To support the free and open dissemination of research findings and information on alcoholism and alcohol-related problems. To encourage open access to peer-reviewed articles free for all to view.

For full versions of posted research articles readers are encouraged to email requests for "electronic reprints" (text file, PDF files, FAX copies) to the corresponding or lead author, who is highlighted in the posting.


Friday, January 1, 2010

Age-period-cohort modelling of alcohol volume and heavy drinking days in the US National Alcohol Surveys: Divergence in younger and older adult trends

The decomposition of trends in alcohol volume and heavy drinking days into age, period, cohort and demographic effects offers an important perspective on the dynamics of change in alcohol use patterns in the US.

Trend analyses show that while mean values of drinking measures have continued to decline for those aged 26 and older, there has been a substantial increase in both alcohol volume and 5+ days among those aged 18 to 25. Age-period-cohort models indicate a potential positive cohort effect among those born after 1975. However, an alternative interpretation of an age-cohort interaction where drinking falls off more steeply in the late twenties than was the case in the oldest surveys cannot be ruled out. For women only, the 1956–60 birth cohort appears to drink more heavily than those born just before or after. Models also indicate the importance of income, ethnicity, education and marital status in determining these alcohol measures.

Increased heavy drinking among young adults in recent surveys presents a significant challenge for alcohol policy and may indicate a sustained increase in future US alcohol consumption.

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There is a need for safe medications that can effectively support recovery by treating symptoms of protracted abstinence in alcoholics that may precipitate relapse e.g., craving and disturbances in sleep and mood.

This proof-of-concept study reports on the effectiveness of gabapentin 1200 mg for attenuating these symptoms in a non treatment-seeking sample of cue-reactive, alcohol-dependent individuals.

Subjects were 33 paid volunteers with current DSM-IV alcohol dependence and a strength of craving rating 1σ or greater for alcohol than water cues. Subjects were randomly assigned to gabapentin or placebo for 1-week and then participated in a within-subjects trial where each was exposed to standardized sets of pleasant, neutral, and unpleasant visual stimuli followed by alcohol or water cues.

We found a significant attenuating effect of gabapentin (vs. placebo) on several measures of subjective craving for alcohol as well as for affectively-evoked craving. Gabapentin was also found to significantly improve several measures of sleep quality. Side effects were minimal, and gabapentin effects were not found to resemble any major classes of abused drugs.

Results suggest that gabapentin may be effective for treating the protracted abstinence phase in alcohol dependence and, hence, that a randomized clinical trial would be an appropriate next step.

The study also suggests the value of cue reactivity studies as proof-of-concept screens for potential anti relapse drugs.

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Estimating risk of alcohol dependence using alcohol screening scores

Brief alcohol counseling interventions can reduce alcohol consumption and related morbidity among non-dependent risky drinkers, but more intensive alcohol treatment is recommended for persons with alcohol dependence.

This study evaluated whether scores on common alcohol screening tests could identify patients likely to have current alcohol dependence so that more appropriate follow-up assessment and/or intervention could be offered.

Based on the prevalence of past-year alcohol dependence in this sample (men: 12.2%; women: 5.8%), zones of the AUDIT and AUDIT-C identified wide variability in the post-screening risk of alcohol dependence in men and women, even among those who screened positive for alcohol misuse.

Among men, AUDIT zones 5–10, 11–14 and 15–40 were associated with post-screening probabilities of past-year alcohol dependence ranging from 18 to 87%, and AUDIT-C zones 5–6, 7–9 and 10–12 were associated with probabilities ranging from 22 to 75%.

Among women, AUDIT zones 3–4, 5–8, 9–12 and 13–40 were associated with post-screening probabilities of past-year alcohol dependence ranging from 6 to 94%, and AUDIT-C zones 3, 4–6, 7–9 and 10–12 were associated with probabilities ranging from 9 to 88%.

AUDIT or AUDIT-C scores could be used to estimate the probability of past-year alcohol dependence among patients who screen positive for alcohol misuse and inform clinical decision-making.

