second day). The highest levels of deprivation are experienced by lone parents (63%), unemployed people (55%) and people not at work because of illness or disability (53%). The experience of the Vincentian Partnership for Social Justice (VPSJ) is that expenditure on food tends to be one of the least important considerations when households are dealing with competing demands on an inadequate income. - See more at: http://www.safefood.eu/Publications/Research-reports/The-cost-of-a-healthy-food-basket.aspx#sthash.RiBpj5no.dpuf A Minimum Essential Standard of Living (MESL) is derived from a negotiated consensus on what people believe is a minimum standard. It is a standard of living that meets an individual’s or a household’s physical, psychological and social needs. This is calculated by identifying the goods and services required by different household types in order to meet their needs. While an MESL is based on needs, not wants, it is a standard of living below which nobody should be expected to live. This report focuses on food, one of the 16 elements of the Minimum Essential Standard of Living (MESL) data. It is based on a methodology called Consensual Budget Standards (CBS). The report is presented in the context of increasing concerns about the issue of food poverty in the Republic of Ireland (ROI) and an increase in the number of people reporting that they do not have enough money to buy food. Recent data from The Organisation for Economic Co-operation and Development (OECD) have shown that the number of people believing they cannot afford food doubled from 4.2% in 2008 to 9% in 2014. Data from Eurostat show that in 2013, food and non-alcoholic beverage prices in Ireland were 17% higher than the EU average. Moreover, research by Carney and Maitre, using data from the Survey on Income and Living Conditions (SILC), found that one in ten people are living in food poverty in Ireland. Food poverty is defined as the inability to have an adequate and nutritious diet due to issues of affordability and access to food. This has related effects on health, culture and social participation. The 2013 data from the Survey on Income and Living Conditions (SILC) show that 1.4 million people, almost 31% of the population, suffer from deprivation. This means that they are unable to afford two items from a list of 11 very basic items (of which one is not being able to eat a meal with meat, chicken, fish or a vegetarian equivalent every second day). The highest levels of deprivation are experienced by lone parents (63%), unemployed people (55%) and people not at work because of illness or disability (53%). The experience of the Vincentian Partnership for Social Justice (VPSJ) is that expenditure on food tends to be one of the least important considerations when households are dealing with competing demands on an inadequate income. - See more at: http://www.safefood.eu/Publications/Research-reports/The-cost-of-a-healthy-food-basket.aspx#sthash.RiBpj5no.dpuf

Energy drinks in Ireland - a review

Energy drinks have risen in popularity in recent years and are now sold in over 165 countries worldwide. On the island of Ireland, energy drinks advertising accounted for 20% of the total soft drinks market advertising in 2014. In the United States, sales increased by 60% between 2008 and 2012, and in 2006, a staggering 500 new brands of energy drinks were released worldwide. In the UK, the energy drinks market is worth £491 million and is growing by 7% year on year. This report has found an eightfold increase in the number of energy drinks available in 2015 compared to 2002. While no standard definition of an energy drink is used in the scientific literature, it is commonly understood to be a non-alcoholic drink that contains caffeine (usually its main ingredient), taurine, vitamins and sometimes a combination of other ingredients (such as guarana and ginseng, among others), and it is marketed for its perceived or actual benefits as a stimulant, for improving performance and for increasing energy. As this report will highlight, there is some confusion amongst the public as to what the term "energy drink" means, as some soft and sports drinks, while containing little or no caffeine, use the term ‘energy’ in the product label, for example, Lucozade. Both the scientific community and the public have raised health concerns about the caffeine and calorie intakes associated with energy drinks and the use of these drinks as a mixer with alcohol. These concerns are disputed by the energy drinks industry.

Estudo Comparado entre Alcoólicos e Não Alcoólicos: sintomas psicopatológicos: amostra brasileira

