Simultaneous quantification of cardiovascular disease related metabolic risk factors using liquid chromatography tandem mass spectrometry in human serum.

PubMed

Wang, Mo; Yang, Ruiyue; Dong, Jun; Zhang, Tianjiao; Wang, Siming; Zhou, Weiyan; Li, Hongxia; Zhao, Haijian; Zhang, Lijiao; Wang, Shu; Zhang, Chuanbao; Chen, Wenxiang

2016-01-15

Recent observations from metabonomic studies have consistently found that branched-chain amino acids (BCAAs), aromatic amino acids (AAAs), glutamine (Gln), glutamic acid (Glu), Gln/Glu ratio, carnitine, and several species of acylcarnitines and lysophosphatidylcholines (LPCs) are possible risk factors for metabolic diseases such as diabetes mellitus (DM) and cardiovascular diseases (CVD). We described here a simple and reliable method for simultaneous quantification of these metabolic risk factors by liquid chromatography tandem mass spectrometry (LC-MS/MS). Serum samples were extracted with isopropanol, and the extracted metabolites were separated by hydrophilic interaction liquid chromatography (HILIC) and detected with electrospary ionization (ESI) inpositive ion mode with multiple reaction monitor (MRM) mode. All the metabolites were effectively separated within 5.5min. Analytical recoveries were in the range of 92.8-106.9%, with an average of 100.6%. The intra- run and total imprecisions for the measurement of these metabolites were 1.2-3.8% and 1.5-7.4%, respectively. Serum concentrations of the metabolites were analyzed in 123 apparently healthy volunteers. Significant associations between the metabolites and traditional CVD risk factors were observed. The newly developed LC-MS/MS method was simple, precise, and accurate and can be used as an efficient tool in CVD research and studies. Copyright © 2015 Elsevier B.V. All rights reserved.

Serum 6-Bromotryptophan Levels Identified as a Risk Factor for CKD Progression.

PubMed

Tin, Adrienne; Nadkarni, Girish; Evans, Anne M; Winkler, Cheryl A; Bottinger, Erwin; Rebholz, Casey M; Sarnak, Mark J; Inker, Lesley A; Levey, Andrew S; Lipkowitz, Michael S; Appel, Lawrence J; Arking, Dan E; Coresh, Josef; Grams, Morgan E

2018-05-18

Background Metabolite levels reflect physiologic homeostasis and may serve as biomarkers of disease progression. Identifying metabolites associated with APOL1 risk alleles-genetic variants associated with CKD risk commonly present in persons of African descent-may reveal novel markers of CKD progression relevant to other populations. Methods We evaluated associations between the number of APOL1 risk alleles and 760 serum metabolites identified via untargeted profiling in participants of the African American Study of Kidney Disease and Hypertension (AASK) ( n =588; Bonferroni significance threshold P <6.5×10 -5 ) and replicated findings in 678 black participants with CKD in Bio Me , an electronic medical record-linked biobank. We tested the metabolite association with CKD progression in AASK, Bio Me , and the Modification of Diet in Renal Disease (MDRD) Study. Results One metabolite, 6-bromotryptophan, was significant in AASK ( P =4.7×10 -5 ) and replicated in Bio Me ( P =5.7×10 -3 ) participants, with lower levels associated with more APOL1 risk alleles. Lower levels of 6-bromotryptophan were associated with CKD progression in AASK and Bio Me participants and in white participants in the MDRD Study, independent of demographics and clinical characteristics, including baseline GFR (adjusted hazard ratio per two-fold higher 6-bromotryptophan level, AASK, 0.76; 95% confidence interval [95% CI], 0.64 to 0.91; Bio Me , 0.61; 95% CI, 0.43 to 0.85; MDRD, 0.52; 95% CI, 0.34 to 0.79). The interaction between the APOL1 risk alleles and 6-bromotryptophan was not significant. The identity of 6-bromotryptophan was confirmed in experiments comparing its molecular signature with that of authentic standards of other bromotryptophan isomers. Conclusions Serum 6-bromotryptophan is a consistent and novel risk factor for CKD progression. Copyright © 2018 by the American Society of Nephrology.

Development of novel metabolite-responsive transcription factors via transposon-mediated protein fusion.

PubMed

Younger, Andrew K D; Su, Peter Y; Shepard, Andrea J; Udani, Shreya V; Cybulski, Thaddeus R; Tyo, Keith E J; Leonard, Joshua N

2018-02-01

Naturally evolved metabolite-responsive biosensors enable applications in metabolic engineering, ranging from screening large genetic libraries to dynamically regulating biosynthetic pathways. However, there are many metabolites for which a natural biosensor does not exist. To address this need, we developed a general method for converting metabolite-binding proteins into metabolite-responsive transcription factors-Biosensor Engineering by Random Domain Insertion (BERDI). This approach takes advantage of an in vitro transposon insertion reaction to generate all possible insertions of a DNA-binding domain into a metabolite-binding protein, followed by fluorescence activated cell sorting to isolate functional biosensors. To develop and evaluate the BERDI method, we generated a library of candidate biosensors in which a zinc finger DNA-binding domain was inserted into maltose binding protein, which served as a model well-studied metabolite-binding protein. Library diversity was characterized by several methods, a selection scheme was deployed, and ultimately several distinct and functional maltose-responsive transcriptional biosensors were identified. We hypothesize that the BERDI method comprises a generalizable strategy that may ultimately be applied to convert a wide range of metabolite-binding proteins into novel biosensors for applications in metabolic engineering and synthetic biology. © The Author(s) 2018. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Estrogen Metabolites Are Not Associated With Colorectal Cancer Risk In Postmenopausal Women

PubMed Central

Falk, Roni T.; Dallal, Cher M.; Lacey, James V.; Bauer, Douglas C.; Buist, Diana SM; Cauley, Jane A.; Hue, Trisha F.; LaCroix, Andrea; Tice, Jeffrey A.; Pfeiffer, Ruth M.; Xu, Xia; Veenstra, Timothy D.; Brinton, Louise A.

2015-01-01

Background A potential protective role for estrogen in colon carcinogenesis has been suggested based on exogenous hormone use, but it is unclear from previous studies whether endogenous estrogens are related to colorectal cancer (CRC) risk. These few prior studies focused on parent estrogens; none evaluated effects of estrogen metabolism in postmenopausal women. Methods We followed 15,595 women (ages 55–80) enrolled in B~FIT (Breast and Bone Follow-up to the Fracture Intervention Trial (FIT)) who donated blood between 1992 and 1993 for cancer through December 2004. A panel of 15 estrogen metabolites (EM), including estradiol and estrone, were measured in serum from 187 CRC cases and a subcohort of 501 women not using exogenous hormones at blood draw. We examined EM individually, grouped by pathway (hydroxylation at the C-2, C-4, or C-16 position), and by ratios of the groupings using Cox proportional hazards regression models. Results No significant associations were seen for estrone (HRQ4 v Q1=1.15, 95% CI=0.69–1.93, ptrend=0.54), estradiol (HRQ4 v Q1= 0.98, 95% CI=0.58–1.64, ptrend>0.99) or total EM (the sum of all EM; HRQ4 v Q1=1.35. 95% CI=0.81–2.24, ptrend=0.33). Most metabolites in the 2-, 4- or 16-pathway were unrelated to risk, although a borderline trend in risk was associated with high levels of 17-epiestriol. Conclusion Circulating estrogens and their metabolites were generally unrelated to CRC risk in postmenopausal women. Impact Additional studies are needed to understand how exogenous estrogen may prevent CRC PMID:26104910

Correlation between reactive oxygen metabolites & atherosclerotic risk factors in patients with type 2 diabetes mellitus.

PubMed

Kotani, Kazuhiko; Tsuzaki, Kokoro; Taniguchi, Nobuyuki; Sakane, Naoki

2013-04-01

Oxidative stress plays important roles in the pathophysiology of type 2 diabetes mellitus (T2DM). The diacron reactive oxygen metabolites (d-ROMs) test has been used in the clinics. The present study was aimed to investigate the correlation of the oxidative stress status, as evaluated by the d-ROMs, with atherosclerotic risk factors in T2DM patients, in comparison to controls. The study included 200 subjects (100 patients with T2DM and 100 controls; 86 males/114 females; mean age 59.0 yr). Clinical variables including the body mass index, blood pressure (BP), glucose and lipid panels, in addition to the d-ROMs, were measured. Patients with T2DM showed significantly higher d-ROMs levels than controls (322 ± 60 vs. 345 ± 64 U. Carr., P<0.05). A multiple linear regression analysis revealed that systolic BP (β=0.26, P<0.05) and high-density lipoprotein cholesterol (HDL-C: β= -0.30, P<0.05) were independently and significantly correlated with the d-ROMs levels in patients with T2DM, although these correlations were not significant in the controls. The gender-based analysis showed that systolic BP (β = 0.44, P<0.05) and HDL-C (β = -0.36, P<0.05) were independently and significantly correlated with the d-ROMs levels in females with T2DM, while there was a marginally significant correlation between HDL-C and the d-ROMs levels (β = -0.36, P=0.06) in males with T2DM. The present findings may reinforce the importance of BP control in female patients with T2DM, as well as the management of HDL-C in male and female patients with T2DM, under the linkage between oxidative stress and atherosclerosis.

Correlation between reactive oxygen metabolites & atherosclerotic risk factors in patients with type 2 diabetes mellitus

PubMed Central

Kotani, Kazuhiko; Tsuzaki, Kokoro; Taniguchi, Nobuyuki; Sakane, Naoki

2013-01-01

Background & objectives: Oxidative stress plays important roles in the pathophysiology of type 2 diabetes mellitus (T2DM). The diacron reactive oxygen metabolites (d-ROMs) test has been used in the clinics. The present study was aimed to investigate the correlation of the oxidative stress status, as evaluated by the d-ROMs, with atherosclerotic risk factors in T2DM patients, in comparison to controls. Methods: The study included 200 subjects (100 patients with T2DM and 100 controls; 86 males/114 females; mean age 59.0 yr). Clinical variables including the body mass index, blood pressure (BP), glucose and lipid panels, in addition to the d-ROMs, were measured. Results: Patients with T2DM showed significantly higher d-ROMs levels than controls (322 ± 60 vs. 345 ± 64 U. Carr., P<0.05). A multiple linear regression analysis revealed that systolic BP (β=0.26, P<0.05) and high-density lipoprotein cholesterol (HDL-C: β= -0.30, P<0.05) were independently and significantly correlated with the d-ROMs levels in patients with T2DM, although these correlations were not significant in the controls. The gender-based analysis showed that systolic BP (β = 0.44, P<0.05) and HDL-C (β = -0.36, P<0.05) were independently and significantly correlated with the d-ROMs levels in females with T2DM, while there was a marginally significant correlation between HDL-C and the d-ROMs levels (β = -0.36, P=0.06) in males with T2DM. Interpretation & conclusions: The present findings may reinforce the importance of BP control in female patients with T2DM, as well as the management of HDL-C in male and female patients with T2DM, under the linkage between oxidative stress and atherosclerosis. PMID:23703342

Dissipation Pattern, Processing Factors, and Safety Evaluation for Dimethoate and Its Metabolite (Omethoate) in Tea (Camellia Sinensis).

PubMed

Pan, Rong; Chen, Hong-Ping; Zhang, Ming-Lu; Wang, Qing-Hua; Jiang, Ying; Liu, Xin

2015-01-01

Residue levels of dimethoate and its oxon metabolite (omethoate) during tea planting, manufacturing, and brewing were investigated using a modified QuEChERS sample preparation and gas chromatography. Dissipation of dimethoate and its metabolite in tea plantation followed the first-order kinetic with a half-life of 1.08-1.27 d. Tea manufacturing has positive effects on dimethoate dissipation. Processing factors of dimethoate are in the range of 2.11-2.41 and 1.41-1.70 during green tea and black tea manufacturing, respectively. Omethoate underwent generation as well as dissipation during tea manufacturing. Sum of dimethoate and omethoate led to a large portion of 80.5-84.9% transferring into tea infusion. Results of safety evaluation indicated that omethoate could bring higher human health risk than dimethoate due to its higher hazard quotient by drinking tea. These results would provide information for the establishment of maximum residue limit and instruction for the application of dimethoate formulation on tea crop.

