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Publisher: John Wiley and Sons   (Total: 1577 journals)

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Showing 1 - 200 of 1577 Journals sorted alphabetically
Abacus     Hybrid Journal   (Followers: 12, SJR: 0.48, h-index: 22)
About Campus     Hybrid Journal   (Followers: 5)
Academic Emergency Medicine     Hybrid Journal   (Followers: 64, SJR: 1.385, h-index: 91)
Accounting & Finance     Hybrid Journal   (Followers: 46, SJR: 0.547, h-index: 30)
ACEP NOW     Free   (Followers: 1)
Acta Anaesthesiologica Scandinavica     Hybrid Journal   (Followers: 49, SJR: 1.02, h-index: 88)
Acta Archaeologica     Hybrid Journal   (Followers: 148, SJR: 0.101, h-index: 9)
Acta Geologica Sinica (English Edition)     Hybrid Journal   (Followers: 3, SJR: 0.552, h-index: 41)
Acta Neurologica Scandinavica     Hybrid Journal   (Followers: 5, SJR: 1.203, h-index: 74)
Acta Obstetricia et Gynecologica Scandinavica     Hybrid Journal   (Followers: 15, SJR: 1.197, h-index: 81)
Acta Ophthalmologica     Hybrid Journal   (Followers: 5, SJR: 0.112, h-index: 1)
Acta Paediatrica     Hybrid Journal   (Followers: 56, SJR: 0.794, h-index: 88)
Acta Physiologica     Hybrid Journal   (Followers: 6, SJR: 1.69, h-index: 88)
Acta Polymerica     Hybrid Journal   (Followers: 9)
Acta Psychiatrica Scandinavica     Hybrid Journal   (Followers: 35, SJR: 2.518, h-index: 113)
Acta Zoologica     Hybrid Journal   (Followers: 6, SJR: 0.459, h-index: 29)
Acute Medicine & Surgery     Hybrid Journal   (Followers: 3)
Addiction     Hybrid Journal   (Followers: 35, SJR: 2.086, h-index: 143)
Addiction Biology     Hybrid Journal   (Followers: 13, SJR: 2.091, h-index: 57)
Adultspan J.     Hybrid Journal   (SJR: 0.127, h-index: 4)
Advanced Energy Materials     Hybrid Journal   (Followers: 26, SJR: 6.411, h-index: 86)
Advanced Engineering Materials     Hybrid Journal   (Followers: 26, SJR: 0.81, h-index: 81)
Advanced Functional Materials     Hybrid Journal   (Followers: 50, SJR: 5.21, h-index: 203)
Advanced Healthcare Materials     Hybrid Journal   (Followers: 13, SJR: 0.232, h-index: 7)
Advanced Materials     Hybrid Journal   (Followers: 255, SJR: 9.021, h-index: 345)
Advanced Materials Interfaces     Hybrid Journal   (Followers: 6, SJR: 1.177, h-index: 10)
Advanced Optical Materials     Hybrid Journal   (Followers: 5, SJR: 2.488, h-index: 21)
Advanced Science     Open Access   (Followers: 5)
Advanced Synthesis & Catalysis     Hybrid Journal   (Followers: 17, SJR: 2.729, h-index: 121)
Advances in Polymer Technology     Hybrid Journal   (Followers: 13, SJR: 0.344, h-index: 31)
Africa Confidential     Hybrid Journal   (Followers: 19)
Africa Research Bulletin: Economic, Financial and Technical Series     Hybrid Journal   (Followers: 12)
Africa Research Bulletin: Political, Social and Cultural Series     Hybrid Journal   (Followers: 9)
African Development Review     Hybrid Journal   (Followers: 35, SJR: 0.275, h-index: 17)
African J. of Ecology     Hybrid Journal   (Followers: 15, SJR: 0.477, h-index: 39)
Aggressive Behavior     Hybrid Journal   (Followers: 15, SJR: 1.391, h-index: 66)
Aging Cell     Open Access   (Followers: 10, SJR: 4.374, h-index: 95)
Agribusiness : an Intl. J.     Hybrid Journal   (Followers: 6, SJR: 0.627, h-index: 14)
Agricultural and Forest Entomology     Hybrid Journal   (Followers: 14, SJR: 0.925, h-index: 43)
Agricultural Economics     Hybrid Journal   (Followers: 45, SJR: 1.099, h-index: 51)
AIChE J.     Hybrid Journal   (Followers: 30, SJR: 1.122, h-index: 120)
Alcoholism and Drug Abuse Weekly     Hybrid Journal   (Followers: 7)
Alcoholism Clinical and Experimental Research     Hybrid Journal   (Followers: 7, SJR: 1.416, h-index: 125)
Alimentary Pharmacology & Therapeutics     Hybrid Journal   (Followers: 34, SJR: 2.833, h-index: 138)
Alimentary Pharmacology & Therapeutics Symposium Series     Hybrid Journal   (Followers: 3)
Allergy     Hybrid Journal   (Followers: 50, SJR: 3.048, h-index: 129)
Alternatives to the High Cost of Litigation     Hybrid Journal   (Followers: 3)
American Anthropologist     Hybrid Journal   (Followers: 135, SJR: 0.951, h-index: 61)
American Business Law J.     Hybrid Journal   (Followers: 24, SJR: 0.205, h-index: 17)
American Ethnologist     Hybrid Journal   (Followers: 89, SJR: 2.325, h-index: 51)
American J. of Economics and Sociology     Hybrid Journal   (Followers: 27, SJR: 0.211, h-index: 26)
American J. of Hematology     Hybrid Journal   (Followers: 33, SJR: 1.761, h-index: 77)
American J. of Human Biology     Hybrid Journal   (Followers: 12, SJR: 1.018, h-index: 58)
American J. of Industrial Medicine     Hybrid Journal   (Followers: 16, SJR: 0.993, h-index: 85)
American J. of Medical Genetics Part A     Hybrid Journal   (Followers: 16, SJR: 1.115, h-index: 61)
American J. of Medical Genetics Part B: Neuropsychiatric Genetics     Hybrid Journal   (Followers: 4, SJR: 1.771, h-index: 107)
American J. of Medical Genetics Part C: Seminars in Medical Genetics     Partially Free   (Followers: 6, SJR: 2.315, h-index: 79)
American J. of Physical Anthropology     Hybrid Journal   (Followers: 37, SJR: 1.41, h-index: 88)
American J. of Political Science     Hybrid Journal   (Followers: 262, SJR: 5.101, h-index: 114)
American J. of Primatology     Hybrid Journal   (Followers: 15, SJR: 1.197, h-index: 63)
American J. of Reproductive Immunology     Hybrid Journal   (Followers: 3, SJR: 1.347, h-index: 75)
American J. of Transplantation     Hybrid Journal   (Followers: 17, SJR: 2.792, h-index: 140)
American J. on Addictions     Hybrid Journal   (Followers: 9, SJR: 0.843, h-index: 57)
Anaesthesia     Hybrid Journal   (Followers: 125, SJR: 1.404, h-index: 88)
Analyses of Social Issues and Public Policy     Hybrid Journal   (Followers: 10, SJR: 0.397, h-index: 18)
Analytic Philosophy     Hybrid Journal   (Followers: 16)
Anatomia, Histologia, Embryologia: J. of Veterinary Medicine Series C     Hybrid Journal   (Followers: 3, SJR: 0.295, h-index: 27)
Anatomical Sciences Education     Hybrid Journal   (Followers: 1, SJR: 0.633, h-index: 24)
Andrologia     Hybrid Journal   (Followers: 2, SJR: 0.528, h-index: 45)
Andrology     Hybrid Journal   (Followers: 2, SJR: 0.979, h-index: 14)
Angewandte Chemie     Hybrid Journal   (Followers: 219)
Angewandte Chemie Intl. Edition     Hybrid Journal   (Followers: 212, SJR: 6.229, h-index: 397)
Animal Conservation     Hybrid Journal   (Followers: 37, SJR: 1.576, h-index: 62)
Animal Genetics     Hybrid Journal   (Followers: 9, SJR: 0.957, h-index: 67)
Animal Science J.     Hybrid Journal   (Followers: 6, SJR: 0.569, h-index: 24)
Annalen der Physik     Hybrid Journal   (Followers: 5, SJR: 1.46, h-index: 40)
Annals of Anthropological Practice     Partially Free   (Followers: 2, SJR: 0.187, h-index: 5)
Annals of Applied Biology     Hybrid Journal   (Followers: 7, SJR: 0.816, h-index: 56)
Annals of Clinical and Translational Neurology     Open Access   (Followers: 1)
Annals of Human Genetics     Hybrid Journal   (Followers: 9, SJR: 1.191, h-index: 67)
Annals of Neurology     Hybrid Journal   (Followers: 48, SJR: 5.584, h-index: 241)
Annals of Noninvasive Electrocardiology     Hybrid Journal   (Followers: 2, SJR: 0.531, h-index: 38)
Annals of Public and Cooperative Economics     Hybrid Journal   (Followers: 9, SJR: 0.336, h-index: 23)
Annals of the New York Academy of Sciences     Hybrid Journal   (Followers: 5, SJR: 2.389, h-index: 189)
Annual Bulletin of Historical Literature     Hybrid Journal   (Followers: 13)
Annual Review of Information Science and Technology     Hybrid Journal   (Followers: 14)
Anthropology & Education Quarterly     Hybrid Journal   (Followers: 24, SJR: 0.72, h-index: 31)
Anthropology & Humanism     Hybrid Journal   (Followers: 17, SJR: 0.137, h-index: 3)
Anthropology News     Hybrid Journal   (Followers: 15)
Anthropology of Consciousness     Hybrid Journal   (Followers: 11, SJR: 0.172, h-index: 5)
Anthropology of Work Review     Hybrid Journal   (Followers: 11, SJR: 0.256, h-index: 5)
Anthropology Today     Hybrid Journal   (Followers: 91, SJR: 0.545, h-index: 15)
Antipode     Hybrid Journal   (Followers: 47, SJR: 2.212, h-index: 69)
Anz J. of Surgery     Hybrid Journal   (Followers: 7, SJR: 0.432, h-index: 59)
Anzeiger für Schädlingskunde     Hybrid Journal   (Followers: 1)
Apmis     Hybrid Journal   (Followers: 1, SJR: 0.855, h-index: 73)
Applied Cognitive Psychology     Hybrid Journal   (Followers: 68, SJR: 0.754, h-index: 69)
Applied Organometallic Chemistry     Hybrid Journal   (Followers: 7, SJR: 0.632, h-index: 58)
Applied Psychology     Hybrid Journal   (Followers: 152, SJR: 1.023, h-index: 64)
Applied Psychology: Health and Well-Being     Hybrid Journal   (Followers: 48, SJR: 0.868, h-index: 13)
Applied Stochastic Models in Business and Industry     Hybrid Journal   (Followers: 5, SJR: 0.613, h-index: 24)
Aquaculture Nutrition     Hybrid Journal   (Followers: 14, SJR: 1.025, h-index: 55)
Aquaculture Research     Hybrid Journal   (Followers: 31, SJR: 0.807, h-index: 60)
Aquatic Conservation Marine and Freshwater Ecosystems     Hybrid Journal   (Followers: 36, SJR: 1.047, h-index: 57)
Arabian Archaeology and Epigraphy     Hybrid Journal   (Followers: 11, SJR: 0.453, h-index: 11)
Archaeological Prospection     Hybrid Journal   (Followers: 12, SJR: 0.922, h-index: 21)
Archaeology in Oceania     Hybrid Journal   (Followers: 13, SJR: 0.745, h-index: 18)
Archaeometry     Hybrid Journal   (Followers: 27, SJR: 0.809, h-index: 48)
Archeological Papers of The American Anthropological Association     Hybrid Journal   (Followers: 15, SJR: 0.156, h-index: 2)
Architectural Design     Hybrid Journal   (Followers: 25, SJR: 0.261, h-index: 9)
Archiv der Pharmazie     Hybrid Journal   (Followers: 4, SJR: 0.628, h-index: 43)
Archives of Drug Information     Hybrid Journal   (Followers: 4)
Archives of Insect Biochemistry and Physiology     Hybrid Journal   (SJR: 0.768, h-index: 54)
Area     Hybrid Journal   (Followers: 12, SJR: 0.938, h-index: 57)
Art History     Hybrid Journal   (Followers: 229, SJR: 0.153, h-index: 13)
Arthritis & Rheumatology     Hybrid Journal   (Followers: 51, SJR: 1.984, h-index: 20)
Arthritis Care & Research     Hybrid Journal   (Followers: 27, SJR: 2.256, h-index: 114)
Artificial Organs     Hybrid Journal   (Followers: 1, SJR: 0.872, h-index: 60)
ASHE Higher Education Reports     Hybrid Journal   (Followers: 14)
Asia & the Pacific Policy Studies     Open Access   (Followers: 15)
Asia Pacific J. of Human Resources     Hybrid Journal   (Followers: 312, SJR: 0.494, h-index: 19)
Asia Pacific Viewpoint     Hybrid Journal   (Followers: 1, SJR: 0.616, h-index: 26)
Asia-Pacific J. of Chemical Engineering     Hybrid Journal   (Followers: 8, SJR: 0.345, h-index: 20)
Asia-pacific J. of Clinical Oncology     Hybrid Journal   (Followers: 6, SJR: 0.554, h-index: 14)
Asia-Pacific J. of Financial Studies     Hybrid Journal   (SJR: 0.241, h-index: 7)
Asia-Pacific Psychiatry     Hybrid Journal   (Followers: 4, SJR: 0.377, h-index: 7)
Asian Economic J.     Hybrid Journal   (Followers: 8, SJR: 0.234, h-index: 21)
Asian Economic Policy Review     Hybrid Journal   (Followers: 4, SJR: 0.196, h-index: 12)
Asian J. of Control     Hybrid Journal   (SJR: 0.862, h-index: 34)
Asian J. of Endoscopic Surgery     Hybrid Journal   (SJR: 0.394, h-index: 7)
Asian J. of Organic Chemistry     Hybrid Journal   (Followers: 4, SJR: 1.443, h-index: 19)
Asian J. of Social Psychology     Hybrid Journal   (Followers: 5, SJR: 0.665, h-index: 37)
Asian Politics and Policy     Hybrid Journal   (Followers: 12, SJR: 0.207, h-index: 7)
Asian Social Work and Policy Review     Hybrid Journal   (Followers: 5, SJR: 0.318, h-index: 5)
Asian-pacific Economic Literature     Hybrid Journal   (Followers: 5, SJR: 0.168, h-index: 15)
Assessment Update     Hybrid Journal   (Followers: 4)
Astronomische Nachrichten     Hybrid Journal   (Followers: 2, SJR: 0.701, h-index: 40)
Atmospheric Science Letters     Open Access   (Followers: 29, SJR: 1.332, h-index: 27)
Austral Ecology     Hybrid Journal   (Followers: 13, SJR: 1.095, h-index: 66)
Austral Entomology     Hybrid Journal   (Followers: 9, SJR: 0.524, h-index: 28)
Australasian J. of Dermatology     Hybrid Journal   (Followers: 8, SJR: 0.714, h-index: 40)
Australasian J. On Ageing     Hybrid Journal   (Followers: 7, SJR: 0.39, h-index: 22)
Australian & New Zealand J. of Statistics     Hybrid Journal   (Followers: 13, SJR: 0.275, h-index: 28)
Australian Accounting Review     Hybrid Journal   (Followers: 4, SJR: 0.709, h-index: 14)
Australian and New Zealand J. of Family Therapy (ANZJFT)     Hybrid Journal   (Followers: 3, SJR: 0.382, h-index: 12)
Australian and New Zealand J. of Obstetrics and Gynaecology     Hybrid Journal   (Followers: 44, SJR: 0.814, h-index: 49)
Australian and New Zealand J. of Public Health     Hybrid Journal   (Followers: 11, SJR: 0.82, h-index: 62)
Australian Dental J.     Hybrid Journal   (Followers: 7, SJR: 0.482, h-index: 46)
Australian Economic History Review     Hybrid Journal   (Followers: 4, SJR: 0.171, h-index: 12)
Australian Economic Papers     Hybrid Journal   (Followers: 27, SJR: 0.23, h-index: 9)
Australian Economic Review     Hybrid Journal   (Followers: 6, SJR: 0.357, h-index: 21)
Australian Endodontic J.     Hybrid Journal   (Followers: 3, SJR: 0.513, h-index: 24)
Australian J. of Agricultural and Resource Economics     Hybrid Journal   (Followers: 3, SJR: 0.765, h-index: 36)
Australian J. of Grape and Wine Research     Hybrid Journal   (Followers: 5, SJR: 0.879, h-index: 56)
Australian J. of Politics & History     Hybrid Journal   (Followers: 14, SJR: 0.203, h-index: 14)
Australian J. of Psychology     Hybrid Journal   (Followers: 18, SJR: 0.384, h-index: 30)
Australian J. of Public Administration     Hybrid Journal   (Followers: 401, SJR: 0.418, h-index: 29)
Australian J. of Rural Health     Hybrid Journal   (Followers: 4, SJR: 0.43, h-index: 34)
Australian Occupational Therapy J.     Hybrid Journal   (Followers: 69, SJR: 0.59, h-index: 29)
Australian Psychologist     Hybrid Journal   (Followers: 11, SJR: 0.331, h-index: 31)
Australian Veterinary J.     Hybrid Journal   (Followers: 19, SJR: 0.459, h-index: 45)
Autism Research     Hybrid Journal   (Followers: 31, SJR: 2.126, h-index: 39)
Autonomic & Autacoid Pharmacology     Hybrid Journal   (SJR: 0.371, h-index: 29)
Banks in Insurance Report     Hybrid Journal   (Followers: 1)
Basic & Clinical Pharmacology & Toxicology     Hybrid Journal   (Followers: 10, SJR: 0.539, h-index: 70)
Basic and Applied Pathology     Open Access   (Followers: 2, SJR: 0.113, h-index: 4)
Basin Research     Hybrid Journal   (Followers: 5, SJR: 1.54, h-index: 60)
Bauphysik     Hybrid Journal   (Followers: 2, SJR: 0.194, h-index: 5)
Bauregelliste A, Bauregelliste B Und Liste C     Hybrid Journal  
Bautechnik     Hybrid Journal   (Followers: 1, SJR: 0.321, h-index: 11)
Behavioral Interventions     Hybrid Journal   (Followers: 9, SJR: 0.297, h-index: 23)
Behavioral Sciences & the Law     Hybrid Journal   (Followers: 24, SJR: 0.736, h-index: 57)
Berichte Zur Wissenschaftsgeschichte     Hybrid Journal   (Followers: 9, SJR: 0.11, h-index: 5)
Beton- und Stahlbetonbau     Hybrid Journal   (Followers: 2, SJR: 0.493, h-index: 14)
Biochemistry and Molecular Biology Education     Hybrid Journal   (Followers: 6, SJR: 0.311, h-index: 26)
Bioelectromagnetics     Hybrid Journal   (Followers: 1, SJR: 0.568, h-index: 64)
Bioengineering & Translational Medicine     Open Access  
BioEssays     Hybrid Journal   (Followers: 10, SJR: 3.104, h-index: 155)
Bioethics     Hybrid Journal   (Followers: 14, SJR: 0.686, h-index: 39)
Biofuels, Bioproducts and Biorefining     Hybrid Journal   (Followers: 1, SJR: 1.725, h-index: 56)
Biological J. of the Linnean Society     Hybrid Journal   (Followers: 16, SJR: 1.172, h-index: 90)
Biological Reviews     Hybrid Journal   (Followers: 3, SJR: 6.469, h-index: 114)
Biologie in Unserer Zeit (Biuz)     Hybrid Journal   (Followers: 42, SJR: 0.12, h-index: 1)
Biology of the Cell     Full-text available via subscription   (Followers: 9, SJR: 1.812, h-index: 69)
Biomedical Chromatography     Hybrid Journal   (Followers: 6, SJR: 0.572, h-index: 49)
Biometrical J.     Hybrid Journal   (Followers: 5, SJR: 0.784, h-index: 44)
Biometrics     Hybrid Journal   (Followers: 36, SJR: 1.906, h-index: 96)
Biopharmaceutics and Drug Disposition     Hybrid Journal   (Followers: 10, SJR: 0.715, h-index: 44)
Biopolymers     Hybrid Journal   (Followers: 18, SJR: 1.199, h-index: 104)
Biotechnology and Applied Biochemistry     Hybrid Journal   (Followers: 45, SJR: 0.415, h-index: 55)
Biotechnology and Bioengineering     Hybrid Journal   (Followers: 187, SJR: 1.633, h-index: 146)
Biotechnology J.     Hybrid Journal   (Followers: 14, SJR: 1.185, h-index: 51)
Biotechnology Progress     Hybrid Journal   (Followers: 39, SJR: 0.736, h-index: 101)
Biotropica     Hybrid Journal   (Followers: 19, SJR: 1.374, h-index: 71)
Bipolar Disorders     Hybrid Journal   (Followers: 9, SJR: 2.592, h-index: 100)
Birth     Hybrid Journal   (Followers: 37, SJR: 0.763, h-index: 64)
Birth Defects Research Part A : Clinical and Molecular Teratology     Hybrid Journal   (Followers: 2, SJR: 0.727, h-index: 77)
Birth Defects Research Part B: Developmental and Reproductive Toxicology     Hybrid Journal   (Followers: 5, SJR: 0.468, h-index: 47)
Birth Defects Research Part C : Embryo Today : Reviews     Hybrid Journal   (SJR: 1.513, h-index: 55)
BJOG : An Intl. J. of Obstetrics and Gynaecology     Partially Free   (Followers: 225, SJR: 2.083, h-index: 125)

