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The article presents a study which examined the relationship between respiratory symptoms and pesticide poisoning in farm residents in northeastern Colorado. The researchers conducted cross-sectional survey on 761 farm operators and their spouses in 476 farms from 1993 to 1997 about their respiratory conditions and experiences of pesticide poisoning. The study showed that pesticide poisoning was related with cough, allergy, wheeze and organic dust toxic syndrome (ODTS) in unadjusted models.

OBJECTIVE: This nested case-control study evaluated the association between depression and pesticide exposure among women. METHODS: The study population included 29,074 female spouses of private pesticide applicators enrolled in the Agricultural Health Study between 1993 and 1997. Cases were women who had physician-diagnosed depression requiring medication. Lifetime pesticide use was categorized as never mixed/applied pesticides, low exposure (up to 225 days), high exposure (>225 days), and a history of diagnosed pesticide poisoning. RESULTS: After adjustment for state, age, race, off-farm work, alcohol, cigarette smoking, physician visits, and solvent exposure, depression was significantly associated with a history of pesticide poisoning (odds ratio [OR] = 3.26; 95% confidence interval [CI] = 1.72-6.19) but not low (OR = 1.09; CI = 0.91-1.31) or high (OR = 1.09; 95% CI = 0.91-1.31) cumulative pesticide exposure. CONCLUSION: Pesticide poisoning may contribute to risk of depression. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of the study presented is to evaluate the association between pesticides and depressive symptoms among a population exposed to chemicals as a result of agricultural use. Chronic sequelae of acute pesticide poisoning from organophosphate compounds may include anxiety and depression. In some states, farmers have been reported to have higher rates of depression than other population groups. Little work has been done to describe the effects of exposure to organophosphate compounds and depressive symptoms among the farming population.Methods: Data for this study came from a cross sectional survey of farmers and their spouses conducted in an eight county area in northeastern Colorado. Personal interviews were conducted with the study participants. Depressive symptoms were assessed using the Center for Epidemiologic Studies-Depression (CES-D) scale. Pesticides applied on the farms were assessed using self-reported questionnaires. Conditional logistic regression was used to model the relationship between depression and pesticide-related illness in a stratified analysis.Results: Between 1992-1997, 761 individuals were enrolled in this cross sectional survey. Adjusting for a number of potential confounders, the odds ratio for depression associated with pesticide-related illness was 5.87 [95% confidence interval (CI) = 2.56-13.44].Conclusions: Exposure to pesticides at a high enough concentration to cause self reported poisoning symptoms was associated with high depressive symptoms independently of other known risk factors for depression among farm residents. [ABSTRACT FROM AUTHOR]

Objectives: Hazardous materials (HAZMAT) pose risks to the health and safety of professionals involved with transportation and emergency responses. Two distinct occupational groups that encounter HAZMAT events are first responders and professional drivers. Wearable technology is a tool that can assist with monitoring the health of professionals involved in HAZMAT events. The aim of this study was to compare and evaluate the perceptions of first responders and professional drivers on wearable technology and attitudes toward health monitoring., Methods: A survey was administered to first responders (n = 112) and professional drivers (n = 218). Statistical approaches included bivariate analysis, latent class analysis, logistic regression analysis, and path analysis for the variables of interest., Results: There were significant differences between the groups in perceptions of the benefits of monitoring certain health indicators. Professional drivers were more likely to have a history of wearable technology use compared with first responders (odds ratio [OR] = 10.1; 95% CI, 4.42-22.9), reported greater exposure to HAZMAT (OR = 4.32; 95% CI, 2.24-8.32), and were more willing to have their health data monitored by someone other than themselves (OR = 9.27; 95% CI, 3.67-23.4). A multinomial regression model revealed that occupation was not a significant predictor of class preference for acceptance of monitoring specific health indicators., Conclusions: Occupation appeared to be important but further analysis uncovered that characteristics of individuals within the occupations were more salient to the use of wearable technology. HAZMAT exposure, someone else monitoring health data, and experience with wearable technology use were found to be important factors for perceptions about benefits of health monitoring with wearable technology., (© The Author(s) [2023]. Published by Oxford University Press on behalf of Journal of Occupational Health.)