Issues in the Pharmacokinetics of Trichloroethylene and Its Metabolites

PubMed Central

Chiu, Weihsueh A.; Okino, Miles S.; Lipscomb, John C.; Evans, Marina V.

2006-01-01

Much progress has been made in understanding the complex pharmacokinetics of trichloroethylene (TCE). Qualitatively, it is clear that TCE is metabolized to multiple metabolites either locally or into systemic circulation. Many of these metabolites are thought to have toxicologic importance. In addition, efforts to develop physiologically based pharmacokinetic (PBPK) models have led to a better quantitative assessment of the dosimetry of TCE and several of its metabolites. As part of a mini-monograph on key issues in the health risk assessment of TCE, this article is a review of a number of the current scientific issues in TCE pharmacokinetics and recent PBPK modeling efforts with a focus on literature published since 2000. Particular attention is paid to factors affecting PBPK modeling for application to risk assessment. Recent TCE PBPK modeling efforts, coupled with methodologic advances in characterizing uncertainty and variability, suggest that rigorous application of PBPK modeling to TCE risk assessment appears feasible at least for TCE and its major oxidative metabolites trichloroacetic acid and trichloroethanol. However, a number of basic structural hypotheses such as enterohepatic recirculation, plasma binding, and flow- or diffusion-limited treatment of tissue distribution require additional evaluation and analysis. Moreover, there are a number of metabolites of potential toxicologic interest, such as chloral, dichloroacetic acid, and those derived from glutathione conjugation, for which reliable pharmacokinetic data is sparse because of analytical difficulties or low concentrations in systemic circulation. It will be a challenge to develop reliable dosimetry for such cases. PMID:16966104

Fundamental Design Principles for Transcription-Factor-Based Metabolite Biosensors.

PubMed

Mannan, Ahmad A; Liu, Di; Zhang, Fuzhong; Oyarzún, Diego A

2017-10-20

Metabolite biosensors are central to current efforts toward precision engineering of metabolism. Although most research has focused on building new biosensors, their tunability remains poorly understood and is fundamental for their broad applicability. Here we asked how genetic modifications shape the dose-response curve of biosensors based on metabolite-responsive transcription factors. Using the lac system in Escherichia coli as a model system, we built promoter libraries with variable operator sites that reveal interdependencies between biosensor dynamic range and response threshold. We developed a phenomenological theory to quantify such design constraints in biosensors with various architectures and tunable parameters. Our theory reveals a maximal achievable dynamic range and exposes tunable parameters for orthogonal control of dynamic range and response threshold. Our work sheds light on fundamental limits of synthetic biology designs and provides quantitative guidelines for biosensor design in applications such as dynamic pathway control, strain optimization, and real-time monitoring of metabolism.

Genetic risk factors for clozapine-induced neutropenia and agranulocytosis in a Dutch psychiatric population.

PubMed

van der Weide, K; Loovers, H; Pondman, K; Bogers, J; van der Straaten, T; Langemeijer, E; Cohen, D; Commandeur, J; van der Weide, J

2017-10-01

Prescription of clozapine is complicated by the occurrence of clozapine-induced reduction of neutrophils. The aim of this study was to identify genetic risk factors in a population of 310 Dutch patients treated with clozapine, including 38 patients developing neutropenia and 31 patients developing agranulocytosis. NQO2 1541AA (NRH quinone oxidoreductase 2; protects cells against oxidative metabolites) was present at a higher frequency in agranulocytosis patients compared with control (23% versus 7%, P=0.03), as was ABCB1 (ABC-transporter-B1; drug efflux transporter) 3435TT (32% versus 20%, P=0.05). In patients developing neutropenia, ABCB1 3435TT and homozygosity for GSTT1 null (glutathione-S-transferase; conjugates reactive clozapine metabolites into glutathione) were more frequent compared with control (34% versus 20%, P=0.05 and 31% versus 14%, P=0.03), whereas GSTM1 null was less frequent in these patients (31% versus 52%, P=0.03). To investigate whether combinations of the identified genetic risk factors have a higher predictive value, should be confirmed in a larger case-control study.

Pesticides in ground water: Do atrazine metabolites matter?

USGS Publications Warehouse

Liu, S.; Yen, S.T.; Kolpin, D.W.

1996-01-01

Atrazine and atrazine-residue (atrazine + two metabolites - deethylatrazine and deisopropylatrazine) concentrations were examined to determine if consideration of these atrazine metabolites substantially adds to our understanding of the distribution of this pesticide in groundwater of the midcontinental United States. The mean of atrazine.residue concentrations was 53 percent greater than that of atrazine alone for those observations above the detection limit (> 0.05 μg/l). Furthermore, a censored regression analysis using atrazine-residue concentrations revealed significant factors not identified when only atrazine concentrations were used. Thus, knowledge of concentrations of these atrazine metabolites is required to obtain a true estimation of risk of using these aquifers as sources for drinking water, and such knowledge also provides information that ultimately may be important for future management policies designed to reduce atrazine concentrations in ground water.

High-throughput method for the quantitation of metabolites and co-factors from homocysteine-methionine cycle for nutritional status assessment.

PubMed

Da Silva, Laeticia; Collino, Sebastiano; Cominetti, Ornella; Martin, Francois-Pierre; Montoliu, Ivan; Moreno, Sergio Oller; Corthesy, John; Kaput, Jim; Kussmann, Martin; Monteiro, Jacqueline Pontes; Guiraud, Seu Ping

2016-09-01

There is increasing interest in the profiling and quantitation of methionine pathway metabolites for health management research. Currently, several analytical approaches are required to cover metabolites and co-factors. We report the development and the validation of a method for the simultaneous detection and quantitation of 13 metabolites in red blood cells. The method, validated in a cohort of healthy human volunteers, shows a high level of accuracy and reproducibility. This high-throughput protocol provides a robust coverage of central metabolites and co-factors in one single analysis and in a high-throughput fashion. In large-scale clinical settings, the use of such an approach will significantly advance the field of nutritional research in health and disease.

Dissipation Pattern, Processing Factors, and Safety Evaluation for Dimethoate and Its Metabolite (Omethoate) in Tea (Camellia Sinensis)

PubMed Central

Pan, Rong; Chen, Hong-Ping; Zhang, Ming-Lu; Wang, Qing-Hua; Jiang, Ying; Liu, Xin

2015-01-01

Residue levels of dimethoate and its oxon metabolite (omethoate) during tea planting, manufacturing, and brewing were investigated using a modified QuEChERS sample preparation and gas chromatography. Dissipation of dimethoate and its metabolite in tea plantation followed the first-order kinetic with a half-life of 1.08–1.27 d. Tea manufacturing has positive effects on dimethoate dissipation. Processing factors of dimethoate are in the range of 2.11–2.41 and 1.41–1.70 during green tea and black tea manufacturing, respectively. Omethoate underwent generation as well as dissipation during tea manufacturing. Sum of dimethoate and omethoate led to a large portion of 80.5–84.9% transferring into tea infusion. Results of safety evaluation indicated that omethoate could bring higher human health risk than dimethoate due to its higher hazard quotient by drinking tea. These results would provide information for the establishment of maximum residue limit and instruction for the application of dimethoate formulation on tea crop. PMID:26406463

Non-infective occupational risk factors for hepatocellular carcinoma: A review

PubMed Central

Ledda, Caterina; Loreto, Carla; Zammit, Christian; Marconi, Andrea; Fago, Lucrezia; Matera, Serena; Costanzo, Valentina; Sanzà, Giovanni Fuccio; Palmucci, Stefano; Ferrante, Margherita; Costa, Chiara; Fenga, Concettina; Biondi, Antonio; Pomara, Cristoforo; Rapisarda, Venerando

2017-01-01

Liver cancer is the second leading worldwide cause of cancer-associated mortalities. Hepatocellular carcinoma, which accounts for the majority of liver tumors, ranks fifth among types of human cancer. Well-established risk factors for liver cancer include the hepatitis B and C viruses, aflatoxins, alcohol consumption, and oral contraceptives. Tobacco smoking, androgenic steroids, and diabetes mellitus are suspected risk factors. Current knowledge regarding non-infective occupational risk factors for liver cancer is inconclusive. The relevance of liver disorders to occupational medicine lies in the fact that the majority of chemicals are metabolized in the liver, and toxic metabolites generated via metabolism are the predominant cause of liver damage. However, their non-specific clinical manifestations that are similar in a number of liver diseases make diagnosis difficult. Furthermore, concomitant conditions, such as viral hepatitis and alcohol or drug abuse, may mask liver disorders that result from occupational hepatotoxic agents and block the demonstration of an occupational cause. The identification of environmental agents that result in human cancer is a long and often difficult process. The purpose of the present review is to summarize current knowledge regarding the association of non-infective occupational risk exposure and HCC, to encourage further research and draw attention to this global occupational public health problem. PMID:28000892

Sulindac metabolites inhibit epidermal growth factor receptor activation and expression.

PubMed

Pangburn, Heather A; Kraus, Hanna; Ahnen, Dennis J; Rice, Pamela L

2005-09-02

Regular use of nonsteroidal anti-inflammatory drugs (NSAIDs) is associated with a decreased mortality from colorectal cancer (CRC). NSAIDs induce apoptotic cell death in colon cancer cells in vitro and inhibit growth of neoplastic colonic mucosa in vivo however, the biochemical mechanisms required for these growth inhibitory effects are not well defined. We previously reported that metabolites of the NSAID sulindac downregulate extracellular-signal regulated kinase 1/2 (ERK1/2) signaling and that this effect is both necessary and sufficient for the apoptotic effects of these drugs. The goal of this project was to specifically test the hypothesis that sulindac metabolites block activation and/or expression of the epidermal growth factor (EGF) receptor (EGFR). HT29 human colon cancer cells were treated with EGF, alone, or in the presence of sulindac sulfide or sulindac sulfone. Cells lysates were assayed by immunoblotting for phosphorylated EGFR (pEGFR, pY1068), total EGFR, phosphorylated ERK1/2 (pERK1/2), total ERK1/2, activated caspase-3, and alpha-tubulin. EGF treatment rapidly induced phosphorylation of both EGFR and ERK1/2 in HT29 colon cancer cells. Pretreatment with sulindac metabolites for 24 h blocked EGF-induced phosphorylation of both EGFR and ERK1/2 and decreased total EGFR protein expression. Under basal conditions, downregulation of pEGFR and total EGFR was detected as early as 12 h following sulindac sulfide treatment and persisted through at least 48 h. Sulindac sulfone induced downregulation of pEGFR and total EGFR was detected as early as 1 h and 24 h, respectively, following drug treatment, and persisted through at least 72 h. EGFR downregulation by sulindac metabolites was observed in three different CRC cell lines, occurred prior to the observed downregulation of pERK1/2 and induction of apoptosis by these drugs, and was not dependent of caspase activation. These results suggest that downregulation of EGFR signaling by sulindac metabolites may

Multiple Interacting Risk Factors: On Methods for Allocating Risk Factor Interactions.