Os sintomas psicológicos nos indivíduos consumidores de álcool é o tema investigado neste trabalho, que se dedicou a analisar as diferenças entre grupos de indivíduos alcoólicos e não alcoólicos homens e mulheres. A oportunidade desta investigação se originou no trabalho de psicologia clínica com pacientes alcoólicos e, principalmente, frente às carências bibliográficas no mercado sobre o assunto. O presente trabalho, buscou, portanto, investigar-se, a partir das hipóteses, a intensidade de problemas psicológicos e sintomas psicopatológicos em sujeitos alcoólicos de ambos os sexos. Para tal, foram realizadas entrevistas orientadas para a aplicação do instrumento. O instrumento utilizado na pesquisa foi o SCL 90-R (Symptom Check List 90 - Revised) (DEROGATIS, 1983) que se propõe a medir a intensidade dos sintomas, especificamente em casos de alcoolismo, sendo este instrumento validado no Brasil (LALONI, 2001). Os sintomas psicológicos avaliados foram: Psicose, Relações Interpessoais, Ansiedade, Ideação Paranóide, Hostilidade, Depressão, Fobia e Obsessivo Compulsivo. A população investigada abrangeu pessoas não consumidoras de álcool da comunidade e pessoas alcoólicas pertencentes aos AA (Alcoólicos Anônimos). Os dois grupos pertencem à Região Metropolitana de Porto Alegre no Estado do Rio Grande do Sul, Brasil. A comparação foi abrangente em relação aos aspectos de gênero, pois além de comparar o grupo de alcoólicos e não alcoólicos verificou as relações de gênero, analisando as diferenças entre o grupo de homens e mulheres alcoólicos e não alcoólicos. Os resultados encontrados demonstram que os alcoólicos são mais sintomáticos que os não alcoólicos e as mulheres apresentam-se em relação aos sintomas avaliados com médias mais altas que os homens. Os alcoólicos homens e mulheres não diferem de forma estatisticamente significativa em seus sintomas psicológicos. Da mesma forma homens e mulheres não alcoólicos não diferem em seus sintomas psicológicos. / The subject of this research concerns about psychological symptoms on alcohol consuming individuals, analyzing the differences between groups of alcoholic and non alcoholic individuals, men and women. This investigation arose from the psychological clinic work with alcoholic patients in face of the lack of literature about this subject. Based on the hypothesis we investigated the intensity of psychological problems and psychopathological symptoms in alcoholic individuals of both sexes. We also evaluated the presence and intensity of psychological problems and psychopathological symptoms in non alcoholic individuals of both sexes. For this research we performed interviews oriented to the application of the instrument. The instrument employed in the research was SCL 90-R (Symptom Check List 90 - Revised) (DEROGATIS, 1983) which measures the intensity of the symptoms. The instrument was validated in Brazil (LALONI, 2001) and is specific to evaluate symptoms in case of alcoholism. The psychological symptoms we evaluated were: Psychosis, Interpersonal Relations, Anxiety, Paranoid Ideation, Hostility, Depression, Phobia, and Obsessive Compulsive. The population investigated is formed by non alcohol consuming people and alcoholics belonging to the Anonymous Alcoholics (AA). Both groups are from the Metropolitan Region of Porto Alegre in the southern sate of Rio Grande do Sul, Brazil. The comparison was comprehensive regarding the aspects of gender, since besides comparing the group of alcoholics and non alcoholics, it compared alcoholic men and women among themselves, and non alcoholic men and women as well. The results that were found demonstrate that alcoholics are more symptomatic than non alcoholics and women, regarding the evaluated symptoms, present themselves with higher averages than men. Alcoholic men and women do not expressively differ in their psychological symptoms, as non alcoholic men and women do not expressively differ in their psychological symptoms as well.

A decrease in dkk1, a Wnt inhibitor, contributes to placental and fetal lipid accumulation in an obesity-prone rat model