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Association of SOD2, a Mitochondrial Antioxidant Enzyme, with Gray Matter Volume Shrinkage in Alcoholics

Chronic alcoholism leads to gray matter shrinkage and induces the formation of superoxide anions (O2) that can cause neuronal cell death. The mitochondrial superoxide dismutase 2 (SOD2) enzyme is critical in the metabolism of superoxide. An Ala16Val polymorphism putatively affects SOD2 enzyme activity in vivo.

Brain volumes of 76 treatment-seeking alcohol-dependent individuals were measured with a 1.5T MRI. Intracranial tissue margins were manually outlined on coronal sections. Gray matter, white matter, sulcal, and ventricular CSF volumes were estimated using intensity-based K-means clustering. Ala16Val (rs4880) and a second haplotype tagging SNP, rs10370, were genotyped. The q-value package was used to correct for multiple comparisons.

In the alcoholics, cerebrospinal fluid and intra-cranial volumes showed significant differences across the six diplotype categories. The homozygous Ala16-containing diplotype rs10370TT-rs4880GG was associated with lowest gray matter ratio (greater shrinkage; p=0.005). Presence of one or two copies of the low activity Ala16 allele was a risk factor for lower gray matter volume in alcoholics below the median alcohol consumption (p=0.03) but not in alcoholics above this level. White matter ratio was associated with sex (p=0.002) and lifetime total alcohol consumption (p=0.01) but not with diplotypes.

In this exploratory analysis, a putative functional missense variant of SOD2 appears to influence gray matter loss in alcoholics. This may be due to impaired clearance of reactive oxygen species formed as a result of alcohol exposure.

The risk/protective effect was observed in alcoholics with lower levels of lifetime alcohol consumption. Highest levels of exposure may overwhelm the protective action of the SOD2 enzyme.

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Too much of the hard stuff: what alcohol costs the NHS

Consumption of alcohol in the UK has increased by 19 per cent over the last three decades and is now higher than in any other European country. Recent reports indicate that 10.5 million adults in England drink above sensible limits and around 1.1 million have a level of alcohol addiction. Alcohol is the third leading cause of disease burden in developed countries and, as a result, the cost of providing alcohol-related services is escalating. The burden on the NHS will be unsustainable if this continues.

This Briefing, produced with the Royal College of Physicians, outlines the extent of the problem and gives examples of where the NHS is managing problem drinkers effectively and efficiently. The NHS Confederation visited hospitals between August and November 2009 and gathered evidence from members to gain an understanding of the extent of the burden and the ways in which hospitals can improve their services.

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News Release - NIH Opportunity Network to Expand Basic Behavioral and Social Sciences Research

National Institutes of Health (NIH) Director Francis Collins, M.D., Ph.D., today announced the launch of the Basic Behavioral and Social Science Opportunity Network (OppNet), a trans-NIH initiative to expand the agency’s funding of basic behavioral and social sciences research (b-BSSR).

The b-BSSR field studies mechanisms and processes that influence behavior at the individual, group, community and population level. Research results lead to new approaches for reducing risky behaviors and improving the adoption of healthy practices. . . . . .

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Russia fixes minimum vodka price

Russia introduced on Friday a minimum price of vodka in an effort to fight counterfeit alcohol production in the country.

From January 1, any 0.5l vodka bottle selling at below 89 rubles (almost $3) will be outlawed. The price ban is one of the first government steps toward regulating the domestic alcohol market.

First Deputy Prime Minister Viktor Zubkov said earlier other measures in the sphere would be accomplished by July 1, 2010. Theses include the licensing of alcohol supplies, the introduction of a unified excise duty on alcohol, and tougher responsibility for the production and marketing of fake vodka.
. . . . . .

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Thursday, December 31, 2009

Media Release - Positive signs that teenagers increasingly shun the most problematic drugs

More teenagers in England who need it are receiving help for problems involving drug and alcohol use, but fewer have problems severe enough to require treatment for addiction, new national statistics reported today by the National Treatment Agency for Substance Misuse (NTA), show.

