Alcohol-related Disease Research Articles

Ethanol influence on gingival fibroblasts - areal-time in vitro study.

Alcohol consumption is the world's third largest risk factor for disease and disability. According to the WHO report from 2011: 71% of urban respondents ty and 77% of rural respondents admit to alcohol consumption]. Lower socio-economic status and educational levels result in a greater risk of alcohol-related injury, disease and death. Alcohol is a common component of many medicines, as well as an ingredient in many oral hygiene home products. Mouthwashes containing alcohol are considered to inhibit wound healing in the oral cavity. Due to the fact that many different results are described for different concentrations of alcohol at different times, an attemptwas made to visualise the direct impact of 7.2% and 22% alcohol on human gingival fibroblasts. PANsystem 2000 was used for visualisation of the reaction of human gingival fibroblasts isolated from gingiva on ethanol in 2 different concentrations. PANsys 3000 is a multi-system fully-automated cell culture device used for in vitro culture and to study a variety of cell lines under conditions similar to in vivo. Observations were carried out for 48 hours since alcohol addition. Pictures were taken in a continuous process at 5 minute intervalds and combined into a film. Both contamination of 7.2% and 22% ethyl alcohol negatively affected morphology and cell proliferation. Addition of ethanol at a concentration 7.2% enabled cells to regain their ability to divide and recover normal morphology after 10 hours; changes caused by 22% ethanol, however, were irreversible. The obtained results suggest that daily usage of 7.2% alcohol contained in mouthwashes is non-toxic for gingival fibroblasts, and could be recommended after periodontal surgery.

HIMH0021 attenuates ethanol-induced liver injury and steatosis in mice.

Chronic alcohol consumption causes alcohol-induced lipogenesis and promotes hepatic injury by preventing the oxidation of hepatocellular fatty acids through the suppression of the activation of AMP-activated protein kinase (AMPK). HIMH0021, an active flavonoid compound, which is a component of the Acer tegmentosum extract, has been shown to protect against liver damage caused by alcohol consumption. Therefore, in this study, we aimed to determine whether HIMH0021 could regulate alcoholic fatty liver and liver injury in mice. Oral administration of 10 days of Lieber-DeCarli ethanol plus a single binge of 30% ethanol (chronic-plus-binge model) induced steatosis and liver injury and inflammation in mice, which appears similar to the condition observed in human patients with alcohol-related diseases. HIMH0021, which was isolated from the active methanol extract of A. tegmentosum, inhibited alcohol-induced steatosis and attenuated the serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) during hepatocellular alcohol metabolism, both of which promote lipogenesis as well as liver inflammation. Treatment with HIMH0021 conferred protection against lipogenesis and liver injury, inhibited the expression of cytochrome P4502E1, and increased serum adiponectin levels in the mice subjected to chronic-plus-binge feeding. Furthermore, in hepatocytes, HIMH0021 activated fatty acid oxidation by activating pAMPK, which comprises pACC and CPT1a. These findings suggested that HIMH0021 could be used to target a TNFα-related pathway for treating patients with alcoholic hepatitis.

Chapter 13 - Alcohol-related diseases

Alcohol abuse and dependence are serious medical and economic problems in Western countries. Brain changes encountered in alcoholism are manifold and encompass brain atrophy, selective neuronal loss, astroglial, and microglial changes. Alcohol-related disorders are complex multifactorial disorders where the interaction of multiple genes and environment plays an important role in the pathogenesis.

Virtual Morris task responses in individuals in an abstinence phase from alcohol.