PubMed

Price, Bertram; MacNicoll, Michael

2015-05-01

A persistent problem in health risk analysis where it is known that a disease may occur as a consequence of multiple risk factors with interactions is allocating the total risk of the disease among the individual risk factors. This problem, referred to here as risk apportionment, arises in various venues, including: (i) public health management, (ii) government programs for compensating injured individuals, and (iii) litigation. Two methods have been described in the risk analysis and epidemiology literature for allocating total risk among individual risk factors. One method uses weights to allocate interactions among the individual risk factors. The other method is based on risk accounting axioms and finding an optimal and unique allocation that satisfies the axioms using a procedure borrowed from game theory. Where relative risk or attributable risk is the risk measure, we find that the game-theory-determined allocation is the same as the allocation where risk factor interactions are apportioned to individual risk factors using equal weights. Therefore, the apportionment problem becomes one of selecting a meaningful set of weights for allocating interactions among the individual risk factors. Equal weights and weights proportional to the risks of the individual risk factors are discussed. © 2015 Society for Risk Analysis.

Untargeted metabolomics of colonic digests reveals kynurenine pathway metabolites, dityrosine and 3-dehydroxycarnitine as red versus white meat discriminating metabolites

PubMed Central

Rombouts, Caroline; Hemeryck, Lieselot Y.; Van Hecke, Thomas; De Smet, Stefaan; De Vos, Winnok H.; Vanhaecke, Lynn

2017-01-01

Epidemiological research has demonstrated that the consumption of red meat is an important risk factor for the development of colorectal cancer (CRC), diabetes mellitus and cardiovascular diseases. However, there is no holistic insight in the (by-) products of meat digestion that may contribute to disease development. To address this hiatus, an untargeted mass spectrometry (MS)-based metabolomics approach was used to create red versus white meat associated metabolic fingerprints following in vitro colonic digestion using the fecal inocula of ten healthy volunteers. Twenty-two metabolites were unequivocally associated with simulated colonic digestion of red meat. Several of these metabolites could mechanistically be linked to red meat-associated pathways including N’-formylkynurenine, kynurenine and kynurenic acid (all involved in tryptophan metabolism), the oxidative stress marker dityrosine, and 3-dehydroxycarnitine. In conclusion, the used MS-based metabolomics platform proved to be a powerful platform for detection of specific metabolites that improve the understanding of the causal relationship between red meat consumption and associated diseases. PMID:28195169

Association of polycyclic aromatic hydrocarbons metabolites and risk of diabetes in coke oven workers.

PubMed

Yang, Liangle; Yan, Kai; Zeng, Dan; Lai, Xuefeng; Chen, Xuguang; Fang, Qin; Guo, Huan; Wu, Tangchun; Zhang, Xiaomin

2017-04-01

Elevated polycyclic aromatic hydrocarbons (PAHs) metabolites have recently been linked to increased risk of diabetes in the general population, but little is known about the risk of diabetes due to high pollution levels of PAHs exposure. We aimed to examine whether occupational exposure to PAHs would be one of the important risk factors for diabetes in the coke oven workers. A total of 1472 coke oven workers with complete data were qualified for the present study. We measured 12 urinary monohydroxy polycyclic aromatic hydrocarbons (OH-PAHs) by gas chromatography-mass spectrometry (GC-MS). Multiple logistic regression was used to evaluate the associations between urinary OH-PAHs and risk of diabetes, with adjustment for the potential confounders. We found that elevated urinary 4-hydroxyphenanthrene (4-OHPh) was significantly associated, in a dose-dependent manner, with increased risk of diabetes (P trend  = 0.003). Compared with individuals with 4-OHPh in the lowest quartile, the adjusted odds ratio (OR) of diabetes among those in the highest quartile was 2.80 (95% CI = 1.37-5.71). In stratified analysis, the association was more prominent in those who were smokers, overweight (BMI ≥24 kg/m 2 ), with longer working years (≥20 years) and worked at coke oven settings. In addition, high levels of 4-OHPh combined with longer working years or overweight had a joint effect on the risk of diabetes. Our data suggested that elevated 4-OHPh was dose-responsive associated with increased risk of diabetes in the coke oven workers. The risk assessment of diabetes related to occupational PAHs exposure should take working years and BMI into consideration. Copyright © 2017 Elsevier Ltd. All rights reserved.

Metabolism and metabolites of polychlorinated biphenyls (PCBs)

PubMed Central

Grimm, FA; Hu, D; Kania-Korwel, I; Lehmler, HJ; Ludewig, G; Hornbuckle, KC; Duffel, MW; Bergman, A; Robertson, LW

2015-01-01

The metabolism of polychlorinated biphenyls (PCBs) is complex and has an impact on toxicity and thereby assessment of PCB risks. A large number of reactive and stable metabolites are formed in the processes of biotransformation in biota in general and in humans in particular. The aim of this document is to provide an overview of PCB metabolism and to identify metabolites of concern and their occurrence. Emphasis is given to mammalian metabolism of PCBs and their hydroxyl, methylsulfonyl, and sulfated metabolites, especially those that persist in human blood. Potential intracellular targets and health risks are also discussed. PMID:25629923

Clinical observations and risk factors for tinnitus in a Sicilian cohort.

PubMed

Martines, Francesco; Sireci, Federico; Cannizzaro, Emanuele; Costanzo, Roberta; Martines, Enrico; Mucia, Mariana; Plescia, Fulvio; Salvago, Pietro

2015-10-01

The aims of this study were to determine the distribution of risk factors associated with tinnitus analysing their role in the development of tinnitus and the effects of their interaction; to evidence the importance of a suitable and adequate clinical and audiologic assessment to avoid those modifiable risk factors responsible for cochlear dysfunction and tinnitus onset. 46 subjects with tinnitus and 74 controls were studied according to: age, sex, Body Mass Index (BMI), neck circumference, tobacco smoking, feeling fatigue or headache, self reporting snoring, hypertension, diabetes, coronary heart disease, and/or hyperlipidemia, and laboratory finding as lipid profile and levels of reactive oxygen metabolites (d-ROM). Audiological assessment was performed by multi-frequency audiometry (PTA(0.5-16 kHz)) and transient-evoked otoacoustic emissions (TEOAE diagnostic). Univariate analysis was performed to examine the association between determinants and occurrence of tinnitus; Mantel-Haenszel test (G.or) was used to investigate the joint effect of determinants on tinnitus. Tinnitus was more frequent among males with age >50 years; BMI >30 kg/m(2), neck circumference >40 cm, headache, hypertension, hypercholesterolemia resulted significant risk factors for tinnitus (P < 0.0001). Tinnitus group had more comorbidity (P < 0.0001) and worse audiometric thresholds (60.87 Vs 21.62% hearing loss; P < 0.0001) with respect to control group. The interaction between hypertension-BMI ≥ 30 kg/m(2) (G.or = 8.45) and smoking-hypercholesterolemia (G.or = 5.08) increases the risk of tinnitus (P < 0.0001). Our results underline that several factors either individually or jointly contribute to tinnitus onset; a comprehensive knowledge about tinnitus risk factors and associated clinical conditions could contribute to minimizing this disorder.

Heart disease - risk factors

MedlinePlus

Heart disease - prevention; CVD - risk factors; Cardiovascular disease - risk factors; Coronary artery disease - risk factors; CAD - risk ... a certain health condition. Some risk factors for heart disease you cannot change, but some you can. ...

Prediction of future risk of insulin resistance and metabolic syndrome based on Korean boy's metabolite profiling.

PubMed

Lee, AeJin; Jang, Han Byul; Ra, Moonjin; Choi, Youngshim; Lee, Hye-Ja; Park, Ju Yeon; Kang, Jae Heon; Park, Kyung-Hee; Park, Sang Ick; Song, Jihyun

2015-01-01

Childhood obesity is strongly related to future insulin resistance and metabolic syndrome. Thus, identifying early biomarkers of obesity-related diseases based on metabolic profiling is useful to control future metabolic disorders. We compared metabolic profiles between obese and normal-weight children and investigated specific biomarkers of future insulin resistance and metabolic syndrome. In all, 186 plasma metabolites were analysed at baseline and after 2 years in 109 Korean boys (age 10.5±0.4 years) from the Korean Child Obesity Cohort Study using the AbsoluteIDQ™ p180 Kit. We observed that levels of 41 metabolites at baseline and 40 metabolites at follow-up were significantly altered in obese children (p<0.05). Obese children showed significantly higher levels of branched-chain amino acids (BCAAs) and several acylcarnitines and lower levels of acyl-alkyl phosphatidylcholines. Also, baseline BCAAs were significantly positively correlated with both homeostasis model assessment for insulin resistance (HOMA-IR) and continuous metabolic risk score at the 2-year follow-up. In logistic regression analyses with adjustments for degree of obesity at baseline, baseline BCAA concentration, greater than the median value, was identified as a predictor of future risk of insulin resistance and metabolic syndrome. High BCAA concentration could be "early" biomarkers for predicting future metabolic diseases. Copyright © 2014 Asian Oceanian Association for the Study of Obesity. Published by Elsevier Ltd. All rights reserved.

Development of an inhalation unit risk factor for isoprene.

PubMed

Haney, Joseph T; Phillips, Tracie; Sielken, Robert L; Valdez-Flores, Ciriaco

2015-12-01

A unit risk factor (URF) was developed for isoprene based on evaluation of three animal studies with adequate data to perform dose-response modeling (NTP, 1994, 1999; Placke et al., 1996). Ultimately, the URF of 6.2E-08 per ppb (2.2E-08 per μg/m(3)) was based on the 95% lower confidence limit on the effective concentration corresponding to 10% extra risk for liver carcinoma in male B6C3F1 mice after incorporating appropriate adjustment factors for species differences in target tissue metabolite concentrations and inhalation dosimetry. The corresponding lifetime air concentration at the 1 in 100,000 no significant excess risk level is 160 ppb (450 μg/m(3)). This concentration is almost 4400 times lower than the lowest exposure level associated with statistically increased liver carcinoma in B6C3F1 mice in the key study (700 ppm in Placke et al., 1996) and is above typical isoprene breath concentrations reported in the scientific literature. Continuous lifetime environmental exposure to the 1 in 100,000 excess risk level of 160 ppb would be expected to raise the human blood isoprene area under the curve (AUC) less than one-third of the standard deviation of the endogenous mean blood AUC. The mean for ambient air monitoring sites in Texas (2005-2014) is approximately 0.13 ppb. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

A prospective evaluation of serum kynurenine metabolites and risk of pancreatic cancer.

PubMed

Huang, Joyce Y; Butler, Lesley M; Midttun, Øivind; Ulvik, Arve; Wang, Renwei; Jin, Aizhen; Gao, Yu-Tang; Ueland, Per M; Koh, Woon-Puay; Yuan, Jian-Min

2018-01-01

Serum pyridoxal 5'-phosphate (PLP), the active form of vitamin B6, is associated with reduced risk of pancreatic cancer. Data on functional measures of vitamin B6 status and risk of pancreatic cancer is lacking. A nested case-control study involving 187 incident cases of pancreatic cancer and 362 individually matched controls were conducted within two prospective cohorts to evaluate the associations between kynurenine metabolites in pre-diagnostic serum samples and risk of pancreatic cancer. Higher serum concentrations of 3-hydroxyanthranilic acid (HAA) and the HAA:3-hydroxykynurenine (HK) ratio (a measure for in vivo functional status of PLP) were significantly associated with reduced risk of pancreatic cancer. Compared with the lowest tertile, odds ratios (95% confidence intervals) of pancreatic cancer for the highest tertile was 0.62 (0.39, 1.01) for HAA, and 0.59 (0.35-0.98) for the HAA:HK ratio, after adjustment for potential confounders and serum PLP (both Ps for trend<0.05). The kynurenine:tryptophan ratio or neopterin was not significantly associated with pancreatic cancer risk. The inverse association between HAA or the HAA:HK ratio and risk of pancreatic cancer supports the notion that functional status of PLP may be a more important measure than circulating PLP alone for the development of pancreatic cancer.

