Quantitative NanoLC/NSI+-HRMS Method for 1,3-Butadiene Induced bis-N7-guanine DNA-DNA Cross-Links in Urine

1,3-Butadiene (BD) is a common environmental and industrial chemical widely used in plastic and rubber manufacturing and also present in cigarette smoke and automobile exhaust. BD is classified as a known human carcinogen based on evidence of carcinogenicity in laboratory animals treated with BD by inhalation and epidemiological studies revealing an increased risk of leukemia and lymphohematopoietic cancers in workers occupationally exposed to BD. Upon exposure via inhalation, BD is bioactivated to several toxic epoxides including 3,4-epoxy-1-butene (EB), 3,4-epoxy-1,2-butanediol (EBD), and 1,2,3,4-diepoxybutane (DEB); these are conjugated with glutathione and excreted as 2-(N-acetyl-L-cystein-S-yl)-1-hydroxybut-3-ene/1-(N-acetyl-L-cystein-S-yl)-2-hydroxybut-3-ene (MHBMA), 4-(N-acetyl-L-cystein-S-yl)-1,2-dihydroxybutane (DHBMA), and 1,4-bis-(N-acetyl-L-cystein-S-yl)butane-2,3-diol (bis-BDMA). Exposure to DEB generates monoalkylated DNA adducts, DNA-DNA crosslinks, and DNA-protein crosslinks, which can cause base substitutions, genomic rearrangements, and large genomic deletions. In this study, we developed a quantitative nanoLC/NSI+-HRMS methodology for 1,4-bis-(gua-7-yl)-2,3-butanediol (bis-N7G-BD) adducts in urine (LOD: 0.1 fmol/mL urine, LOQ: 1.0 fmol/mL urine). This novel method was used to quantify bis-N7G-BD in urine of mice treated with 590 ± 150 ppm BD for 2 weeks (6 h/day, 5 days/week). Bis-N7G-BD was detected in urine of male and female BD-exposed mice (574.6 ± 206.0 and 571.1 ± 163.4 pg/mg of creatinine, respectively). In addition, major urinary metabolites of BD, bis-BDMA, MHBMA and DHBMA, were measured in the same samples. Urinary bis-N7G-BD adduct levels correlated with DEB-derived metabolite bis-BDMA (r = 0.80, Pearson correlation), but not with the EB-derived DNA adducts (EB-GII) or EB-derived metabolites MHBMA and DHBMA (r = 0.24, r = 0.14, r = 0.18, respectively, Pearson correlations). Urinary bis-N7G-BD could be employed as a novel non-invasive biomarker of exposure to BD and bioactivation to its most mutagenic metabolite, DEB. This method will be useful for future studies of 1,3-butadiene exposure and metabolism.

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Epidemiological Trends in Attempted Suicide in Adolescents and Young Adults Between 1996 and 2004

Crisis ◽

10.1027/0227-5910.30.3.115 ◽

2009 ◽

Vol 30 (3) ◽

pp. 115-119 ◽

Cited By ~ 10

Author(s):

Stephanie De Munck ◽

Gwendolyn Portzky ◽

Kees Van Heeringen

Keyword(s):

Young Adults ◽

Attempted Suicide ◽

Suicide Attempts ◽

Epidemiological Studies ◽

Adolescents And Young Adults ◽

University Hospital ◽

International Studies ◽

Suicide Attempters ◽

Increased Risk ◽

Epidemiological Trends

Background: Notwithstanding the epidemiological studies indicating an increased risk of attempted suicide among adolescents and young adults, there is a scarcity of international studies that examine long-term epidemiological trends in rates and characteristics of this vulnerable group. Aims: This article describes the results of a 9-year monitoring study of suicide attempts in adolescents and young adults referred to the Accident and Emergency Department of the Gent University Hospital (Belgium). Methods: Between January 1996 and December 2004, trends, sociodemographic, and methodrelated characteristics of suicide attempts were assessed by a psychiatrist on data sheets. Results: Attempted suicide rates declined from 1996 to 2001 and then rose until 2004, but did not exceed previous rates. During the 9 years of monitoring, there was a preponderance of female suicide attempters, except for 1997. Rates of attempts and of fatal suicide were negatively correlated. Significantly more males than females deliberately injured themselves. Younger attempters, especially females, significantly more often poisoned themselves with analgesics. In nearly one in five attempts, alcohol was used in combination with other methods, and alcohol intake was more commonly observed in older suicide attempters. Nearly half of the adolescents were identified as repeaters. Conclusions: The results of this study warrant further monitoring of trends and characteristics of young suicide attempters.