The present study was aimed at examining spatial learning and memory, in 33 men and 12 women with alcohol use disorder (AUD) undergoing ethanol detoxification, by using a virtual Morris task. As controls, we recruited 29 men and 10 women among episodic drinkers without a history of alcohol addiction or alcohol-related diseases. Elevated latency to the first movement in all trials was observed only in AUD persons; furthermore, control women had longer latencies compared with control men. Increased time spent to reach the hidden platform in the learning phase was found for women of both groups compared with men, in particular during trial 3. As predicted, AUD persons (more evident in men) spent less time in the target quadrant during the probe trial; however, AUD women had longer latencies to reach the platform in the visible condition during trials 6 and 7 that resulted in a greater distance moved. As for the probe trial, men of both groups showed increased virtual locomotion compared with the women of both groups. The present investigation confirms and extends previous studies showing (i) different gender responses in spatial learning tasks, (ii) some alterations due to alcohol addiction in virtual spatial learning, and (iii) differences between AUD men and AUD women in spatial-behaviour-related paradigms.

Ethanol-induced inhibition of C2C12 muscle cell differentiation

Abstract Alcoholic myopathy affects 40–60% of long-term alcoholics and is more prevalent than other common alcohol-related diseases, such as cirrhosis of the liver. The process by which ethanol consumption leads to the development of myopathy in skeletal muscle is not well understood, and multiple factors are thought to contribute to the progression of the disease. A key event in the formation of skeletal muscle is the fusion of myoblasts to form multinucleated muscle fibers. There are conflicting reports in the literature with regard to the effect of alcohol on fusion of myoblasts during differentiation. The purpose of this study was to address this discrepancy by assessing the effect of ethanol on the differentiation of C2C12 skeletal muscle cells, utilizing the fusion index calculation as a measurement of differentiation. Our results demonstrate a significant reduction in the fusion of myoblasts when they are treated with a physiologically relevant concentration of ethanol at the start of differentiation.

An improved PCR-CTPP assay for the detection of ADH1B Arg48His polymorphism.

ADH1B Arg48His polymorphism is associatedwith the development of alcohol-related diseases. In this study, we aimed to explore an improved polymerase chain reaction with confronting two-pair primers (PCR-CTPP) assay for the detection of ADH1B Arg48His polymorphism. A mismatch was introduced at the 3' end of each of the two allele-specific to increase the specificity of the reaction. But beyond that, a new mismatch at-3 positions of outer primers was designed to decrease the efficiency of the aforementioned primers and depresses the amplification of an internal nonspecific DNA control. A total of 180 samples from healthy volunteers Han Chinese were tested to evaluate this new assay. The protocol of PCR-CTPP was successful for genotyping of ADH1B Arg48His. The results from the improved PCR-CTPP assay were confirmed by Sanger sequencing, and correct genotyping rates were 100%.The genotype frequencies were 49.44% (89 cases) for His/His, 46.67% (84 cases) for Arg/His, and 3.89% (seven cases) for Arg/Arg respectively. This improved PCR-CTPP assay is simple, rapid, cost-effective, and reliable, specific for the detection ofADH1B Arg48His polymorphism in most clinical diagnostic laboratories.

Pneumonia is an independent risk factor for pyogenic liver abscess: A population-based, nested, case-control study.

BackgroundBacteremic pneumonia is considered a potential cause of distal organ abscess formation. Therefore, we hypothesize that pneumonia is a risk factor for pyogenic liver abscess (PLA).The aim of this study is to explore the association between pneumonia and PLA.Methodology/Principal findingsA nationwide, population-based, nested, case–control study was conducted using data from the Taiwan National Health Insurance Research Database. In total, 494 patients with PLA and 1,976 propensity score matched controls were enrolled. Conditional logistic regression was used to estimate adjusted odds ratios (aORs) in patients with exposure to pneumonia before PLA. After matched and adjusted for confounding factors including age, sex, urbanization, income, chronic liver disease, alcohol-related disease, biliary stone, chronic kidney disease, diabetes mellitus, chronic liver disease, and cancer, hospitalization for pneumonia remained an independent risk factor for PLA with an aORs of 2.104 [95% confidence interval (CI) = 1.309–3.379, p = 0.0021]. Moreover, the aORs were significantly higher among patients hospitalized for pneumonia within 30 days (aORs = 10.73, 95% CI = 3.381–34.054), 30–90 days (aORs = 4.698, 95% CI = 1.541–14.327) and 90–180 (aORs = 4.000, 95% CI = 1.158–13.817) days before PLA diagnosis.ConclusionPneumonia is an independent risk factor for subsequent PLA. Moreover, hospitalization for pneumonia within 180 days before PLA diagnosis was associated with an increased risk of PLA.