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Journal Cover Alcoholism Clinical and Experimental Research
  [SJR: 1.416]   [H-I: 125]   [7 followers]  Follow
    
   Hybrid Journal Hybrid journal (It can contain Open Access articles)
   ISSN (Print) 0145-6008 - ISSN (Online) 1530-0277
   Published by John Wiley and Sons Homepage  [1577 journals]
  • Continued Alcohol Misuse in Human Cirrhosis is Associated with An Impaired
           Gut-Liver Axis
    • Authors: Jasmohan S Bajaj; Genta Kakiyama, Derrick Zhao, Hajime Takei, Andrew Fagan, Phillip Hylemon, Huiping Zhou, William M Pandak, Hiroshi Nittono, Oliver Fiehn, Nita Salzman, Mary Holtz, Pippa Simpson, Edith A Gavis, Douglas M Heuman, Runping Liu, Dae Joong Kang, Masoumeh Sikaroodi, Patrick M Gillevet
      Abstract: BackgroundCirrhosis and alcohol can independently affect the gut-liver axis with systemic inflammation. However their concurrent impact in humans is unclear.AimDetermine the effect of continued alcohol misuse on the gut-liver axis in cirrhotic patients.MethodsAge and MELD-balanced cirrhotic patients who were currently drinking (Alc) or abstinent (NAlc), and healthy controls underwent serum and stool collection. A subset underwent upper endoscopy and colonoscopy for biopsies and duodenal fluid collection. The groups were compared regarding (1) inflammation/intestinal barrier: systemic TNF levels, intestinal inflammatory cytokine (duodenum, ileum, sigmoid) and ileal anti-microbial peptide expression (2) microbiota composition: 16SrRNA sequencing of duodenal, ileal, colonic mucosal and fecal microbiota (3) microbial functionality: duodenal fluid and fecal BA profile (conjugation and dehydroxylation status), intestinal BA transporter (ASBT, FXR, FGF-19, SHP) expression and stool metabolomics using GC/MS.ResultsAlc patients demonstrated a significant duodenal, ileal and colonic mucosal and fecal dysbiosis, compared to NAlc and controls with lower autochthonous bacterial taxa. BA profile skewed towards a potentially toxic profile (higher secondary and glycine-conjugated BAs) in duodenal fluid and stool in Alc patients. Duodenal fluid demonstrated conjugated secondary BAs only in the Alc group. There was a greater expression of all ileal BA transporters in Alc patients. This group also showed higher endotoxemia, systemic and ileal inflammatory expression and lower amino acid and bioenergetic-associated metabolites, without change in anti-microbial peptide expression.ConclusionsDespite cirrhosis, continued alcohol misuse predisposes patients to widespread dysbiosis with alterations in microbial functionality such as a toxic bile acid profile, which can lead to intestinal and systemic inflammation.This article is protected by copyright. All rights reserved.
      PubDate: 2017-09-19T02:47:21.00067-05:0
      DOI: 10.1111/acer.13498
       
  • Alcohol Reduces Arterial Remodeling by Inhibiting Sonic
           Hedgehog-Stimulated Sca1+ Progenitor Stem Cell Expansion
    • Authors: Emma Fitzpatrick; Xu Han, Weimin Liu, Eoin Corcoran, Denise Burtenshaw, Maryam Alshamrani, David Morrow, Jay-Christian Helt, Paul A. Cahill, Eileen M. Redmond
      Abstract: BackgroundCell and molecular mechanisms mediating the cardiovascular effects of alcohol are not fully understood. Our aim was to determine the effect of moderate Ethanol (EtOH) on Sonic Hedgehog (SHh) signaling in regulating possible Sca1+ progenitor stem cell involvement during pathologic arterial remodeling.Methods and ResultsPartial ligation or sham-operation of the left carotid artery was performed in transgenic Sca1-eGFP mice gavaged with or without ‘daily moderate’ EtOH. The EtOH group had reduced adventitial thickening and less neo-intimal formation, compared to ligated controls. There was expansion of eGFP expressing (i.e., Sca1+) cells in remodeled vessels post-ligation (14d), especially in the neo-intima. Ethanol treatment reduced the number of Sca1+ cells in ligated vessel cross-sections concomitant with diminished remodeling, compared to control ligated vessels. Moreover, EtOH attenuated SHh signaling in injured carotids as determined by immunohistochemical analysis of the target genes patched 1 (Ptch1) and Gli2, and RT-PCR of whole vessel Gli2 mRNA levels. Intraperitoneal injection of ligated Sca1 - eGFP mice with the SHh signaling inhibitor cyclopamine diminished hedgehog target gene expression, reduced the number of Sca1+ cells, and ameliorated carotid remodeling. EtOH treatment of purified Sca1+ adventitial progenitor stem cells in vitro inhibited SHh signaling, and their rSHh-induced differentiation to vascular smooth muscle cells.ConclusionsEtOH reduces SHh - responsive Sca1+ progenitor cell myogenic differentiation/expansion in vitro and during arterial remodeling in response to ligation injury in vivo. Regulation of vascular Sca1+ progenitor cells in this way may be an important novel mechanism contributing to alcohol's cardiovascular protective effects.This article is protected by copyright. All rights reserved.
      PubDate: 2017-09-18T02:05:22.557836-05:
      DOI: 10.1111/acer.13499
       
  • Influence of cocaine-related images and alcohol administration on
           inhibitory control in cocaine users
    • Authors: Erika Pike; Katherine R. Marks, William W. Stoops, Craig R. Rush
      Abstract: BackgroundAlcohol use and impulsivity, including decreased inhibitory control, predict poor treatment outcomes for individuals with cocaine use disorders. This study sought to determine the effects of alcohol administration on inhibitory control following cocaine-related and neutral cues on the Attentional Bias-Behavioral Activation (ABBA) task in cocaine users. We hypothesized that the proportion of inhibitory failures would increase following cocaine cues compared to neutral cues. We further hypothesized that there would be an interaction between alcohol administration and task version, such that alcohol would impair inhibitory control following cocaine, but not neutral cues.MethodsFifty current cocaine users completed this mixed-model, double-blind, placebo-controlled, cross-over study over two experimental sessions. The ABBA task was completed following alcohol administration (0.0 and 0.65 g/kg). Subject-rated drug-effect and physiological measures were collected prior to and after alcohol administration.ResultsProportion of inhibitory failures was increased following cocaine-related cues compared to neutral cues independent of alcohol dose. Alcohol administration also produced prototypical subject-rated drug-effects.ConclusionsA better understanding of the relationship between alcohol consumption and inhibitory control in cocaine users could direct the development of interventions to decrease the risk of relapse in individuals who drink and display impaired inhibitory control.This article is protected by copyright. All rights reserved.
      PubDate: 2017-09-16T10:20:24.363151-05:
      DOI: 10.1111/acer.13500
       
