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The Center for Research on the Acts of Man conducted a survey of the use of alcohol among the Inupiat of Barrow, Alaska, in 1979. The study resulted in grievances among many individuals and institutions associated with the community. In a retrospective analysis of the factors contributing to these misalliances, the author raises important ethical and procedural questions to be considered carefully in future projects of this nature.
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Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
PURPOSE: This study was conducted to examine the impact of a change in local alcohol laws on alcohol-related hospital usage. Heavy alcohol consumption and its complications are major health problems in the Arctic. For many years, the sale of alcohol in Barrow was illegal, i.e., "damp" status. In October 1994, the residents of Barrow voted to make both the sale and importation of alcohol illegal, i.e., "dry" status. METHODS: The Public Health Service Hospital in Barrow is the only physician-staffed health care facility for 4,000 residents in Barrow, as well as for five of its seven outlying, dry villages (approximately 2,000 more residents). We retrospectively studied the number of alcohol-related outpatient visits to our hospital from November 1993 through October 1994 (the damp year), and from November 1994 through October 1995 (the dry year). The data used were from the emergency visit log in our outpatient department. RESULTS: We found a 76.5% to 93.2% decrease in alcohol-related outpatient visits when comparing corresponding months during the dry year to those during the damp year. The average overall decrease in alcohol-related outpatient visits was 84.7%. These results were highly significant with a p-value of 0.0022. We conclude that the prohibition of alcohol in remote areas can be an effective method in reducing the amount of alcohol-related health problems and can help make a healthier community.
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The cyanobacterium Microcystis aeruginosa is widely known for its production of the potent hepatotoxin microcystin. This cyclic heptapeptide is synthesized non-ribosomally by the thio-template function of a large modular enzyme complex encoded within the 55-kb microcystin synthetase gene (mcy) cluster. The mcy gene cluster also encodes several stand-alone enzymes, putatively involved in the tailoring and export of microcystin. This study describes the characterization of the 2-hydroxy-acid dehydrogenase McyI, putatively involved in the production of d-methyl aspartate at position 3 within the microcystin cyclic structure. A combination of bioinformatics, molecular, and biochemical techniques was used to elucidate the structure, function, regulation, and evolution of this unique enzyme. The recombinant McyI enzyme was overexpressed in Escherichia coli and enzymatically characterized. The hypothesized native activity of McyI, the interconversion of 3-methyl malate to 3-methyl oxalacetate, was demonstrated using an in vitro spectrophotometric assay. The enzyme was also able to reduce alpha-ketoglutarate to 2-hydroxyglutarate and to catalyze the interconversion of malate and oxalacetate. Although NADP(H) was the preferred cofactor of the McyI-catalyzed reactions, NAD(H) could also be utilized, although rates of catalysis were significantly lower. The combined results of this study suggest that hepatotoxic cyanobacteria such as M. aeruginosa PCC7806 are capable of producing methyl aspartate via a novel glutamate mutase-independent pathway, in which McyI plays a pivotal role.
BACKGROUND AND PURPOSE: Endovascular transvenous embolization has been advocated as the treatment technique for dural carotid cavernous fistulas (dCCFs). Most centers use platinum coils primarily. The purpose of this study was to evaluate the technical aspects, efficacy, and safety of transvenous n-butyl cyanoacrylate (n-BCA) infusion in dCCFs as a primary alternative or adjunct to coil embolization. METHODS: We retrospectively evaluated 14 patients with dCCFs who were treated at this institution from 1999 to 2004 by using n-BCA infusion alone or in combination with coils. The efficacy of treatment and safety aspects were studied in dCCFs of Barrow type B (4/14), C (2/14), and D (8/14). Six patients were treated with transvenous n-BCA infusion alone in the cavernous sinus, 7 with a combination of transvenous n-BCA and coil embolization, and one with transvenous n-BCA combined with transarterial polyvinyl alcohol (PVA)-particle embolization of the feeding arteries. RESULTS: An angiographic obliteration and clinical cure was achieved in all patients. Technical complications were nonsymptomatic and included spillage of an n-BCA droplet into a middle cerebral artery branch retrograde through the arteriovenous fistulas in one patient and perforation of the inferior petrosal sinus during microcatheter placement in another. A third patient developed temporary palsy of the sixth cranial nerve a few days after the treatment. CONCLUSION: In this small series, the use of n-BCA either alone or in conjunction with detachable coils was a safe and effective technique for the treatment of symptomatic patients presenting with complex dCCFs.