How do population, general practice and hospital factors influence ambulatory care sensitive admissions: a cross sectional study

BackgroundReducing unplanned hospital admissions is a key priority within the UK and other healthcare systems, however it remains uncertain how this can be achieved. This paper explores the relationship between unplanned ambulatory care sensitive condition (ACSC) admission rates and population, general practice and hospital characteristics. Additionally, we investigated if these factors had a differential impact across 28 conditions.MethodsWe used the English Hospital Episode Statistics to calculate the number of unplanned ACSC hospital admissions for 28 conditions at 8,029 general practices during 2011/12. We used multilevel negative binomial regression to estimate the influence of population (deprivation), general practice (size, access, continuity, quality, A&E proximity) and hospital (bed availability, % day cases) characteristics on unplanned admission rates after adjusting for age, sex and chronic disease prevalence.ResultsPractices in deprived areas (at the 90th centile) had 16% (95% confidence interval: 14 to 18) higher admission rates than those in affluent areas (10th centile). Practices with poorer care continuity (9%; 8 to 11), located closest to A&E (8%; 6 to 9), situated in areas with high inpatient bed availability (14%; 10 to 18) or in areas with a larger proportion of day case admissions (17%; 12 to 21) had more admissions. There were smaller associations for primary care access, clinical quality, and practice size. The strength of associations varied by ACSC. For example, deprivation was most strongly associated with alcohol related diseases and COPD admission rates, while continuity of primary care was most strongly associated with admission rates for chronic diseases such as hypertension and iron-deficiency anaemia.ConclusionsThe drivers of unplanned ACSC admission rates are complex and include population, practice and hospital factors. The importance of these varies markedly across conditions suggesting that multifaceted interventions are required to avoid hospital admissions and reduce costs. Several of the most important drivers of admissions are largely beyond the control of GPs. However, strategies to improve primary care continuity and avoid unnecessary short-stay admissions could lead to improved efficiency.

Alcohol dependence and risk of somatic diseases and mortality: a cohort study in 19 002 men and women attending alcohol treatment.

To (1) estimate sex-specific risks of a comprehensive spectrum of somatic diseases in alcohol-dependent individuals versus a control population, and in the same population to (2) estimate sex-specific risks of dying from the examined somatic diseases. Register-based matched cohort study. Alcohol-dependent individuals were identified from the Copenhagen Alcohol Cohort. Controls were selected randomly from the Danish Civil Registration System. Information on somatic diseases was obtained from the Danish National Patient Registry and causes of death obtained from the Cause of Death Registry. Cox proportional hazards model was applied to estimate hazard ratios (HRs). Denmark. A total of 19 002 alcohol-dependent individuals and 186 767 controls. Outcome variables included 11 disease groups and 29 subgroups, defined according to the International Classification of Diseases (ICD). The main predictor variable was diagnosis of alcohol dependence according to ICD. Alcohol-dependent men and women compared with controls had statistically significantly higher risks of all disease groups and the majority of subgroups when analysed as disease events. HRs were elevated for well-established alcohol-related diseases but also for diseases such as dementia [men, HR=2.0, 95% confidence interval (CI)=1.6-2.3; women, HR=2.4, 95% CI=1.8-3.2], psoriasis (men, HR=4.3, 95% CI=3.5-5.2; women, HR=5.4, 95% CI=3.7-7.8) and breast cancer in men (HR=3.3, 95% CI=1.6-7.0). Similar results were found when disease groups and subgroups were analysed as causes of death. Alcohol-dependent men and women have significantly higher risks of a comprehensive spectrum of somatic diseases, both as disease events and as causes of death, relative to individuals from the general population.

Use of Alcohol and Alcohol-Related Morbidity in Finnish Former Elite Athletes.