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Comparative Proteomic Analysis of Carbonylated Proteins from the Striatum and Cortex of Pesticide-Treated Mice

Parkinson s Disease ◽

10.1155/2015/812532 ◽

2015 ◽

Vol 2015 ◽

pp. 1-11 ◽

Cited By ~ 3

Author(s):

Christina Coughlan ◽

Douglas I. Walker ◽

Kelly M. Lohr ◽

Jason R. Richardson ◽

Laura M. Saba ◽

...

Keyword(s):

Oxidative Stress ◽

Pesticide Exposure ◽

Epidemiological Studies ◽

Cytoskeletal Proteins ◽

Synaptic Function ◽

Behavioral Alterations ◽

Mechanisms Of Toxicity ◽

Kegg Pathways ◽

Increased Risk ◽

Proteomic Analyses

Epidemiological studies indicate exposures to the herbicide paraquat (PQ) and fungicide maneb (MB) are associated with increased risk of Parkinson’s disease (PD). Oxidative stress appears to be a premier mechanism that underlies damage to the nigrostriatal dopamine system in PD and pesticide exposure. Enhanced oxidative stress leads to lipid peroxidation and production of reactive aldehydes; therefore, we conducted proteomic analyses to identify carbonylated proteins in the striatum and cortex of pesticide-treated mice in order to elucidate possible mechanisms of toxicity. Male C57BL/6J mice were treated biweekly for 6 weeks with saline, PQ (10 mg/kg), MB (30 mg/kg), or the combination of PQ and MB (PQMB). Treatments resulted in significant behavioral alterations in all treated mice and depleted striatal dopamine in PQMB mice. Distinct differences in 4-hydroxynonenal-modified proteins were observed in the striatum and cortex. Proteomic analyses identified carbonylated proteins and peptides from the cortex and striatum, and pathway analyses revealed significant enrichment in a variety of KEGG pathways. Further analysis showed enrichment in proteins of the actin cytoskeleton in treated samples, but not in saline controls. These data indicate that treatment-related effects on cytoskeletal proteins could alter proper synaptic function, thereby resulting in impaired neuronal function and even neurodegeneration.

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Detection of aflatoxin B1 adducts in Mexican women with cervical lesions

World Mycotoxin Journal ◽

10.3920/wmj2020.2602 ◽

2021 ◽

pp. 1-12

Author(s):

L. Díaz de León-Martínez ◽

C.M. López-Mendoza ◽

Y. Terán-Figueroa ◽

R. Flores-Ramírez ◽

F. Díaz-Barriga ◽

...

Keyword(s):

Human Papillomavirus ◽

Dna Adducts ◽

Hpv Infection ◽

Mexican Women ◽

Cervical Lesions ◽

Increased Risk ◽

Secondary Objective ◽

E6 And E7 ◽

Aflatoxin B ◽

Potent Carcinogen

Cervical cancer (CC) is one of the most serious threats to the lives of women; co-factors in addition to oncogenic human papillomavirus (HPV) infection may be important in causing CC. Women in Mexico are exposed to dietary aflatoxin B1, a potent carcinogen, which may act as a co-factor, in inducing progression to CC. Scarce studies are addressing environmental risks associated with the development of CC, thus the study aimed to establish a relationship between the presence of AFB1 and the detection of human papillomavirus in the genome of Mexican women. Forty samples from cervical tissue of women infected with HPV were obtained; positive results regarding the HPV type (16 and/or 18) were found in 92.5% women and the presence of AFB1-DNA adducts were detected in 77.5% of the same positive HPV samples. Detection of AFB1-DNA adducts and genomic concentrations were correlated with the detection of two oncogenic types of HPV 16 and 18. AFB1-DNA positivity and higher genomic concentrations of AFB1-DNA adducts were correlated with an increased risk of oncogenic detection of HPV in cervical samples from women in Mexico. As a secondary objective, a hypothetical interaction of the adducts with the NRF2 pathway has been proposed, therefore activation of p62 and in turn E6 and E7 (HPV proteins) would inhibit the formation of autophagosomes, which would result in a presence or recurrence of CC.