  • Alcohol Advertising in Magazines and Underage Readership: Are Underage
           Youth Disproportionately Exposed'
    • Authors: Charles King; Michael Siegel, Craig S. Ross, David H. Jernigan
      Abstract: BackgroundThe question of whether underage youth are disproportionately exposed to alcohol advertising lies at the heart of the public health debate about whether restrictions on alcohol advertising are warranted. The aim of this study was to determine whether alcohol brands popular among underage (ages 12 to 20 years) drinkers (“underage brands”) are more likely than others (“other brands”) to advertise in magazines with high underage readerships.MethodsWe analyze the advertising of 680 alcohol brands in 49 magazines between 2006 and 2011. Using a random effects probit model, we examine the relationship between a magazine's underage readership and the probability of an underage or other brand advertising in a magazine, controlling for young adult (ages 21 to 29 years) and total readerships, advertising costs and expenditures, and readership demographics.ResultsWe find that underage brands are more likely than other brands to advertise in magazines with a higher percentage of underage readers. Holding all other variables constant at their sample means, the probability of an “other” brand advertising in a magazine remains essentially constant over the range of underage readership from 0.010 (95% confidence interval [CI], 0.007 to 0.013) at 5% to 0.012 (95% CI, 0.008 to 0.016) at 35%. In contrast, the probability of an underage brand advertising nearly quadruples, ranging from 0.025 (95% CI, 0.015 to 0.035) to 0.096 (95% CI, 0.057 to 0.135), where underage brands are 7.90 (95% CI, 3.89 to 11.90) times more likely than other brands to advertise.ConclusionsAlcohol brands popular among underage drinkers are more likely than other brands to advertise in magazines with high underage readerships, resulting in the disproportionate exposure of underage youth. Current voluntary advertising industry guidelines are not adequate to protect underage youth from high and disproportionate exposure to alcohol advertising in magazines. To limit advertising exposure among underage youth, policy makers may want to consider regulation of alcohol advertising in magazines.Alcohol brands that are popular among youth (“youth brands”) are much more likely to advertise in magazines with higher youth readership. In contrast, alcohol brands that are not popular among youth (“other brands”) are no more likely to advertise in magazines as youth readership increases. This finding suggests that alcohol companies are preferentially advertising to reach underage youth, who are disproportionately exposed to this advertising.
      PubDate: 2017-09-13T17:00:03.951741-05:
      DOI: 10.1111/acer.13477
       
  • Alcohol and Road Traffic Injuries in Latin America and the Caribbean: A
           Case-Crossover Study
    • Authors: Guilherme Borges; Maristela Monteiro, Cheryl J. Cherpitel, Ricardo Orozco, Yu Ye, Vladimir Poznyak, Margie Peden, Flavio Pechansky, Mariana Cremonte, Sandra D. Reid, Jesus Mendez
      Abstract: BackgroundThis study reports dose–response estimates for the odds ratio (OR) and population attributable risk of acute alcohol use and road traffic injury (RTI).MethodsData were analyzed on 1,119 RTI patients arriving at 16 emergency departments (EDs) in Argentina, Brazil, Costa Rica, Dominican Republic, Guatemala, Guyana, Mexico, Nicaragua, Panama, and Trinidad and Tobago. Case-crossover analysis, pair-matching the number of standard drinks consumed within the 6 hours prior to the RTI with 2 control periods (prior d/wk), was performed using fractional polynomial analysis for dose–response.ResultsAbout 1 in 6 RTI patients in EDs were positive for self-reported alcohol 6 hours prior to the injury (country range 8.6 to 24.1%). The likelihood of an RTI with any drinking prior (compared to not drinking) was 5 times higher (country range OR 2.50 to 15.00) and the more a person drinks the higher the risk. Every drink (12.8 g alcohol) increased the risk of an RTI by 13%, even 1 to 2 drinks were associated with a sizable increase in risk of an RTI and a dose–response was found. Differences in ORs for drivers (OR = 3.51; 95% CI = 2.25 to 5.45), passengers (OR = 8.12; 95% CI = 4.22 to 15.61), and pedestrians (OR = 6.30; 95% CI = 3.14 to 12.64) and attributable fractions were noted. Acute use of alcohol was attributable to 14% of all RTIs, varying from 7% for females to 19% for being injured as a passenger.ConclusionsThe finding that the presence of alcohol increases risk among drivers and nondrivers alike may further help to urge interventions targeting passengers and pedestrians. Routine screening and brief interventions in all health services could also have a beneficial impact in decreasing rates of RTIs. Higher priority should be given to alcohol as a risk factor for RTIs, particularly in Latin America and the Caribbean.Data on the prevalence and risk associated with drinking and driving are scarce or plainly unavailable for most countries in the Americas region. We performed a case-crossover study among 1,119 patients that suffered a road traffic injury at 16 emergency departments in Argentina, Brazil, Costa Rica, Dominican Republic, Guatemala, Guyana, Mexico, Nicaragua, Panama and Trinidad & Tobago. Differences in Odds Ratios (OR) for drivers (OR = 3.51; 95% CI = 2.25–5.45), passengers (OR = 8.12; 95% CI = 4.22–15.61) and pedestrians (OR = 6.30; 95% CI = 3.14–12.64), risk curves and attributable fractions were reported. Odds ratios of road traffic injury by alcohol volume consumed before injury, by type. X axis trimmed to 30 drinks.
      PubDate: 2017-09-13T17:00:02.477953-05:
      DOI: 10.1111/acer.13467
       
  • Cloninger's Temperament and Character Dimensions of Personality and Binge
           Drinking Among College Students
    • Authors: Fabien Gierski; Farid Benzerouk, Elodie De Wever, Theodora Duka, Arthur Kaladjian, Véronique Quaglino, Mickaël Naassila
      Abstract: BackgroundTemperament and character dimensions of personality remain largely unexplored in young adults exhibiting binge drinking patterns. Moreover, the available studies do not consider gender differences, and dismiss possible personality heterogeneity among binge drinkers. In the present study, we aimed to compare temperament and character dimensions between young binge drinkers and age- and sex-matched social drinkers. We further applied cluster analysis to investigate the potential heterogeneity of personality patterns among binge drinking college students.MethodsThis study included 200 university students of 18–24 years of age, who were recruited via an invitation to take an alcohol use survey. These participants included 100 individuals (50 female and 50 male) with a binge drinking pattern, and 100 participants (50 female and 50 male) with a social drinking pattern. These subjects were evaluated with regards to their use of alcohol and other substances, impulsiveness, sensation-seeking, mood, and Cloninger's Temperament and Character Inventory.ResultsBetween-group comparisons revealed that both male and female binge drinkers were characterized by high levels of novelty-seeking, and low levels of persistence and self-directedness. However, cluster analyses within the binge drinker group revealed two distinct groups that differed between males and females. These groups shared similarities with Cloninger's type I (high harm-avoidance) and II (high novelty-seeking) alcoholism typology.ConclusionsThe present findings support the subdivision of binge drinkers according to gender and personality dimensions. Male and female binge drinkers should not be considered a unitary group, but rather a population of individuals that encompasses at least two distinct personality patterns. These findings have major implications for prevention and treatment approaches.This article is protected by copyright. All rights reserved.
      PubDate: 2017-09-13T10:05:23.417416-05:
      DOI: 10.1111/acer.13497
       
  • Supplementation with the methyl donor betaine prevents congenital defects
           induced by prenatal alcohol exposure
    • Authors: Ganga Karunamuni; Megan M. Sheehan, Yong Qiu Doughman, Shi Gu, Jiayang Sun, Youjun Li, James P. Strainic, Andrew M. Rollins, Michael W. Jenkins, Michiko Watanabe
      Abstract: BackgroundDespite decades of public education about dire consequences of prenatal alcohol exposure, drinking alcohol during pregnancy remains prevalent. As high as 40% of live-born infants exposed to alcohol during gestation and diagnosed with Fetal Alcohol Syndrome have congenital heart defects that can be life-threatening. In animal models, the methyl donor betaine, found in foods such as wheat bran, quinoa, beets and spinach, ameliorated neurobehavioral deficits associated with prenatal alcohol exposure (PAE) but effects on heart development are unknown.MethodsPreviously we modeled a binge drinking episode during the first trimester in avian embryos. Here we investigated whether betaine could prevent adverse effects of alcohol on heart development. Embryos exposed to ethanol with and without an optimal dose of betaine (5 μM) were analyzed at late developmental stages. Cardiac morphology parameters were rapidly analyzed and quantified using optical coherence tomography. DNA methylation at early stages was detected by immunofluorescent staining for 5-methylcytosine in sections of embryos treated with ethanol or co-treated with betaine.ResultsCompared to ethanol-exposed embryos, betaine-supplemented embryos had higher late-stage survival rates and fewer gross head and body defects than seen after alcohol exposure alone. Betaine also reduced the incidence of late-stage cardiac defects such as absent vessels, abnormal atrio-ventricular (AV) valves, and hypertrophic ventricles. Furthermore, betaine co-treatment brought measurements of great vessel diameters, interventricular septum (IVS) thickness, and AV leaflet volumes in betaine-supplemented embryos close to control values. Early-stage 5-methycytosine staining revealed that DNA methylation levels were reduced by ethanol exposure and normalized by co-administration with betaine.ConclusionsThis is the first study demonstrating efficacy of the methyl donor betaine in alleviating cardiac defects associated with PAE. These findings highlight the therapeutic potential of low-concentration betaine doses in mitigating PAE induced birth defects and has implications for prenatal nutrition policies, especially for women who may not be responsive to folate supplementation.This article is protected by copyright. All rights reserved.
      PubDate: 2017-09-09T10:20:26.29147-05:0
      DOI: 10.1111/acer.13495
       
  • MiR-21-mediated suppression of Smad7 induces TGFβ1 and can be inhibited
           by activation of Nrf2 in alcohol-treated lung fibroblasts
    • Authors: Lucian T. Marts; David E. Green, Stephen T. Mills, Tamara Murphy, Viranuj Sueblinvong
      Abstract: BackgroundWe previously demonstrated that chronic alcohol ingestion augments TGFβ1 expression in the lung fibroblast and increases the risk of fibroproliferative disrepair in a mouse model of acute lung injury. The effect of alcohol on TGFβ1 is mitigated by treatment with sulforaphane, which can activate nuclear factor (erythroid-derived 2)-like 2 (Nrf2). However, the mechanisms by which alcohol amplifies, or SFP attenuates, TGFβ1 expression in the fibroblast are not known. MicroRNA (miR)-21 has been shown to inhibit Smad7, a TGFβ1 signaling inhibitor. In the present study, we hypothesized that alcohol augments TGFβ1 expression through up-regulation of miR-21, which subsequently inhibits Smad7.MethodsPrimary mouse lung fibroblasts were cultured ± alcohol ± SFP and assessed for gene expression of miR-21, and gene and/or protein expression of Nrf2, Nrf2-regulated anti-oxidant enzymes, Smad7, STAT3, and TGFβ1. NIH 3T3 fibroblasts were transfected with a miR-21 inhibitor and cultured ± alcohol. α-SMA, Smad7, and TGFβ1 protein expression were then assessed. In parallel, NIH 3T3 lung fibroblasts were transfected with Nrf2 silencing RNA (siRNA) and cultured ± alcohol ± SFP. Gene expression of miR-21, Nrf2, Smad7, and TGFβ1 were assessed.ResultsMiR-21 gene expression was increased by 12-fold at 48 hours and Smad7 gene and protein expression were reduced by ~30% in alcohol-treated fibroblasts. In parallel, inhibition of miR-21 attenuated alcohol-mediated decrease in Smad7 and increase in TGFβ1 and alpha-smooth muscle actin protein expression. Treatment with SFP mitigated the effect of alcohol on miR-21, Smad7, and total and phosphorylated STAT3, and restored Nrf2-regulated antioxidant gene expression. Silencing of Nrf2 prevented the effect of SFP on miR-21, Smad7, and TGFβ1 gene expression in alcohol-treated NIH 3T3 fibroblasts.ConclusionsAlcohol treatment increases TGFβ1 in fibroblasts, at least in part, through augmentation of miR-21, which then inhibits Smad7 expression. These effects can be attenuated by activation of Nrf2 with SFP.This article is protected by copyright. All rights reserved.
      PubDate: 2017-09-09T10:20:22.302537-05:
      DOI: 10.1111/acer.13496
       
  • The causal role of alcohol use in adolescent externalizing and
           internalizing problems: a Mendelian randomization study
    • Authors: Miao Chao; Xinying Li, Matt McGue
      Abstract: BackgroundThe co-occurrence of alcohol use and externalizing/internalizing problems threatens adolescents’ mental health. Research on whether alcohol use and these problems are causal and the direction of the potential causal relationships is needed to understand the mechanisms of the co-occurrence.MethodA Mendelian randomization analysis was conducted in which the aldehyde dehydrogenase 2 (ALDH2) rs671 polymorphism was used as an instrumental variable for alcohol use phenotypes. In total, 1,608 Chinese adolescents (mean age 14.11 ± 1.83 years) were genotyped for the ALDH2 rs671 polymorphism. Three externalizing problems (aggression, delinquency and attention problems) were measured with the Youth Self-Report Inventory (YSR), and two internalizing problems (depression and anxiety) were measured with the self-reported Children's Depression Inventory (CDI) and the Trait subscale of the State-Trait Anxiety Inventory (STAI-T).ResultsAlcohol use was positively associated with all three externalizing and two internalizing problems, and the ALDH2 polymorphism had a significant effect on alcohol use. Aggression and attention problems were also significantly affected by the ALDH2 polymorphism, whereas no significant association was observed between the ALDH2 polymorphism and delinquency, anxiety or depression.ConclusionThe results suggest that alcohol use is a cause of adolescent aggression and attention problems but not adolescent delinquency, anxiety or depression.This article is protected by copyright. All rights reserved.
      PubDate: 2017-09-06T09:42:32.834891-05:
      DOI: 10.1111/acer.13493
       