The effect of a history of competitive sports on later use of alcohol and occurrence of alcohol-related diseases is poorly known. We investigated how a history of elite level sports was associated with alcohol consumption in middle-age and with alcohol-related morbidity and mortality. The occurrence of alcohol-related diseases and deaths were followed using national registers from 1970 to 2008 among Finnish male former elite athletes (n = 2202) and matched controls (n = 1403) alive in 1970 (mean age = 45.1 yr). Hazard ratios were calculated by Cox proportional hazards model. In 1985, surviving participants questionnaire-reported their alcohol consumption and engagement in physical activity/sports. The risk of any alcohol-related diseases or deaths did not differ between former athletes and controls (hazard ratio = 0.93, 95% confidence interval [CI] = 0.73-1.20, P = 0.59), although the risk was higher among both combat sports athletes and weightlifters compared with endurance sports athletes, shooters or jumpers, and hurdlers (P < 0.05). In 1985, athletes consumed more alcohol (417 g·month, 95% CI = 386-447) compared with controls (397 g·month, 95% CI = 355-441) (P < 0.05). Consumption was lower among endurance sports athletes than among controls (P < 0.05). Team sports athletes consumed more alcohol (P < 0.05), especially beer (P < 0.01), compared with other athletes and controls. Athletes no longer engaged in leisure-time sports consumed more alcohol than those who continued to be physically active (P < 0.05). Overall, former athletes reported higher alcohol consumption than controls. There was no difference in alcohol-related morbidity, but the risk varied between different sports groups. Alcohol consumption after top sports career was greater if participation in leisure-time sports was discontinued.

Alcohol-related hospitalization is associated with increased risk of ischaemic stroke among low-risk patients with atrial fibrillation.

Patients with atrial fibrillation (AF) under the age of 65 and CHA2DS2-VASc risk score of 0 in men or 1 in women are considered to be at low risk for ischaemic stroke, and therefore without benefit of oral anticoagulation therapy. The objective of this study is to assess the incidence and predictors of ischaemic stroke among low-risk patients with AF identified from a National Patient Register. A retrospective study of 25252 low-risk AF patients (age 18-64) out of total 345123 AF patients identified from the Swedish Nationwide Patient Register for the period 1 January 2006 to 31 December 2012. During a median follow-up of 5.0 (interquartile range 2.9-6.8) years, ischaemic stroke occurred at an annual rate of 0.34 per 100 patient-years [95% confidence interval (CI) 0.31-0.38]. Significant predictors of stroke were age, hazard ratio (HR) 1.06 (CI 1.05-1.08) per incremental year, and previous alcohol-related hospitalization HR 2.01 (CI 1.45-2.79). Intracerebral bleeding events were rare and not statistically different HR 2.05 (CI 0.76-5.56) between patients with and without alcohol-related hospitalizations. Use of oral anticoagulants was associated with lower risk for ischaemic stroke, HR 0.78 (CI 0.63-0.97). The presence of a previous hospitalization with an alcohol-related disease was associated with a small but significant increase in the risk of stroke among low-risk AF patients. More research about relation between alcohol use and ischaemic stroke in AF patients is warranted.

Drunk bugs: Chronic vapour alcohol exposure induces marked changes in the gut microbiome in mice