Risk Factors for Scleroderma

MedlinePlus

... You are here: Home For Patients Risk Factors Risk Factors for Scleroderma The cause of scleroderma is ... what biological factors contribute to scleroderma pathogenesis. Genetic Risk Scleroderma does not tend to run in families ...

Is NAA reduction in normal contralateral cerebral tissue in stroke patients dependent on underlying risk factors?

PubMed

Walker, P M; Ben Salem, D; Giroud, M; Brunotte, F

2006-05-01

This retrospective study investigated the dependence of N-acetyl aspartate (NAA) ratios on risk factors for cerebral vasculopathy such as sex, age, hypertension, diabetes mellitus, carotid stenosis, and dyslipidaemia, which may have affected brain vessels and induced metabolic brain abnormalities prior to stroke. We hypothesise that in stroke patients metabolic alterations in the apparently normal contralateral brain are dependent on the presence or not of such risk factors. Fifty nine patients (31 male, 28 female: 58.8+/-16.1 years old) with cortical middle cerebral artery (MCA) territory infarction were included. Long echo time chemical shift imaging spectroscopy was carried out on a Siemens 1.5 T Magnetom Vision scanner using a multi-voxel PRESS technique. Metabolite ratios (NAA/choline, NAA/creatine, lactate/choline, etc) were studied using uni- and multivariate analyses with respect to common risk factors. The influence of age, stroke lesion size, and time since stroke was studied using a linear regression approach. Age, sex, and hypertension all appeared to individually influence metabolite ratios, although only hypertension was significant after multivariate analysis. In both basal ganglia and periventricular white matter regions in apparently normal contralateral brain, the NAA/choline ratio was significantly lower in hypertensive (1.37+/-0.16 and 1.50+/-0.19, respectively) than in normotensive patients (1.72+/-0.19 and 1.85+/-0.15, respectively). Regarding MCA infarction, contralateral tissue remote from the lesion behaves abnormally in the presence of hypertension, the NAA ratios in hypertensive patients being significantly lower. These data suggest that hypertension may compromise the use of contralateral tissue data as a reference for comparison with ischaemic tissue.

Metabolite profiling in retinoblastoma identifies novel clinicopathological subgroups

PubMed Central

Kohe, Sarah; Brundler, Marie-Anne; Jenkinson, Helen; Parulekar, Manoj; Wilson, Martin; Peet, Andrew C; McConville, Carmel M

2015-01-01

Background: Tumour classification, based on histopathology or molecular pathology, is of value to predict tumour behaviour and to select appropriate treatment. In retinoblastoma, pathology information is not available at diagnosis and only exists for enucleated tumours. Alternative methods of tumour classification, using noninvasive techniques such as magnetic resonance spectroscopy, are urgently required to guide treatment decisions at the time of diagnosis. Methods: High-resolution magic-angle spinning magnetic resonance spectroscopy (HR-MAS MRS) was undertaken on enucleated retinoblastomas. Principal component analysis and cluster analysis of the HR-MAS MRS data was used to identify tumour subgroups. Individual metabolite concentrations were determined and were correlated with histopathological risk factors for each group. Results: Multivariate analysis identified three metabolic subgroups of retinoblastoma, with the most discriminatory metabolites being taurine, hypotaurine, total-choline and creatine. Metabolite concentrations correlated with specific histopathological features: taurine was correlated with differentiation, total-choline and phosphocholine with retrolaminar optic nerve invasion, and total lipids with necrosis. Conclusions: We have demonstrated that a metabolite-based classification of retinoblastoma can be obtained using ex vivo magnetic resonance spectroscopy, and that the subgroups identified correlate with histopathological features. This result justifies future studies to validate the clinical relevance of these subgroups and highlights the potential of in vivo MRS as a noninvasive diagnostic tool for retinoblastoma patient stratification. PMID:26348444

Metabolite changes in risk of type 2 diabetes mellitus in cohort studies: A systematic review and meta-analysis.

PubMed

Park, Jeong-Eun; Lim, Hye Rin; Kim, Jun Woo; Shin, Kwang-Hee

2018-06-01

Fasting plasma glucose, oral glucose tolerance test, and glycated hemoglobin are diagnostic markers for type 2 diabetes mellitus (T2DM). However, it is necessary to detect physiological changes in T2DM rapidly and stratify diabetic stage using other biomarkers. We performed a systematic review and meta-analysis to contribute to the development of objective and sensitive diagnostic indicators by integrating metabolite biomarkers derived from large-scale cohort studies. We searched for metabolomics studies of T2DM cohort in PubMed, Scopus, and Web of Science for studies published within the last 10 years from January 2008 to February 2017. The concentrations of metabolites and odds ratios (ORs) were integrated and risk ratio (RR) values were estimated to distinguish subjects with T2DM and normal participants. Fourteen cohort studies were investigated in this meta-analysis. There were 4592 patients in the case group and 11,492 participants in the control group. We noted a 1.89-, 1.63-, and 1.87-fold higher risk of T2DM associated with leucine (RR 1.89 [95% CI 1.57-2.29]), alanine (RR 1.63 [95% CI 1.48-1.79]), and oleic acid (RR 1.87 [95% CI 1.62-2.17]), respectively. Lysophosphatidylcholine C18:0 (RR 0.80 [95% CI 0.72-0.90]) and creatinine (RR 0.63 [95% CI 0.53-0.74]) were associated with 20% and 37% decreased T2DM risks, respectively. Most amino acids in patients were positively related to diabetes, while creatinine and some lysophosphatidylcholines showed a negative relationship. This suggests that diabetic risk prediction using metabolites that sensitively reflect changes in the body will improve individual diagnosis and personalize medicine. Copyright © 2018 Elsevier B.V. All rights reserved.

Residue behaviors and risk assessment of flonicamid and its metabolites in the cabbage field ecosystem.

PubMed

Wang, Shanshan; Jin, Fen; Cao, Xiaolin; Shao, Yong; Wang, Jian; She, Yongxin; Qi, Yan; Zhang, Chao; Li, Hui; Jin, Maojun; Wang, Jing; Shao, Hua; Zheng, Lufei

2018-06-13

Flonicamid, a novel selective systemic pesticide, can effectively control a broad range of insect pests. However, the dissipation behaviors and the terminal residues of flonicamid and its metabolites in some crops and soils remain unclear. Herein, an easy, sensitive and reliable method using a modified QuEChERS extraction coupled with LC-MS/MS for the simultaneous analysis of flonicamid and its metabolites in cabbage and soil was developed. Based on this method, the dissipation behaviors of flonicamid and its metabolites as well as their persistence in cabbage and soil during harvest were investigated. Flonicamid degraded rapidly, and the half-lives of flonicamid only and total residues (the sum of flonicamid and its metabolites) were 1.49-4.59 and 1.97-4.99 days in cabbage, and 2.12-7.97 and 2.04-7.62 days in soil, respectively. When 50% flonicamid WG was sprayed once or twice at the recommended dose and 1.5-fold the recommended dose, the highest residues of total flonicamid in cabbage and soil from different pre-harvest intervals (3, 7 and 14 days) were 0.070 and 0.054 mg kg -1 , respectively. The risk quotient (RQ) of flonicamid based on the consumption data from China was below 16.84%, indicating that the use of flonicamid is non-hazardous to humans. These results could not only guide the safe and responsible use of flonicamid in agriculture but also help the Chinese government establish the maximum residue level (MRL) for flonicamid in cabbage. Copyright © 2018 Elsevier Inc. All rights reserved.

Modifiable risk factors for schizophrenia and autism--shared risk factors impacting on brain development.

PubMed

Hamlyn, Jess; Duhig, Michael; McGrath, John; Scott, James

2013-05-01

Schizophrenia and autism are two poorly understood clinical syndromes that differ in age of onset and clinical profile. However, recent genetic and epidemiological research suggests that these two neurodevelopmental disorders share certain risk factors. The aims of this review are to describe modifiable risk factors that have been identified in both disorders, and, where available, collate salient systematic reviews and meta-analyses that have examined shared risk factors. Based on searches of Medline, Embase and PsycINFO, inspection of review articles and expert opinion, we first compiled a set of candidate modifiable risk factors associated with autism. Where available, we next collated systematic-reviews (with or without meta-analyses) related to modifiable risk factors associated with both autism and schizophrenia. We identified three modifiable risk factors that have been examined in systematic reviews for both autism and schizophrenia. Advanced paternal age was reported as a risk factor for schizophrenia in a single meta-analysis and as a risk factor in two meta-analyses for autism. With respect to pregnancy and birth complications, for autism one meta-analysis identified maternal diabetes and bleeding during pregnancy as risks factors for autism whilst a meta-analysis of eight studies identified obstetric complications as a risk factor for schizophrenia. Migrant status was identified as a risk factor for both autism and schizophrenia. Two separate meta-analyses were identified for each disorder. Despite distinct clinical phenotypes, the evidence suggests that at least some non-genetic risk factors are shared between these two syndromes. In particular, exposure to drugs, nutritional excesses or deficiencies and infectious agents lend themselves to public health interventions. Studies are now needed to quantify any increase in risk of either autism or schizophrenia that is associated with these modifiable environmental factors. Copyright © 2012 Elsevier Inc

Influence of abiotic stress signals on secondary metabolites in plants

PubMed Central

Ramakrishna, Akula; Ravishankar, Gokare Aswathanarayana

2011-01-01

Plant secondary metabolites are unique sources for pharmaceuticals, food additives, flavors, and industrially important biochemicals. Accumulation of such metabolites often occurs in plants subjected to stresses including various elicitors or signal molecules. Secondary metabolites play a major role in the adaptation of plants to the environment and in overcoming stress conditions. Environmental factors viz. temperature, humidity, light intensity, the supply of water, minerals, and CO2 influence the growth of a plant and secondary metabolite production. Drought, high salinity, and freezing temperatures are environmental conditions that cause adverse effects on the growth of plants and the productivity of crops. Plant cell culture technologies have been effective tools for both studying and producing plant secondary metabolites under in vitro conditions and for plant improvement. This brief review summarizes the influence of different abiotic factors include salt, drought, light, heavy metals, frost etc. on secondary metabolites in plants. The focus of the present review is the influence of abiotic factors on secondary metabolite production and some of important plant pharmaceuticals. Also, we describe the results of in vitro cultures and production of some important secondary metabolites obtained in our laboratory. PMID:22041989

Fracture Risk and Risk Factors for Osteoporosis.

PubMed

Schürer, Christian; Wallaschofski, Henri; Nauck, Matthias; Völzke, Henry; Schober, Hans-Christof; Hannemann, Anke

2015-05-25

As the population ages, diseases of the elderly are becoming more common, including osteoporosis. Ways to assess the risk of fracture and the distribution and effects of known risk factors for osteoporosis will be important in planning for future healthcare needs, as well as in the development of preventive strategies. The study population included 6029 men and women aged 20-90 who underwent examination in the second follow-up wave of the Study of Health in Pomerania (SHIP-2) or in the basal SHIP-Trend Study. The risk of fracture was estimated on the basis of quantitative ultrasonography of the calcaneus. Prior fractures and risk factors for osteoporosis were ascertained in standardized interviews. 4.6% of the male subjects and 10.6% of the female subjects were judged to have an elevated risk of fracture. The corresponding percentages among subjects over age 65 were 8.8% for men and 28.2% for women. Even among subjects under age 55, risk factors for osteoporosis were associated with lower bone stiffness: the mean stiffness index was 103/98 (men/women) without risk factors, 99/96 with one risk factor, and 93/95 with more than one risk factor. Logistic regression analysis yielded an odds ratio of 1.89 (95% confidence interval: 1.44-2.50; p<0.01) for prevalent fractures among subjects aged 75 and older compared to subjects under age 55. The data indicate a high prevalence of osteoporosis from age 65 onward. These findings are consistent with those of other studies from Germany and across Europe. Younger men and women should already begin taking steps to counteract modifiable risk factors.