  • Prenatal alcohol exposure leads to enhanced serine 9 phosphorylation of
           glycogen synthase kinase-3β (GSK-3β) in the hippocampal dentate gyrus of
           adult mouse
    • Authors: Lee Anna Cunningham; Jessie Newville, Phillip Tapia, Andrea M. Allan, C. Fernando Valenzuela
      Abstract: BackgroundThe goal of the present study was to evaluate the expression and serine 9 phosphorylation of glycogen synthase kinase (GSK-3β) within the adult hippocampal dentate gyrus (DG) in a preclinical mouse model of fetal alcohol spectrum disorder (FASD). GSK-3β is a multifunctional kinase that modulates many hippocampal processes affected by gestational alcohol, including synaptic plasticity and adult neurogenesis. GSK-3β is a constitutively active kinase that is negatively regulated by phosphorylation at the serine-9 residue.MethodsWe utilized a well-characterized limited access “drinking-in-the-dark” paradigm of prenatal alcohol exposure (PAE) and measured p(Ser9)GSK-3β and total GSK-3β within adult dentate gyrus by western blot analysis. In addition, we evaluated the expression pattern of both p(Ser9)GSK-3β and total GSK-3β within the adult hippocampal dentate of PAE and control mice using high resolution confocal microscopy.ResultsOur findings demonstrate a marked 2.0-fold elevation of p(Ser9)GSK-3β in PAE mice, concomitant with a more moderate 36% increase in total GSK-3β. This resulted in an approximate 63% increase in the p(Ser9)GSK-3β/GSK-3β ratio. Immunostaining revealed robust GSK-3β expression within Cornu Amonis (CA) pyramidal neurons, hilar mossy cells and a subset of GABAergic interneurons, with low levels of expression within hippocampal progenitors and dentate granule cells (DGCs).ConclusionsThese findings suggest that PAE may lead to a long-term disruption of GSK-3β signaling within the dentate gyrus, and implicate mossy cells, GABAergic interneurons and CA primary neurons as major targets of this dysregulation.This article is protected by copyright. All rights reserved.
      PubDate: 2017-09-01T21:00:32.467509-05:
      DOI: 10.1111/acer.13489
       
  • Reduced levels of mGlu2 receptors within the prelimbic cortex not
           associated with elevated glutamate transmission or high alcohol drinking
    • Authors: Zheng-Ming Ding; Cynthia M. Ingraham, Sheketha R. Hauser, Amy W. Lasek, Richard L. Bell, William J. McBride
      Abstract: BackgroundA Grm2 cys407* stop codon mutation, which results in a loss of the metabotropic glutamate 2 (mGlu2) receptor protein, was identified as being associated with high alcohol drinking by alcohol preferring (P) rats. The objectives of the current study were to characterize the effects of reduced levels of mGlu2 receptors on glutamate transmission and alcohol drinking.MethodsQuantitative no-net-flux microdialysis was used to test the hypothesis that basal extracellular glutamate levels in the prelimbic (PL) cortex and nucleus accumbens shell (NACsh) will be higher in P than Wistar rats. A lentiviral-delivered short-hairpin RNA (shRNA)-mediated knockdown was used to test the hypothesis that reduced levels of mGlu2 receptors within the PL cortex will increase voluntary alcohol drinking by Wistar rats. A linear regression analysis was used to test the hypothesis that there will be a significant correlation between the Grm2 cys407* mutation and level of alcohol intake.ResultsExtracellular glutamate concentrations within the PL cortex (3.6 ± 0.6 vs 6.4 ± 0.6 μM) and NACsh (3.2 ± 0.4 vs 6.6 ± 0.6 μM) were significantly lower in female P than female Wistar rats. Western blot detected the presence of mGlu2 receptors in these regions of female Wistar rats, but not female P rats. Micro-infusion of shRNAs into the PL cortex significantly reduced local mGlu2 receptor levels (by 40%), but did not alter voluntary alcohol drinking in male Wistar rats. In addition, there was no significant correlation between the Grm2 mutation and alcohol intake in 36 rodent lines (r = 0.29, p> 0.05).ConclusionsCollectively, these results suggest a lack of association between the loss of mGlu2 receptors and glutamate transmission in the NACsh and PL cortex of female P rats, and between the level of mGlu2 receptors in the PL cortex and alcohol drinking of male Wistar rats.This article is protected by copyright. All rights reserved.
      PubDate: 2017-08-31T09:45:28.03133-05:0
      DOI: 10.1111/acer.13488
       
  • Age of Drinking Initiation as a Risk Factor for Alcohol Use Disorder
           Symptoms is Moderated by ALDH2*2 and Ethnicity
    • Authors: Susan E. Luczak; Tiebing Liang, Tamara L. Wall
      Abstract: BackgroundAn early age of drinking initiation (ADI) has been associated with increased risk for alcohol use disorders (AUDs), but the consistency of this risk across diverse samples has not been well studied. The purpose of this study was to examine whether the pathway from ADI to AUD symptoms by early adulthood is moderated by ethnicity and possessing an alcohol-metabolizing gene ALDH2*2 variant allele.MethodsWe used multigroup structural equation modeling, including 5 groups split by ethnicity and ALDH2*2, to examine the consistency of the path from ADI to AUD symptoms in 604 Chinese-, Korean-, and White-American college students. We further examined the effects of ALDH2*2, ethnicity, and their interaction in Asians to better understand their unique contributions to the moderation.ResultsThe association between ADI and AUD symptoms was moderated, with ADI negatively associated with AUD symptoms among Koreans without ALDH2*2 and Whites, but not among Koreans with ALDH2*2 or Chinese regardless of ALDH2*2. Both ALDH2*2 and ethnicity within Asians contributed unique variability in the effect.ConclusionsEthnicity and ALDH2*2 altered the relationship of ADI as a risk factor for AUD symptoms. Being Chinese and possessing an ALDH2*2 allele within Koreans both buffered against the risk for AUD symptoms associated with earlier ADI, indicating that this relationship can be attenuated by protective factors.An early age of drinking initiation (ADI) has been associated with increased risk for alcohol use disorders (AUDs), but the consistency of this risk across diverse samples has not been well studied. We found both ethnicity (Chinese, Korean, White) and the alcohol metabolizing gene variant ALDH2*2 moderated this relationship. Being Chinese and possessing an ALDH2*2 allele within Koreans both buffered against the risk for AUD symptoms associated with earlier ADI, indicating that this relationship can be attenuated by protective factors.
      PubDate: 2017-08-28T16:00:01.721232-05:
      DOI: 10.1111/acer.13469
       
  • Maternal Age and Trajectories of Risky Alcohol Use: A Prospective Study
    • Authors: Natacha M. De Genna; Lidush Goldschmidt, Michael Marshal, Nancy L. Day, Marie D. Cornelius
      Abstract: BackgroundNo prospective study of maternal alcohol use has focused on age at transition to motherhood as a predictor of trajectories of risky drinking. The goal of this study was to examine the impact of maternal age at first birth on trajectories of alcohol use beyond recommended levels over a 17-year span.MethodsPregnant women (N = 456) were recruited at an urban prenatal clinic. The women (13 to 42 years old; 64% African American, 36% White) were interviewed about alcohol use during pregnancy and at 6, 10, 14, and 16 years postpartum. Growth mixture modeling (GMM) was used to identify trajectories of risky drinking. Maternal age at first birth was then regressed onto trajectory class membership.ResultsThe GMM on maternal alcohol use identified 3 groups of mothers as a function of alcohol use before, during, and after the pregnancy. The majority of mothers (66%) were identified as having low-risk trajectories of alcohol use over the 17-year span. However, 2 groups were in the higher-risk categories, with 23% identified as being in a long-term high-risk trajectory, and 11% in a short-term high-risk trajectory group. Maternal age at first birth predicted membership in a high-risk group: Younger mothers were more likely to be classified into a long-term high-risk alcohol use group.ConclusionsYounger mothers were more likely to engage in risky drinking early in pregnancy, continuing 6 to 14 years postpartum. These results can help physicians target mothers who are likely to exceed current NIAAA guidelines of abstinence during pregnancy, and no more than 7 drinks per week in the postpartum.These findings predict which women are more likely to exhibit risky drinking before, during and after a pregnancy, and ultimately, who is at greater risk of alcohol use disorder. Younger mothers and those who used marijuana during pregnancy were more likely to be long-term high-risk drinkers (see trajectory groups in Figure 1). These results can help physicians target the women most likely to exceed current NIAAA guidelines of abstinence during pregnancy and 7 drinks per week for non-pregnant women.
      PubDate: 2017-08-23T17:00:01.951007-05:
      DOI: 10.1111/acer.13451
       
  • Analysis of the association of non-synonymous polymorphisms in ADH genes
           with hazardous drinking in HIV-1 positive individuals
    • Authors: Jonas Michel Wolf; Daniel Simon, Jorge Umberto Béria, Daniela Cardoso Tietzmann, Airton Tetelbom Stein, Vagner Ricardo Lunge
      Abstract: BackgroundHazardous drinking (HD) is a serious health problem in people infected with human immunodeficiency virus type 1 (HIV-1). Single nucleotide polymorphisms (SNPs) in alcohol dehydrogenase (ADH) genes have been associated with HD in different populations, but there was no data about this in HIV-1 positive individuals. This study investigated the association of four non-synonymous SNPs in ADH genes (Arg48His and Arg370Cys in ADH1B gene; Arg272Gln and Ile350Val in ADH1C gene) with HD in people living with HIV-1.MethodsThis case-control study included 365 HIV-1 positive individuals (121 with HD and 244 without HD). Socio-demographic variables were collected with a standardized individual questionnaire. HD (score ≥8) and binge drinking (BD) (drinks on the same occasion ≥5) were detected with the Alcohol Use Disorders Identification Test (AUDIT). The four SNPs were genotyped by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Adjusted odds ratios (aOR) and 95% confidence intervals (CIs) were calculated using logistic regression analysis. The Bonferroni correction was used (considering the four SNPs studied).ResultsThere were not significant differences in the frequencies of Arg370Cys, Arg272Gln, and Ile350Val polymorphisms between HD cases and controls. Otherwise, Arg/His genotype (rs1229984) in ADH1B gene showed a protective effect against HD (aOR = 0.36; 95% CI: 0.14-0.90) and BD (aOR = 0.49; 95% CI: 0.21-0.95). Nevertheless, these differences were no longer significant after Bonferroni correction.ConclusionsThe results of this study suggest a possible effect of the Arg48His genotype on the protection against HD in HIV-1 positive individuals.This article is protected by copyright. All rights reserved.
      PubDate: 2017-08-23T05:12:25.554943-05:
      DOI: 10.1111/acer.13486
       
  • Tailoring an alcohol intervention for AIAN women of childbearing age:
           listening to the community
    • Authors: Annika C Montag; Marlené L Dusek, Marina L Ortega, Alexandrea Camp-Mazzetti, Dan J Calac, Christina D Chambers
      Abstract: BackgroundReduction of risky drinking in women of childbearing age is one strategy that may be employed to prevent fetal alcohol spectrum disorder, a sequela of prenatal alcohol-exposure. Communities differ in risk and protective factors, necessitating culturally informed interventions for maximal efficacy. This manuscript describes the modification of an existing web-based SBIRT intervention to reduce risky drinking among AIAN women of child-bearing age in Southern California into a peer-to-peer based intervention using motivational interviewing.MethodsThe modification process was iterative and included various community focus groups, interviews, and a final review.ResultsIntervention modification was required for cultural congruence. Components of the peer-to-peer intervention designed by this project included a flip chart used to guide the motivational interviewing, charts of the financial and physical costs of alcohol consumption, revised baseline and follow-up questionnaires, and guidance regarding the application of motivational interviewing techniques.ConclusionsThis study may inform the modification of future interventions among AIAN communities.This article is protected by copyright. All rights reserved.
      PubDate: 2017-08-23T05:05:21.178-05:00
      DOI: 10.1111/acer.13485
       
  • CRF1 receptor-dependent increases in irritability-like behavior during
           abstinence from chronic intermittent ethanol vapor exposure
    • Authors: Adam Kimbrough; Giordano Guglielmo, Jenni Kononoff, Marsida Kallupi, Eric P. Zorrilla, Olivier George
      Abstract: BackgroundIn humans, emotional and physical signs of withdrawal from ethanol are commonly seen. Many of these symptoms, including anxiety-like and depression-like behavior, have been characterized in animal models of ethanol dependence. One issue with several current behavioral tests that measure withdrawal in animal models is they are often not repeatable within subjects over time. Additionally, irritability, one of the most common symptoms of ethanol withdrawal in humans, has not been well characterized in animal models. The corticotropin-releasing factor (CRF)-CRF1 receptor system has been suggested to be critical for the emergence of anxiety-like behavior in ethanol dependence, but the role of this system in irritability-like behavior has not been characterized.MethodsThe present study compared the effects of chronic intermittent ethanol vapor exposure (CIE)-induced ethanol dependence on irritability-like behavior in rats using the bottle-brush test during acute withdrawal and protracted abstinence. Rats were trained to self-administer ethanol in operant chambers and then either left in a nondependent state or made dependent via CIE. Naive, nondependent, and dependent rats were tested for irritability-like behavior in the bottle-brush test 8 h and 2 weeks into abstinence from ethanol. Separate cohorts of dependent and nondependent rats were used to examine the effect of the specific CRF1 receptor antagonist R121919 on irritability-like behavior.ResultsDependent rats exhibited escalated ethanol intake compared with their own pre-CIE baseline and nondependent rats. At both time-points of abstinence, ethanol-dependent rats exhibited increased aggressive-like responses compared with naive and nondependent rats. R121919 reduced irritability-like behavior in both dependent and nondependent rats, but dependent rats were more sensitive to R121919.ConclusionsIrritability-like behavior is a clinically relevant and reliable measure of negative emotional states that is partially mediated by activation of the CRF-CRF1 system and remains elevated during protracted abstinence in ethanol-dependent rats.This article is protected by copyright. All rights reserved.
      PubDate: 2017-08-23T05:00:28.428671-05:
      DOI: 10.1111/acer.13484
       