The gut microbiota includes a community of bacteria that play an integral part in host health and biological processes. Pronounced and repeated findings have linked gut microbiome to stress, anxiety, and depression. Currently, however, there remains only a limited set of studies focusing on microbiota change in substance abuse, including alcohol use disorder. To date, no studies have investigated the impact of vapour alcohol administration on the gut microbiome. For research on gut microbiota and addiction to proceed, an understanding of how route of drug administration affects gut microbiota must first be established. Animal models of alcohol abuse have proven valuable for elucidating the biological processes involved in addiction and alcohol-related diseases. This is the first study to investigate the effect of vapour route of ethanol administration on gut microbiota in mice. Adult male C57BL/6J mice were exposed to 4 weeks of chronic intermittent vapourized ethanol (CIE, N=10) or air (Control, N=9). Faecal samples were collected at the end of exposure followed by 16S sequencing and bioinformatic analysis. Robust separation between CIE and Control was seen in the microbiome, as assessed by alpha (p<0.05) and beta (p<0.001) diversity, with a notable decrease in alpha diversity in CIE. These results demonstrate that CIE exposure markedly alters the gut microbiota in mice. Significant increases in genus Alistipes (p<0.001) and significant reductions in genra Clostridium IV and XIVb (p<0.001), Dorea (p<0.01), and Coprococcus (p<0.01) were seen between CIE mice and Control. These findings support the viability of the CIE method for studies investigating the microbiota-gut-brain axis and align with previous research showing similar microbiota alterations in inflammatory states during alcoholic hepatitis and psychological stress.

Ethnic Variations in Liver- and Alcohol-Related Disease Hospitalisations and Mortality: The Scottish Health and Ethnicity Linkage Study.

Aims Preventing alcohol-related harms, including those causing liver disease, is a public health priority in the UK, especially in Scotland, but the effects of ethnicity are not known. We assessed liver- and alcohol-related events (hospitalisations and deaths) in Scotland using self-reported measures of ethnicity. Methods Linking Scottish NHS hospital admissions and mortality to the Scottish Census 2001, we explored ethnic differences in hospitalisations and mortality (2001–2010) of all liver diseases, alcoholic liver disease (ALD) and specific alcohol-related diseases (ARD). Risk ratios (RR) were calculated using Poisson regression with robust variance, by sex, adjusted for age, country of birth and the Scottish Index of Multiple Deprivation (SIMD) presented below. The White Scottish population was the standard reference population with 95% confidence intervals (CI) calculated to enable comparison (multiplied by 100 for results). Results For all liver diseases, Chinese had around 50% higher risks for men (RR 162; 95% CI 127–207) and women (141; 109–184), as did Other South Asian men (144; 104–201) and Pakistani women (140; 116–168). Lower risks for all liver diseases occurred in African origin men (42; 24–74), other White British men (72; 63–82) and women (80; 70–90) and other White women (80; 67–94). For ALD, White Irish had a 75% higher risk for men (175; 107–287). Other White British men had about a third lower risk of ALD (63; 50–78), as did Pakistani men (65; 42–99). For ARD, almost 2-fold higher risks existed for White Irish men (182; 161–206) and Any Mixed Background women (199; 152–261). Lower risks of ARD existed in Pakistani men (67; 55–80) and women (48; 33–70), and Chinese men (55; 41–73) and women (54; 32–90). Conclusions Substantial variations by ethnicity exist for both alcohol-related and liver disease hospitalisations and deaths in Scotland: these exist in subgroups of both White and non-White populations and practical actions are required to ameliorate these differences.

Menopausal hormone therapy and the risk of esophageal and gastric cancer.

A protective effect of female sex hormones has been suggested to explain the male predominance in esophageal and gastric adenocarcinoma, but evidence is lacking. We aimed to test whether menopausal hormone therapy (MHT) decreases the risk of these tumors. For comparison, esophageal squamous cell carcinoma was also assessed. This population-based matched cohort study included all women who had ever used systemic MHT in Sweden in 2005-2012. A comparison cohort of non-users of MHT was matched to the MHT-users regarding age, parity, thrombotic events, hysterectomy, diabetes, obesity, smoking-related diseases and alcohol-related diseases. Individuals with any previous cancer were excluded. Data on MHT use, cancer, comorbidity and mortality were collected from well-established Swedish nationwide registers. Odds ratios (OR) with 95% confidence intervals (CI) were calculated using conditional logistic regression. Different MHT regimens and age groups were compared in sub-group analyses. We identified 290,186 ever-users and 870,165 non-users of MHT. Ever-users had decreased ORs of esophageal adenocarcinoma (OR = 0.62, 95% CI 0.45-0.85, n = 46), gastric adenocarcinoma (OR = 0.61, 95% CI 0.50-0.74, n = 123) and esophageal squamous cell carcinoma (OR = 0.57, 95% CI 0.39-0.83, n = 33). The ORs were decreased for both estrogen-only MHT and estrogen and progestin combined MHT, and in all age groups. The lowest OR was found for esophageal adenocarcinoma in MHT-users younger than 60 years (OR = 0.20, 95% CI 0.06-0.65). Our study suggests that MHT-users are at a decreased risk of esophageal and gastric adenocarcinoma and also of esophageal squamous cell carcinoma. The mechanisms behind these associations remain to be elucidated.