Placenta, as the sole transport mechanism between mother and fetus, links the maternal physical state and the immediate and life-long outcomes of the offspring. The present study examined the mechanisms behind the effect of maternal obesity on placental lipid accumulation and metabolism. Pregnant Obese Prone (OP) and Obese Resistant (OR) rat strains were fed a control diet throughout gestation. Placentas were collected on gestational d21 for analysis and frozen placental sections were analyzed for fat accumulation as well as β-Catenin and Dkk1 localization. Additionally, DKK1 was overexpressed in JEG3 trophoblast cells, followed by treatment with NEFA and Oil Red O stain quantification and mRNA analysis to determine the relationship between placental DKK1 and lipid accumulation. Maternal plasma and placental NEFA and TG were elevated in OP dams, and offspring of OP dams were smaller than OR. Placental Dkk1 mRNA content was 4-fold lower in OP placentas, and there was a significant increase in β-Catenin accumulation as well as mRNA content of fat transport and TG synthesis enzymes, including Ppar-delta, Fatp1, Fat/Cd36, Lipin1, and Lipin3. There was significant lipid accumulation within the decidual zones in OP but not OR placentas, and the thickness of the decidual and junctional zones was significantly smaller in OP than OR placentas. Overexpression of DKK1 in JEG3 cells decreased lipid accumulation and the mRNA content of PPAR-Delta, FATP1, FAT/CD36, LIPIN1, and LIPIN3. Our results indicate that Dkk1 may be regulating placental lipid metabolism through Wnt-mediated mechanisms. Additionally, recent studies have suggested that maternal obesity may also program early development of non-alcoholic fatty liver disease (NAFLD), rates of which have correlated with the increase in the obesity epidemic. In the current study, livers of OP offspring had significantly increased TG content (P<0.05) and lipid accumulation when compared to offspring of OR dams. Additionally, hepatic Dkk1 mRNA content was significantly decreased in OP livers when compared to OR (P<0.05), and treating H4IIECR rat hepatocyte cells with NEFA showed that Dkk1 mRNA was also decreased in NEFA-treated cells (P<0.05) that also had lipid accumulation. Chromatin Immunoprecipitation (ChIP) analysis of the Dkk1 promoter in fetal livers showed a pattern of histone modifications associated with decreased gene transcription in OP offspring, which agrees with our gene expression data. These results demonstrate that the hepatic Dkk1 gene is epigenetically regulated via histone modification in neonatal offspring in the current model of gestational obesity, and future studies will be needed to determine whether these changes contribute to excessive hepatic lipid accumulation in offspring of obese dams.

Mouse models of diet-induced nonalcoholic steatohepatitis reproduce the heterogeneity of the human disease

International audience

STANDARDIZATION OF CASSAVA MAHEWU FERMENTATION AND ASSESSMENT OF THE EFFECTS OF IRON SOURCES USED FOR FORTIFICATION

Cassava root is the main staple for 70% of the population in Mozambique, particularly in inaccessible rural areas, but is known to be low in iron. Anaemia is a public health problem in mothers and preschool children in Mozambique and up to 40% of these cases are probably due to dietary iron deficiency. The World Health Organization (WHO) and Food and Agriculture Organization of the United Nations (FAO) recognize the fortification of foodstuff as an effective method to remedy dietary deficiencies of micronutrients, including iron. Cassava mahewu, a non-alcoholic fermented beverage is prepared at subsistence level from cassava roots using indigenous procedures. The aim of the study was to standardize mahewu fermentation and investigate if the type of cassava fermented, or the iron compound used for fortification affected the final product. Roots of sweet and bitter varieties of cassava from four districts (Rapale, Meconta, Alto Molocue and Zavala) in Mozambique, were peeled, dried and pounded to prepare flour. Cassava flour was cooked and fermented under controlled conditions (45°C for 24 h). The fermentation period and temperature were set, based on the findings of a pilot study which showed that an end-point pH of about 4.5 was regularly reached after 24 h at 45°C. Cassava mahewu was fortified with ferrous sulfate (FeSO4.7H2O) or ferrous fumarate (C4H2FeO4) at the beginning (time zero) and at the end of fermentation (24 h). The amount of iron added to the mahewu was based on the average of the approved range of iron used for the fortification of maize meal. The mean pH at the endpoint was 4.5, with 0.29% titratable acidity. The pH and acidity were different to those reported in previous studies on maize mahewu, whereas the solid extract of 9.65% was found to be similar. Lactic acid bacteria (LAB) and yeast growth were not significantly different in mahewu fortified with either of the iron compounds. There was no significant difference between cassava mahewu made from bitter or sweet varieties. A standard method for preparation and iron fortification of cassava mahewu was developed. It is recommended that fortification occurs at the end of fermentation when done at household level.