The number of teenagers entering treatment for heroin and crack has fallen by a third in four years according to the NTA report ‘Substance misuse among young people – The data for 2008/09’; this echoes the trend already seen in young adults (aged 18-24) in drug treatment.

The overall number of under-18s accessing specialist substance misuse services in England during 2008/9 was 24,053. This is a modest increase of about 150 over 2007/8, and indicates that demand for such services is levelling out. The vast majority of these young people are receiving help for problems associated with the misuse of cannabis and/or alcohol, which are treated with structured counselling. Drug treatment services in England are now widely available and anyone who needs help can get it quickly.

Evidence continues to suggest that overall drug and alcohol use among the general population of young people is declining, and the increasing availability of specialist substance misuse services ensures that many more of the minority who do need help are getting it. . . . . .

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This is the time of the holiday season when New Year's partiers are inundated with warnings about the risks of drinking and driving.

Little is ever heard, though, about the risks of drinking and walking, which can be just as dangerous, said trauma surgeon Dr. Thomas Esposito at Loyola University Health System in Maywood.

"Alcohol impairs your physical ability to walk and to drive," Esposito said. "It impairs your judgment, reflexes and coordination. It's nothing more than a socially acceptable, over-the-counter stimulant/depressant."

A trauma surgeon for more than 20 years, Esposito has witnessed the tragic aftermath of drunken walking professionally and personally. Several years ago, Esposito's cousin opted to walk instead of driving home from a party where he had been drinking.

"A driver, who I don't believe was intoxicated, did not see him and hit him and he was killed," said Esposito, who is also professor of surgery and chief of the division of trauma, surgical critical care and burns in the department of surgery, Loyola University Chicago Stritch School of Medicine. "They found him on the side of the road on New Year's Day." . . . . .

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Alcohol consumption and non-Hodgkin lymphoma survival

Epidemiological studies have shown that moderate alcohol drinkers have a lower death rate for all causes. Alcohol drinking has also been associated with reduced risk of non-Hodgkin lymphoma (NHL).

Here, we examined the role of alcohol consumption on NHL survival by type of alcohol consumed and NHL subtype.

Compared to never drinkers, wine drinkers experienced better overall survival (75% vs. 69% five-year survival rates, p-value for log-rank test = 0.030) and better disease free survival (70% vs. 67% five-year disease-free survival rates, p-value for log-rank test = 0.049). Analysis by NHL subtype shows that the favorable effect of wine consumption was mainly seen for patients diagnosed with diffuse large B-cell lymphoma (DLBCL) (wine drinkers for more than 25 years vs. never drinkers: HR = 0.36, 95% CI 0.14–0.94 for overall survival; HR = 0.38, 95% CI 0.16–0.94 for disease-free survival), and the adverse effect of liquor consumption was also observed among DLBCL patients (liquor drinkers vs. never drinkers: HR=2.49, 95% CI 1.26–4.93 for disease-free survival).

Our results suggest a moderate relationship between pre-diagnostic alcohol consumption and NHL survival, particularly for DLBCL. The results need to be replicated in larger studies.

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SAMHSA’s Award-Winning Newsletter November/December 2009, Volume 17, Number 6

In this issue:

Screening, Brief Interventions: New Populations, Effectiveness Data

Pamela S. Hyde Sworn in as New Administrator

Parity Law: Lessons Learned from California

Voice Awards Honor Consumer Leaders

TIP 52: Treatment Guide to Clinical Supervision

Guidelines: Responding to Mental Health Crises

Substance-Exposed Infants: How States Help

Gender Differences in Adolescents

New Wallet Cards for 1-800-662-HELP

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Latest IAS Alcohol Alert available

The final 'Alcohol Alert' magazine of 2009 has been released by the Institute of Alcohol Studies (IAS), reporting and commenting on some of the main goings on over the last quarter. All articles can be accessed individually from the above link.

Wednesday, December 30, 2009

The Good-for-You Gimlet?

Some spirit makers boast natural ingredients and nutritional additives in an effort to attract a health-conscious clientele. But can alcohol really be healthy? . . . . .