Introduction: The purpose of the study was to identify barriers and facilitators of colorectal cancer (CRC) screening use among agricultural operators in Nebraska, US., Methods: The concept mapping approach was used to engage participants and enhance the generation of ideas and opinions regarding CRC screening. Two focus groups (seven women and seven men) were conducted., Results: Among women, the cost domain was most agreed upon as important, followed by experiencing symptoms, awareness, and family. Among men, the important concepts related to CRC screening were family and friend support, feeling too young to get CRC, family or personal history of CRC, and lack of awareness of the need to be screened. Some gender differences regarding barriers were observed, such as women were more concerned about the cost of screening while men were far more concerned about the embarrassment associated with CRC screening., Conclusion: These findings will be crucial to developing educational materials to increase knowledge of risk factors for CRC and of CRC screening in the agricultural population.

We recently reported that multiple sclerosis (MS) plasma contains IgG aggregates and induces complement-dependent neuronal cytotoxicity (Zhou et al., 2023). Using ELISA, we report herein that plasma IgG levels in the aggregates can be used as biomarkers for MS. We enriched the IgG aggregates from samples of two cohorts (190 MS and 160 controls) by collecting flow-through after plasma binding to Protein A followed by detection of IgG subclass. We show that there are significantly higher levels of IgG1, IgG3, and total IgG antibodies in MS IgG aggregates, with an AUC >90%; higher levels of IgG1 distinguish secondary progressive MS from relapsing-remitting MS (AUC = 91%). Significantly, we provided the biological rationale for MS plasma IgG biomarkers by demonstrating the strong correlation between IgG antibodies and IgG aggregate-induced neuronal cytotoxicity. These non-invasive, simple IgG-based blood ELISA assays can be adapted into clinical practice for diagnosing MS and SPMS and monitoring treatment responses., Competing Interests: Declaration of Competing Interest We declare that there are no conflicts of interest for all authors., (Copyright © 2023. Published by Elsevier Inc.)

Grey matter pathology is central to the progression of multiple sclerosis (MS). We discovered that MS plasma immunoglobulin G (IgG) antibodies, mainly IgG1, form large aggregates (>100 nm) which are retained in the flow-through after binding to Protein A. Utilizing an annexin V live-cell apoptosis detection assay, we demonstrated six times higher levels of neuronal apoptosis induced by MS plasma IgG aggregates (n = 190, from two cohorts) compared to other neurological disorders (n = 116) and healthy donors (n = 44). MS IgG aggregate-mediated, complement-dependent neuronal apoptosis was evaluated in multiple model systems including primary human neurons, primary human astrocytes, neuroblastoma SH-SY5Y cells, and newborn mouse brain slices. Immunocytochemistry revealed the co-deposition of IgG, early and late complement activation products (C1q, C3b, and membrane attack complex C5b9), as well as active caspase 3 in treated neuronal cells. Furthermore, we found that MS plasma cytotoxic antibodies are not present in Protein G flow-through, nor in the paired plasma. The neuronal apoptosis can be inhibited by IgG depletion, disruption of IgG aggregates, pan-caspase inhibitor, and is completely abolished by digestion with IgG-cleaving enzyme IdeS. Transmission electron microscopy and nanoparticle tracking analysis revealed the sizes of MS IgG aggregates are greater than 100 nm. Our data support the pathological role of MS IgG antibodies and corroborate their connection to complement activation and axonal damage, suggesting that apoptosis may be a mechanism of neurodegeneration in MS., (© 2023. The Author(s).)