Exploring the role of miR-34a in regulating adipose inflammation during obesity

Background: Obesity is not a new disease, with roots that can be traced back to 400 BC. However, with the staggering increase in individuals that are overweight and obese since the 1980s, now over a quarter of individuals in Europe and the Americas are classed as obese. This presents a global health problem that needs to be addressed with novel therapies. It is now well accepted that obesity is a chronic, low-grade inflammatory condition that could predispose individuals to a number of comorbidities. Obesity is associated with cardiovascular diseases (CVDs) and type 2 diabetes (T2D) as part of “the metabolic syndrome,” and as first identified by Dr Vauge, central distribution of white adipose tissue (WAT) is an important risk factor in the development of these diseases. Subsequently, visceral WAT (vWAT) was shown to be an important factor in this association with CVDs and T2D, and increasing inflammation. As the obese WAT expands, mainly through hypertrophy, there is an increase in inflammation that recruits numerous immune cells to the tissue that further exacerbate this inflammation, causing local and systemic inflammatory and metabolic effects. One of the main types of immune cell involved in this pathogenic process is pro-inflammatory M1 adipose tissue macrophages (ATMs). MicroRNAs (miRNAs) are a species of small RNAs that post-transcriptionally regulate gene expression by targeting gene mRNA, causing its degradation or translational repression. These miRNAs are promiscuous, regulating numerous genes and pathways involved in a disease, making them useful therapeutic targets, but also difficult to study. miR-34a has been shown to increase in the serum, liver, pancreas, and subcutaneous (sc)WAT of patients with obesity, non- alcoholic fatty liver disease (NAFLD) and T2D. Additionally, miR-34a has been shown to regulate a number of metabolic and inflammatory genes in numerous cell types, including those in macrophages. However, the role of miR-34a in regulating vWAT metabolism and inflammation is poorly understood. Hypothesis: miR-34a is dysregulated in the adipose tissue during obesity, causing dysregulation of metabolic and inflammatory pathways in adipocytes and ATMs that contribute to adipose inflammation and obesity’s comorbidities, particularly T2D. Method/Results: The role of miR-34a in adipose inflammation was investigated using a murine miR-34a-/- diet-induced obesity model, and primary in vitro models of adipocyte differentiation and inflammatory bone marrow-derived macrophages (BMDMs). miR-34a was shown to be ubiquitously expressed throughout the murine epididymal (e)WAT of obese high-fat diet (HFD)-fed WT mice and ob/ob mice, as well as omental WAT from patients with obesity. Additionally, miR-34a transcripts were increased in the liver and brown adipose tissue (BAT) of ob/ob and HFD-fed WT mice, compared to WT controls. When miR-34a-/- mice were fed HFD ad libitum for 24 weeks they were significantly heavier than their WT counterparts by the end of the study. Ex vivo examinations showed that miR-34a-/- eWAT had a smaller adipocyte area on chow, which significantly increased to WT levels during HFD-feeding. Additionally, miR-34a-/- eWAT showed basal increases in cholesterol and fatty acid metabolism genes Cd36, Hmgcr, Lxrα, Pgc1α, and Fasn. miR-34a-/- iBAT showed basal reductions in Cebpα and Cebpβ, with increased Pgc1α expression during HFD- feeding. The miR-34a-/- liver additionally showed increased basal transcript expression of Pgc1α, suggesting miR-34a may broadly regulate PGC1α. Accompanying the ex vivo changes in cholesterol and fatty acid metabolism genes, in vitro miR-34a-/- white adipocytes showed increased lipid content. An F4/80high macrophage population was identified in HFD-fed miR-34a-/- eWAT, with increased Il-10 transcripts and serum IL-5 protein. Following these ex vivo observations, BMDMs from WT mice upregulated miR-34a expression in response to TNFα stimulation. Additionally, miR-34a-/- BMDMs showed an ablated CXCL1 response to TNFα. Conclusion: These findings suggest miR-34a has a multi-factorial role in controlling a susceptibility to obesity, by regulating inflammatory and metabolic pathways, potentially through regulation of PGC1α.

Guía de práctica clínica para la enfermedad hepática grasa no alcohólica

Objetivo: Brindar una guía de práctica clínica basada con la evidencia más reciente para el diagnóstico y tratamiento de la Enfermedad Hepática Grasa No alcohólica teniendo en cuenta la efectividad y seguridad de las intervenciones dirigidas a pacientes, personal asistencial, administrativo y entes gubernamentales de cualquier servicio de atención en Colombia. Materiales y métodos: Esta guía fue desarrollada por un equipo multidisciplinario con apoyo de la Asociación Colombiana de Gastroenterología, el Grupo Cochrane ITS y el Instituto de Investigaciones Clínicas de la Universidad Nacional de Colombia. Se desarrollaron preguntas clínicas relevantes y se realizó la búsqueda de guías nacionales e internacionales en bases de datos especializadas. Las guías existentes fueron evaluadas en términos de calidad y aplicabilidad. Una guía cumplió los criterios de adaptación, por lo que se decidió adaptar 3 preguntas clínicas. El Grupo Cochrane realizó la búsqueda sistemática de la literatura. Las tablas de evidencia y recomendaciones fueron realizadas con base a la metodología GRADE. Las recomendaciones de la guía fueron socializadas en una reunión de expertos con entes gubernamentales y pacientes. Resultados: Se desarrolló una guía de práctica clínica basada en la evidencia para el diagnóstico y tratamiento de la Enfermedad Hepática Grasa No alcohólica en Colombia Conclusiones: El diagnóstico y manejo oportuno de la Enfermedad Hepática Grasa No alcohólica contribuirá a disminuir la carga de la enfermedad en Colombia y las enfermedades asociadas