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THE RELATIONSHIP BETWEEN AUDITORY REACTION TIME AND BODY BALANCE IN ELEMENTARY SCHOOL CHILDREN AT BAHA VILLAGE

Majalah Ilmiah Fisioterapi Indonesia ◽

10.24843/mifi.2019.v07.i03.p02 ◽

2019 ◽

Vol 7 (3) ◽

pp. 5

Author(s):

Putu Rian Pradhiva ◽

Ari Wibawa ◽

Ni Wayan Tianing

Keyword(s):

Elementary School ◽

Reaction Time ◽

School Children ◽

Elementary School Children ◽

Pearson Correlation ◽

Body Balance ◽

Increased Risk ◽

Data Output ◽

Auditory Reaction Time ◽

The Relationship

Balance in children is one of the most important things to notice during its development. Increased risk of loss ofbalance is often associated with a slow reaction time. The purpose of this study was to determine the relationshipbetween auditory reaction time and body balance in students at Elementary School in Baha village. This research wasconducted in March 2018 with cross sectional analytic study design. Samples were taken by simple random samplingmethod with 96 samples. The sample age range is 8 - 10 years. The independent variable is auditory reaction timemeasured using computerized reaction time test software. Dependent variable is body balance measured usingPediatric Balance Scale. The relationship between two variables was analyze using Pearson Correlation test. There isa significant correlation between auditory reaction time to body balance, based on data output from analysis withsignificance <? (p = 0,006). Furthermore, based on data output known Correlation Coefficient of -0.228 which meansthe existence of negative and linear relationship. There was a significant relationship between auditory reaction timeand body balance in elementary school children in Baha Village.Keywords: Reaction Time, Auditory, Balance, Children

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Depressive symptoms in a treated multiple sclerosis cohort

Multiple Sclerosis Journal ◽

10.1191/1352458503ms960oa ◽

2003 ◽

Vol 9 (6) ◽

pp. 616-620 ◽

Cited By ~ 46

Author(s):

Scott B Patten ◽

Shanika Fridhandler ◽

Cynthia A Beck ◽

Luanne M Metz

Keyword(s):

Multiple Sclerosis ◽

Depressive Symptoms ◽

Interferon Beta ◽

Rating Scale ◽

Epidemiological Studies ◽

Treatment Groups ◽

Increased Risk ◽

The University ◽

Depression Ratings

Background: Recent side effect data from clinical trials of interferon beta in multiple sclerosis (MS) have failed to confirm that these medications are associated with an increased risk of depression. However, these studies have used highly selected samples and the results may not be generalizable to real world settings. Methods: C linical data on subjects from southern A lberta who have applied for, or are receiving, public reimbursement for MS treatment are maintained in a database at the University of C algary Multiple Sclerosis C linic. Depression ratings obtained using the C enter for Epidemiological Studies Depression Rating Scale (C ES-D) are included in this database. In the current analysis, these longitudinal data were used to determine whether depressive symptoms were associated with disease-modifying treatments. Results: A t baseline, ratings were available for 163 subjects. Those choosing interferon beta resembled those choosing glatiramer acetate in most respects. During follow-up, no differences were observed in the prevalence or incidence of depression and C ES-D scores were not found to differ between the treatment groups. Conclusions: The failure to identify higher rates of depression both in previous intervention studies and in the current observational study provides confirmation that these drugs are not substantially associated with the occurrence of depression.

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The association between insulin therapy and depression in patients with type 2 diabetes mellitus: a meta-analysis

BMJ Open ◽

10.1136/bmjopen-2017-020062 ◽

2018 ◽

Vol 8 (11) ◽

pp. e020062 ◽

Cited By ~ 10

Author(s):

Xiaosu Bai ◽

Zhiming Liu ◽

Zhisen Li ◽

Dewen Yan

Keyword(s):

