Adipose tissue inflammation, liver fat and insulin resistance in humans

BACKGROUND: Obesity is closely associated with insulin resistance, which is a pathophysiologic condition contributing to the important co-morbidities of obesity, such as the metabolic syndrome and type 2 diabetes mellitus. In obese subjects, adipose tissue is characterized by inflammation (macrophage infiltration, increased expression insulin resistance genes and decreased expression of insulin sensitivity genes). Increased liver fat, without excessive alcohol consumption, is defined as non-alcoholic fatty liver disease (NAFLD) and also associated with obesity and insulin resistance. It is unknown whether and how insulin resistance is associated with altered expression of adipocytokines (adipose tissue-derived signaling molecules), and whether adipose tissue inflammation and NAFLD coexist independent of obesity. Genetic factors could explain variation in liver fat independent of obesity but the heritability of NAFLD is unknown. AIMS: To determine whether acute regulation of adipocytokine expression by insulin in adipose tissue is altered in obesity. To investigate the relationship between adipose tissue inflammation and liver fat content independent of obesity. To assess the heritability of serum alanine aminotransferase (ALT) activity, a surrogate marker of liver fat. METHODS: 55 healthy normal-weight and obese volunteers were recruited. Subcutaneous adipose tissue biopsies were obtained for measurement of gene expression before and during 6 hours of euglycemic hyperinsulinemia. Liver fat content was measured by proton magnetic resonance spectroscopy, and adipose tissue inflammation was assessed by gene expression, immunohistochemistry and lipidomics analysis. Genetic factors contributing to serum ALT activity were determined in 313 twins by statistical heritability modeling. RESULTS: During insulin infusion the expression of insulin sensitivity genes remains unchanged, while the expression of insulin resistance genes increases in obese/insulin-resistant subjects compared to insulin-sensitive subjects. Adipose tissue inflammation is associated with liver fat content independent of obesity. Adipose tissue of subjects with high liver fat content is characterized infiltrated macrophages and increased expression of inflammatory genes, as well as by increased concentrations of ceramides compared to equally obese subjects with normal liver fat. A significant heritability for serum ALT activity was verified. CONCLUSIONS: Effects of insulin infusion on adipose tissue gene expression in obese/insulin-resistant subjects are not only characterized by hyporesponse of insulin sensitivity genes but also by hyperresponse of insulin resistance and inflammatory genes. This suggests that in obesity, the impaired insulin action contributes or self-perpetuates alterations in adipocytokine expression in adipose tissue. Adipose tissue inflammation is increased in subjects with high liver fat compared to equally obese subjects with normal liver fat content. Concentrations of ceramides, the putative mediators of insulin resistance, are increased in adipose tissue in subjects with high liver fat. Genetic factors contribute significantly to variation in serum ALT activity, a surrogate marker of liver fat. These data imply that adipose tissue inflammation and increased liver fat content are closely interrelated, and determine insulin resistance even independent of obesity.

Composite scheme using localized relaxation with non-standard finite difference method for hyperbolic conservation laws

Non-standard finite difference methods (NSFDM) introduced by Mickens [Non-standard Finite Difference Models of Differential Equations, World Scientific, Singapore, 1994] are interesting alternatives to the traditional finite difference and finite volume methods. When applied to linear hyperbolic conservation laws, these methods reproduce exact solutions. In this paper, the NSFDM is first extended to hyperbolic systems of conservation laws, by a novel utilization of the decoupled equations using characteristic variables. In the second part of this paper, the NSFDM is studied for its efficacy in application to nonlinear scalar hyperbolic conservation laws. The original NSFDMs introduced by Mickens (1994) were not in conservation form, which is an important feature in capturing discontinuities at the right locations. Mickens [Construction and analysis of a non-standard finite difference scheme for the Burgers–Fisher equations, Journal of Sound and Vibration 257 (4) (2002) 791–797] recently introduced a NSFDM in conservative form. This method captures the shock waves exactly, without any numerical dissipation. In this paper, this algorithm is tested for the case of expansion waves with sonic points and is found to generate unphysical expansion shocks. As a remedy to this defect, we use the strategy of composite schemes [R. Liska, B. Wendroff, Composite schemes for conservation laws, SIAM Journal of Numerical Analysis 35 (6) (1998) 2250–2271] in which the accurate NSFDM is used as the basic scheme and localized relaxation NSFDM is used as the supporting scheme which acts like a filter. Relaxation schemes introduced by Jin and Xin [The relaxation schemes for systems of conservation laws in arbitrary space dimensions, Communications in Pure and Applied Mathematics 48 (1995) 235–276] are based on relaxation systems which replace the nonlinear hyperbolic conservation laws by a semi-linear system with a stiff relaxation term. The relaxation parameter (λ) is chosen locally on the three point stencil of grid which makes the proposed method more efficient. This composite scheme overcomes the problem of unphysical expansion shocks and captures the shock waves with an accuracy better than the upwind relaxation scheme, as demonstrated by the test cases, together with comparisons with popular numerical methods like Roe scheme and ENO schemes.