Purpose: Tobacco use during early adolescence can harm brain development and cause adverse health outcomes. Identifying susceptibility in early adolescence before initiation presents an opportunity for tobacco use prevention., Methods: Data were drawn from the Adolescent Brain and Cognitive Development study that enrolled 9-10-year-old children in 21 US cities between 2016 and 2018 at baseline. Separate nested hierarchical models were performed to incrementally examine the associations of sociodemographic factors, psychosocial influences, parental substance use, immediate social contacts, and perceived neighborhood safety with tobacco use susceptibility among never tobacco users (n = 10,449), overall and stratified by gender., Results: A total of 16.6% of youths who have never used tobacco reported susceptibility to tobacco. Females (vs. males, adjusted odds ratio [AOR] [95% confidence interval {CI}] = 0.80 [0.70-0.91]), positive parental monitoring (AOR [95% CI] = 0.76 [0.66-0.87]) and positive school environment (AOR [95% CI] = 0.95 [0.93-0.98]) were associated with reduced susceptibility to tobacco use. Parental education level (high school, AOR [95% CI] = 1.52 [1.02-2.28]; bachelor's degree, AOR [95% CI] = 1.53 [1.03-2.28]; or postgraduate degree, AOR [95% CI] = 1.54 [1.03-2.3] vs. less than high school), youth substance ever use (AOR [95% CI] = 2.24 [1.95-2.58]), internalizing problems (AOR [95% CI] = 1.03 [1-1.06]), and high scores on negative urgency, lack of premeditation, lack of perseverance, sensation seeking, and positive urgency-impulsive behavior scale were associated with increased susceptibility to tobacco use. Stratified analysis showed that parent-perceived neighborhood safety was associated with reduced susceptibility to tobacco use among males but not among females (AOR [95% CI] = 0.89 [0.81-0.99]) vs. (AOR [95% CI] = 1.01 [0.9-1.13]). A positive school environment was associated with lower susceptibility to tobacco use among females but not among males., Discussion: Parental, environmental, and psychosocial factors influence early childhood tobacco susceptibility. Family and school-based tobacco prevention programs should consider integrating these factors into primary school curricula to reduce youth tobacco susceptibility and later initiation., (Copyright © 2022 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.)

The number of agricultural fatalities and injuries related to agricultural quad bike use has risen substantially in the last two decades. Safe engineering design features such as crush protection and roll bars have proven potential to lessen the burden of injury but have traditionally not been included in many quad bike safety training programs. The aim of this study was to survey more than 700 young adults working in U.S. and Canadian agriculture to examine self-reported quad bike safety behaviors and awareness of quad bike safety design engineering features. We found that U.S. males continue to be at higher risk for quad bike-rollover incidents when compared to other groups. Even when accounting for other factors such as age and country, we found that participants who reported youth occupational quad bike use (≤14 years old) were up to 200% more likely to allow extra riders and up to 489% more likely to not wear a helmet when compared to participants who reported beginning occupational quad bike use in adulthood. These findings support the Agricultural Youth Work Guideline (AYWG) for occupational quad bike use at age 16. Less than 20% of young adults working in agriculture were aware of safe design features such as wide frames, stability ratings, crush protection devices, and accessories made by the original equipment manufacturer. There is tremendous need to educate the future agricultural workforce about the importance of choosing quad bikes with safer design features.

Objective: This study addressed the relationship of hearing loss and coexposure to solvents and noise among farmers and ranchers in central United States., Methods: The surveillance study included surveys to stratified random samples of operations in 2018 and 2020 (n = 34,146), requesting information on injuries, illnesses, exposures, and preventive measures. Responses (n = 7495) were analyzed using hierarchical multinomial logistic regression, adjusting for personal and work characteristics., Results: Nearly 60% of respondents exposed to both solvents and noise reported hearing loss. The exposures increased the adjusted odds of moderate/severe hearing loss as follows: solvents alone, (odds ratio [OR], 1.49; 95% confidence interval [CI], 0.93-2.38), noise alone (OR, 4.42; 95% CI, 3.39-5.76), and coexposure to both noise and solvents (OR, 6.03; 95% CI, 4.67-7.78)., Conclusions: Solvent exposure, along with noise, should be considered in hearing conservation programs among farmers and ranchers., Competing Interests: Conflict of interest: None declared., (Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American College of Occupational and Environmental Medicine.)

Background: Varicella zoster virus (VZV) vasculopathy is characterized by persistent arterial inflammation leading to stroke. Studies show that VZV induces amyloid formation that may aggravate vasculitis. Thus, we determined if VZV central nervous system infection produces amyloid., Methods: Aβ peptides, amylin, and amyloid were measured in cerebrospinal fluid (CSF) from 16 VZV vasculopathy subjects and 36 stroke controls. To determine if infection induced amyloid deposition, mock- and VZV-infected quiescent primary human perineurial cells (qHPNCs), present in vasculature, were analyzed for intracellular amyloidogenic transcripts/proteins and amyloid. Supernatants were assayed for amyloidogenic peptides and ability to induce amyloid formation. To determine amylin's function during infection, amylin was knocked down with small interfering RNA and viral complementary DNA (cDNA) was quantitated., Results: Compared to controls, VZV vasculopathy CSF had increased amyloid that positively correlated with amylin and anti-VZV antibody levels; Aβ40 was reduced and Aβ42 unchanged. Intracellular amylin, Aβ42, and amyloid were seen only in VZV-infected qHPNCs. VZV-infected supernatant formed amyloid fibrils following addition of amyloidogenic peptides. Amylin knockdown decreased viral cDNA., Conclusions: VZV infection increased levels of amyloidogenic peptides and amyloid in CSF and qHPNCs, indicating that VZV-induced amyloid deposition may contribute to persistent arterial inflammation in VZV vasculopathy. In addition, we identified a novel proviral function of amylin., (© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