Diabetes Mellitus ◽

Type 2 Diabetes ◽

Type 2 Diabetes Mellitus ◽

Insulin Therapy ◽

Depressive Disorders ◽

Meta Analysis ◽

Epidemiological Studies ◽

Cochrane Library ◽

Increased Risk

ObjectivesSeveral patients with type 2 diabetes mellitus (T2DM) have depressive disorders. Whether insulin treatment was associated with increased risk of depression remains controversial. We performed a meta-analysis to evaluate the association of insulin therapy and depression.DesignA meta-analysis.MethodsWe conducted a systematic search of PubMed, PsycINFO, Embase and the Cochrane Library from their inception to April 2016. Epidemiological studies comparing the prevalence of depression between insulin users and non-insulin users were included. A random-effects model was used for meta-analysis. The adjusted and crude data were analysed.ResultsTwenty-eight studies were included. Of these, 12 studies presented with adjusted ORs. Insulin therapy was significantly associated with increased risk of depression (OR=1.41, 95% CI 1.13 to 1.76, p=0.003). Twenty-four studies provided crude data. Insulin therapy was also associated with an odds for developing depression (OR=1.59, 95% CI 1.41 to 1.80, p<0.001). When comparing insulin therapy with oral antidiabetic drugs, significant association was observed for adjusted (OR=1.42, 95% CI 1.08 to 1.86, p=0.008) and crude (OR=1.61, 95% CI 1.35 to 1.93, p<0.001) data.ConclusionsOur meta-analysis confirmed that patients on insulin therapy were significantly associated with the risk of depressive symptoms.

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Summary of Utah Project on Exfoliation Syndrome (UPEXS): using a large database to identify systemic comorbidities

BMJ Open Ophthalmology ◽

10.1136/bmjophth-2021-000803 ◽

2021 ◽

Vol 6 (1) ◽

pp. e000803

Author(s):

Christian James Pompoco ◽

Karen Curtin ◽

Samuel Taylor ◽

Chase Paulson ◽

Caleb Shumway ◽

...

Keyword(s):

Extracellular Matrix ◽

Lysyl Oxidase ◽

Genetic Disorders ◽

Epidemiological Studies ◽

Pelvic Organ ◽

Chronic Obstructive ◽

Exfoliation Syndrome ◽

Population Database ◽

Obstructive Sleep ◽

Increased Risk

The purpose of the Utah Project on Exfoliation Syndrome (UPEXS) is to identify associations between exfoliation syndrome (XFS) and other diseases that share the commonality of abnormalities in elastin and Lysyl Oxidase-Like 1 gene regulation. The UPEXS is unique because it uses the Utah Population Database, which is linked to the Utah genealogy, that contains a compilation of large pedigrees of most families in the state of Utah that go back multiple generations (3 to ≥11). The health and medical records of these family members are linked to vital records and can be used effectively in studies focused on genetic disorders like XFS, where familial clustering of a disorder is a trend. There is increasing evidence that patients with XFS have a higher risk of certain systemic disorders that reflect the systemic tissue abnormalities of XFS. Epidemiological studies focused on patients with XFS have shown that there is an increased risk of these individuals developing other pathologies that have abnormalities in extracellular matrix metabolism and repair. UPEXS has focused on suspected comorbidities that involve abnormalities in elastin maintenance, a protein that plays a role in the makeup of the extracellular matrix. In this paper, the results from the analysis of chronic obstructive pulmonary disease, inguinal hernias, pelvic organ prolapse, obstructive sleep apnoea and atrial fibrillation are summarised along with the utility of using such a large dataset.

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Mental disorders and risk of suicide attempt in prisoners

10.31234/osf.io/5fhgu ◽

2020 ◽

Author(s):

Louis Favril

Keyword(s):

Suicidal Ideation ◽

Mental Disorders ◽

Suicide Attempt ◽

Prison Population ◽

Total Sample ◽

Epidemiological Studies ◽

High Risk Population ◽

Increased Risk ◽

History Of ◽

Mere Presence

Background: Mental disorders are overrepresented in prisoners, placing them at an increased risk of suicide. Advancing our understanding of how different mental disorders relate to distinct stages of the suicidal process—the transition from ideation to action—would provide valuable information for clinical risk assessment in this high-risk population. Methods: Data were drawn from a representative sample of 1212 adults (1093 men) incarcerated across 13 New Zealand prisons, accounting for 14% of the national prison population. Guided by an ideation-to-action framework, three mutually exclusive groups of participants were compared on the presence of mental disorders assessed by validated DSM-IV diagnostic criteria: prisoners without any suicidal history (controls; n = 778), prisoners who thought about suicide but never made a suicide attempt (ideators; n = 187), and prisoners who experienced suicidal ideation and acted on such thoughts (attempters; n = 247). Results: One-third (34.6%) of participants reported a lifetime history of suicidal ideation, of whom 55.6% attempted suicide (19.2% of all prisoners). Suicidal outcomes in the absence of mental disorders were rare. Whilst each disorder increased the odds of suicidal ideation (OR range 1.73–4.13) and suicide attempt (OR range 1.82–4.05) in the total sample (n = 1212), only a select subset of disorders was associated with suicide attempt among those with suicidal ideation (n = 434). Drug dependence (OR = 1.65, 95% CI 1.10-2.48), alcohol dependence (OR = 1.89, 95% CI 1.26-2.85), and posttraumatic stress disorder (OR = 2.09, 95% CI 1.37-3.17) distinguished attempters from ideators. Conclusion: Consistent with many epidemiological studies in the general population, our data suggest that most mental disorders are best conceptualized as risk factors for suicidal ideation rather than for suicide attempt. Once prisoners consider suicide, other biopsychosocial factors beyond the mere presence of mental disorders may account for the progression from thoughts to acts of suicide.