‘Enough is enough’: Songs and messages about alcohol in remote Central Australia

This article examines some of the ways in which Australia’s First Peoples have responded to serious community health concerns about alcohol through the medium of popular music. The writing, performing and recording of popular songs about alcohol provide an important example of community-led responses to health issues, and the effectiveness of music in communicating stories and messages about alcohol has been recognised through various government-funded recording projects. This article describes some of these issues in remote Australian Aboriginal communities, exploring a number of complexities that arise through arts-based ‘instrumentalist’ approaches to social and health issues. It draws on the author’s own experience and collaborative work with Aboriginal musicians in Tennant Creek, a remote town in Australia’s Northern Territory.

Visual Impairment in Finnish Children : Prevalence, causes and morbidity of full-term and preterm children with visual impairment born from 1972 through 1989

The prevalence and the causes of childhood visual impairment in Finland during the 1970s and the 1980s were investigated, with special attention to risk factors and further prevention of visual impairment in children. The primary data on children with visual impairment were obtained from the Finnish Register of Visual Impairment, one of the patient registers kept up by the National Research and Development Centre for Welfare and Health (Stakes). The data were supplemented from other registers in Stakes and from patient records of the children in Finnish central hospitals. Visual impairment had been registered in 556 children from a population of 1,138,326 children between ages 0-17, born from 1972 through 1989. The age-specific prevalence of registered visual impairment was 49/100,000 in total. Of them, 23/100,000 were blind children and 11/100,000 were children born prematurely. Boys were impaired more often and more severely than girls. Congenital malformations (52%), systemic diseases (48%), and multiple impairments (50%) were common. The main ophthalmic groups of visual impairment were retinal diseases (35%), ocular malformations (29%), and neuro-ophthalmological disorders (29%). Optic nerve atrophy was the most common diagnosis of visual impairment (22%), followed by congenital cataract (11%), retinopathy of prematurity (10%), and cerebral visual impairment (8%). Genetic factors (42%) were the most common etiologies of visual impairment, followed by prenatal (30%) and perinatal (21%) factors. The highest rates of blindness were seen in cerebral visual impairment (83%) and retinopathy of prematurity (82%). Retinopathy of prematurity had developed in the children born at a gestational age of 32 weeks or earlier. Significant risks for visual impairment were found in the association with preterm births, prenatal infections, birth asphyxia, neonatal respiratory difficulties, mechanical ventilation lasting over two weeks, and hyperbilirubinemia. A rise in blind and multi-impaired children was seen during the study period, associating with increases in the survival of preterm infants with extremely low birth weight. The incidence of visual impairment in children born prematurely was seven times higher than in children born at full term. A reliable profile of childhood visual impairment was obtained. The importance of highly qualified antenatal, neonatal, and ophthalmological care was clearly proved. The risks associated with pre- and perinatal disorders during pregnancy must be emphasized, e.g. the risks associated with maternal infections and the use of tobacco, alcohol, and drugs during pregnancy. Obvious needs for gene therapies and other new treatments for hereditary diseases were also proved.

Craving mediates stress in predicting lapse during alcohol dependence treatment

Background Stress, craving, and depressed mood have all been implicated in alcohol use treatment lapses. Few studies have examined all 3 factors. Progress has been limited because of difficulties with craving assessment. The Alcohol Craving Experience Questionnaire (ACE) is a new measure of alcohol craving. It is both psychometrically sound and conceptually rigorous. This prospective study examines a stress–treatment response model that incorporates mediation by craving and moderation by depressed mood and pharmacotherapy. Methods Five hundred and thirty-nine consecutively treated alcohol-dependent patients voluntarily participated in an abstinence-based 12-week cognitive-behavioral therapy (CBT) program at a hospital alcohol and drug outpatient clinic. Measures of stress, craving, depressed mood, and alcohol dependence severity were administered prior to treatment. Treatment lapse and treatment dropout were assessed over the 12-week program duration. Results Patients reporting greater stress experienced stronger and more frequent cravings. Stronger alcohol craving predicted lapse, after controlling for dependence severity, stress, depression, and pharmacotherapy. Alcohol craving mediated stress to predict lapse. Depressed mood and anticraving medication were not significant moderators. Conclusions Among treatment seeking, alcohol-dependent patients, craving mediated the relationship between stress and lapse. The effect was not moderated by depressed mood or anticraving medication.