The Effects of Acupuncture Stimulation for Brain Activation and Alcohol Abstinence Self-Efficacy: Functional MRI Study.

We attempted to investigate whether acupuncture stimulation at HT7 can have an effect on brain activation patterns and alcohol abstinence self-efficacy. Thirty-four right-handed healthy subjects were recruited for this study. They were randomly assigned into two groups: the HT7 (Shenmen) group and the LI5 (Yangxi) group. Acupuncture stimulation was performed using a block paradigm during fMRI scanning. Additionally, the Korean version of Alcohol Abstinence Self-Efficacy Scale (AASES) was used to determine the effect of acupuncture stimulation on self-efficacy to abstain from alcohol use. According to the result of fMRI group analysis, the activation induced by HT7 stimulation was found on the bilateral postcentral gyrus, inferior parietal lobule, inferior frontal gyrus, claustrum, insula, and anterior lobe of the cerebellum, as well as on the left posterior lobe of the cerebellum (p < 0.001, uncorrected). According to the AASES analysis, the interaction effect for gender and treatment was marginally significant (F(1, 30) = 4.152, p = 0.050). For female group, the simple main effect of treatment was significant (F(1, 11) = 8.040, p = 0.016), indicating that the mean change score was higher in the HT7 stimulation than in the LI5 stimulation. Therefore, our study has provided evidence to support that HT7 stimulation has a positive therapeutic effect on the alcohol-related diseases.

Shifting from heroin to alcohol addiction: descriptive survey

Addiction is a disease which affects the relation between the person and the object of his addiction. One of the major risks for people addicted to heroin treated with Methadone Maintenance Treatment (MMT) is to develop addiction from another substance, particularly alcohol, while treating heroin addiction, "shifting" this way from heroin addic- tion to alcoholism. describing such "shifting" process within the population taken into considera- tion for this study. dA questionnaire made up of 38 items with multiple choice answer was devised. This was administered to a sample of clients within the ambulatory Pronta Assistenza (Pr.Assi) of the Department for Addiction of a Turin hospital (ASL TO2).Written informed consensus before filling in the questionnaire was acquired and anonymity was assured. The sample is made up by 51 individuals who filled in the questionnaire. Among the sample 46% seem to be at risk of development of alcohol related disease such as, but not only, alcoholism. 28% of them seem to be unaware of using alcohol. Considering all factors which affect the possibility to develop alcoholism while treating heroin addiction with MMT, the fact that alcohol is socially more tolerated than heroin seem to be crucial for the genesis of such a "shifting process": use of huge quantity of alcohol (more than 2UA) is far more tolerated in our socio-cultural environ- ment than use of even lowest quantity of heroin apart from behavioural alteration substance-related.

Premature mortality due to alcohol-related diseases of the liver in Poland according to voivodships

Premature mortality due to alcohol-related diseases of the liver in Poland according to voivodships

Association Between the Birth of an Infant With Major Congenital Anomalies and Subsequent Risk of Mortality in Their Mothers

