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1.
Nature ; 574(7780): 717-721, 2019 10.
Article in English | MEDLINE | ID: mdl-31645761

ABSTRACT

Emerging evidence suggests that epigenetic regulation is dependent on metabolic state, and implicates specific metabolic factors in neural functions that drive behaviour1. In neurons, acetylation of histones relies on the metabolite acetyl-CoA, which is produced from acetate by chromatin-bound acetyl-CoA synthetase 2 (ACSS2)2. Notably, the breakdown of alcohol in the liver leads to a rapid increase in levels of blood acetate3, and alcohol is therefore a major source of acetate in the body. Histone acetylation in neurons may thus be under the influence of acetate that is derived from alcohol4, with potential effects on alcohol-induced gene expression in the brain, and on behaviour5. Here, using in vivo stable-isotope labelling in mice, we show that the metabolism of alcohol contributes to rapid acetylation of histones in the brain, and that this occurs in part through the direct deposition of acetyl groups that are derived from alcohol onto histones in an ACSS2-dependent manner. A similar direct deposition was observed when mice were injected with heavy-labelled acetate in vivo. In a pregnant mouse, exposure to labelled alcohol resulted in the incorporation of labelled acetyl groups into gestating fetal brains. In isolated primary hippocampal neurons ex vivo, extracellular acetate induced transcriptional programs related to learning and memory, which were sensitive to ACSS2 inhibition. We show that alcohol-related associative learning requires ACSS2 in vivo. These findings suggest that there is a direct link between alcohol metabolism and gene regulation, through the ACSS2-dependent acetylation of histones in the brain.


Subject(s)
Brain/metabolism , Epigenesis, Genetic , Ethanol/administration & dosage , Histones/metabolism , Acetates/metabolism , Acetylation , Animals , Chromatin , Hippocampus/drug effects , Hippocampus/metabolism , Histones/genetics , Injections, Intraperitoneal , Male , Mice , Mice, Inbred C57BL , Primary Cell Culture
2.
Am J Public Health ; 95(8): 1322-4, 2005 Aug.
Article in English | MEDLINE | ID: mdl-16043665

ABSTRACT

Dental caries is a potentially preventable infectious disease that, untreated, can cause significant morbidity requiring costly treatment. The Access to Baby and Child Dentistry (ABCD) program increases access to prevention and early treatment for Medicaid-eligible children aged younger than 6 years in Washington State. The program is a partnership of Washington Dental Service Foundation, the University of Washington School of Pediatric Dentistry, the state Medical Assistance Administration, and local stakeholders. Through training in pediatric dental techniques and enhanced reimbursement, ABCD equips and encourages dentists to serve young Medicaid patients. Family counseling increases oral care compliance and reduces no-show rates. Program evaluation demonstrates changing attitudes and behavior among participating families and dentists, with more young, low-income Washington children receiving oral health care.


Subject(s)
Dental Care for Children/economics , Dental Caries/therapy , Medicaid/organization & administration , Oral Health , Public Health Administration , State Health Plans/organization & administration , Adolescent , Child , Child, Preschool , Dental Caries/epidemiology , Humans , Prevalence , Schools, Dental , United States , Washington/epidemiology
3.
Public Health Nurs ; 17(5): 386-91, 2000.
Article in English | MEDLINE | ID: mdl-11013001

ABSTRACT

The clinical specialist (CS) in community health nursing (CHN) addresses health problems in populations and communities in ways that are different from and complimentary to strategies used by practitioners of individualized patient care. Four programs based on comprehensive assessments, systematic program planning, deliberate implementation, and both formative and summative evaluation are presented. The programs were developed by graduate students in the CHN clinical specialization major at the Frances Payne Bolton School of Nursing. With expert faculty guidance and a competency-driven program of study, strategies were implemented to promote the health of community-dwelling well elderly people, home health care nurses who provide service to patients with respiratory problems, and high school students in a private religious school. Experienced parish nurses also benefited from a program designed to enhance their skills in theological reflection. This article also describes the curricular design developed to educate this clinician for the 21st century. Lastly, continued attention to the dynamic criteria of the American Nurses Association Standards of Community Health Nursing Practice is recommended as crucial to the further development of this clinical specialization.


Subject(s)
Community Health Nursing/education , Curriculum , Nurse Clinicians/education , Adolescent , Aged , Community Health Nursing/trends , Health Services for the Aged , Home Care Services , Humans , Nurse Clinicians/trends , School Nursing/education , United States
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