  • Lawrence Lumeng: Researcher, Clinician, Leader, Mentor
    • Authors: David W. Crabb; William J. McBride, Nicholas J. Grahame, Richard L. Bell, David A. Kareken
      Abstract: We sadly note the loss of Dr. Lawrence Lumeng on June 21, 2017 at age 76 years following a long battle against progressive pulmonary fibrosis. As a founding member of the Indiana Alcohol Research Center, he made numerous seminal contributions to the field of the genetics of alcoholism, alcohol metabolism, and alcoholic liver disease.This article is protected by copyright. All rights reserved.
      PubDate: 2017-08-21T06:00:18.309594-05:
      DOI: 10.1111/acer.13482
       
  • The glycine receptor – a functionally important primary brain target
           of ethanol
    • Authors: Bo Söderpalm; Helga HöifödtLidö, Mia Ericson
      Abstract: Identification of ethanol's primary molecular brain targets and determination of their functional importance is an ongoing, important quest. Pentameric ligand-gated ion-channels (pLGIC), i.e. the nicotinic acetylcholine receptor, the γ-aminobutyric acid type A receptor, the 5-hydroxytryptamine3 and the glycine receptor (GlyR) are such targets. Here, aspects of the structure and function of these receptors and ethanol′s interaction with them are briefly reviewed, with special emphasis on the GlyR and the importance of this receptor and its ligands for ethanol pharmacology. It is suggested that GlyRs are involved in 1) the dopamine activating effect of ethanol, 2) regulating ethanol intake and 3) the relapse preventing effect of acamprosate. Exploration of the GlyR subtypes involved and efforts to develop subtype specific agonists or antagonists may offer new pharmacotherapies for alcohol use disorders.This article is protected by copyright. All rights reserved.
      PubDate: 2017-08-21T05:00:21.147344-05:
      DOI: 10.1111/acer.13483
       
  • Impulsive decision making in young adult social drinkers and detoxified
           alcohol-dependent patients: A cross-sectional and longitudinal study
    • Authors: Nadine Bernhardt; Stephan Nebe, Shakoor Pooseh, Miriam Sebold, Christian Sommer, Julian Birkenstock, Ulrich S. Zimmermann, Andreas Heinz, Michael N. Smolka
      Abstract: BackgroundImpulsive decision making relates to problematic substance use. Specifically, altered delay discounting has been suggested as a behavioral marker for addiction, while other relevant facets of choice impulsivity such as probability discounting or loss aversion are clearly understudied.MethodsTwo studies were performed collecting behavioral data on choice impulsivity with a value-based decision-making battery providing estimates of delay discounting, probability discounting for gains and losses, and loss aversion. Study 1) In a sample of 198 male 18-year-old social drinkers, we analyzed impulsive choice behavior and its association with alcohol consumption and self-report measures of substance use related personality traits on a cross-sectional level. Additionally, the predictive value of baseline choice behavior for the trajectories of alcohol consumption over a 12-month follow-up period was evaluated. Study 2) Behavioral data on choice impulsivity was collected for 114 detoxified patients with alcohol use disorder (AUD) and 98 control participants. We analyzed group differences at baseline and assessed the predictive value of choice impulsivity for relapse to heavy alcohol use in patients during a follow-up period of 48 weeks.ResultsStudy 1) Only delay discounting was associated with baseline alcohol use, but no measure of choice impulsivity predicted the drinking trajectories over the following 12 months. Study 2) Compared to the control group, AUD patients showed higher delay discounting, lower risk aversion regarding probabilistic gains, lower risk seeking regarding probabilistic losses, and lower loss aversion facing mixed prospects. Further, shallow discounting of probabilistic losses at baseline was predictive for relapse in patients.ConclusionsAll four domains of impulsive decision making were considerably altered in AUD patients though mostly not related to alcohol use in young-adult social drinkers. This suggests that these facets of impulsive behavior may develop as consequences of chronic alcohol consumption. Furthermore, discounting of probabilistic losses might prove valuable in identifying patients vulnerable for relapse.This article is protected by copyright. All rights reserved.
      PubDate: 2017-08-17T03:25:30.389994-05:
      DOI: 10.1111/acer.13481
       
  • Associations between Genomic Variants in Alcohol Dehydrogenase (ADH) Genes
           and Alcohol Symptomatology in American Indians and European Americans:
           Distinctions and Convergence
    • Authors: Q. Peng; Ian R. Gizer, K.C. Wilhelmsen, C.L. Ehlers
      Abstract: BackgroundHigher rates of alcohol use disorders (AUD) have been observed in some Native American (NA) populations than other ethnic groups such as Euro-Americans (EA) in the U.S. Previous studies have shown that variation in the alcohol dehydrogenase (ADH) genes may affect the risk for development of AUD, and that the prevalence of these variants differs depending on the ancestral origins of a population.MethodsIn the present study, we assessed sequencing variants in the ADH genomic region (ADH1-7) and tested for their associations with AUD phenotypes in two independent populations: an American Indian (AI) community sample and an EA cohort from the San Francisco Family Alcohol Study. Association tests were conducted for both common and rare variants using sequencing data for two phenotypes: the number of alcohol-related life events, and the count of alcohol dependence drinking symptoms. A regularized regression method was used to select the best set of ADH variants associated with phenotypes. Variance component model was incorporated in all analyses to leverage the admixture and relatedness.ResultsTwo variants near ADH4 and two near ADH1C exhibited significant associations with AUD in AI; no variant was significant in EA. Common risk variants in AI were either absent from or much less frequent in EA. The feature selection method selected mostly distinct yet often co-located subsets of ADH variants to be associated with AUD phenotypes between the two cohorts. In the rare variant analyses, the only association was observed between the whole region and the alcohol-related life events in AI.ConclusionsOur results suggest that ADH variants, both common and rare, are more likely to impact risk for alcohol-related symptomatology in this AI population than in this EA sample; and ADH variants that might affect AUD are likely different but convergent on similar regions between the two populations.This article is protected by copyright. All rights reserved.
      PubDate: 2017-08-16T10:20:33.464392-05:
      DOI: 10.1111/acer.13480
       
  • The role of social, familial, and individual-level factors on multiple
           alcohol use outcomes during the first year of university
    • Authors: Megan E. Cooke; Zoe E. Neale, Peter B. Barr, John Myers, Danielle M. Dick, Kenneth S. Kendler, Alexis C. Edwards
      Abstract: BackgroundThe first year of university attendance represents a critical time frame for the development of alcohol use and misuse given changes in autonomy and increased access to alcohol. Prior studies have demonstrated that the establishment of drinking patterns during this period is impacted by an array of demographic, environmental, and familial factors. It is critical to consider such factors jointly, and to understand potentially differential effects on stages of alcohol use/misuse, in order to identify robust predictors that may be targeted in prevention and intervention programming.MethodsAs part of a longitudinal study, students at a large, public US university were invited to complete online surveys that included questions related to alcohol use, emotional and behavioral health, environmental factors, sociodemographic factors, and familial environment. The current study uses data from surveys administered in the fall and spring of the first year of university. We used univariate (maximum N=7291) and multivariate (maximum N=4788) logistic and linear regressions to evaluate the associations between potential risk and protective factors with four alcohol use outcomes: initiation, consumption, problems, and addiction resistance.ResultsIn multivariate models, we observed associations between demographic, social/environmental, and personal-level predictors with all four alcohol outcomes, several of which were consistent across each stage of alcohol use. A deviant high school peer group was one of the strongest predictors of risk across outcomes. The influence of drinking motives and alcohol expectancies varied by alcohol use outcome. Externalizing characteristics were associated with increased risk across outcomes, while internalizing symptoms were associated with more problems and lower addiction resistance.ConclusionsThese findings underscore the complex network of factors influencing stages of alcohol use during the first year of university. Importantly, these findings demonstrate that the impact of predictors changes across stages of alcohol use/misuse, which presents opportunities for targeted prevention efforts.This article is protected by copyright. All rights reserved.
      PubDate: 2017-08-14T07:25:21.966805-05:
      DOI: 10.1111/acer.13478
       
  • Chronic Ethanol Metabolism Inhibits Hepatic Mitochondrial Superoxide
           Dismutase via Lysine Acetylation
    • Authors: Mohammed A. Assiri; Samantha R. Roy, Peter S. Harris, Hadi Ali, Yongliang Liang, Colin T. Shearn, David J. Orlicky, James R. Roede, Matthew D. Hirschey, Donald S. Backos, Kristofer S. Fritz
      Abstract: BackgroundChronic ethanol consumption is a major cause of liver disease worldwide. Oxidative stress is a known consequence of ethanol metabolism and is thought to contribute significantly to alcoholic liver disease (ALD). Therefore, elucidating pathways leading to sustained oxidative stress and downstream redox imbalances may reveal how ethanol consumption leads to ALD. Recent studies suggest that ethanol metabolism impacts mitochondrial antioxidant processes through a number of proteomic alterations, including hyperacetylation of key antioxidant proteins.MethodsIn order to elucidate mechanisms of ethanol-induced hepatic oxidative stress, we investigate a role for protein hyperacetylation in modulating mitochondrial superoxide dismutase (SOD2) structure and function in a 6-week Lieber-DeCarli murine model of ethanol consumption. Our experimental approach includes immunoblotting, immunohistochemistry, activity assays, mass spectrometry, and in silico modeling.ResultsWe found that ethanol metabolism significantly increased the acetylation of SOD2 at two functionally relevant lysine sites, K68 and K122, resulting in a 40% decrease in enzyme activity while overall SOD2 abundance was unchanged. In vitro studies also reveal which lysine residues are more susceptible to acetylation. Immunohistochemical analysis demonstrates that SOD2 hyperacetylation occurs near zone 3 within the liver, which is the main ethanol-metabolizing region of the liver.ConclusionOverall, the findings presented in this study support a role for ethanol-induced lysine acetylation as an adverse post-translational modification within the mitochondria that directly impacts SOD2 charge-state and activity. Lastly, the data presented here indicate that protein hyperacetylation may be a major factor contributing to an imbalance in hepatic redox homeostasis due to chronic ethanol metabolism.This article is protected by copyright. All rights reserved.
      PubDate: 2017-08-14T02:18:29.32908-05:0
      DOI: 10.1111/acer.13473
       
  • Increased autolysis of μ-calpain in skeletal muscles of chronic
           alcohol-fed rats
    • Authors: Yulia V. Gritsyna; Nikolay N. Salmov, Alexander G. Bobylev, Anna D. Ulanova, Nikolay I. Kukushkin, Zoya A. Podlubnaya, Ivan M. Vikhlyantsev
      Abstract: BackgroundProteolysis can proceed via several distinct pathways such as the lysosomal, calcium-dependent, and ubiquitin (Ub)-proteasome-dependent pathways. Calpains are the main proteases that cleave a large variety of proteins, including the giant sarcomeric proteins titin and nebulin. Chronic ethanol feeding for 6 weeks did not affect the activities of μ-calpain and m-calpain in the m. gastrocnemius. In our research, changes in μ-calpain activity were studied in the m. gastrocnemius and m. soleus of chronically alcohol-fed rats after 6 months of alcohol intake.MethodsSDS-PAGE analysis was applied to detect changes in titin and nebulin contents. Titin phosphorylation analysis was performed using the fluorescent dye Pro-Q Diamond. Western blotting was used to determine μ-calpain autolysis as well as μ-calpain and calpastatin contents. The titin and nebulin mRNA levels were assessed by real-time PCR.ResultsThe amounts of the autolysed isoform (78 kDa) of full-length μ-calpain (80 kDa) increased in the m. gastrocnemius and m. soleus of alcohol-fed rats. The calpastatin content increased in m. gastrocnemius. Decreased intact titin-1 (T1) and increased T2-proteolytic fragment contents were found in the m. gastrocnemius and m. soleus of the alcohol-fed rats. The nebulin content decreased in the rat gastrocnemius muscle of the alcohol-fed group. The phosphorylation levels of T1 and T2 were increased in the m. gastrocnemius and m. soleus, and decreased titin and nebulin mRNA levels were observed in the m. gastrocnemius. The nebulin mRNA level was increased in the soleus muscle of the alcohol-fed rats.ConclusionIn summary, our data suggest that prolonged chronic alcohol consumption for 6 months resulted in increased autolysis of μ-calpain in rat skeletal muscles. These changes were accompanied by reduced titin and nebulin contents, titin hyperphosphorylation, and development of hindlimb muscle atrophy in the alcohol-fed rats.This article is protected by copyright. All rights reserved.
      PubDate: 2017-08-11T10:05:21.837132-05:
      DOI: 10.1111/acer.13476
       