Microbiota metabolites: Pivotal players of cardiovascular damage in chronic kidney disease.

PubMed

Cosola, Carmela; Rocchetti, Maria Teresa; Cupisti, Adamasco; Gesualdo, Loreto

2018-04-01

In chronic kidney disease (CKD), cardiovascular (CV) damage is present in parallel which leads to an increased risk of CV disease. Both traditional and non-traditional risk factors contribute to CV damage in CKD. The systemic role of the microbiota as a central player in the pathophysiology of many organs is progressively emerging in the literature: the microbiota is indeed involved in a complex, bi-directional network between many organs, including the kidney and heart connection, although many of these relationships still need to be elucidated through in-depth mechanistic studies. The aim of this review is to provide evidence that microbiota metabolites influence non-traditional risk factors, such as inflammation and endothelial dysfunction in CKD-associated CV damage. Here, we report our current understanding and hypotheses on the gut-kidney and gut-heart axes and provide details on the potential mechanisms mediated by microbial metabolites. More specifically, we summarize some novel hypotheses linking the microbiota to blood pressure regulation and hypertension. We also emphasise the idea that the nutritional management of CKD should be redesigned and include the new findings from research on the intrinsic plasticity of the microbiota and its metabolites in response to food intake. The need is felt to integrate the classical salt and protein restriction approach for CKD patients with foods that enhance intestinal wellness. Finally, we discuss the new perspectives, especially the importance of taking care of the microbiota in order to prevent the risk of developing CKD and hypertension, as well as the still not tested but very promising CKD innovative treatments, such as postbiotic supplementation and bacteriotherapy. This interesting area of research offers potential complementary approaches to the management of CKD and CV damage assuming that the causal mechanisms underlying the gut-kidney and gut-heart axes are clarified. This will pave the way to the design

Antifungal activity of microbial secondary metabolites.

PubMed

Coleman, Jeffrey J; Ghosh, Suman; Okoli, Ikechukwu; Mylonakis, Eleftherios

2011-01-01

Secondary metabolites are well known for their ability to impede other microorganisms. Reanalysis of a screen of natural products using the Caenorhabditis elegans-Candida albicans infection model identified twelve microbial secondary metabolites capable of conferring an increase in survival to infected nematodes. In this screen, the two compound treatments conferring the highest survival rates were members of the epipolythiodioxopiperazine (ETP) family of fungal secondary metabolites, acetylgliotoxin and a derivative of hyalodendrin. The abundance of fungal secondary metabolites indentified in this screen prompted further studies investigating the interaction between opportunistic pathogenic fungi and Aspergillus fumigatus, because of the ability of the fungus to produce a plethora of secondary metabolites, including the well studied ETP gliotoxin. We found that cell-free supernatant of A. fumigatus was able to inhibit the growth of Candida albicans through the production of a secreted product. Comparative studies between a wild-type and an A. fumigatus ΔgliP strain unable to synthesize gliotoxin demonstrate that this secondary metabolite is the major factor responsible for the inhibition. Although toxic to organisms, gliotoxin conferred an increase in survival to C. albicans-infected C. elegans in a dose dependent manner. As A. fumigatus produces gliotoxin in vivo, we propose that in addition to being a virulence factor, gliotoxin may also provide an advantage to A. fumigatus when infecting a host that harbors other opportunistic fungi.

Antifungal Activity of Microbial Secondary Metabolites

PubMed Central

Okoli, Ikechukwu; Mylonakis, Eleftherios

2011-01-01

Secondary metabolites are well known for their ability to impede other microorganisms. Reanalysis of a screen of natural products using the Caenorhabditis elegans-Candida albicans infection model identified twelve microbial secondary metabolites capable of conferring an increase in survival to infected nematodes. In this screen, the two compound treatments conferring the highest survival rates were members of the epipolythiodioxopiperazine (ETP) family of fungal secondary metabolites, acetylgliotoxin and a derivative of hyalodendrin. The abundance of fungal secondary metabolites indentified in this screen prompted further studies investigating the interaction between opportunistic pathogenic fungi and Aspergillus fumigatus, because of the ability of the fungus to produce a plethora of secondary metabolites, including the well studied ETP gliotoxin. We found that cell-free supernatant of A. fumigatus was able to inhibit the growth of Candida albicans through the production of a secreted product. Comparative studies between a wild-type and an A. fumigatus ΔgliP strain unable to synthesize gliotoxin demonstrate that this secondary metabolite is the major factor responsible for the inhibition. Although toxic to organisms, gliotoxin conferred an increase in survival to C. albicans-infected C. elegans in a dose dependent manner. As A. fumigatus produces gliotoxin in vivo, we propose that in addition to being a virulence factor, gliotoxin may also provide an advantage to A. fumigatus when infecting a host that harbors other opportunistic fungi. PMID:21966496

Plasma choline metabolites and colorectal cancer risk in the Women's Health Initiative Observational Study.

PubMed

Bae, Sajin; Ulrich, Cornelia M; Neuhouser, Marian L; Malysheva, Olga; Bailey, Lynn B; Xiao, Liren; Brown, Elissa C; Cushing-Haugen, Kara L; Zheng, Yingye; Cheng, Ting-Yuan David; Miller, Joshua W; Green, Ralph; Lane, Dorothy S; Beresford, Shirley A A; Caudill, Marie A

2014-12-15

Few studies have examined associations between plasma choline metabolites and risk of colorectal cancer. Therefore, we investigated associations between plasma biomarkers of choline metabolism [choline, betaine, dimethylglycine, and trimethylamine N-oxide (TMAO)] and colorectal cancer risk among postmenopausal women in a case-control study nested within the Women's Health Initiative Observational Study. We selected 835 matched case-control pairs, and cases were further stratified by tumor site (proximal, distal, or rectal) and stage (local/regional or metastatic). Colorectal cancer was assessed by self-report and confirmed by medical records over the mean of 5.2 years of follow-up. Baseline plasma choline metabolites were measured by LC/MS-MS. In multivariable-adjusted conditional logistic regression models, plasma choline tended to be positively associated with rectal cancer risk [OR (95% confidence interval, CI)(highest vs. lowest quartile) = 2.44 (0.93-6.40); P trend = 0.08], whereas plasma betaine was inversely associated with colorectal cancer overall [0.68 (0.47-0.99); P trend = 0.01] and with local/regional tumors [0.64 (0.42-0.99); P trend = 0.009]. Notably, the plasma betaine:choline ratio was inversely associated with colorectal cancer overall [0.56 (0.39-0.82); P trend = 0.004] as well as with proximal [0.66 (0.41-1.06); P trend = 0.049], rectal [0.27 (0.10-0.78); P trend = 0.02], and local/regional [0.50 (0.33-0.76); P trend = 0.001] tumors. Finally, plasma TMAO, an oxidative derivative of choline produced by intestinal bacteria, was positively associated with rectal cancer [3.38 (1.25-9.16); P trend = 0.02] and with overall colorectal cancer risk among women with lower (vs. higher) plasma vitamin B12 levels (P interaction = 0.003). Collectively, these data suggest that alterations in choline metabolism, which may arise early in disease development, may be associated with higher risk of colorectal cancer. The positive association between plasma TMAO and

Aquatic toxicity of the macrolide antibiotic clarithromycin and its metabolites.

PubMed

Baumann, Michaela; Weiss, Klaus; Maletzki, Dirk; Schüssler, Walter; Schudoma, Dieter; Kopf, Willi; Kühnen, Ute

2015-02-01

The human macrolide antibiotic clarithromycin is widespread in surface waters. Our study shows that its major metabolite 14-hydroxy(R)-clarithromycin is found in surface waters in comparable amounts. This metabolite is known to be pharmacologically active. Additionally, clarithromycin is partly metabolised to N-desmethyl-clarithromycin, which has no antimicrobial activity. For clarithromycin, some ecotoxicological studies on aquatic organisms have been published. However, many of them are not conform with the scientific principles as given in the "Technical guidance for deriving environmental quality standards" (TGD-EQS), because numerous studies were poorly documented and the methods did not contain analytical measurements confirming that the exposure concentrations were in the range of ± 20% of the nominal concentrations. Ecotoxicological effects of clarithromycin and its two metabolites on the zebrafish Danio rerio (embryo test), the microcrustacean Daphnia magna, the aquatic monocotyledonous macrophyte Lemna minor, the freshwater green alga Desmodesmus subspicatus (Chlorophyta) and the cyanobacterium Anabaena flosaquae were investigated in compliance with the TGD-EQS. Environmental risk assessment was performed using ErC10 values of Anabaena, the species most sensitive to clarithromycin and 14-hydroxy(R)-clarithromycin in our testing. Based oncomparable toxicity and similar concentrations of clarithromycin and its active metabolite 14-hydroxy(R)-clarithromycin in surface waters, an additional multiplication factor of 2 to the assessment factor of 10 on the ErC10 of clarithromycin should be used. Consequently, a freshwater quality standard of 0.130 μg L(-1) is proposed for clarithromycin as the "lead substance". Taking this additional multiplication factor of 2 into account, single monitoring of clarithromycin may be sufficient, in order to reduce the number of substances listed for routine monitoring programs. Copyright © 2014 Elsevier Ltd. All rights

From genomics to metabolomics, moving toward an integrated strategy for the discovery of fungal secondary metabolites.

PubMed

Hautbergue, T; Jamin, E L; Debrauwer, L; Puel, O; Oswald, I P

2018-02-21

Fungal secondary metabolites are defined by bioactive properties that ensure adaptation of the fungus to its environment. Although some of these natural products are promising sources of new lead compounds especially for the pharmaceutical industry, others pose risks to human and animal health. The identification of secondary metabolites is critical to assessing both the utility and risks of these compounds. Since fungi present biological specificities different from other microorganisms, this review covers the different strategies specifically used in fungal studies to perform this critical identification. Strategies focused on the direct detection of the secondary metabolites are firstly reported. Particularly, advances in high-throughput untargeted metabolomics have led to the generation of large datasets whose exploitation and interpretation generally require bioinformatics tools. Then, the genome-based methods used to study the entire fungal metabolic potential are reported. Transcriptomic and proteomic tools used in the discovery of fungal secondary metabolites are presented as links between genomic methods and metabolomic experiments. Finally, the influence of the culture environment on the synthesis of secondary metabolites by fungi is highlighted as a major factor to consider in research on fungal secondary metabolites. Through this review, we seek to emphasize that the discovery of natural products should integrate all of these valuable tools. Attention is also drawn to emerging technologies that will certainly revolutionize fungal research and to the use of computational tools that are necessary but whose results should be interpreted carefully.

Risk behaviours among early adolescents: risk and protective factors.

PubMed

Wang, Ruey-Hsia; Hsu, Hsiu-Yueh; Lin, Shu-Yuan; Cheng, Chung-Ping; Lee, Shu-Li

2010-02-01

This paper is a report of a study conducted to examine the influence of risk/protective factors on risk behaviours of early adolescents and whether protective factors moderate their impact. An understanding of how risk and protective factors operate to influence risk behaviours of early adolescents will better prepare nurses to perform interventions appropriately to reduce risk behaviours of early adolescents. A cross-sectional study was carried out, based on a sample of public junior high schools (from 7th to 9th grades) in one city and one county in Taiwan. An anonymous questionnaire designed to measure five risk factors, six protective factors and risk behaviours was administered from October 2006 to March 2007. Data from 878 students were used for the present analysis. Pearson's correlations, anova with random effect models, and generalized linear models were used to analyse the statistically significant explanatory variables for risk behaviours. Gender, perceived father's risk behaviour, perceived mother's risk behaviour, health self-efficacy, interaction of health self-efficacy and perceived peers' risk behaviour, and interaction of emotional regulation and perceived peers' risk behaviour were statistically significant explanatory variables of risk behaviours. Health self-efficacy and emotional regulation moderated the negative effects of peers' perceived risk behaviour on risk behaviours. All protective factors were negative statistically correlated with risk behaviours, and all risk factors positively statistically correlated with risk behaviours. Male adolescents should be considered an at-risk group for risk behaviour intervention. Nurses could provide early adolescents with training regarding health self-efficacy improvement, self-esteem enhancement, emotional regulation skills to reduce their risk behaviours.