The fermentation characteristics and effects of lignocellulosic toxic compounds on recombinant Zymomonas mobilis ZM4(pZB5), which is capable of converting both glucose and xylose to ethanol, and its parental strain, ZM4, were characterized using 13C and 31P nuclear magnetic resonance (NMR) in vivo. From the 31P NMR data, the levels of nucleoside triphosphates (NTP) of ZM(pZB5) using xylose were lower than those of glucose. This can be related to the intrinsically slower assimilation and/or metabolism of xylose compared to glucose and is evidence of a less energized state of ZM4(pZB5) cells during xylose fermentation. Acetic acid was shown to be strongly inhibitory to ZM4(pZB5) on xylose medium, with xylose utilization being completely inhibited at pH 5.0 or lower in the presence of 10.9 g/L of sodium acetate. From the 31P NMR results, the addition of sodium acetate caused decreased NTP and sugar phosphates, together with acidification of the cytoplasm. Intracellular deenergization and acidification appear to be the major mechanisms by which acetic acid exerts its toxic effects on this recombinant strain.
OBJECTIVE: The authors' goal was to determine the prevalence of major mental disorders and substance abuse in adolescents admitted to a juvenile detention center. METHOD: As part of a routine mental health screening, modules from the Diagnostic Interview Schedule for Children were administered to 50 youths (11-17 years old) at an urban juvenile detention center. RESULTS: A high rate of affective disorder (42%) was found among these adolescents: 10 (20%) met criteria for mania, another 10 met criteria for major depressive disorder, and one met criteria for bipolar disorder, mixed type. Thirty (60%) met criteria for conduct disorder, and very high rates of alcohol, marijuana, and other substance dependence were found. There was a strong association between affective disorder and conduct disorder; adolescents with mania had much higher rates of reported abuse of substances other than alcohol or marijuana. CONCLUSIONS: Juvenile offenders have high rates of affective disorder. Further studies are needed to examine the relationship of affective disorder to substance abuse as well as to antisocial behavior.
Developmental ethanol exposure produces significant central nervous system (CNS) abnormalities. The cellular mechanisms of ethanol neurotoxicity, however, remain elusive. Recent data implicate altered neurotrophin signaling pathways in ethanol-mediated neuronal death. The present study investigated ethanol-induced alterations in neurotrophin receptor proteins in the rat CNS following chronic ethanol treatment during gestation, via liquid diet to pregnant dams. Brains were dissected on P1 and P10, and Western blots for the neurotrophin receptors TrkA, TrkB, TrkC, and p75 were quantified. Such ethanol treatment produced significant changes in neurotrophin receptor levels in the hippocampus, septum, cerebral cortex, and cerebellum. Receptor levels in hippocampus, septum, and cerebellum, tended to be decreased, while levels in cortex were consistently increased. Males were generally more affected than females. While most of these alterations were transient, sustained or delayed changes were present in P10 septum, cortex, and cerebellum. These results indicate that developmental ethanol exposure produces major changes in the normal physiological levels of the neurotrophin receptors throughout the CNS. These changes in the receptor complement during critical prenatal stages could relate to the anomalous development of the CNS seen in the fetal alcohol syndrome. This relationship is discussed, together with the potential biological effects of such dramatic changes in neurotrophin receptor expression.