  • High-Intensity Drinking versus Heavy Episodic Drinking: Prevalence Rates
           and Relative Odds of Alcohol Use Disorder across Adulthood
    • Authors: Ashley N. Linden-Carmichael; Sara A. Vasilenko, Stephanie T. Lanza, Jennifer L. Maggs
      Abstract: BackgroundHeavy episodic drinking (HED) or consuming 4+/5+ drinks in one occasion for women/men is linked consistently with alcohol-related harms. Recent research suggests that many individuals drink at levels more than twice this cutoff (8+/10+ drinks), commonly referred to as “high-intensity drinking.” Prevalence rates of high-intensity drinking and its dynamic association with alcohol use disorder across all ages, however, remain unknown. The current study used data from a nationally representative sample to document age-varying prevalence rates of HED-only drinking and high-intensity drinking, prevalence rates of alcohol use disorder for HED-only drinkers and high-intensity drinkers, and relative odds of experiencing an alcohol use disorder for high-intensity drinkers as compared to HED-only drinkers.MethodsData were from the National Epidemiologic Survey on Alcohol and Related Conditions-III (NESARC-III). The final analytic sample consisted of past-year drinkers aged 18 to 64 years (n=22,776).ResultsTime-varying effect modeling (TVEM) revealed that high-intensity drinking and HED-only drinking were equally prevalent during young adulthood and prevalence rates of both types of drinking generally became less common with increasing age. At all ages, high-intensity drinkers were at three or more times greater odds of meeting criteria for an alcohol use disorder than HED-only drinkers. The association between high-intensity relative to HED-only drinking was strongest earlier in adulthood with approximately 83% of 18-year-old high-intensity drinkers having AUD relative to 42% of HED-only drinkers.ConclusionsFuture research aiming to identify drinkers most at risk for harms and in need of treatment may benefit from assessing the extent to which an individual exceeds the 8+/10+ threshold of drinking.This article is protected by copyright. All rights reserved.
      PubDate: 2017-08-11T09:50:20.407398-05:
      DOI: 10.1111/acer.13475
       
  • Alcohol-mediated missplicing of Mcl-1 pre-mRNA is involved in
           neurotoxicity
    • Authors: Rahsan Sariyer; Francesca I. De Simone, Martina Donadoni, Jan B Hoek, Sulie L. Chang, Ilker Kudret Sariyer
      Abstract: BackgroundHeavy and chronic ethanol (EtOH) exposure can cause significant structural and functional damage to the adult brain. The most devastating consequence of EtOH exposure is the neurotoxicity associated with the depletion of neurons. Regulation of splice variants in the brain can modulate protein functions, which may ultimately affect behaviors associated with alcohol dependence and EtOH-mediated neurotoxicity. Since alcohol consumption is associated with neurotoxicity, it is possible that altered splicing of survival and pro-survival factors during the development of alcoholism may contribute to the neurotoxicity.MethodsPrimary human neurons and a neuroblastoma cell line were exposed to different concentrations of EtOH for various time periods. Cell viability and neuronal marker expression were analyzed by MTT assay and immunoblotting, respectively. Effect of EtOH exposure on splicing regulatory protein expression and alternative splicing of candidate genes were analyzed by a biochemical approach. Transcriptional activity of SRSF1 gene was determined by reporter gene analysis.ResultsOur results suggest that EtOH exposure to neuronal cells at 25 mM and higher concentrations are detrimental. In addition, EtOH exposure caused a dramatic reduction in serine-arginine rich splicing factor 1 (SRSF1) expression levels. Furthermore, EtOH exposure led to pre-mRNA missplicing of Mcl-1, a pro-survival member of the Bcl-2 family, by downregulating the expression levels of serine/arginine rich splicing factor 1 (SRSF1). Moreover, ectopic expression of both SRSF1 and MCL-1L isoform was able to recover EtOH-mediated neurotoxicity.ConclusionsOur results suggest that ethanol exposure can lead to pre-mRNA missplicing of Mcl-1 in neuronal cells. Our results indicate that ethanol exposure of neurons leads to a decrease in the ratio of Mcl-1L/Mcl-1S by favoring pro-apoptotic Mcl-1S splicing over anti-apoptotic Mcl-1L isoform suggesting that Mcl-1S may play a crucial role in neurotoxicity associated with alcohol consumption.This article is protected by copyright. All rights reserved.
      PubDate: 2017-08-11T09:45:24.373816-05:
      DOI: 10.1111/acer.13474
       
  • Women's Alcohol Sensitivity Predicts Alcohol-Related Regretted Sex
    • Authors: Liana S. E. Hone; Bruce D. Bartholow, Thomas M. Piasecki, Kenneth J. Sher
      Abstract: BackgroundLow sensitivity (LS) to alcohol's acute effects is a known risk factor for heavy drinking and its negative consequences. However, LS could be protective due to LS drinkers being less impaired at a given level of consumption. Here, we tested whether LS is associated with differences in men's and women's reports of alcohol-related regretted sex.MethodsEight hundred and one young adults (393 women) aged 21 to 35 (M = 23.11 years) recruited for a study of alcohol's effects on cognition completed self-report measures of alcohol sensitivity, typical alcohol use, and alcohol consequences (including regretted sex).ResultsParticipants whose alcohol sensitivity scores classified them as LS were more likely to experience alcohol-related regretted sex than were high-sensitivity (HS) participants. However, when controlling for typical alcohol use and experience of alcohol consequences in general, alcohol sensitivity was negatively associated with risk of alcohol-related regretted sex, but only among women.ConclusionsAt a given level of consumption, and controlling for experience of alcohol consequences other than regretted sex, reduced sensitivity to certain effects of alcohol may be a protective factor for women against risk for alcohol-related regretted sexual situations. This study provides insight on the unique risks of drinking among LS and HS women.
      PubDate: 2017-08-10T16:00:02.497933-05:
      DOI: 10.1111/acer.13447
       
  • Delay Discounting of Losses in Alcohol Use Disorders and Antisocial
           Psychopathology: Effects of a Working Memory Load
    • Authors: Kyle Gerst; Rachel L Gunn, Peter R Finn
      Abstract: BackgroundAlcohol use disorders (AUDs) are associated with increased discounting of delayed rewards and reduced executive working memory (eWM) capacity. This association is amplified when comorbid with antisocial psychopathology (AP). Furthermore, recent studies suggest that reduced WM capacity is associated with disinhibited decisions reflected by increased impulsive decision-making on the delay discounting of rewards task. While discounting of delayed rewards is well studied, the discounting of delayed losses (DDL) has received significantly less experimental attention.MethodsThe current study investigated: 1) the rate of DDL in individuals with AUD only (n=61), AUD with comorbid AP (n=79) and healthy controls (n=64); 2) the relationship between eWM capacity and discounting of delayed losses; and 3) the effect of a WM load on discounting of delayed losses. Discounting performance was assessed using a computerized discounting of delayed losses task.ResultsResults showed that the AUD-only and AUD-AP groups had higher rates of DDL and lower eWM capacity compared to the control groups. Lower individual eWM capacity was associated with increased discounting of delayed losses. However, WM load did not increase discounting rates overall.ConclusionsThese results support the hypothesis that greater discounting of delayed losses is associated with AUD and comorbid AP problems and lower individual eWM capacity.This article is protected by copyright. All rights reserved.
      PubDate: 2017-08-09T10:00:21.824318-05:
      DOI: 10.1111/acer.13472
       
  • Proteomic Profiling of Liver and Plasma in Chronic Ethanol Feeding Model
           of Hepatic Alcohol Dehydrogenase-Deficient Deer Mice
    • Authors: Kamlesh K. Bhopale; Samir M. Amer, Lata Kaphalia, Kizhake V. Soman, John E. Wiktorowicz, G. A. Shakeel Ansari, Bhupendra S. Kaphalia
      Abstract: BackgroundChronic alcohol abuse, a major risk factor for such diseases as hepatitis and cirrhosis, impairs hepatic alcohol dehydrogenase (ADH, key ethanol metabolizing enzyme). Therefore, differentially altered hepatic and plasma proteomes were identified in chronic ethanol feeding model of hepatic ADH-deficient (ADH-) deer mice to understand the metabolic basis of alcoholic liver disease (ALD).MethodsADH- deer mice were fed 3.5g% ethanol via Lieber-DeCarli liquid diet daily for three months, and histology of the liver assessed. Liver and plasma proteins were separated by 2-dimensional gel electrophoresis. The proteins differentially expressed were identified by MALDI-TOF/TOF mass spectrometry (MS).ResultsHistology of the liver showed panlobular steatosis and infiltration of T-lymphocytes. Using the criteria of ≥1.5 for fold change (p value ≤0.05) with expectation value (E ≤10-3) and protein score (≥64), eighteen proteins in the livers and five in the plasma of ethanol-fed mice were differentially expressed and identified. Prolyl 4-hydroxylase, cytochrome b-5, endo A cytokeratin, ATP synthase, heat shock 70kD proteins, enoyl CoA hydratase, stress-70 protein, peroxiredoxin 1 and ornithine carbamoyl-transferase were up regulated in the livers. However, carbonic anhydrase 3, mitochondrial ATP synthase, aldolase 2, actin γ, laminin receptor and carbamoyl-phosphate synthase were down regulated. Contrary to the increased expression of creatine kinase m-type, a decreased expression of serine protease inhibitor A3A precursor, sulfated glycoprotein-2 (clusterin) and apolipoprotein E isoforms were found in the plasma of ethanol group.ConclusionsChronic ethanol feeding in ADH- deer mice causes steatosis and infiltration of T-lymphocytes in the livers along with increased expression of proteins involved in ER stress, fibrosis, fatty acid β oxidation and biogenesis, and decreased expression of proteins involved in ATP synthesis, carbohydrate metabolism, in cell regulation and architecture. Reduced expression of various carrier proteins as found in the plasma of ethanol group has a biomarker potential.This article is protected by copyright. All rights reserved.
      PubDate: 2017-08-09T07:45:54.030429-05:
      DOI: 10.1111/acer.13470
       
  • Cut-point Levels of Phosphatidylethanol to Identify Alcohol Misuse in a
           Mixed Cohort including Critically Ill Patients
    • Authors: Majid Afshar; Ellen L. Burnham, Cara Joyce, Brendan J. Clark, Meagan Yong, Jeannette Gaydos, Richard S. Cooper, Gordon S. Smith, Elizabeth J. Kovacs, Erin M. Lowery
      Abstract: BackgroundAlthough alcohol misuse is associated with deleterious outcomes in critically ill patients, its detection by either self-report or examination of biomarkers is difficult to obtain consistently. Phosphatidylethanol (PEth) is a direct alcohol biomarker that can characterize alcohol consumption patterns; however, its diagnostic accuracy in identifying misuse in critically ill patients is unknown.MethodsPEth values were obtained in a mixed cohort comprised of 122 individuals from medical and burn intensive care units (n=33), alcohol detoxification unit (n=51), and healthy volunteers (n=38). Any alcohol misuse and severe misuse were referenced by AUDIT and AUDIT-C scores separately. Mixed effects logistic regression analysis was performed and the discrimination of PEth was evaluated using the area under the receiver operating characteristic (ROC) curve.ResultsThe area under the ROC curve for PEth was 0.927 (95% CI: 0.877, 0.977) for any misuse and 0.906 (95% CI: 0.850, 0.962) for severe misuse defined by AUDIT. By AUDIT-C, the area under the ROC curves were 0.948 (95% CI: 0.910, 0.956) for any misuse and 0.913 (95% CI: 0.856, 0.971) for severe misuse. The PEth cut-points of ≥ 250 ng/mL and ≥ 400 ng/mL provided optimal discrimination for any misuse and severe misuse, respectively. The positive predictive value for ≥ 250 ng/mL was 88.7% (95% CI: 77.5%, 95.0%) and negative predictive value was 86.7% (95% CI: 74.9%, 93.7%). PEth ≥ 400 ng/mL achieved similar values and similar results were shown for AUDIT-C. In a subgroup analysis of critically ill patients only, test characteristics were similar to the mixed cohort.ConclusionsPEth is a strong predictor and has good discrimination for any and severe alcohol misuse in a mixed cohort that includes critically ill patients. Cut-points at 250 ng/mL for any, and 400 ng/mL for severe, are favorable. External validation will be required to establish these cut-points in critically ill patients.This article is protected by copyright. All rights reserved.
      PubDate: 2017-08-09T07:45:26.073144-05:
      DOI: 10.1111/acer.13471
       
  • Erratum: Meta-Analysis Reveals Significant Association of the 3′-UTR
           VNTR in SLC6A3 With Alcohol Dependence
    • Authors: Yunlong Ma; Rongli Fan, Ming D. Li
      PubDate: 2017-08-07T07:05:25.864786-05:
      DOI: 10.1111/acer.13465
       
  • Cloninger type 2 score and Lesch typology predict hospital readmission of
           
    • Authors: Christian Weinland; Birgit Braun, Christiane Mühle, Johannes Kornhuber, Bernd Lenz
      Abstract: BackgroundRelapse after detoxification treatment is a common problem in alcohol dependence. However, its prediction still lacks reliability. We here investigated whether the easily accessible clinical Cloninger and Lesch classifications predict alcohol-related hospital readmission following in-patient withdrawal treatment.MethodsIn this bicentric prospective clinical study, 67 female and 84 male alcohol-dependent in-patients were characterized according to the Cloninger items and the Lesch typology. The patients’ records were followed for 24 months. Because of the well-established sex differences in alcohol dependence, we studied females and males separately.ResultsOverall, 53% of the female patients and 66% of the male patients sustained at least one alcohol-related hospital readmission during the follow-up. Readmission was related to a higher Cloninger type 2 score than non-readmission (females, p=0.007, males p=0.044). In females, the Cloninger type 2 score correlated with the number of readmissions (Rho=0.384, p=0.001) and the days to first readmission (Rho=-0.333, p=0.006). The effects were stronger in patients with age at onset of alcohol dependence over 25 years. We found gender dimorphisms concerning the Cloninger items. In female patients, the four Lesch subtypes differed in their risk (p=0.010), the number (p=0.040), and the days to first readmission (p=0.031). Lesch type 1 was associated with an increased risk (OR=4.83, p=0.041) and Lesch type 2 with a reduced risk (OR=0.07, p=0.004). In addition, the number of previous in-patient alcohol withdrawals predicted the patients’ outcomes (p
      PubDate: 2017-08-05T06:55:20.680327-05:
      DOI: 10.1111/acer.13468
       