This study reports on the development of a comprehensive assessment of exposure to guns and gun-related violence for evaluating the risk of gun-related trauma. Gun access, gun attitudes, gun safety education, and exposure to gun violence were measured. Participants were 630 youth, aged 2-17. Youth, ages 10-17, completed a self-report survey and caregivers of young children, ages 2-9, completed the survey as a proxy for that child. The youth were from urban ( n = 286) and rural ( n = 344) areas. Factor analysis, item response theory, and structural equation modeling were used. Two factors described access to guns, two factors described gun attitudes, and a single construct captured gun safety education. The gun violence exposure factor showed strong associations with trauma symptomatology. The individual constructs showed good psychometric properties and measurement noninvariance by urbanicity., (© Copyright 2020 Springer Publishing Company, LLC.)

Objective: The repair of unruptured intracranial aneurysms has increased since 2000. In this study, we analyzed the Nationwide Readmission Database (NRD) to determine the rate of 90-day readmission. Our objective is to examine readmission trends after unruptured aneurysm repair., Methods: This study used the 2013 and 2014 NRD. Patient data included standard demographic, comorbidity, and payer information. We selected patients who had undergone microsurgical or endovascular repair for a nonruptured aneurysm. We excluded patients who were under 18 years of age, had a subarachnoid hemorrhage, or were discharged to home the same day. Readmission was calculated by counting the number of days between the end of the index visit and earliest readmission date., Results: A total of 2180 of 29,694 patients (7.34%) were readmitted within 90 days of their initial hospitalization. They were younger (mean, 52.6 years; 95% confidence interval [CI], 51.4-53.8) than patients not readmitted (mean, 57.4 years; 95% CI, 57.1-57.8; P < 0.0001). In total, endovascular repair was more frequent than microsurgery (79.8% vs. 20.2%, respectively). Mean days to readmission was 41.8 (95% CI, 39.7-43.9) and was higher for women (P < 0.0001). The odds ratio for readmission after an endovascular repair was 1.54 (95% CI, 1.27-1.86)., Conclusions: In this study of over 28,000 patients treated for an unruptured aneurysm, the 90-day readmission rate was 7.34%. Endovascular patients had higher odds of readmission than microsurgical patients. Patients with common medical comorbidities (hypertension, obesity, renal failure, and diabetes) were less likely to be readmitted than patients without those conditions., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Herpes zoster is associated with an increased dementia and neovascular macular degeneration risk and a decline in glycemic control in diabetes mellitus. Because amyloid is present and pathogenic in these diseases, we quantified amyloid, Aβ40, Aβ42, and amylin in 14 zoster and 10 control plasmas. Compared with controls, zoster plasma had significantly elevated amyloid that correlated with Aβ42 and amylin levels and increased amyloid aggregation with addition of exogenous Aβ42 or amylin. These results suggest that zoster plasma contains factor(s) that promotes aggregation of amyloidogenic peptides, potentially contributing to the toxic amyloid burden and explaining accelerated disease progression following zoster.

In the 1980s and 1990s, with decreasing numbers of full-time farmers and adverse economic conditions, chronic stress was common in farmers, and remains so today. A neural network was implemented to conduct an in-depth analysis of stress risk factors. Two Colorado farm samples (1992-1997) were combined (n = 1501) and divided into training and test samples. The outcome, stress, was measured using seven stress-related items from the Center for Epidemiologic Studies-Depression Scale. The initial model contained 32 predictors. Mean squared error and model fit parameters were used to identify the best fitting model in the training data. Upon testing for reproducibility, the test data mirrored the training data results with 20 predictors. The results highlight the importance of health, debt, and pesticide-related illness in increasing the risk of stress. Farmers whose primary occupation was farming had lower stress levels than those who worked off the farm. Neural networks reflect how the brain processes signals from its environment and algorithms allow the neurons "to learn". This approach handled correlated data and gave greater insight into stress than previous approaches. It revealed how important providing health care access and reducing farm injuries are to reducing farm stress., Competing Interests: Conflicts of Interest: The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.