Mothers' sleepiness and driving in the postpartum period

The postpartum period is typically a time of increased sleepiness, however little research has investigated mothers' sleepiness whilst driving during this period. The research presented in this thesis details three studies systematically designed to assess postpartum mothers' sleepiness and driving, followed by the utilisation of this information in the development of an information-based program designed to convey pertinent evidence-based information about postpartum sleepiness, sleep, and sleepy driving.

Older male and female drivers in car-dependent settings: How much do they use other modes, and do they compensate for reduced driving to maintain mobility?

Among the societal and health challenges of population ageing is the continued transport mobility of older people who retain their driving licence, especially in highly car-dependent societies. While issues surrounding loss of a driving licence have been researched, less attention has been paid to variations in physical travel by mode among the growing proportion of older people who retain their driving licence. It is unclear how much they reduce their driving with age, the degree to which they replace driving with other modes of transport, and how this varies by age and gender. This paper reports research conducted in the state of Queensland, Australia, with a sample of 295 older drivers (>60 years). Time spent driving is considerably greater than time spent as a passenger or walking across age groups and genders. A decline in travel time as a driver with increasing age is not redressed by increases in travel as a passenger or pedestrian. The patterns differ by gender, most likely reflecting demographic and social factors. Given the expected considerable increase in the number of older women in particular, and their reported preference not to drive alone, there are implications for policies and programmes that are relevant to other car-dependent settings. There are also implications for the health of older drivers, since levels of walking are comparatively low.

Review of Diagnostic Screening Instruments for Alcohol and Other Drug Use and Other Psychiatric Disorders

In recent years there has been a growing recognition that many people with drug or alcohol problems are also experiencing a range of other psychiatric and psychological problems. The presence of concurrent psychiatric or psychological problems is likely to impact on the success of treatment services. These problems vary greatly, from undetected major psychiatric illnesses that meet internationally accepted diagnostic criteria such as those outlined in the Diagnostic and Statistical Manual (DSM-IV) of the American Psychiatric Association (1994), to less defined feelings of low mood and anxiety that do not meet diagnostic criteria but nevertheless impact on an individual’s sense of wellbeing and affect their quality of life. Similarly, the presence of a substance misuse problem among those suffering from a major psychiatric illness, often goes undetected. For example, the use of illicit drugs such as cannabis and amphetamine is higher among those individuals suffering from schizophrenia (Hall, 1992) and the misuse of alcohol in people suffering from schizophrenia is well documented (e.g., Gorelick et al., 1990; Searles et al., 1990; Soyka et al., 1993). High rates of alcohol misuse have also been reported in a number of groups including women presenting for treatment with a primary eating disorder (Holderness, Brooks Gunn, & Warren, 1994), individuals suffering from post-traumatic stress disorder (Seidel, Gusman and Aubueg, 1994), and those suffering from anxiety and depression. Despite considerable evidence of high levels of co-morbidity, drug and alcohol treatment agencies and mainstream psychiatric services often fail to identify and respond to concurrent psychiatric or drug and alcohol problems, respectively. The original review was conducted as a first step in providing clinicians with information on screening and diagnostic instruments that may be used to assess previously unidentified co-morbidity. The current revision was conducted to extend the original review by updating psychometric findings on measures in the original review, and incorporating other frequently used measures that were not previously included. The current revision has included information regarding special populations, specifically Indigenous Australians, older persons and adolescents. The objectives were to: ● update the original review of AOD and psychiatric screening/diagnostic instruments, ● recommend when these instruments should be used, by whom and how they should be interpreted, ● identify limitations and provide recommendations for further research, ● refer the reader to pertinent Internet sites for further information and/or purchasing of assessment instruments.