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Cannabis as a substitute for alcohol and other drugs

Substitution can be operationalized as the conscious choice to use one drug (legal or illicit) instead of, or in conjunction with, another due to issues such as: perceived safety; level of addiction potential; effectiveness in relieving symptoms; access and level of acceptance. This practice of substitution has been observed among individuals using cannabis for medical purposes. This study examined drug and alcohol use, and the occurrence of substitution among medical cannabis patients.

Fifty three percent of the sample currently drinks alcohol, 2.6 was the average number of drinking days per week, 2.9 was the average number of drinks on a drinking occasion. One quarter currently uses tobacco, 9.5 is the average number of cigarettes smoked daily. Eleven percent have used a non-prescribed, non OTC drug in the past 30 days with cocaine, MDMA and Vicodin reported most frequently. Twenty five percent reported growing up in an abusive or addictive household. Sixteen percent reported previous alcohol and/or drug treatment, and 2% are currently in a 12-step or other recovery program. Forty percent have used cannabis as a substitute for alcohol, 26% as a substitute for illicit drugs and 66% as a substitute for prescription drugs. The most common reasons given for substituting were: less adverse side effects (65%), better symptom management (57%), and less withdrawal potential (34%) with cannabis.

The substitution of one psychoactive substance for another with the goal of reducing negative outcomes can be included within the framework of harm reduction. Medical cannabis patients have been engaging in substitution by using cannabis as an alternative to alcohol, prescription and illicit drugs

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Functional characterization of human variants of the mu-opioid receptor gene

Opioids and their receptors have an important role in analgesia and alcohol and substance use disorders (ASUD). We have identified several naturally occurring amino acid changing variants of the human mu-opioid receptor (MOR), and assessed the functional consequences of these previously undescribed variants in stably expressing cell lines. Several of these variants had altered trafficking and signaling properties.

We found that an L85I variant showed significant internalization in response to morphine, in contrast to the WT MOR, which did not internalize in response to morphine. Also, when L85I and WT receptor were coexpressed, WT MOR internalized with the L85I MOR, suggesting that, in the heterozygous condition, the L85I phenotype would be dominant.

This finding is potentially important, because receptor internalization has been associated with development of tolerance to opiate analgesics. In contrast, an R181C variant abolished both signaling and internalization in response to saturating doses of the hydrolysis-resistant enkephalin [D-Ala2,
N-MePhe4,Gly5-ol]enkephalin (DAMGO). Coexpression of the R181C and WT receptor led to independent trafficking of the 2 receptors. S42T and C192F variants showed a rightward shift in potency of both morphine and DAMGO, whereas the S147C variant displayed a subtle leftward shift in morphine potency.

These data suggest that these and other such variants may have clinical relevance to opioid responsiveness to both endogenous ligands and exogenous drugs, and could influence a broad range of phenotypes, including ASUD, pain responses, and the development of tolerance to morphine.

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Average drinker thinks a unit of wine is twice what it actually is

People drinking spirits at home in England are giving themselves more than double (12 percent extra) what they would get in a pub if they ordered a single shot according to new figures revealed today by the Know Your Limits campaign.

A series of experiments across England found that the average ‘home barman’ pours themselves 57ml when they drink a spirit such as vodka, gin or whisky – 32ml more than a standard single 25ml measure.

If that average English drinker knocked back eight spirits drinks over a week at home, they would be drinking nearly half a litre (456ml) of vodka, gin or whisky, compared to 200ml if they’d ordered the same number of single measures in a pub or bar.

These extra sips equate to 17 units instead of 7.5 units over a week – which can make all the difference for people who might wrongly think they are drinking within the NHS recommended limits of 2-3 units a day for women and 3-4 units a day for men. . . . .

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Heavy in utero ethanol exposure is associated with the use of other drugs of abuse in a high-risk population

Many ethanol dependent women also use other drugs of abuse that may affect pregnancy outcome and long-term child neurodevelopment.

This study investigated the association between drugs of abuse and concurrent use of ethanol in pregnancy.