  • A randomised trial of effects of alcohol on cytochrome P450 eicosanoids,
           mediators of inflammation resolution and blood pressure in men
    • Authors: Anne E. Barden; Venus Chavez, Michael Phillips, Emilie Mas, Lawrence J Beilin, Kevin D Croft, Trevor A Mori, Ian B Puddey
      Abstract: BackgroundCardiovascular effects of alcohol consumption may be influenced by both pro- and anti-inflammatory mechanisms. We previously showed that chronic alcohol consumption increased blood pressure (BP), oxidative stress and 20-hydroxyeicosatetraenoic acid (20-HETE), a vasoconstrictor and pro-inflammatory eicosanoid synthesised by CYP450 enzymes from arachidonic acid. This study in men examined the effect of consuming red wine (RW) on BP in relation to changes in 20-HETE, oxidative stress (F2-isoprostanes), markers of inflammation, anti-inflammatory CYP450 epoxyeicosatrienoic acids (EETs) and specialised pro-resolving mediators of inflammation (SPMs) derived from eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA).MethodsNormotensive men (n=22) were randomly allocated to drink RW (375ml/day) or the equivalent volume of de-alcoholised red wine (DRW) or water for 4 weeks in a 12 week, 3-period crossover trial. BP, heart rate, 20-HETE, F2-isoprostanes and SPM were measured at baseline, 4, 8, and 12 weeks.ResultsDrinking RW increased BP (P
      PubDate: 2017-08-02T08:05:23.518375-05:
      DOI: 10.1111/acer.13466
       
  • Stress Facilitates the Development of Cognitive Dysfunction After Chronic
           Ethanol Exposure
    • Authors: Ellen M. Rodberg; Carolina R. Hartog, Rachel I. Anderson, Howard C. Becker, David E. Moorman, Elena M. Vazey
      Abstract: BackgroundChronic exposure to stress or alcohol can drive neuroadaptations that alter cognition. Alterations in cognition may contribute to alcohol use disorders by reducing cognitive control over drinking and maintenance of abstinence. Here we examined effects of combined ethanol (EtOH) and stress exposure on prefrontal cortex (PFC)-dependent cognition.MethodsAdult male C57BL/6J mice were trained to drink EtOH (15%, v/v) on a 1 h/d 1-bottle schedule. Once stable, mice were exposed to cycles of chronic intermittent EtOH (CIE) or air-control vapor exposure (Air), followed by test cycles of 1 h/d EtOH drinking. During test drinking, mice received no stress (NS) or 10 minutes of forced swim stress (FSS) 4 hours before each test. This schedule produced 4 experimental groups: control, Air/NS; EtOH-dependent no stress, CIE/NS; nondependent stress, Air/FSS; or EtOH-dependent stress, CIE/FSS. After 2 cycles of CIE and FSS exposure, we assessed PFC-dependent cognition using object/context recognition and attentional set shifting. At the end of the study, mice were perfused and brains were collected for measurement of c-Fos activity in PFC and locus coeruleus (LC).ResultsCIE/FSS mice escalated EtOH intake faster than CIE/NS and consumed more EtOH than Air/NS across all test cycles. After 2 cycles of CIE/FSS, mice showed impairments in contextual learning and extradimensional set-shifting relative to other groups. In addition to cognitive dysfunction, CIE/FSS mice demonstrated widespread reductions in c-Fos activity within prelimbic and infralimbic PFC as well as LC.ConclusionsTogether, these findings show that interactions between EtOH and stress exposure rapidly lead to disruptions in signaling across cognitive networks and impairments in PFC-dependent cognitive function.
      PubDate: 2017-07-28T16:00:01.704778-05:
      DOI: 10.1111/acer.13444
       
  • Decisions to Attend and Drink at Party Events: The Effects of Incentives
           and Disincentives and Lifetime Alcohol and Antisocial Problems
    • Authors: Peter R. Finn; Kyle Gerst, Allison Lake, Tim Bogg
      Abstract: BackgroundAlcohol use disorders are associated with patterns of impulsive/risky decision making on behavioral economic decision tasks, but little is known about the factors affecting drinking-related decisions.MethodsThe effects of incentives and disincentives to attend and drink at hypothetical alcohol-related party events as a function of lifetime (LT) alcohol and antisocial problems were examined in a sample of 434 young adults who varied widely in LT alcohol and antisocial problems.ResultsModerate and high disincentives substantially discouraged decisions to attend the party events and were associated with decisions to drink less at the party events. High versus low party incentives were associated with more attendance decisions. LT antisocial problems were associated with being less deterred from attending by moderate and high disincentives. LT alcohol problems were associated with greater attendance at high party incentive contexts. LT alcohol problems were associated with drinking more at the majority of events; however, the results indicate that young adults with high levels of alcohol problems moderate their drinking in response to moderate and high disincentives. Finally, attendance and drinking decisions on this hypothetical task were significantly related to actual drinking practices.ConclusionsThe results suggest that antisocial symptoms are associated with a reduced sensitivity to the potential negative consequences of drinking, while alcohol problems are associated with a greater sensitivity to the rewarding aspects of partying. The results also underline the value of directly assessing drinking-related decisions in different hypothetical contexts as well as assessing decisions about attendance at risky drinking events in addition to drinking amount decisions.The results show that lifetime antisocial problems moderated the effects of disincentives on decisions to attend drinking events (panel A). Those high in lifetime antisocial problems were less deterred from deciding to attend party events with moderate and high disincentives (where there is an increased likelihood that drinking will interfere with important responsibilities. Panel B shows that those high in lifetime alcohol problems were more responsive to high party reward incentives when deciding to attend drinking events.
      PubDate: 2017-07-25T17:00:02.459519-05:
      DOI: 10.1111/acer.13443
       
  • Is Personality Associated with Secondhand Harm from Drinking'
    • Authors: Parnell Davis MacNevin; Kara Thompson, Michael Teehan, Heather Stuart, Sherry Stewart
      Abstract: BackgroundPrior research suggests more than 70% of undergraduates have experienced harm from other students’ drinking. This study built on the literature by, first, investigating whether secondhand harm cluster into latent factors that reflect distinct but related types of harm. Second, given the paucity of research examining factors that increase students’ vulnerability to secondhand harm, we examined dimensions from Castellanos-Ryan and Conrod's 4-factor personality model for alcohol disorders (impulsivity [IMP], sensation seeking [SS], hopelessness [HOP], anxiety sensitivity [AS]) as predictors of secondhand harm exposure. We also investigated the possible mediating role of students’ own problematic alcohol use in explaining personality–secondhand harm relationships.MethodsAn online survey was administered to 1,537 first-year Canadian undergraduates (68% women). Problematic alcohol use was measured by the Alcohol Use Disorders Identification Test, and personality was measured by the Substance Use Risk Profile Scale. Eleven secondhand harm items were included.ResultsThe secondhand harm clustered into 3 distinct but related factors: “strains” (e.g., interruption of sleep or study), “threats” (e.g., harassment or assault), and “interpersonal harm” (e.g., arguments with peers). Sixty-eight percent of respondents reported strains, 44% threats, and 64% interpersonal harm, and 35% reported experiencing all 3 types of harm, in the last term. All 4 personality dimensions were independently associated with greater secondhand harm exposure. HOP was directly associated with threats and interpersonal harm, and AS was directly associated with all 3 types of harm. SS and IMP were both indirectly associated with all 3 types of harm through students’ own problematic alcohol use. In addition, IMP was directly related to threats.ConclusionsThe prevalence of secondhand harm from alcohol is high among undergraduates. Findings suggest that distinct personality risks may predispose students to experience secondhand harm, albeit perhaps through different mechanisms. Implications for future research, prevention, and policy development are discussed.Over 70% of undergraduates experience harm from their peers’ drinking. We investigated whether personality dimensions confer risk of exposure to 3 types of secondhand harm: “strains” (e.g., sleep/study interruption), “threats” (e.g., assault), and “interpersonal harm” (e.g., arguments with peers). Findings suggest students high on impulsivity and sensation seeking tend to drink more, and are subsequently exposed to secondhand harms through heavy-drinking contexts. Inhibited personalities (hopelessness, anxiety sensitivity) were also associated with increased risk of secondhand harms directly, independent of drinking.
      PubDate: 2017-07-24T16:00:01.527493-05:
      DOI: 10.1111/acer.13440
       
  • Alcohol-related Knowledge and Alcohol-related Norms in Four to Six Year
           Olds - Evidence from the Dutch Electronic Appropriate Beverage Task
    • Authors: Carmen Voogt; Roy Otten, Marloes Kleinjan, Rutger Engels, Emmanuel Kuntsche
      Abstract: BackgroundLimited research is available on children's alcohol-related knowledge and alcohol-related norms, yet a better comprehension of these factors may be crucial in explaining alcohol use later in life. This study provides insights into alcohol-related knowledge and alcohol-related norms in four- to six-year-olds.MethodsParticipating children (N=329; 48.9% boys) were shown, on a tablet, 18 drawings depicting 72 male and female adults and/or children in various situations and were asked to indicate what the depicted persons drank by touching one of 12 depicted beverages (four alcoholic; eight non-alcoholic). Subsequently, the children were asked to name the beverages and indicate whether they contained alcohol.ResultsChildren identified 30.7% of the alcoholic beverages (i.e., beer, champagne, red wine, and white wine) correctly by name and they identified 41.6% of the alcoholic beverages correctly as alcohol-containing. Children more often correctly identified the name and non-alcoholic content of non-alcoholic beverages compared to the name and alcoholic content of alcoholic beverages. No sex differences emerged in the correct identification of the name and the content of both alcoholic beverages and non-alcoholic beverages. However, alcohol-related knowledge was age-graded. Alcoholic beverages were more often assigned to male adults (39.2%) than to female adults (24.8%) or to children (13.2%). Additionally, alcoholic beverages were more often assigned to adults depicted in the presumably more appropriate situations (e.g., ‘when having an indoor party’: 37.0%) than to those depicted in the presumably more inappropriate situations (e.g., ‘when driving a car’: 28.6%).ConclusionsFour- to six-year-olds already have knowledge about alcohol and its norms in adult culture. Insight into the development of children's alcohol-related knowledge and alcohol-related norms over time is required to investigate the transitions to alcohol expectancies, drinking motives, and alcohol initiation often occurring in adolescence.This article is protected by copyright. All rights reserved.
      PubDate: 2017-07-21T10:11:00.070833-05:
      DOI: 10.1111/acer.13452
       
  • Children with Heavy Prenatal Alcohol Exposure Exhibit Atypical Gait
           Characteristics
    • Authors: Tenille C. Taggart; Roger W. Simmons, Jennifer D. Thomas, Edward P. Riley
      Abstract: BackgroundImpaired motor function in children with histories of prenatal exposure to alcohol has been previously reported but, to date, no studies using quantitatively-based analyses have been performed to assess gait in these children.MethodsGait of children with (n = 18) or without (n = 26) prenatal alcohol exposure was assessed using an electronically instrumented walkway. Children completed blocks of trials traversing the walkway with different combinations of walking condition (increased, self-paced, and decreased cadence) and direction (forward and backward). Gait velocity, cadence, stride length, step width, foot angle, and double support time, as well as the variability of these temporal-spatial markers, were used to assess gait.ResultsResults indicated that, in comparison to typically developing children, alcohol-exposed children produced exaggerated foot angle and increased step width. Additionally, alcohol-exposed children produced greater intra-subject variability of gait velocity and walking cadence while walking forward and backward, and greater variability in step width when walking backward and for all three walking conditions.ConclusionsThe results indicate that selected gait markers are adversely affected by prenatal exposure to alcohol. Clinicians and front line personnel (e.g., teachers) should provide movement enriched experiences to help ameliorate these alcohol-related deficits.This article is protected by copyright. All rights reserved.
      PubDate: 2017-07-20T07:45:40.2714-05:00
      DOI: 10.1111/acer.13450
       
  • Placental Proteomics Reveal Insights into Fetal Alcohol Spectrum Disorders
    • Authors: Katie L. Davis-Anderson; Sebastian Berger, Emilie R. Lunde-Young, Vishal D. Naik, Heewon Seo, Greg A. Johnson, Hanno Steen, Jayanth Ramadoss
      Abstract: BackgroundFetal alcohol spectrum disorders (FASD) describe many of the well-known neurodevelopmental deficits afflicting children exposed to alcohol in utero. The effects of alcohol on the maternal-fetal interface, especially the placenta, have been less explored. We herein hypothesized that chronic binge alcohol exposure during pregnancy significantly alters the placental protein profile in a rat FASD modelMethodsPregnant rats were orogastrically treated daily with alcohol (4.5 g/kg, gestational day (GD) 5-10; 6.0 g/kg, GD 11-19) or 50% maltose dextrin (isocalorically matched pair-fed controls). On GD 20, placentae were collected, flash frozen, and stored until tissues were homogenized. Protein lysates were denatured, reduced, captured on a 10 kDa spin filter and digested. Peptides were eluted, reconstituted, and analyzed by a Q Exactive™ Hybrid Quadrupole-Orbitrap™ mass spectrometerResultsMass spectrometry analysis identified 2,285 placental proteins based on normalized spectral counts and 2000 proteins by intensity based absolute quantification. 45 placental proteins were significantly (P
      PubDate: 2017-07-19T06:00:21.543917-05:
      DOI: 10.1111/acer.13448
       