Alcohol and depression

"A large proportion of people who experience drug problems also experience a range of mental health problems. Similarly, many people who experience mental health problems engage in hazardous drug use. The experience of these co-occurring disorders increases use of treatment services, but is associated with poorer prognosis. The implementation of effective responses has been hindered by the disaggregated systems of care that have been adopted in many countries; many problems are the outcome of poorly organised systems of care that do not reflect the needs of a large proportion of clients who experience various problems. There is a dearth of quality research to guide the development of evidence-based responses to co-occurring drug and mental health problems. This book introduces the reader to the issues, guided by a series of questions. These encourage the reader to consider the evidence about the nature and prevalence of co-occurring disorders and the challenges they create for individuals, the community and service providers. The diverse range of expertise of the contributors provides the opportunity to consider the challenges of navigating the various systems of care from the perspective of consumers, parents and clinicians. Researchers and clinicians examine the available evidence about the links between the various disorders and discuss the implications for treatment through a series of case studies. The reader is guided through evidence-based clinical decision-making. The editor and contributors argue that, while our knowledge and expertise is improving, there is a need to better resource and integrate treatment services to foster the adoption of evidence-based and effective responses. Poor systems of care don’t necessarily cause co-occurring mental health and drug problems, but they can contribute to poor outcomes."--Publisher website

Effect of Chain Length of Alcohol on the Lipase-Catalyzed Esterification of Propionic Acid in Supercritical Carbon Dioxide

The esterification of propionic acid was investigated using three different alcohols, namely, isopropyl alcohol, isobutyl alcohol, and isoamyl alcohol. The variation of conversion with time for the synthesis of isoamyl propionate was investigated in the presence of five enzymes. Novozym 435 showed the highest activity, and this was used as the enzyme for investigating the various parameters that influence the esterification reaction. The Ping-Pong Bi-Bi model with inhibition by both acid and alcohol was used to model the experimental data and determine the kinetics of the esterification reaction.

The effects of the 2004 reduction in the price of alcohol on alcohol-related harm in Finland : A natural experiment based on register data

Changes in alcohol pricing have been documented as inversely associated with changes in consumption and alcohol-related problems. Evidence of the association between price changes and health problems is nevertheless patchy and is based to a large extent on cross-sectional state-level data, or time series of such cross-sectional analyses. Natural experimental studies have been called for. There was a substantial reduction in the price of alcohol in Finland in 2004 due to a reduction in alcohol taxes of one third, on average, and the abolition of duty-free allowances for travellers from the EU. These changes in the Finnish alcohol policy could be considered a natural experiment, which offered a good opportunity to study what happens with regard to alcohol-related problems when prices go down. The present study investigated the effects of this reduction in alcohol prices on (1) alcohol-related and all-cause mortality, and mortality due to cardiovascular diseases, (2) alcohol-related morbidity in terms of hospitalisation, (3) socioeconomic differentials in alcohol-related mortality, and (4) small-area differences in interpersonal violence in the Helsinki Metropolitan area. Differential trends in alcohol-related mortality prior to the price reduction were also analysed. A variety of population-based register data was used in the study. Time-series intervention analysis modelling was applied to monthly aggregations of deaths and hospitalisation for the period 1996-2006. These and other mortality analyses were carried out for men and women aged 15 years and over. Socioeconomic differentials in alcohol-related mortality were assessed on a before/after basis, mortality being followed up in 2001-2003 (before the price reduction) and 2004-2005 (after). Alcohol-related mortality was defined in all the studies on mortality on the basis of information on both underlying and contributory causes of death. Hospitalisation related to alcohol meant that there was a reference to alcohol in the primary diagnosis. Data on interpersonal violence was gathered from 86 administrative small-areas in the Helsinki Metropolitan area and was also assessed on a before/after basis followed up in 2002-2003 and 2004-2005. The statistical methods employed to analyse these data sets included time-series analysis, and Poisson and linear regression. The results of the study indicate that alcohol-related deaths increased substantially among men aged 40-69 years and among women aged 50-69 after the price reduction when trends and seasonal variation were taken into account. The increase was mainly attributable to chronic causes, particularly liver diseases. Mortality due to cardiovascular diseases and all-cause mortality, on the other hand, decreased considerably among the-over-69-year-olds. The increase in alcohol-related mortality in absolute terms among the 30-59-year-olds was largest among the unemployed and early-age pensioners, and those with a low level of education, social class or income. The relative differences in change between the education and social class subgroups were small. The employed and those under the age of 35 did not suffer from increased alcohol-related mortality in the two years following the price reduction. The gap between the age and education groups, which was substantial in the 1980s, thus further broadened. With regard to alcohol-related hospitalisation, there was an increase in both chronic and acute causes among men under the age of 70, and among women in the 50-69-year age group when trends and seasonal variation were taken into account. Alcohol dependence and other alcohol-related mental and behavioural disorders were the largest category in both the total number of chronic hospitalisation and in the increase. There was no increase in the rate of interpersonal violence in the Helsinki Metropolitan area, and even a decrease in domestic violence. There was a significant relationship between the measures of social disadvantage on the area level and interpersonal violence, although the differences in the effects of the price reduction between the different areas were small. The findings of the present study suggest that that a reduction in alcohol prices may lead to a substantial increase in alcohol-related mortality and morbidity. However, large population group differences were observed regarding responsiveness to the price changes. In particular, the less privileged, such as the unemployed, were most sensitive. In contrast, at least in the Finnish context, the younger generations and the employed do not appear to be adversely affected, and those in the older age groups may even benefit from cheaper alcohol in terms of decreased rates of CVD mortality. The results also suggest that reductions in alcohol prices do not necessarily affect interpersonal violence. The population group differences in the effects of the price changes on alcohol-related harm should be acknowledged, and therefore the policy actions should focus on the population subgroups that are primarily responsive to the price reduction.