A study cohort of neonates with FAEE levels above 2
nmol per gram meconium, indicative of heavy in utero ethanol exposure, was identified (n=114). Meconium and hair analyses for the presence of other drugs of abuse were obtained for some of these neonates and the rates of drug exposure were compared with the rates in a cohort of neonates who were tested negative (FAEE below 2nmol per gram meconium) for ethanol exposure (n=622). Odds ratios (ORs) for various drugs were calculated with ethanol exposure.

A 15.5% positive rate for intrauterine ethanol exposure was detected. A high rate of in utero drug exposure was detected in neonates with and without in utero ethanol exposure, 60.5% versus 62.7% respectively.

Neonates with heavy in utero ethanol exposure were almost twice as likely to be exposed to narcotic opiates (OR
=1.90; 95% confidence interval [CI]: 1.13–3.20) and 3.3 times as likely to be exposed to amphetamine (OR=3.30; 95% CI 1.06–10.27) when compared to neonates with no ethanol exposure.

Exposure to cannabinoids predicted less likely exposure to ethanol (OR
=0.61; 95% CI: 0.38–0.98) and no significant difference was noted in the exposure to cocaine (OR=1.24, 95% CI: 0.81–1.91).

Neonates suspected of heavy in utero ethanol exposure should be tested for other drugs of abuse and vice versa. Early detection of drug exposures can facilitate early intervention to both the neonate and the mother, thus decreasing the risk of long-term neurodevelopmental outcomes for the child, including secondary disabilities associated with fetal alcohol spectrum disorder.

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A neurodevelopmental framework for the development of interventions for children with fetal alcohol spectrum disorders

Despite considerable data published on cognitive and behavioral disabilities in children with fetal alcohol spectrum disorders (FASD), relatively little information is available on behavioral or pharmacological interventions for alcohol-affected children.

The main goals of this article, therefore, are to summarize published intervention studies of FASD and to present a neurodevelopmental framework, based on recent findings from a number of disciplines, for designing new therapies for alcohol-affected children.

This framework assumes a neuroconstructionist view, which posits that reciprocal interactions between neural activity and the brain's hardware lead to the progressive formation of intra- and interregional neural connections. In this view, behavioral interventions can be conceptualized as a series of guided experiences that are designed to produce neural activation.

Based on evidence from cognitive neuroscience, it is hypothesized that specific interventions targeting executive attention and self-regulation may produce greater generalizable results than those aimed at domain-specific skills in children with FASD.

In view of reciprocal interactions between environmental effects and neural structures, the proposed framework suggests that the maximum effects of interventions can eventually be achieved by optimally combining behavioral methods and cognition-enhancing drugs.

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Implementation of a shared data repository and common data dictionary for fetal alcohol spectrum disorders research

Many previous attempts by fetal alcohol spectrum disorders researchers to compare data across multiple prospective and retrospective human studies have failed because of both structural differences in the collected data and difficulty in coming to agreement on the precise meaning of the terminology used to describe the collected data.

Although some groups of researchers have an established track record of successfully integrating data, attempts to integrate data more broadly among different groups of researchers have generally faltered. Lack of tools to help researchers share and integrate data has also hampered data analysis. This situation has delayed improving diagnosis, intervention, and treatment before and after birth.

We worked with various researchers and research programs in the Collaborative Initiative on Fetal Alcohol Spectrum Disorders (CI-FASD) to develop a set of common data dictionaries to describe the data to be collected, including definitions of terms and specification of allowable values. The resulting data dictionaries were the basis for creating a central data repository (CI-FASD Central Repository) and software tools to input and query data. Data entry restrictions ensure that only data that conform to the data dictionaries reach the CI-FASD Central Repository.

The result is an effective system for centralized and unified management of the data collected and analyzed by the initiative, including a secure, long-term data repository. CI-FASD researchers are able to integrate and analyze data of different types, using multiple methods, and collected from multiple populations, and data are retained for future reuse in a secure, robust repository.

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Zebrafish fetal alcohol syndrome model: effects of ethanol are rescued by retinoic acid supplement

This study was designed to develop a zebrafish experimental model to examine defects in retinoic acid (RA) signaling caused by embryonic ethanol exposure. RA deficiency may be a causative factor leading to a spectrum of birth defects classified as fetal alcohol spectrum disorder (FASD).