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The role of high-protein diets in body weight management and health

10.26686/wgtn.12831860.v1 ◽

2020 ◽

Author(s):

Lisa Te Morenga ◽

J Mann

Keyword(s):

Weight Maintenance ◽

Epidemiological Studies ◽

High Protein ◽

Cholesterol Ratio ◽

The Metabolic Syndrome ◽

Increased Risk ◽

Ad Libitum ◽

Risk Of Cancer ◽

High Protein Diets ◽

Protein Diets

Studies examining the health benefits of high-protein diets typical of most affluent and many developing countries are not consistent. Prospective epidemiological studies relating dietary protein to clinical and metabolic endpoints suggest increased weight gain and increased risk of diabetes amongst those with a high protein intake and an increased risk of cancer with high intakes of red meat, but lower blood pressure and possibly a reduced risk of heart disease with higher protein intakes. The potential for high-protein diets to confer greater benefit than other diets has been examined using ad libitum and energy restricted diets. Of greatest interest have been the comparisons between high-protein and high-carbohydrate diets. Many trials have reported greater weight loss especially in the context of ad libitum diets over the short-to medium-term, sparing of lean body mass, lowering of triglyceride levels, improved HDL: total cholesterol ratio and improved glycaemic control. Limited data regarding insulin sensitivity are less consistent. A major difficulty in interpreting the results of these studies is that carbohydrate quality has not been taken into account. Furthermore, longer term comparisons of weight reducing diets differing in macronutrient composition have reported similar outcomes, suggesting that compliance is a more important consideration. Nevertheless dietary patterns with high-protein intakes are appropriate for weight reduction and weight maintenance and may be useful for those who have high triglyceride levels and other features of the metabolic syndrome. © 2012 The Authors.

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Analysis of Influencing Factors of Compliance with Non-Vitamin K Antagonist Oral Anticoagulant in Patients with Nonvalvular Atrial Fibrillation and Correlation with the Severity of Ischemic Stroke

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2021/1021127 ◽

2021 ◽

Vol 2021 ◽

pp. 1-7

Author(s):

Li Zhu ◽

Xiaodan Zhang ◽

Jing Yang

Keyword(s):

Atrial Fibrillation ◽

Ischemic Stroke ◽

Influencing Factors ◽

Clinical Supervision ◽

Vitamin K ◽

Pearson Correlation ◽

Anticoagulation Therapy ◽

Vitamin K Antagonist ◽

Nonvalvular Atrial Fibrillation ◽

Increased Risk

Nonvalvular atrial fibrillation (NVAF) is associated with an increased risk of stroke and thrombus, and anticoagulant therapy is a key link in the prevention of stroke. At present, the anticoagulation rate of atrial fibrillation in China is low, and there are many factors affecting the adherence of patients with atrial fibrillation to anticoagulation. Non-vitamin K antagonist oral anticoagulants (NOACs) are anticoagulant with high application value due to their high safety and low risk of intracranial hemorrhage, stroke, and death. However, the compliance of NOACs is poor, and the current situation of anticoagulants in China is not optimistic. In this study, a total of 156 patients with NVAF who received NOAC anticoagulation therapy in our hospital from January 2018 to January 2019 were retrospectively analyzed. The results showed that education background, place of residence, number of complications, CHA2DS2-VASc score, and HAS-BLED score were independent influencing factors for NOACS compliance of NVAF patients. Also, the Pearson correlation analysis showed that there was a negative correlation (r = −0.465, P < 0.001 ) between NOAC compliance and severity of ischemic stroke in patients with NVAF. Therefore, clinical supervision and management of patients with NVAF after NOACs should be strengthened to improve the compliance of patients with NVAF after NOACs, reduce the damage of ischemic stroke, and improve their prognosis.

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