Introduction: Intrathecal immunoglobulin G (IgG) and oligoclonal bands (OCBs) are the most consistent and characteristic features of Multiple Sclerosis (MS). OCBs in MS are considered products of clonally expanded B cells in the cerebrospinal fluid (CSF), representing the sum of contributions from B cells in the brain. However, large amounts of IgG can be eluted from MS plaques in which lymphocytes are absent, and there is no correlation between levels of plaque-associated IgG and the presence of lymphocytes. It is calculated that it would take 3.2 billion lymphocytes to generate such large amounts of intrathecal IgG (30 mg in 500 ml CSF) in MS patients. Therefore, circulating lymphocytes in CSF could only account for <0.1% of the extra IgG in MS., Methods: We analyzed clinical laboratory parameters from sera and CSF of 115 patients including 91 patients with MS and 24 patients with other inflammatory central nervous system (CNS) disorders (IC). We investigated the relationship between oligoclonal bands, IgG antibodies, CSF cells, IgG Index, albumin, and total protein., Results: MS patients have significantly elevated serum concentrations of IgG antibodies, albumin, and total protein, lower levels of lymphocytes, albumin, and total protein in the cerebrospinal fluid, but no difference in CSF IgG concentration compared to those with other inflammatory neurological disorders. Furthermore, in MS there was no linear relationship between the numbers of OCBs, CSF lymphocytes, CSF IgG, and IgG Index, and between serum IgG and serum albumin, but significant correlation between IgG in CSF and serum, and between CSF IgG and CSF albumin., Conclusion: There are unique differences between MS and patients with other inflammatory neurological disorders. Our data suggest that in MS patient (a) B cells and their products in the CSF may not be the sole source of intrathecal IgG; (b) oligoclonal bands may not be the products of single B cell clones in the CSF; and (c) there is a strong connection between serum components in the peripheral circulation and the central nervous system.

The association between pesticide exposure and neurobehavioral and neurodevelopmental effects is an area of increasing concern. This symposium brought together participants to explore the neurotoxic effects of pesticides across the lifespan. Endpoints examined included neurobehavioral, affective and neurodevelopmental outcomes among occupational (both adolescent and adult workers) and non-occupational populations (children). The symposium discussion highlighted many challenges for researchers concerned with the prevention of neurotoxic illness due to pesticides and generated a number of directions for further research and policy interventions for the protection of human health, highlighting the importance of examining potential long-term effects across the lifespan arising from early adolescent, childhood or prenatal exposure., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Background: A number of changes have been proposed and investigated in the criteria for substance use disorders in DSM-5. However, although clinical utility of DSM-5 is a high priority, relatively little of the empirical evidence supporting the changes was obtained from samples of substance abuse patients., Methods: Proposed changes were examined in 663 patients in treatment for substance use disorders, evaluated by experienced clinicians using the Psychiatric Research Interview for Substance and Mental Disorders (PRISM). Factor and item response theory analysis was used to investigate the dimensionality and psychometric properties of alcohol, cannabis, cocaine and heroin abuse and dependence criteria, and craving., Results: The seven dependence criteria, three of the abuse criteria (hazardous use; social/interpersonal problems related to use; neglect of roles to use), and craving form a unidimensional latent trait for alcohol, cannabis, cocaine and heroin. Craving did not add significantly to the total information offered by the dependence criteria, but adding the three abuse criteria and craving together did significantly increase total information for the criteria sets associated with alcohol, cannabis and heroin., Conclusion: Among adult patients in treatment for substance disorders, the alcohol, cannabis, cocaine and heroin criteria for dependence, abuse (with the exception of legal problems), and craving measure a single underlying dimension. Results support the proposal to combine abuse and dependence into a single diagnosis in the DSM-5, omitting legal problems. Mixed support was provided for the addition of craving as a new criterion, warranting future studies of this important construct in substance use disorders., (Copyright © 2011. Published by Elsevier Ireland Ltd.)