Risk factors for stress fractures.

PubMed

Bennell, K; Matheson, G; Meeuwisse, W; Brukner, P

1999-08-01

Preventing stress fractures requires knowledge of the risk factors that predispose to this injury. The aetiology of stress fractures is multifactorial, but methodological limitations and expediency often lead to research study designs that evaluate individual risk factors. Intrinsic risk factors include mechanical factors such as bone density, skeletal alignment and body size and composition, physiological factors such as bone turnover rate, flexibility, and muscular strength and endurance, as well as hormonal and nutritional factors. Extrinsic risk factors include mechanical factors such as surface, footwear and external loading as well as physical training parameters. Psychological traits may also play a role in increasing stress fracture risk. Equally important to these types of analyses of individual risk factors is the integration of information to produce a composite picture of risk. The purpose of this paper is to critically appraise the existing literature by evaluating study design and quality, in order to provide a current synopsis of the known scientific information related to stress fracture risk factors. The literature is not fully complete with well conducted studies on this topic, but a great deal of information has accumulated over the past 20 years. Although stress fractures result from repeated loading, the exact contribution of training factors (volume, intensity, surface) has not been clearly established. From what we do know, menstrual disturbances, caloric restriction, lower bone density, muscle weakness and leg length differences are risk factors for stress fracture. Other time-honoured risk factors such as lower extremity alignment have not been shown to be causative even though anecdotal evidence indicates they are likely to play an important role in stress fracture pathogenesis.

Semen quality and insulin-like factor 3: Associations with urinary and seminal levels of phthalate metabolites in adult males.

PubMed

Chang, Wei-Hsiang; Wu, Meng-Hsing; Pan, Hsien-An; Guo, Pao-Lin; Lee, Ching-Chang

2017-04-01

Certain phthalates have adverse effects on male reproductive functions in animals, and potentially affect human testicular function and spermatogenesis, but little is known about the active mechanisms. We measured the urinary and seminal phthalate metabolites and explored their associations on insulin-like factor 3 (INSL3) and semen quality. Urine, blood, and semen samples were collected from the male partners of subfertile (n = 253) and fertile (n = 37) couples in a reproductive center in southern Taiwan. INSL3, reproductive hormones, semen-quality, and 11 phthalate metabolites in urine and semen were measured. There were significant correlations in the distribution pattern of metabolites, such as the relative contribution of low or high molecular weight phthalate metabolites. The significantly monotonic trends in semen volume, sperm concentration and motility were associated with increasing quartiles of INSL3 (all p-trend < 0.001). In adjusted regression models, increases in urinary phthalate metabolites levels were adversely associated with sperm concentration (monobenzyl phthalate [MBzP], mono-2-ethylhexyl phthalate [MEHP] and MEHP%), motility (MBzP and MEHP) and INSL3 (MBzP, MEHP and MEHP%) (all p < 0.01). Higher seminal phthalate metabolite levels were associated with decreases in sperm concentration (MEHP and mono-2-ethyl-5-hydroxyhexyl phthalate), motility (mono-ethyl phthalate [MEP] and di-(2-ethylhexyl) phthalate [DEHP] metabolites), normal morphology (MEP), and INSL3 (monomethyl phthalate and MEP) (all p < 0.05). Our data suggest that INSL3 secretion, reproductive hormone balance, and sperm production and quality might be simultaneously adversely affected for individuals excreting increasing levels of phthalates metabolites (especially di-ethyl phthalate, butylbenzyl phthalate, and DEHP) in urine and semen samples. Copyright © 2017 Elsevier Ltd. All rights reserved.

Flavonoid metabolites reduce tumor necrosis factor-α secretion to a greater extent than their precursor compounds in human THP-1 monocytes.

PubMed

di Gesso, Jessica L; Kerr, Jason S; Zhang, Qingzhi; Raheem, Saki; Yalamanchili, Sai Krishna; O'Hagan, David; Kay, Colin D; O'Connell, Maria A

2015-06-01

Flavonoids are generally studied in vitro, in isolation, and as unmetabolized precursor structures. However, in the habitual diet, multiple flavonoids are consumed together and found present in the circulation as complex mixtures of metabolites. Using a unique study design, we investigated the potential for singular or additive anti-inflammatory effects of flavonoid metabolites relative to their precursor structures. Six flavonoids, 14 flavonoid metabolites, and 29 combinations of flavonoids and their metabolites (0.1-10 μM) were screened for their ability to reduce LPS-induced tumor necrosis factor-α (TNF-α) secretion in THP-1 monocytes. One micromolar peonidin-3-glucoside, cyanidin-3-glucoside, and the metabolites isovanillic acid (IVA), IVA-glucuronide, vanillic acid-glucuronide, protocatechuic acid-3-sulfate, and benzoic acid-sulfate significantly reduced TNF-α secretion when in isolation, while there was no effect on TNF-α mRNA expression. Four combinations of metabolites that included 4-hydroxybenzoic acid (4HBA) and/or protocatechuic acid also significantly reduced TNF-α secretion to a greater extent than the precursors or metabolites alone. The effects on LPS-induced IL-1β and IL-10 secretion and mRNA expression were also examined. 4HBA significantly reduced IL-1β secretion but none of the flavonoids or metabolites significantly modified IL-10 secretion. This study provides novel evidence suggesting flavonoid bioactivity results from cumulative or additive effects of circulating metabolites. © 2015 The Authors. Molecular Nutrition & Food Research published by Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Associations Between the Serum Metabolome and All-Cause Mortality Among African Americans in the Atherosclerosis Risk in Communities (ARIC) Study

PubMed Central

Yu, Bing; Heiss, Gerardo; Alexander, Danny; Grams, Morgan E.; Boerwinkle, Eric

2016-01-01

Early and accurate identification of people at high risk of premature death may assist in the targeting of preventive therapies in order to improve overall health. To identify novel biomarkers for all-cause mortality, we performed untargeted metabolomics in the Atherosclerosis Risk in Communities (ARIC) Study. We included 1,887 eligible ARIC African Americans, and 671 deaths occurred during a median follow-up period of 22.5 years (1987–2011). Chromatography and mass spectroscopy identified and quantitated 204 serum metabolites, and Cox proportional hazards models were used to analyze the longitudinal associations with all-cause and cardiovascular mortality. Nine metabolites, including cotinine, mannose, glycocholate, pregnendiol disulfate, α-hydroxyisovalerate, N-acetylalanine, andro-steroid monosulfate 2, uridine, and γ-glutamyl-leucine, showed independent associations with all-cause mortality, with an average risk change of 18% per standard-deviation increase in metabolite level (P < 1.23 × 10−4). A metabolite risk score, created on the basis of the weighted levels of the identified metabolites, improved the predictive ability of all-cause mortality over traditional risk factors (bias-corrected Harrell's C statistic 0.752 vs. 0.730). Mannose and glycocholate were associated with cardiovascular mortality (P < 1.23 × 10−4), but predictive ability was not improved beyond the traditional risk factors. This metabolomic analysis revealed potential novel biomarkers for all-cause mortality beyond the traditional risk factors. PMID:26956554

Salivary Gland Cancer: Risk Factors

MedlinePlus

... Cancer: Risk Factors Request Permissions Salivary Gland Cancer: Risk Factors Approved by the Cancer.Net Editorial Board , ... To see other pages, use the menu. A risk factor is anything that increases a person’s chance ...

Metabolic Networks and Metabolites Underlie Associations Between Maternal Glucose During Pregnancy and Newborn Size at Birth

PubMed Central

Bain, James R.; Reisetter, Anna C.; Muehlbauer, Michael J.; Nodzenski, Michael; Stevens, Robert D.; Ilkayeva, Olga; Lowe, Lynn P.; Metzger, Boyd E.; Newgard, Christopher B.; Lowe, William L.

2016-01-01

Maternal metabolites and metabolic networks underlying associations between maternal glucose during pregnancy and newborn birth weight and adiposity demand fuller characterization. We performed targeted and nontargeted gas chromatography/mass spectrometry metabolomics on maternal serum collected at fasting and 1 h following glucose beverage consumption during an oral glucose tolerance test (OGTT) for 400 northern European mothers at ∼28 weeks' gestation in the Hyperglycemia and Adverse Pregnancy Outcome Study. Amino acids, fatty acids, acylcarnitines, and products of lipid metabolism decreased and triglycerides increased during the OGTT. Analyses of individual metabolites indicated limited maternal glucose associations at fasting, but broader associations, including amino acids, fatty acids, carbohydrates, and lipids, were found at 1 h. Network analyses modeling metabolite correlations provided context for individual metabolite associations and elucidated collective associations of multiple classes of metabolic fuels with newborn size and adiposity, including acylcarnitines, fatty acids, carbohydrates, and organic acids. Random forest analyses indicated an improved ability to predict newborn size outcomes by using maternal metabolomics data beyond traditional risk factors, including maternal glucose. Broad-scale association of fuel metabolites with maternal glucose is evident during pregnancy, with unique maternal metabolites potentially contributing specifically to newborn birth weight and adiposity. PMID:27207545

Plasma choline metabolites and colorectal cancer risk in the Women’s Health Initiative Observational Study

PubMed Central

Bae, Sajin; Ulrich, Cornelia M.; Neuhouser, Marian L.; Malysheva, Olga; Bailey, Lynn B.; Xiao, Liren; Brown, Elissa C.; Cushing-Haugen, Kara L.; Zheng, Yingye; Cheng, Ting-Yuan David; Miller, Joshua W.; Green, Ralph; Lane, Dorothy S.; Beresford, Shirley A. A.; Caudill, Marie A.

2014-01-01

Few studies have examined associations between plasma choline metabolites and risk of colorectal cancer (CRC). Therefore, we investigated associations between plasma biomarkers of choline metabolism [choline, betaine, dimethylglycine and trimethylamine N-oxide (TMAO)] and CRC risk among postmenopausal women in a case-control study nested within the Women’s Health Initiative Observational Study. We selected 835 matched case-control pairs, and cases were further stratified by tumor site (proximal, distal, or rectal) and stage (local/regional or metastatic). CRC was assessed by self-report and confirmed by medical records over the mean 5.2y of follow-up. Baseline plasma choline metabolites were measured by liquid chromatography-tandem mass spectrometry. In multivariable-adjusted conditional logistic regression models, plasma choline tended to be positively associated with rectal cancer risk [OR (95% CI)highest vs. lowest quartile=2.44 (0.93–6.40);P-trend=0.08], while plasma betaine was inversely associated with CRC overall [0.68 (0.47–0.99);P-trend=0.01] and with local/regional tumors [0.64 (0.42–0.99);P-trend=0.009]. Notably, the plasma betaine:choline ratio was inversely associated with CRC overall [0.56 (0.39–0.82);P-trend=0.004] as well as with proximal [0.66 (0.41–1.06);P-trend=0.049], rectal [0.27 (0.10–0.78);P-trend=0.02] and local/regional [0.50 (0.33–0.76);P-trend=0.001] tumors. Finally, plasma TMAO, an oxidative derivative of choline produced by intestinal bacteria, was positively associated with rectal cancer [3.38 (1.25–9.16);P-trend=0.02] and with overall CRC risk among women with lower (vs. higher) plasma vitamin B12 levels (P-interaction=0.003). Collectively, these data suggest that alterations in choline metabolism, which may arise early in disease development, may be associated with higher risk of CRC. The positive association between plasma TMAO and CRC risk is consistent with an involvement of the gut microbiome in CRC pathogenesis

Analysis, occurrence, fate and risks of proton pump inhibitors, their metabolites and transformation products in aquatic environment: A review.