Experimental support for this hypothesis using Xenopus showed that effects of treatment with ethanol could be partially rescued by adding retinoids during ethanol treatment.

Previous studies show that treating zebrafish embryos during gastrulation and somitogenesis stages with a pathophysiological concentration of ethanol (100mM) produces effects that are characteristic features of FASD.

We found that treating zebrafish embryos with RA at a low concentration (10−9M) and 100mM ethanol during gastrulation and somitogenesis stages significantly rescued a spectrum of defects produced by treating embryos with 100mM ethanol alone.

The rescued phenotype that we observed was quantitatively more similar to embryos treated with 10−9M RA alone (RA toxicity) than to untreated or 100mM ethanol-treated embryos. RA rescued defects caused by 100mM ethanol treatment during gastrulation and somitogenesis stages that include early gastrulation cell movements (anterior–posterior axis), craniofacial cartilage formation, and ear development.

Morphological evidence also suggests that other characteristic features of FASD (e.g., neural axis patterning) are rescued by RA supplement.

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A 14-year retrospective maternal report of alcohol consumption in pregnancy predicts pregnancy and teen outcomes

Detecting patterns of maternal drinking that place fetuses at risk for fetal alcohol spectrum disorders (FASDs) is critical to diagnosis, treatment, and prevention but is challenging because information on antenatal drinking collected during pregnancy is often insufficient or lacking.

Although retrospective assessments have been considered less favored by many researchers due to presumed poor reliability, this perception may be inaccurate because of reduced maternal denial and/or distortion.

The present study hypothesized that fetal alcohol exposure, as assessed retrospectively during child adolescence, would be related significantly to prior measures of maternal drinking and would predict alcohol-related behavioral problems in teens better than antenatal measures of maternal alcohol consumption.

Drinking was assessed during pregnancy, and retrospectively about the same pregnancy, at a 14-year follow-up in 288 African-American women using well-validated semistructured interviews. Regression analysis examined the predictive validity of both drinking assessments on pregnancy outcomes and on teacher-reported teen behavior outcomes.

Retrospective maternal self-reported drinking assessed 14 years postpartum was significantly higher than antenatal reports of consumption. Retrospective report identified 10.8 times more women as risk drinkers (≥ one drink per day) than the antenatal report. Antenatal and retrospective reports were moderately correlated and both were correlated with the Michigan Alcoholism Screening Test.

Self-reported alcohol consumption during pregnancy based on retrospective report identified significantly more teens exposed prenatally to at-risk alcohol levels than antenatal, in-pregnancy reports.

Retrospective report predicted more teen behavior problems (e.g., attention problems and externalizing behaviors) than the antenatal report. Antenatal report predicted younger gestational age at birth and retrospective report predicted smaller birth size; neither predicted teen IQ. These results suggest that if only antenatal, in-pregnancy maternal report is used, then a substantial proportion of children exposed prenatally to risk levels of alcohol might be misclassified.

The validity of retrospective assessment of prior drinking during pregnancy as a more effective indicator of prenatal exposure was established by predicting more behavioral problems in teens than antenatal report.

Retrospective report can provide valid information about drinking during a prior pregnancy and may facilitate diagnosis and subsequent interventions by educators, social service personnel, and health-care providers, thereby reducing the life-long impact of FASDs.

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Collaborative initiative on fetal alcohol spectrum disorders: methodology of clinical projects

The Collaborative Initiative on Fetal Alcohol Spectrum Disorders (CIFASD) was created in 2003 to further understanding of fetal alcohol spectrum disorders.

Clinical and basic science projects collect data across multiple sites using standardized methodology.

This article describes the methodology being used by the clinical projects that pertain to assessment of children and adolescents.

Domains being addressed are dysmorphology, neurobehavior, 3-D facial imaging, and brain imaging.