The neurotransmitter dopamine is oxidized to its quinone (DA-Q), which at neutral pH undergoes intramolecular cyclization by 1,4-Michael addition, followed by oxidation to form leukochrome, then aminochrome, and finally neuromelanin. At lower pH, the amino group of DA is partially protonated, allowing the competitive intermolecular 1,4-Michael addition with nucleophiles in DNA to form the depurinating adducts, DA-6-N3Ade and DA-6-N7Gua. Catechol estrogen-3,4-quinones react by 1,4-Michael addition to form the depurinating 4-hydroxyestrone(estradiol)-1-N3Ade [4-OHE1(E2)-1-N3Ade] and 4-OHE1(E2)-1-N7Gua adducts, which are implicated in the initiation of breast and other human cancers. The effect of pH was studied by reacting tyrosinase-activated DA with DNA and measuring the formation of depurinating adducts. The most adducts were formed at pH 4, 5, and 6, and their level was nominal at pH 7 and 8. The N3Ade adduct depurinated instantaneously, but N7Gua had a half-life of 3 H. The slow loss of the N7Gua adduct is analogous to that observed in previous studies of natural and synthetic estrogens. The antioxidants N-acetylcysteine and resveratrol efficiently blocked formation of the DA-DNA adducts. Thus, slightly acidic conditions render competitive the reaction of DA-Q with DNA to form depurinating adducts. We hypothesize that formation of these adducts could lead to mutations that initiate Parkinson's disease. If so, use of N-acetylcysteine and resveratrol as dietary supplements may prevent initiation of this disease., (Copyright © 2011 Wiley Periodicals, Inc.)

The human BRD2 gene has been linked and associated with a form of common epilepsy and electroencephalographic abnormalities. Disruption of Brd2 in the mouse revealed that it is essential for embryonic neural development and that viable Brd2(+/-) heterozygotes show both decreased GABAergic neuron counts and increased susceptibility to seizures. To understand the molecular mechanisms by which mis-expression of BRD2 might contribute to epilepsy, we examined its regulation at multiple levels. We discovered that BRD2 expresses distinct tissue-specific transcripts that originate from different promoters and have strikingly different lengths of 5' untranslated regions (5'UTR). We also experimentally confirmed the presence of a highly conserved, alternatively spliced exon, inclusion of which would result in a premature termination of translation. Downstream of this alternative exon is a polymorphic microsatellite (GT-repeats). Manipulation of the number of the GT-repeats revealed that the length of the GT-repeats affects the ratio of the two alternative splicing products. In vitro translation and expression in cultured cells revealed that among the four different mRNAs (long and short 5'UTR combined with regular and alternative splicing), only the regularly spliced mRNA with the short 5'UTR yields full-length protein. In situ hybridization and immunohistochemical studies showed that although Brd2 mRNA is expressed in both the hippocampus and cerebellum, Brd2 protein only can be detected in the cerebellar Purkinje cells and not in hippocampal cells. These multiple levels of regulation would likely affect the production of functional BRD2 protein during neural development and hence, its role in the etiology of seizure susceptibility., (Copyright © 2011 Wiley-Liss, Inc.)

Substantial evidence suggests that catechol estrogen-3,4-quinones react with DNA to form predominantly the depurinating adducts 4-hydroxyestrone (estradiol)-1-N3Ade [4-OHE(1)(E(2))-1-N3Ade] and 4-OHE(1)(E(2))-1-N7Gua. Apurinic sites resulting from these adducts generate critical mutations that can initiate cancer. The paradigm of cancer initiation is based on an imbalance in estrogen metabolism between activating pathways that lead to estrogen-DNA adducts and deactivating pathways that lead to estrogen metabolites and conjugates. This imbalance can be improved to minimize formation of adducts by using antioxidants, such as resveratrol (Resv) and N-acetylcysteine (NAcCys). To compare the ability of Resv and NAcCys to block formation of estrogen-DNA adducts, we used the human breast epithelial cell line MCF-10F treated with 4-OHE(2). Resv and NAcCys directed the metabolism of 4-OHE(2) toward protective pathways. NAcCys reacted with the quinones and reduced the semiquinones to catechols. This pathway was also carried out by Resv. In addition, Resv induced the protective enzyme quinone reductase, which reduces E(1)(E(2))-3,4-quinones to 4-OHE(1)(E(2)). Resv was more effective at increasing the amount of 4-OCH(3)E(1)(E(2)) than NAcCys. Inhibition of estrogen-DNA adduct formation was similar at lower doses, but at higher doses Resv was about 50% more effective than NAcCys. Their combined effects were additive. Therefore, these two antioxidants provide an excellent combination to protect catechol estrogens from oxidation to catechol quinones., (Copyright © 2010 Elsevier Inc. All rights reserved.)