PubMed

Kosma, Christina I; Lambropoulou, Dimitra A; Albanis, Triantafyllos A

2016-11-01

Proton pump inhibitors (PPIs) which include omeprazole, esomeprazole, lansoprazole, pantoprazole and rabeprazole, are extensively used for the relief of gastro-intestinal disorders. Despite their high worldwide consumption, PPIs are extensively metabolized in human bodies and therefore are not regularly detected in monitoring studies. Very recently, however, it has been shown that some omeprazole metabolites may enter and are likely to persist in aquatic environment. Hence, to fully assess the environmental exposures and risks associated with PPIs, it is important to better understand and evaluate the fate and behavior not only of the parent compound but also of their metabolites and their transformation products arising from biotic and abiotic processes (hydrolysis, photodegradation, biodegradation etc.) in the environment. In this light, the purpose of this review is to summarize the present state of knowledge on the introduction and behavior of these chemicals in natural and engineering systems and highlight research needs and gaps. It draws attention to their transformation, the increase contamination by their metabolites/TPs in different environmental matrices and their potential adverse effects in the environment. Furthermore, existing research on analytical developments with respect to sample treatment, separation and detection of PPIs and their metabolites/TPs is provided. Copyright © 2016 Elsevier B.V. All rights reserved.

Vitamin C with metabolites reduce oxalate levels compared to ascorbic acid: a preliminary and novel clinical urologic finding.

PubMed

Moyad, Mark A; Combs, Maile A; Crowley, David C; Baisley, Joshua E; Sharma, Prachi; Vrablic, Angelica S; Evans, Malkanthi

2009-01-01

The incidence and prevalence of kidney stones are notable and are projected to increase over the next decade. Risk factors for kidney stones abound, but a prominent risk factor is hyperoxaluria, which has numerous etiologies, including vitamin C (ascorbic acid) dietary supplement intake. This randomized, double-blind, crossover study examined the effects of two different vitamin C formulations and found that vitamin C with metabolites (Ester-C) significantly reduced urine oxalate levels compared to ascorbic acid. This is a potential novel finding that requires further clinical evaluation.

Metabolomic analysis of 92 pulmonary embolism patients from a nested case-control study identifies metabolites associated with adverse clinical outcomes.

PubMed

Zeleznik, O A; Poole, E M; Lindstrom, S; Kraft, P; Van Hylckama Vlieg, A; Lasky-Su, J A; Harrington, L B; Hagan, K; Kim, J; Parry, B A; Giordano, N; Kabrhel, C

2018-03-01

Essentials Risk-stratification often fails to predict clinical deterioration in pulmonary embolism (PE). First-ever high-throughput metabolomics analysis of risk-stratified PE patients. Changes in circulating metabolites reflect a compromised energy metabolism in PE. Metabolites play a key role in the pathophysiology and risk stratification of PE. Background Patients with acute pulmonary embolism (PE) exhibit wide variation in clinical presentation and outcomes. Our understanding of the pathophysiologic mechanisms differentiating low-risk and high-risk PE is limited, so current risk-stratification efforts often fail to predict clinical deterioration and are insufficient to guide management. Objectives To improve our understanding of the physiology differentiating low-risk from high-risk PE, we conducted the first-ever high-throughput metabolomics analysis (843 named metabolites) comparing PE patients across risk strata within a nested case-control study. Patients/methods We enrolled 92 patients diagnosed with acute PE and collected plasma within 24 h of PE diagnosis. We used linear regression and pathway analysis to identify metabolites and pathways associated with PE risk-strata. Results When we compared 46 low-risk with 46 intermediate/high-risk PEs, 50 metabolites were significantly different after multiple testing correction. These metabolites were enriched in the following pathways: tricarboxylic acid (TCA) cycle, fatty acid metabolism (acyl carnitine) and purine metabolism, (hypo)xanthine/inosine containing. Additionally, energy, nucleotide and amino acid pathways were downregulated in intermediate/high-risk PE patients. When we compared 28 intermediate-risk with 18 high-risk PE patients, 41 metabolites differed at a nominal P-value level. These metabolites were enriched in fatty acid metabolism (acyl cholines), and hemoglobin and porphyrin metabolism. Conclusion Our results suggest that high-throughput metabolomics can provide insight into the

Risk Factor Assessment Branch (RFAB)

Cancer.gov

The Risk Factor Assessment Branch (RFAB) focuses on the development, evaluation, and dissemination of high-quality risk factor metrics, methods, tools, technologies, and resources for use across the cancer research continuum, and the assessment of cancer-related risk factors in the population.

Development of a Physiologically-Based Pharmacokinetic Model of Trichloroethylene and Its Metabolites for Use in Risk Assessment

DTIC Science & Technology

2004-09-01

and free trichloroethanol. Toxicol. App!. Pharmacol., 152, 339-359, 1998. 10. Stenner , R.D., Merdink, J.L., Fisher, J.W., and Bull, R...M.V., Stevens, D.K., Stenner , R.D., Bonate, P.L., Tuman, D., and Bull, R.J., Factors affecting species differences in the kinetics of metabolites of

Cardiovascular risk factors and dementia.

PubMed

Fillit, Howard; Nash, David T; Rundek, Tatjana; Zuckerman, Andrea

2008-06-01

Dementias, such as Alzheimer's disease (AD) and vascular dementia, are disorders of aging populations and represent a significant economic burden. Evidence is accumulating to suggest that cardiovascular disease (CVD) risk factors may be instrumental in the development of dementia. The goal of this review was to discuss the relationship between specific CVD risk factors and dementia and how current treatment strategies for dementia should focus on reducing CVD risks. We conducted a review of the literature for the simultaneous presence of 2 major topics, cardiovascular risk factors and dementia (eg, AD). Special emphasis was placed on clinical outcome studies examining the effects of treatments of pharmacologically modifiable CVD risk factors on dementia and cognitive impairment. Lifestyle risk factors for CVD, such as obesity, lack of exercise, smoking, and certain psychosocial factors, have been associated with an increased risk of cognitive decline and dementia. Some evidence suggests that effectively managing these factors may prevent cognitive decline/dementia. Randomized, placebo-controlled trials of antihypertensive medications have found that such therapy may reduce the risk of cognitive decline, and limited data suggest a benefit for patients with AD. Some small open-label and randomized clinical trials of statins have observed positive effects on cognitive function; larger studies of statins in patients with AD are ongoing. Although more research is needed, current evidence indicates an association between CVD risk factors--such as hypertension, dyslipidemia, and diabetes mellitus--and cognitive decline/dementia. From a clinical perspective, these data further support the rationale for physicians to provide effective management of CVD risk factors and for patients to be compliant with such recommendations to possibly prevent cognitive decline/dementia.

Association between Metabolite Profiles, Metabolic Syndrome and Obesity Status.

PubMed

Allam-Ndoul, Bénédicte; Guénard, Frédéric; Garneau, Véronique; Cormier, Hubert; Barbier, Olivier; Pérusse, Louis; Vohl, Marie-Claude

2016-05-27

Underlying mechanisms associated with the development of abnormal metabolic phenotypes among obese individuals are not yet clear. Our aim is to investigate differences in plasma metabolomics profiles between normal weight (NW) and overweight/obese (Ov/Ob) individuals, with or without metabolic syndrome (MetS). Mass spectrometry-based metabolite profiling was used to compare metabolite levels between each group. Three main principal components factors explaining a maximum of variance were retained. Factor 1's (long chain glycerophospholipids) metabolite profile score was higher among Ov/Ob with MetS than among Ov/Ob and NW participants without MetS. This factor was positively correlated to plasma total cholesterol (total-C) and triglyceride levels in the three groups, to high density lipoprotein -cholesterol (HDL-C) among participants without MetS. Factor 2 (amino acids and short to long chain acylcarnitine) was positively correlated to HDL-C and negatively correlated with insulin levels among NW participants. Factor 3's (medium chain acylcarnitines) metabolite profile scores were higher among NW participants than among Ov/Ob with or without MetS. Factor 3 was negatively associated with glucose levels among the Ov/Ob with MetS. Factor 1 seems to be associated with a deteriorated metabolic profile that corresponds to obesity, whereas Factors 2 and 3 seem to be rather associated with a healthy metabolic profile.

Risk factors in school shootings.

PubMed

Verlinden, S; Hersen, M; Thomas, J

2000-01-01

Nine incidents of multiple-victim homicide in American secondary schools are examined and common risk factors are identified. The literature dealing with individual, family, social, societal, and situational risk factors for youth violence and aggression is reviewed along with existing risk assessment methods. Checklists of risk factors for serious youth violence and school violence are used in reviewing each school shooting case. Commonalties among the cases and implications for psychologists practicing in clinical and school settings are discussed.

Cardiovascular risk factors among college students: Knowledge, perception, and risk assessment.

PubMed

Tran, Dieu-My T; Zimmerman, Lani M; Kupzyk, Kevin A; Shurmur, Scott W; Pullen, Carol H; Yates, Bernice C

2017-04-01

To assess college students' knowledge and perception of cardiovascular risk factors and to screen for their cardiovascular risks. The final sample that responded to recruitment consisted of 158 college students from a midwestern university. A cross-sectional, descriptive study was performed using convenience sampling. College students were knowledgeable about cardiovascular risk factors but did not perceive themselves at risk for cardiovascular disease (CVD). Knowledge of cardiovascular risk factors was correlated with the lifetime risk estimates (ρ = .17, p = .048), and perception of cardiovascular risk was positively associated with 30-year CVD risk estimates (ρ = .16, p = .048). More than 50% of the participants had 1 or more cardiovascular risk factors. High knowledge level of cardiovascular risk factors was not sufficient to lower cardiovascular risks within this study population, but changing perception of cardiovascular risk factors may play a bigger role in reducing long-term cardiovascular risks.

Stroke Risk Factors and Symptoms

MedlinePlus

... » [ pdf, 433 kb ] Order Materials » Stroke Risk Factors and Symptoms Risk Factors for a Stroke Stroke prevention is still ... it. Treatment can delay complications that increase the risk of stroke. Transient ischemic attacks (TIAs). Seek help. ...

Seismic Risk Perception compared with seismic Risk Factors

NASA Astrophysics Data System (ADS)

Crescimbene, Massimo; La Longa, Federica; Pessina, Vera; Pino, Nicola Alessandro; Peruzza, Laura

2016-04-01

The communication of natural hazards and their consequences is one of the more relevant ethical issues faced by scientists. In the last years, social studies have provided evidence that risk communication is strongly influenced by the risk perception of people. In order to develop effective information and risk communication strategies, the perception of risks and the influencing factors should be known. A theory that offers an integrative approach to understanding and explaining risk perception is still missing. To explain risk perception, it is necessary to consider several perspectives: social, psychological and cultural perspectives and their interactions. This paper presents the results of the CATI survey on seismic risk perception in Italy, conducted by INGV researchers on funding by the DPC. We built a questionnaire to assess seismic risk perception, with a particular attention to compare hazard, vulnerability and exposure perception with the real data of the same factors. The Seismic Risk Perception Questionnaire (SRP-Q) is designed by semantic differential method, using opposite terms on a Likert scale to seven points. The questionnaire allows to obtain the scores of five risk indicators: Hazard, Exposure, Vulnerability, People and Community, Earthquake Phenomenon. The questionnaire was administered by telephone interview (C.A.T.I.) on a statistical sample at national level of over 4,000 people, in the period January -February 2015. Results show that risk perception seems be underestimated for all indicators considered. In particular scores of seismic Vulnerability factor are extremely low compared with house information data of the respondents. Other data collected by the questionnaire regard Earthquake information level, Sources of information, Earthquake occurrence with respect to other natural hazards, participation at risk reduction activities and level of involvement. Research on risk perception aims to aid risk analysis and policy-making by

[Autism and Autism-associated Metabolites].