Giving birth to a child with a major birth defect is a serious life event for a woman, yet little is known about the long-term health consequences for the mother. To assess whether birth of an infant born with a major congenital anomaly was associated with higher maternal risk of mortality. This population-based cohort study (n = 455 250 women) used individual-level linked Danish registry data for mothers who gave birth to an infant with a major congenital anomaly (41 508) between 1979 and 2010, with follow-up until December 31, 2014. A comparison cohort (413 742) was constructed by randomly sampling, for each mother with an affected infant, up to 10 mothers matched on maternal age, parity, and year of infant's birth. Live birth of an infant with a major congenital anomaly as defined by the European Surveillance of Congenital Anomalies classification system. Primary outcome was all-cause mortality. Secondary outcomes included cause-specific mortality. Hazard ratios (HRs) were adjusted for marital status, immigration status, income quartile (since 1980), educational level (since 1981), diabetes mellitus, modified Charlson comorbidity index score, hypertension, depression, history of alcohol-related disease, previous spontaneous abortion, pregnancy complications, smoking (since 1991), and body mass index (since 2004). Mothers in both groups were a mean (SD) age of 28.9 (5.1) years at delivery. After a median (IQR) follow-up of 21 (12-28) years, there were 1275 deaths (1.60 per 1000 person-years) among 41 508 mothers of a child with a major congenital anomaly vs 10 112 deaths (1.27 per 1000 person-years) among 413 742 mothers in the comparison cohort, corresponding to an absolute mortality rate difference of 0.33 per 1000 person-years (95% CI, 0.24-0.42), an unadjusted HR of 1.27 (95% CI, 1.20-1.35), and an adjusted HR of 1.22 (95% CI, 1.15-1.29). Mothers with affected infants were more likely to die of cardiovascular disease (rate difference, 0.05 per 1000 person-years [95% CI, 0.02-0.08]; adjusted HR, 1.26 [95% CI, 1.04-1.53]), respiratory disease (rate difference, 0.02 per 1000 person-years [95% CI, 0.00-0.04]; adjusted HR, 1.45 [95% CI, 1.01-2.08]), and other natural causes (rate difference, 0.11 per 1000 person-years [95% CI, 0.07-0.15]; adjusted HR, 1.50 [95% CI, 1.27-1.76]). In Denmark, having a child with a major congenital anomaly was associated with a small but statistically significantly increased mortality risk in the mother compared with women without an affected child. However, the clinical importance of this association is uncertain.

Multiscale Metabolic Modeling Approach for Predicting Blood Alcohol Concentration

Alcohol is one of the most widely consumed and abused substances, and is a major factor in many alcohol-related diseases, incidents of impaired driving, and crimes. In this letter, we develop a mechanistic model for alcohol metabolism in the human body based on the dynamic parsimonious flux balance analysis technique. The developed whole body alcohol metabolic model contains two main mechanisms for ethanol metabolism in the body, namely, oxidative and non-oxidative mechanisms. The model is able to demonstrate the effect of variations in biochemical kinetics associated with the alcohol dehydrogenase enzyme, gender differences, physiological properties of the human body such as age, weight, and height, and the meal effect on the alcohol clearance from the body. Simulation results show that the model predictions are consistent with in vivo studies. The results from this letter indicate that the proposed metabolic modeling approach may open the door to new opportunities in the area of metabolic nutrition research and personalized medicine since it accounts for physiological properties and biochemical information related to the human body.

Duplex PCR-RFLP for the Simultaneous Genotyping of Single Nucleotide Polymorphisms in ADH1B and ALDH2 Genes.

Single nucleotide polymorphisms (SNPs) in ADH1B and ALDH2, which encode alcohol dehydrogenase 1B and aldehyde dehydrogenase 2, respectively, are responsible for ethanol-metabolizing activity and alcohol-related disease. We developed a simple and rapid polymerase chain reaction-based restriction fragment length polymorphism (PCR-RFLP) method for the simultaneous genotyping of the genes in a single-tube reaction. Using an alkaline lysate of a human hair root as a template, SNP-containing regions of each gene were PCR-amplified simultaneously. The PCR products were directly applied to double restriction digestion, followed by agarose gel band analysis. The duplex PCR-RFLP allows for the simultaneous and accurate determination of the SNP genotypes of ADH1B and ALDH2 within 1.2 h.