Aims: To prepare for DSM-V, the structure of DSM-IV alcohol dependence and abuse criteria and a proposed additional criterion, at-risk drinking, require study in countries with low per-capita consumption, and comparison of current and lifetime results within the same sample. We investigated DSM-IV Alcohol Use Disorder (AUD) criteria in Israel, where per-capita alcohol consumption is low., Methods: Household residents selected from the Israeli population register (N=1338) were interviewed with the AUDADIS. Item response theory analyses were conducted using MPlus, and diagnostic thresholds were examined with the kappa statistic., Results: Dependence and abuse criteria fit a unidimensional model interspersed across the severity continuum, for both current and lifetime timeframes. Legal problems were rare and did not improve model fit. Weekly at-risk drinking reflected greater severity than in U.S. samples. When dependence and abuse criteria were combined, a diagnostic threshold of > or =3 criteria produced the best agreement with DSM-IV diagnoses (kappa>0.80)., Conclusion: Consistent with other studies, alcohol dependence and abuse criteria reflected a latent variable representing a single AUD. Results suggested little effect in removing legal problems and little gained by adding weekly at-risk drinking. Results contribute to knowledge about AUD criteria by examining them in a low-consumption country., (Copyright 2010 Elsevier Ireland Ltd. All rights reserved.)

A variety of evidence suggests that estrogens may induce non-Hodgkin lymphoma (NHL). The reaction of catechol estrogen quinones with DNA to form depurinating estrogen-DNA adducts is hypothesized to initiate this process. These adducts are released from DNA, shed from cells into the bloodstream and excreted in urine. The aim of this study was to determine whether or not the depurinating estrogen-DNA adducts might be involved in the aetiology of human NHL. Estrogen metabolites, conjugates and depurinating DNA adducts were identified and quantified in spot urine samples from 15 men with NHL and 30 healthy control men by using ultraperformance liquid chromatography/tandem mass spectrometry. The levels of estrogen-DNA adducts were significantly higher in the men with NHL than in the healthy control men. Thus, formation of estrogen-DNA adducts may play a critical role in the aetiology of NHL, and these adducts could be potential biomarkers of NHL risk.

The use of DSM criteria to evaluate liability to substance use disorders (SUDs) and to identify SUD phenotypes may not provide the sensitivity required to identify genes associated with vulnerability to SUDs. The purpose of this study is to evaluate a number of basic aspects of substance use that may be more proximal than full SUDs to risk genes, some of which may thus have greater potential utility as phenotypes in subsequent molecular genetic analyses. In this paper we present results from the first stage of our planned analyses, focusing on how individual symptoms of abuse and dependence may be used to create alternate phenotypes for SUDs. Specifically, we used factor analysis and biometrical modeling on each symptom of illicit substance abuse and dependence within different types of substances, and compared and contrasted factor patterns and heritabilities across the different substances. These analyses were carried out using a population-based sample of 3372 male-male twin pairs from the Vietnam Era Twin Registry who participated in the Harvard Twin Study of Substance Abuse. We obtained extensive data from these participants on substance use and SUDs via telephone interview in 1992, including data on the illicit substances: opiates, cocaine, cannabis, sedatives, stimulants, and psychedelics. The results indicate that: A) although a one-factor model assuming a single underlying liability for abuse and dependence symptoms and behaviors can be rejected for most substances, there is no uniform support for a two-factor model differentiating between abuse versus dependence; B) patterns of symptoms or behaviors reported by substance users vary across substances; C) not all symptoms or behaviors contribute equally to the presentation of an SUD; and D) the heritability of symptoms or behaviors of substance users varies both within and between substances. These results represent important first steps in facilitating the search for SUD-risk genes in subsequent high-throughput molecular genetic analyses by providing alternate phenotypes that may have both optimal validity and increased heritability.