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The pros and cons of drinking: Weighing alcohol's effects on the body

A few months ago I received a book called "The Two Martini Diet" (Authorhouse, 2008), in which Jerry Sorlucco documents his success at losing more than 100 pounds without forgoing his daily cocktails. He doesn't break new diet-book ground: Sorlucco follows well-established practices such as controlling portion sizes, eating plenty of fruits and vegetables, and managing his calorie intake and expenditure to accommodate those drinks.

I've kept the book on my desk because I'm intrigued by the interplay between healthful eating and alcohol consumption. Is it really possible, I've wondered, to incorporate alcoholic beverages into a healthful diet and lifestyle, or are those of us who hope it is possible just fooling ourselves? . . . . .

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Monday, December 28, 2009

Stimulus Checkup A closer look at 100 projects funded by the American Recovery and Reinvestment Act.

As this and the last report, 100 Stimulus Projects: A Second Opinion suggest, billions of dollars of stimulus funding have been wasted, mismanaged, or directed towards silly and shortsighted projects. Many projects may not produce the types of jobs that most Americans had hoped for or expected. . . . . .

17. Buffalo Residents Paid to Keep Daily Journal of Malt Liquor and Marijuana Use ($389,357)

Researchers at the State University of New York at Buffalo will receive nearly $390,000 to study young adults who drink malt liquor and smoke marijuana,

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Hospital admissions data 08/09

The finalised 08/09 NI 39 hospital admissions data was published by the North West Public Health Observatory's (NWPHO) Local Alchol Profiles for England (LAPE) earlier this month. Their December E-bulletin highlighted some key findings in comparison with the previous year’s figures: . . . . .

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Polymorphisms in Alcohol Metabolizing Genes and the Risk of Head and Neck Cancer in a Brazilian Population

The incidence of head and neck cancer (HNC) in Brazil has increased substantially in recent years. This increase is likely to be strongly associated with alcohol and tobacco consumption, but genetic susceptibility also should be investigated in this population.

The aim of this study was to evaluate the association of polymorphisms in genes of alcohol metabolism enzymes and the risk of HNC.

Chronic alcohol intake increased approximately four times the risk of HNC. The mutant genotype ADH1B Arg48His was more frequent in controls (12.7%) than HNC patients (5.8%) conferring protection for the disease , 0.21–0.85). Similar results were observed for individuals with ADH1B*2 or ADH1B*2/ADH1C*1 mutated haplotypes. Multiple regression analyses showed that individuals with the mutant genotype ADH1B Arg48His who consume alcohol >30 g/L/day have more than four times the risk for HNC .

The fast alcohol metabolizing genotypes may prevent HNC when the amount of alcohol intake is <30.655>

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Dopamine D2 Receptor Genotype Is Associated with Increased Mortality at a 10-Year Follow-up of Alcohol-Dependent Individuals

Because the TAQ1 A1 allele may be associated with alcohol-related medical illnesses, and medical illnesses in alcohol-dependent individuals are associated with increased mortality, we test the hypothesis that the TAQ1 A1 allele of the DRD2 gene is associated with increased mortality in alcohol-dependent individuals.

The prevalence of the A1 allele differed between the deceased
and living patients and the controls: 47% of the deceased were A1+, compared to 37% of the living patients and 32% of the controls. The frequency of the TAQ1 A1/A2 genotype also differed between the groups. Thus, 43% had the A1/A2 genotype in comparison with 32% in the living patients and 29% in the controls. The TAQ 1 A1 allele frequency differed between the groups. The frequency of A1 allele was 25% in the deceased patients compared to 21% in the living patients and 17% in the controls.

The TAQ I A1 allele of the DRD2 gene (or DRD2 gene region) was associated with increased mortality over a 10-year period in alcohol-dependent individuals.

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Variant in PNPLA3 is associated with alcoholic liver disease

Two genome-wide association studies (GWAS) have described associations of variants in PNPLA3 with nonalcoholic fatty liver and plasma liver enzyme levels.

We investigated the contributions of these variants to liver disease in Mestizo subjects with a history of alcohol dependence.

We found that rs738409 in
PNPLA3 is strongly associated with alcoholic liver disease and clinically evident alcoholic cirrhosis.

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