Predictors of violent reconvictions and mortality among impulsive alcoholic violent offenders: A prospective study

Acts of violence lays a great burden on humankind. The negative effects of violence could be relieved by accurate prediction of violent recidivism. However, prediction of violence has been considered an inexact science hampered by scare knowledge of its causes. The study at hand examines risk factors of violent reconvictions and mortality among 242 Finnish male violent offenders exhibiting severe alcoholism and severe externalizing personality disorders. The violent offenders were recruited during a court-ordered 2-month inpatient mental status examination between 1990—1998. Controls were 1210 individuals matched by sex-, age-, and place of birth. After a 9-year non-incarcerated follow-up criminal register and mortality data were obtained from national registers. Risk analyses were applied to estimate odds and relative risk for recidivism and mortality. Risk variables that were included in the analyses were antisocial personality disorder (ASPD), borderline personality disorder (BPD), a comorbidity of ASPD and BPD, childhood adversities, alcohol consumption, age, and monoamine oxidase A (MAOA) genotype. In addition to risk analyses, temperament dimensions (Tridimensional Personality Questionnaire [TPQ]) were assessed. The prevalence of recidivistic acts of violence (32%) and mortality (16%) was high among the offenders. Severe personality disorders and childhood adversities increased the risk for recidivism and mortality both among offenders (OR 2.0–10.4) and in comparison between offenders and controls (RR 4.3–53.0). Offenders having BPD and a history of childhood maltreatment emerged as a group with a particularly poor prognosis. MAOA altered the effects of alcohol consumption and ageing. Alcohol consumption (+2.3%) and age (–7.3%) showed significant effects on the risk for violent reconvictions among the high activity MAOA (MAOA-H) offenders, but not among the low activity MAOA (MAOA-L) offenders. The offenders featured temperament dimensions of high novelty seeking, high harm avoidance, and low reward dependence matching Cloninger’s definition of explosive personality. The fact that the risk for recidivistic acts of violence and mortality accumulated into clearly defined subgroups supports future efforts to provide for evidence based violence prevention and risk assessments among violent offenders.

Hematopoietic malignancies associated with viral and alcoholic hepatitis

Hepatitis C virus (HCV) and hepatitis B virus (HBV) have been associated with hematopoietic malignancies, but data for many subtypes are limited. From the U.S. Surveillance, Epidemiology, and End Results-Medicare database, we selected 61,464 cases (=67 years) with hematopoietic malignancies and 122,531 population-based controls, frequency-matched by gender, age, and year (1993-2002). Logistic regression was used to compare the prevalence of HCV, HBV, and alcoholic hepatitis in cases and controls, adjusted for matching factors, race, duration of Medicare coverage, and number of physician claims. HCV, HBV, and alcoholic hepatitis were reported in 195 (0.3%), 111 (0.2%), and 404 (0.7%) cases and 264 (0.2%), 242 (0.2%), and 798 (0.7%) controls, respectively. HCV was associated with increased risk of diffuse large B-cell lymphoma [odds ratio (OR) 1.52, 95% confidence interval (95% CI) 1.05-2.18], Burkitt lymphoma (OR 5.21, 95% CI 1.62-16.8), follicular lymphoma (OR 1.88, 95% CI 1.17-3.02), marginal zone lymphoma (OR 2.20, 95% CI 1.22-3.95), and acute myeloid leukemia (OR 1.54, 95% CI 1.00-2.37). In contrast, HBV was unrelated to any hematopoietic malignancies. Alcoholic hepatitis was associated with decreased risk of non-Hodgkin lymphoma overall, but increased risk of Burkitt lymphoma. In summary, HCV, but not other causes of hepatitis, was associated with the elevated risk of non-Hodgkin lymphoma and acute myeloid leukemia. HCV may induce lymphoproliferative malignancies through chronic immune stimulation. Copyright © 2008 American Association for Cancer Research.


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