Case management in action: An examination of two cases in the area of alcohol related brain damage

‘Practice Forum’ provides a forum for social work practitioners to share their practice with others; to describe what they are doing and assess its effectiveness. The practice of case management is applied in a wide range of service delivery models to meet complex client needs. Unfortunately, cost containment and lack of clarity of the role of the case manager has blurred the definition and practice of case management for both the consumer and professional providers. This article examines two cases of a small non-government agency in Melbourne called Alcohol Related Brain Injury Assessment, Accommodation & Support Inc. (ARBIAS) where case management services are delivered to people with alcohol acquired brain damage. The analysis presented here supports the view that continuity of care and intensive relationship building with clients is vital for successful client outcomes and has application to a variety of programs which service chronically disabled clients.

Sikiöaikana päihteille altistuneiden lasten kasvuympäristö ja kehitys

Life of children exposed to alcohol or drugs in utero This study focused on the growth environment, physical development and socio-emotional development of children, aged 16 and under, who had been exposed to alcohol (n=78) or drugs (n=15) in utero. The aim of the study was to obtain a comprehensive picture of the living conditions of these children and to examine the role of the growth environment in their development. The study was carried out using questionnaires, written life stories and interviews. Attachment theory was used as a background theory in the study. Over half of the children exposed to alcohol were diagnosed with foetal alcohol syndrome (FAS), one quarter was diagnosed with foetal alcohol effects (FAE), and one fifth had no diagnosis. Most of the children exposed to drugs had been exposed to either amphetamines or cannabis, and a smaller number to heroin. Some of the children exposed to alcohol were mentally handicapped or intellectually impaired. The children exposed to drugs did not exhibit any serious learning difficulties but a considerable number of them had socio-emotional development problems. Language and speech problems and attention, concentration and social interaction problems were typical among both the children exposed to alcohol and those exposed to drugs. Only one child had been placed into long-term foster care in a family immediately after leaving the maternity hospital. In biological families there had been neglect, violence, mental health problems, crime and unemployment, and many parents were already dead. Two of the children had been sexually abused and four were suspected of having been abused. From the point of view of the children's development, the three most critical issues were 1) the range of illnesses and handicaps that had impaired their functional capacity as a result of their prenatal exposure to alcohol, 2) child's age at the time of placement on a long-term basis, and 3) the number of their traumatic experiences. The relationship with their biological parents after placement also played a role. Children with symptoms were found in all diagnosis categories and types of exposure. Children with the smallest number of symptoms were found among those who had never lived with their biological parents. Almost all children were exhibiting strong symptoms at the time of placement in foster care. In most cases, they were behaving in a disorderly manner towards others, but some children were withdrawn. The most conspicuous feature among those with the most severe symptoms was their disorganized behaviour. Placement in a foster family enhanced the children's development, but did not solve the problems. The foster parents who brought these children up did not receive as much therapy for the children and support for the upbringing as they appear to have needed. In Finland, transfer to long-term custody is based on strict criteria. The rights of children prescribed in the child protection law are not fulfilled in practice. Key words: FASD, FAS, FAE, alcohol exposure, drugs exposure, illegal drugs, early interaction, child development, attachment

Dehydrogenation of Butyl Alcohol in Fixed Catalyst Beds

The vapor-phase dehydrogenation of 1 -butanol to butyraldehyde was studied in a fixed bed of catalyst from 250° to 360° C. Of all the catalysts studied during preliminary investigation, the one containing 90% copper, 8% chromia, and 2% carbon supported on pumice was best, with high activity and selectivity. The data are expressed in the form of a first-order irreversible reaction rate equation. Single-site surface reaction (hydrogen adsorbed) is the rate-controlling mechanism at all the temperatures studied. The rate data obtained in the entire range of experimental conditions fit the rate equation based on this mechanism with a standard deviation of ± 22.8%.