  • Screening for hazardous drinking in nursing home residents: Evaluating the
           validity of the current cut offs of the Alcohol Use Disorder
           Identification Test – Consumption questions (AUDIT-C) by using ethyl
           glucuronide in hair (HEtG)
    • Authors: Monika Dreher-Weber; Anton-Rupert Laireiter, Anton Kühberger, Isabella Kunz, Michel Yegles, Tina Binz, Hans-Jürgen Rumpf, Rainer Hoffmann, Verena Schmidt, Siegfried Lang, Friedrich M. Wurst
      Abstract: BackgroundBecause of physiological changes, elderly people are much more exposed to the adverse effects of alcohol. Therefore, hazardous drinking is defined at lower levels as compared to younger adults. This work aims to evaluate the validity of the current cut off levels of the Alcohol Use Disorder Identification Test – Consumption questions (AUDIT-C) to detect hazardous drinking in the elderly by using ethyl glucuronide in hair (HEtG).MethodsIn a border region between Austria and Germany, 344 nursing home residents were included from 33 of the 107 nursing homes. Residents were asked to answer the AUDIT-C questions, hair samples were obtained, and nursing staff members were asked for their assessments of the residents’ alcohol consumption. Hair samples were analyzed for HEtG using gas chromatography-mass spectrometry. Receiver-operated characteristics curve (ROC) analysis was performed to determine the validity of cut off values for the AUDIT-C to detect an alcohol consumption of ≥ 10 g of alcohol/day.Results11.3% of nursing home residents (n = 344) drank ≥ 10 g of alcohol/day (4.9%> 60 g of alcohol/day). For the drinking limit of ≥ 10 g of alcohol/day, ROC-curve analysis showed a balanced sensitivity and specificity, with an AUDIT-C cut off of ≥ 4 for men (sensitivity: 70%, specificity: 83.6%; AUC = 0.823, CI = 0.718-0.928, P < 0.001) and ≥ 2 for women (sensitivity: 73.7%, specificity: 81.9%; AUC = 0.783, CI = 0.653-0.914, P < 0.001). Nursing staff (n = 274) underestimated alcohol consumption and evaluated 40% of the chronic-excessive alcohol consumers as being abstinent.ConclusionsOur data suggest that a AUDIT-C cut off of ≥ 4 for men and ≥ 2 for women can be recommended to detect the consumption of ≥ 10 g of alcohol/day in the elderly. Because the nursing staff to a large extent underestimates the alcohol consumption among nursing home residents, further teaching of the staff, improvement of screening instruments for the elderly and the use of objective biomarkers might be helpful for recognizing hazardous drinking and can thus help improve the quality of life of the elderly.This article is protected by copyright. All rights reserved.
      PubDate: 2017-07-18T08:00:21.844255-05:
      DOI: 10.1111/acer.13449
       
  • Acute alcohol binge deteriorates metabolic and respiratory compensation
           capability after blunt chest trauma followed by hemorrhagic shock - a new
           research model
    • Authors: Nils Wagner; Niklas Franz, Scott Dieteren, Mario Perl, Katharina Mörs, Ingo Marzi, Borna Relja
      Abstract: Background and purposeThe clinical relevance of blunt (thoracic) chest trauma (TxT) and hemorrhagic shock is indisputable due to the high prevalence of this injury type, as well as its close association with mortality and/or preventable deaths. Furthermore, there is an ongoing discussion about the influence of alcohol in trauma patients. Thus, we established a model of TxT followed by hemorrhagic shock and resuscitation (H/R) in alcohol-intoxicated rats.Experimental approachDepending on group allocation, twelve (sub-acute) or two (acute) hours before experimentation, the animals received a single oral dose of alcohol (ethanol, EtOH) or saline (NaCl) followed by TxT, hemorrhagic shock (35 ± 3 mm Hg) and resuscitation (TxT+H/R). Arterial blood gas analyses and continuous monitoring of blood pressure were performed during the experimentation period. Survival during the experimentation procedure was determined.Key resultsSub-acute and acute EtOH group exhibited lower baseline mean arterial blood pressure (MABP) values compared with the corresponding NaCl group, respectively. Both EtOH groups showed lower maximal bleed out volume, which was necessary to induce hemorrhagic shock compared to NaCl groups, and the recovery during the resuscitation period was attenuated. During the experimentation in all groups a trend to acidic pH was observed. Acute EtOH group showed lowest pH values compared to all other groups. Higher pCO2 values were observed in both EtOH groups. All groups developed negative base excess and decreasing HCO3- values until the end of hemorrhagic shock, and showed increasing base excess and HCO3- values during resuscitation. Significantly higher mortality rate was found in the acute EtOH group.Conclusions and ImplicationsThis study indicates that alcohol limits the metabolic and respiratory compensation capability, thereby promoting mortality.This article is protected by copyright. All rights reserved.
      PubDate: 2017-07-17T07:55:51.842324-05:
      DOI: 10.1111/acer.13446
       
  • Greater prevalence of proposed ICD-11 alcohol and cannabis dependence
           compared to ICD-10, DSM-IV and DSM-5 in treated adolescents
    • Authors: Tammy Chung; Jack Cornelius, Duncan Clark, Christopher Martin
      Abstract: BackgroundProposed International Classification of Diseases, 11th edition (ICD-11) criteria for substance use disorder (SUD) radically simplify the algorithm used to diagnose substance dependence. Major differences in case identification across Diagnostic and Statistical Manual (DSM) and ICD impact determinations of treatment need and conceptualizations of substance dependence. This study compared the draft algorithm for ICD-11 SUD against DSM-IV, DSM-5, and ICD-10, for alcohol and cannabis.MethodsAdolescents (n=339, ages 14-18) admitted to intensive outpatient addictions treatment completed, as part of a research study, a Structured Clinical Interview for DSM SUDs (SCID) adapted for use with adolescents, and which has been used to assess DSM and ICD SUD diagnoses. Analyses examined prevalence across classification systems, diagnostic concordance, and sources of diagnostic disagreement.ResultsPrevalence of any past year proposed ICD-11 alcohol or cannabis use disorder was significantly lower compared to DSM-IV and DSM-5 (ps
      PubDate: 2017-07-01T10:15:27.939081-05:
      DOI: 10.1111/acer.13441
       
  • Combined Catalase and ADH Inhibition Ameliorates Ethanol-induced
           Myocardial Dysfunction Despite Causing Oxidative Stress in Conscious
           Female Rats
    • Authors: Fanrong Yao; Abdel A. Abdel-Rahman
      Abstract: BackgroundEthanol-evoked oxidative stress, which contributes to myocardial dysfunction in proestrus rats, is mediated by increases in NADPH oxidase activity, malondialdehyde (MDA) and ERK1/2 phosphorylation. Whether these biochemical responses, which are triggered by alcohol-derived acetaldehyde in non-cardiac tissues, occur in proestrus rats’ hearts remains unknown. Therefore, we elucidated the roles of alcohol dehydrogenase (ADH), cytochrome P4502E1 (CYP2E1) and catalase, which catalyze alcohol oxidation to acetaldehyde, in these alcohol-evoked biochemical and hemodynamic responses in proestrus rats.MethodConscious proestrus rats prepared for measurements of left ventricular (LV) function and blood pressure (BP) received ethanol (1.5 g/kg, i.v infusion over 30 min) or saline 30 min after an ADH and CYP2E1 inhibitor, 4-MP (82 mg/kg, i.p), a catalase inhibitor, 3-AT (0.5 g/kg, i.v), their combination or vehicle. LV function and BP were monitored for additional 60 min after ethanol or saline infusion before collecting the hearts for ex vivo measurements of LV reactive oxygen species (ROS), NADPH oxidase activity, MDA, and ERK1/2 phosphorylation.ResultsEthanol reduced LV function (dP/dtmax and LVDP) and BP, and increased cardiac NADPH oxidase activity, ROS and MDA levels, and ERK1/2 phosphorylation. Either inhibitor partially, and their combination significantly, attenuated these responses despite the substantially higher blood ethanol level, and the increased cardiac oxidative stress and reduced BP caused by 3-AT alone or with 4-MP. The inhibitors reduced cardiac MDA level and reversed ethanol effect on cardiac and plasma MDA.ConclusionsEthanol oxidative metabolism plays a pivotal role in the ethanol-evoked LV oxidative stress and dysfunction in proestrous rats. Notably, catalase inhibition (3-AT) caused cardiac oxidative stress and hypotension.This article is protected by copyright. All rights reserved.
      PubDate: 2017-07-01T10:15:26.212693-05:
      DOI: 10.1111/acer.13442
       
  • Interobserver Variability in Scoring Liver Biopsies with a Diagnosis of
           Alcoholic Hepatitis
    • Authors: Bela Horvath; Daniela Allende, Hao Xie, John Guirguis, Jennifer Jeung, James Lapinski, Deepa Patil, Arthur J McCullough, Srinivasan Dasarathy, Xiuli Liu
      Abstract: BackgroundAlcoholic hepatitis (AH) is one of the most severe forms of alcoholic liver disease. Recently, a histologic scoring system for predicting prognosis in this patient cohort was proposed as Alcoholic Hepatitis Histologic Score (AHHS). We aimed to assess interobserver variability in recognizing histologic features of AH, and the effect of this variability on the proposed AHHS categories.DesignHematoxylin-eosin and trichrome stained slides from 32 patients diagnosed with AH with liver biopsies within 1 month of presentation (2000-2015), were reviewed by 5 pathologists including 3 liver pathologists and 2 gastrointestinal (GI) pathologists masked to the clinical findings or outcome. Histologic features of AH were assessed, the AHHS was calculated and an AHHS category (mild, moderate, severe) was assigned. The Fleiss’ kappa coefficient (Kappa) analysis was performed to determine the interobserver agreement.ResultsA slight-to-moderate level of interobserver agreement existed among 5 reviewers on histopathological features of AH with kappa value ranging from 0.20 (95% confidence interval (CI): 0.03-0.46, megamitochondria) to 0.52 [95% CI: 0.40-0.68, polymorphonuclear leukocyte (PMN) infiltration]. There was only a fair level of agreement in assigning AHHS category (K=0.33, 95% CI: 0.20-0.51). While overall fibrosis and neutrophilic inflammation were comparably evaluated by 3 liver pathologists and 2 GI pathologists, bilirubinostasis and megamitochondria were more consistently diagnosed by liver pathologists. Overall, 18 out of 32 (56%) were uniformly assigned to an AHHS category by all liver pathologists with a kappa value of 0.40 (95% CI: 0.22-0.60).ConclusionIn general, features of AH can be recognized with a slight-to-moderate level of interobserver agreement and there was fair interobserver agreement on assigning an AHHS category. Significant interobserver variability among pathologists revealed by the current study can limit its usefulness in everyday clinical practice.This article is protected by copyright. All rights reserved.
      PubDate: 2017-06-27T10:55:19.960012-05:
      DOI: 10.1111/acer.13438
       
  • Problematic Drinking Mediates the Association between Urgency and Intimate
           Partner Aggression During Acute Intoxication
    • Authors: Olivia S. Subramani; Dominic J. Parrott, Christopher I. Eckhardt
      Abstract: BackgroundThis study tested a moderated-mediational model whereby dimensions of impulsivity (i.e., negative urgency, positive urgency, sensation seeking, lack of premeditation, and lack of perseverance) differentially predict perpetration of physical intimate partner aggression through problematic drinking in intoxicated and non-intoxicated heavy drinkers.MethodsParticipants were 249 heavy drinkers (148 men and 101 women) with a recent history of psychological and/or physical intimate partner aggression perpetration toward their current partner recruited from two metropolitan U.S. cities. Participants completed questionnaires that assessed impulsivity and problematic drinking, consumed an alcohol or no-alcohol control beverage, and completed a shock-based aggression task in which they were ostensibly provoked by their intimate partnerResultsResults indicated an indirect effect of urgency on intimate partner aggression through problematic drinking that was significantly more positive in intoxicated individualsConclusionsThese findings implicate a tendency to act rashly in response to emotions as the specific dimension of impulsivity associated with problematic drinking, which in turn exacerbates risk for intimate partner aggression perpetration. Results also suggest acute effects of alcohol are key in facilitating this mechanism.This article is protected by copyright. All rights reserved.
      PubDate: 2017-06-27T10:55:18.472294-05:
      DOI: 10.1111/acer.13437
       
  • Acute Alcohol Exposure and Risk of Mortality of Patients with Traumatic
           Brain Injury: A Systematic Review and Meta-analysis
    • Authors: Qiuping Ding; Zhuo Wang, Meifen Shen, Zhongzhou Su, Liang Shen
      Abstract: After traumatic brain injury (TBI), patients usually live with significant disability and socioeconomic burdens. Acute exposure to alcohol is considered a major risk factor for TBI. Numerous studies have examined whether alcohol exposure is related to the risk of mortality in patients with TBI, yet the results remain inconsistent. We performed a meta-analysis to assess whether acute alcohol exposure affects the mortality rate of TBI patients. We searched PubMed, Embase and the Cochrane Library up to November 2015 for relevant studies. We screened studies based on their inclusion criteria and selected the studies that reported mortality rate, which included 18 observational studies. We used R to analyze the included data. An initial result showed that the presence of a positive blood alcohol concentration (BAC) had no significant relation with mortality rate (OR=0.92, 95%CI=0.83-1.01), but there was notable heterogeneity along with variable results according to sensitivity analysis. For the BAC-positive population, low BAC (1-100 mg/dl) carried a higher risk of mortality than moderate BAC (100-230 mg/dl) (OR=1.40, 95%CI=1.09-1.81), moderate and high BAC as a single category (>100 mg/dl) (OR=1.57, 95%CI=1.28-1.94) or high BAC (>230 mg/dl) (OR=1.76, 95%CI=1.76-2.30). However, moderate BAC did not increase the mortality risk when compared with high BAC (OR=1.20, 95%CI=0.89-1.63). Whether positive BAC at the time of admission after TBI reduces mortality rate compared with the rate under negative BAC remains unknown. In addition, low BAC (1-100 mg/dl) poses a risk of mortality compared with higher BAC. Further studies assessing the effect of alcohol between the BAC-positive group and the BAC-negative group are still needed.This article is protected by copyright. All rights reserved.
      PubDate: 2017-06-27T09:27:36.238345-05:
      DOI: 10.1111/acer.13436
       
  • Issue Information
    • Pages: 1527 - 1530
      PubDate: 2017-09-01T07:57:22.552497-05:
      DOI: 10.1111/acer.13193
       
  • Articles of Public Interest
    • Pages: 1531 - 1531
      PubDate: 2017-09-01T07:57:28.052536-05:
      DOI: 10.1111/acer.13479
       
 
 
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