Background: Sleep patterns have been associated with decreased alertness among adolescents and to a limited extent, increased risk of injuries. The purpose of this study is to describe the relationship between sleep patterns and injury occurrence among adolescents aged 13 to 18 years living on farms in Colorado., Methods: A cross-sectional survey of randomly selected Colorado farm residents aged 13 to 18 years was conducted between August 2003 and April 2004. A total of 262 youth completed the study. Information was obtained on injuries within the preceding year, sleep patterns, sleep hours, daytime sleepiness, and a number of social and demographic variables. Univariate analyses were done to describe relationships of study variables with injuries. Multivariate modeling was done to assess sleep patterns that were associated with injuries controlling for other variables., Results: Sleep patterns associated with increased risk of injuries (p<0.05) included oversleeping and having been late for class; falling asleep in afternoon classes; ever being up past 3 am; sleeping less than an average of 9.25 hours per night on weekends, and on school nights and weekends combined; and sleeping less than an average of 8.5 hours on weekends, and on school nights and weekends combined., Conclusions: Sleep patterns were significantly associated with occurrence of injuries.

Purpose: To examine the association between workload, health status, social support, depression, and safety practices among farm residents. Depression may lead to inattention when performing farm tasks and may reduce the likelihood of engaging in safe practices. There is a paucity of studies examining factors that influence engaging in safety practices among farmers., Methods: Personal interviews were conducted with farm operators and spouses in an eight-county area in Colorado. The Center for Epidemiologic Studies-Depression (CES-D) scale was used to assess depression. Ten safety practices were assessed for those involved in farm work. Proportional odds and logistic regression were used to model the relationship between safety practices and modifiers of safety behavior., Results: A total of 761 individuals were enrolled, of these 710 were actively involved in farm work. In logistic regression analysis, adjusting for age and gender, CES-D scale depression was significantly associated with being in a high-risk category for: being calm around animals (OR, 3.13; 95% CI, 1.23, 7.99); reading instruction manuals for farm machinery (OR, 2.73; CI, 1.14, 6.59); and keeping moving equipment parts shielded (OR, 5.38; CI, 1.96, 14.8)., Conclusions: Depression increased the probability of not exercising specific safety behaviors.

Depression, anxiety, inability to concentrate, and spatial disorientation associated with pesticide poisoning may influence farmers' ability to comply with established safety procedures. The purpose of this article is to describe the relationship between safety practices, neurological symptoms, and pesticide poisoning. A survey of farm residents was conducted in an eight-county area in Colorado. Multivariate logistic regression models were used to determine associations between safety practices, neurological symptoms, and previous pesticide poisoning. A number of safety practices were associated with the following neurological symptoms: difficulty concentrating; feeling irritable; relatives noticing memory difficulties; and difficulty understanding reading materials. The associations between safety practices and neurological symptoms were increased in the presence of pesticide poisoning. Factors associated with failure to engage in established safety practices in this study were neurological symptoms.

The purpose of this study is to evaluate the association between pesticides and neurological symptoms among a population exposed to organophosphate chemicals as a result of agricultural use. Chronic sequelae of acute pesticide poisoning from organophosphate compounds include a variety of neurological symptoms including restlessness, irritability, and trouble sleeping. Individuals who have had an acute pesticide poisoning have been reported to suffer a wide range of neurological symptoms that occur from weeks to months after the initial episode. Data for this study came from a cross-sectional survey of farmers and their spouses conducted in an eight-county area in north-eastern Colorado. Neurological characteristics were assessed to determine their relationship with previously reported pesticide-related illnesses. Symptoms that were significantly associated with a previous poisoning were difficulty concentrating [OR 2.07, 95% confidence interval (CI) 1.22, 3.50]; relatives noticing person had trouble remembering things (OR 2.54, 95% CI 1.47, 4.39); making notes to remember things (OR 2.18, 95% CI 1.20, 3.97); finding it hard to understand the meaning of newspapers, magazines, and books (OR 1.90, 95% CI 1.01, 3.60); felt irritable (OR 1.84, 95% CI 1.08, 3.12); felt depressed (OR 2.82, 95% CI 1.65, 4.81); had heart palpitations without exertion (OR 2.83, 95% CI 1.22, 6.54); sleeping more than usual (OR 3.58, 95% CI 1.95, 6.58); difficulty moving fingers or grasping things (OR 2.08, 95% CI 1.06, 3.24); and headaches at least once a week (OR 1.85, 95% CI 1.06, 3.24). Stepwise regression was used to identify the best explanatory model of pesticide-related illness. Variables that were associated with increased odds of illness were being male, being depressed, sleeping too much, and using crop organophosphates.