The developing central nervous system (CNS) is highly susceptible to ethanol, with acute or chronic exposure producing an array of anomalies and cell loss. Certain periods of vulnerability have been defined for various CNS regions, and are often followed by periods of relative ethanol resistance. In the present study, neonatal rats were acutely exposed to ethanol during a time when peak cell death is found in developing cerebral cortex (postnatal day 7; P7), and during a later neonatal period of ethanol resistance (P21). Comparisons at the two ages were made of basal levels of neurotrophic factors (NTFs), and in addition, ethanol-mediated changes in NTFs, apoptosis-related proteins, antioxidant activities, and generation of reactive oxygen species (ROS) were quantified at 0, 2, and 12 h following termination of exposure. It was found that at P21, basal levels of NTF nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) were considerably higher than at P7, possibly affording protection against ethanol neurotoxicity at this age. Following ethanol treatment at P7, approximately equal numbers of pro-apoptotic and pro-survival changes were produced, although most of the pro-apoptotic alterations occurred rapidly following termination of treatment, a critical period for initiation of apoptosis. At P21, however, the large majority of ethanol-mediated changes were adaptive, favoring survival. We speculate that the capacity of the older CNS to upregulate a number of protective elements within the cellular milieu serves to greatly mitigate ethanol neurotoxicity, while in younger animals, such adjustments are minimal, thus enhancing ethanol vulnerability within this developing region.
BACKGROUND: The past decade has seen the development of epigenetic models of aging that accurately estimate chronological age and predict disease incidence and mortality. These estimates are modulated by lifestyle and environmental factors linked to carcinogenesis, but to date this has primarily been studied in blood. METHODS: We examined epigenetic aging in normal colonic tissue (n = 96), adjacent mucosa (n = 245) and tumors (n = 208), using models trained on age (Horvath, Hannum, Zhang), mortality (PhenoAge, GrimAge), aging rate (DunedinPACE), cellular mitotic history (EpiTOC, epiTOC2, miAGe), and telomere length (DNAmTL). RESULTS: The Horvath model was the most accurate estimator of chronological age in normal colonic mucosa, with high correlation (r > 0.70) between the Horvath, Hannum, Zhang, PhenoAge and GrimAge models, and between mitotic clocks (r > 0.94). All models showed similar performance in normal tissue and adjacent mucosa, but substantially more variation in estimates in tumors. Significant differences in age acceleration were present between normal and adjacent mucosa by six models (Hannum, Zhang, PhenoAge, EpiTOC, epiTOC2 and miAge), while tumors showed highly significant differences by all models. Age acceleration differed by region of the colon, with varying patterns by model type. Physical activity (PhenoAge), smoking history (GrimAge), and alcohol consumption (Horvath, mitotic clocks) were associated with epigenetic aging in adjacent mucosa, while smoking history, smoking intensity, and alcohol consumption were associated with DNAmTL in tumors. CONCLUSIONS: Our study reveals an impact of tissue type, region, and lifestyle factors on epigenetic aging, but also highlights significant heterogeneity between models and the need for careful consideration within study design.
Over 34,000 questionnaires were used to study occurrence and consultations for back pain in the community. The 12-month period prevalence was 24% and 13% of the sample consulted a doctor. Elderly women were at greatest risk of back pain. The consultation rate increased in both sexes throughout middle age, but declined in men over the age of 55 yr. Back pain was associated with the Goldberg General Health Health Questionnaire score suggesting psychiatric morbidity [odds ratio (OR) = 2.05; confidence interval (CI) 1.89-2.23], obesity (OR = 1.59; CI 1.40-1.79), and cigarette smoking (OR = 1.52; CI 1.36-1.70). Vigorous daily activity was positively associated with back pain in men aged 18-39 yr (OR = 1.37; CI 1.02-1.85), and women aged 18-39 yr (OR = 1.50; CI 1.08-2.09), but was negatively associated with back pain in women aged over 65 yr (OR = 0.35; CI 0.16-0.76). Alcohol consumption was also negatively associated with back pain (OR = 0.72; CI 0.62-0.85). The prevalence of arthritis, constipation and respiratory disorders was increased in those who consulted for back pain corrected for the other variables. Thus back pain was substantially more common in women compared to men over 55 yr. Psychiatric morbidity, cigarette smoking and obesity were associated with back pain at all ages, but the effect of physical exercise appeared to change with age. Further studies are required to explain the sex differences and nature of the associations.