PubMed

Watanabe, Kunitomo

2016-06-01

Gene-microbiota interactions are now proposed to be a special case of gene-environmental interaction. Preclinical and clinical data summarized in this article reveal that a specific serum metabolite, associated with alterations in gut microbiome composition, might have an emerging role in the onset and pathogenesis of autism. Altered level of this specified metabolite may induce perturbations in the epigenome and modulate the expression of key disease susceptible genes in neurons and their associated cells during critical periods of neurodevelopment. The gut microbiota itself is now regarded as a reservoir for environmental epigenetic factors.

Synergistic action of the benzene metabolite hydroquinone on myelopoietic stimulating activity of granulocyte/macrophage colony-stimulating factor in vitro

NASA Technical Reports Server (NTRS)

Irons, R. D.; Stillman, W. S.; Colagiovanni, D. B.; Henry, V. A.; Clarkson, T. W. (Principal Investigator)

1992-01-01

The effects of in vitro pretreatment with benzene metabolites on colony-forming response of murine bone marrow cells stimulated with recombinant granulocyte/macrophage colony-stimulating factor (rGM-CSF) were examined. Pretreatment with hydroquinone (HQ) at concentrations ranging from picomolar to micromolar for 30 min resulted in a 1.5- to 4.6-fold enhancement in colonies formed in response to rGM-CSF that was due to an increase in granulocyte/macrophage colonies. The synergism equaled or exceeded that reported for the effects of interleukin 1, interleukin 3, or interleukin 6 with GM-CSF. Optimal enhancement was obtained with 1 microM HQ and was largely independent of the concentration of rGM-CSF. Pretreatment with other authentic benzene metabolites, phenol and catechol, and the putative metabolite trans, trans-muconaldehyde did not enhance growth factor response. Coadministration of phenol and HQ did not enhance the maximal rGM-CSF response obtained with HQ alone but shifted the optimal concentration to 100 pM. Synergism between HQ and rGM-CSF was observed with nonadherent bone marrow cells and lineage-depleted bone marrow cells, suggesting an intrinsic effect on recruitment of myeloid progenitor cells not normally responsive to rGM-CSF. Alterations in differentiation in a myeloid progenitor cell population may be of relevance in the pathogenesis of acute myelogenous leukemia secondary to drug or chemical exposure.

Up-regulation of neurotrophic factors by cinnamon and its metabolite sodium benzoate: therapeutic implications for neurodegenerative disorders.

PubMed

Jana, Arundhati; Modi, Khushbu K; Roy, Avik; Anderson, John A; van Breemen, Richard B; Pahan, Kalipada

2013-06-01

This study underlines the importance of cinnamon, a widely-used food spice and flavoring material, and its metabolite sodium benzoate (NaB), a widely-used food preservative and a FDA-approved drug against urea cycle disorders in humans, in increasing the levels of neurotrophic factors [e.g., brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3)] in the CNS. NaB, but not sodium formate (NaFO), dose-dependently induced the expression of BDNF and NT-3 in primary human neurons and astrocytes. Interestingly, oral administration of ground cinnamon increased the level of NaB in serum and brain and upregulated the levels of these neurotrophic factors in vivo in mouse CNS. Accordingly, oral feeding of NaB, but not NaFO, also increased the level of these neurotrophic factors in vivo in the CNS of mice. NaB induced the activation of protein kinase A (PKA), but not protein kinase C (PKC), and H-89, an inhibitor of PKA, abrogated NaB-induced increase in neurotrophic factors. Furthermore, activation of cAMP response element binding (CREB) protein, but not NF-κB, by NaB, abrogation of NaB-induced expression of neurotrophic factors by siRNA knockdown of CREB and the recruitment of CREB and CREB-binding protein to the BDNF promoter by NaB suggest that NaB exerts its neurotrophic effect through the activation of CREB. Accordingly, cinnamon feeding also increased the activity of PKA and the level of phospho-CREB in vivo in the CNS. These results highlight a novel neutrophic property of cinnamon and its metabolite NaB via PKA - CREB pathway, which may be of benefit for various neurodegenerative disorders.

Enantioselective induction of cytotoxicity by o,p'-DDD in PC12 cells: implications of chirality in risk assessment of POPs metabolites.

PubMed

Wang, Cui; Li, Zhuoyu; Zhang, Quan; Zhao, Meirong; Liu, Weiping

2013-04-16

The increased release of chiral persistent organic pollutants (POPs) into the environment has resulted in more attention to the role of enantioselectivity in the fate and ecotoxicological effects of these compounds. Although the enantioselectivity of chiral POPs has been considered in previous studies, little effort has been expended to discern the enantiospecific effects of chiral POPs metabolites, which may impede comprehensive risk assessments of these chemicals. In the present study, o,p'-DDD, the chiral metabolite of o,p'-DDT, was used as a model chiral metabolite. First, a preferential chiral separation at 100% ethanol was employed to obtain a pure enantiomer. The enantioselective cytotoxicity of o,p'-DDD in rat cells (PC12) was evaluated by detecting activation of the cellular apoptosis and oxidative stress systems and microarray analysis. We have documented for the first time that R-(+)-o,p'-DDD increases apoptosis by selectively disturbing the oxidative system (enzymes and molecules) and regulating the transcription of Aven, Bid, Cideb and Tp53. By comparing the data from the present study to data derived from the parent compound, we concluded that the R-enantiomer is the more detrimental stereostructure for both o,p'-DDT and o,p'-DDD. This observed stereostructural effect is in line with the structure-activity relationship formulated at other structural levels. Biological activities of the chiral metabolites are likely to occur in the same absolute configuration between chiral POPs and their metabolites provided that they have the similar stereostructures.

Association of Tryptophan Metabolites with Incident Type 2 Diabetes in the PREDIMED Trial: A Case-Cohort Study.

PubMed

Yu, Edward; Papandreou, Christopher; Ruiz-Canela, Miguel; Guasch-Ferre, Marta; Clish, Clary B; Dennis, Courtney; Liang, Liming; Corella, Dolores; Fitó, Montserrat; Razquin, Cristina; Lapetra, José; Estruch, Ramón; Ros, Emilio; Cofán, Montserrat; Arós, Fernando; Toledo, Estefania; Serra-Majem, Lluis; Sorlí, José V; Hu, Frank B; Martinez-Gonzalez, Miguel A; Salas-Salvado, Jordi

2018-06-08

Metabolites of the tryptophan-kynurenine pathway (i.e., tryptophan, kynurenine, kynurenic acid, quinolinic acid, 3-hydroxyanthranilic) may be associated with diabetes development. Using a case-cohort design nested in the Prevención con Dieta Mediterránea (PREDIMED) study, we studied the associations of baseline and 1-year changes of these metabolites with incident type 2 diabetes (T2D). Plasma metabolite concentrations were quantified via LC-MS for n = 641 in a randomly selected subcohort and 251 incident cases diagnosed during 3.8 years of median follow-up. Weighted Cox models adjusted for age, sex, body mass index, and other T2D risk factors were used. Contrary to our hypothesis, baseline tryptophan was associated with higher risk of incident T2D (hazard ratio = 1.29; 95% CI, 1.04-1.61 per SD). Positive changes in quinolinic acid from baseline to 1 year were associated with a higher risk of T2D (hazard ratio = 1.39; 95% CI, 1.09-1.77 per SD). Baseline tryptophan and kynurenic acid were directly associated with changes in homeostatic model assessment for insulin resistance (HOMA-IR) from baseline to 1 year. Concurrent changes in kynurenine, quinolinic acid, 3-hydroxyanthranilic acid, and kynurenine/tryptophan ratio were associated with baseline-to-1-year changes in HOMA-IR. Baseline tryptophan and 1-year increases in quinolinic acid were positively associated with incident T2D. Baseline and 1-year changes in tryptophan metabolites predicted changes in HOMA-IR. © 2018 American Association for Clinical Chemistry.

Synthesizing Risk from Summary Evidence Across Multiple Risk Factors.

PubMed

Shrier, Ian; Colditz, Graham A; Steele, Russell J

2018-07-01

Although meta-analyses provide summary effect estimates that help advise patient care, patients often want to compare their overall health to the general population. The Harvard Cancer Risk Index was published in 2004 and uses risk ratio estimates and prevalence estimates from original studies across many risk factors to provide an answer to this question. However, the published version of the formula only uses dichotomous risk factors and its derivation was not provided. The objective of this brief report was to provide the derivation of a more general form of the equation that allows the incorporation of risk factors with three or more levels.

Phytol metabolites are circulating dietary factors that activate the nuclear receptor RXR.

PubMed Central

Kitareewan, S; Burka, L T; Tomer, K B; Parker, C E; Deterding, L J; Stevens, R D; Forman, B M; Mais, D E; Heyman, R A; McMorris, T; Weinberger, C

1996-01-01

RXR is a nuclear receptor that plays a central role in cell signaling by pairing with a host of other receptors. Previously, 9-cis-retinoic acid (9cRA) was defined as a potent RXR activator. Here we describe a unique RXR effector identified from organic extracts of bovine serum by following RXR-dependent transcriptional activity. Structural analyses of material in active fractions pointed to the saturated diterpenoid phytanic acid, which induced RXR-dependent transcription at concentrations between 4 and 64 microM. Although 200 times more potent than phytanic acid, 9cRA was undetectable in equivalent amounts of extract and cannot be present at a concentration that could account for the activity. Phytanic acid, another phytol metabolite, was synthesized and stimulated RXR with a potency and efficacy similar to phytanic acid. These metabolites specifically displaced [3H]-9cRA from RXR with Ki values of 4 microM, indicating that their transcriptional effects are mediated by direct receptor interactions. Phytol metabolites are compelling candidates for physiological effectors, because their RXR binding affinities and activation potencies match their micromolar circulating concentrations. Given their exclusive dietary origin, these chlorophyll metabolites may represent essential nutrients that coordinate cellular metabolism through RXR-dependent signaling pathways. PMID:8856661

Cardiovascular risk-factor knowledge and risk perception among HIV-infected adults.

PubMed

Cioe, Patricia A; Crawford, Sybil L; Stein, Michael D

2014-01-01

Cardiovascular disease (CVD) has emerged as a major cause of morbidity and mortality in HIV-infected adults. Research in noninfected populations has suggested that knowledge of CVD risk factors significantly influences perceptions of risk. This cross-sectional study describes CVD risk factor knowledge and risk perception in HIV-infected adults. We recruited 130 HIV-infected adults (mean age = 48 years, 62% male, 56% current smokers, mean years since HIV diagnosis, 14.7). The mean CVD risk factor knowledge score was fairly high. However, controlling for age, CVD risk factor knowledge was not predictive of perceived risk [F(1, 117) = 0.13, p > .05]. Estimated risk and perceived risk were weakly but significantly correlated; r (126) = .24, p = .01. HIV-infected adults are at increased risk for CVD. Despite having adequate risk-factor knowledge, CVD risk perception was inaccurate. Improving risk perception and developing CVD risk reduction interventions for this population are imperative. Copyright © 2014 Association of Nurses in AIDS Care. Published by Elsevier Inc. All rights reserved.

Modifiable risk factors for migraine progression.

PubMed

Bigal, Marcelo E; Lipton, Richard B

2006-10-01

Migraine is a chronic-recurrent disorder that progresses in some individuals. Transformed migraine is the result of this progression. Since migraine does not progress in most patients, identifying the risk factors for progression has emerged as a very important public health priority. If risk factors can be identified, that might provide a foundation for more aggressive preventive intervention. Risk factors for progression may be divided into non-remediable (gender, age, race) and remediable categories. In this paper, we focus on several already identified remediable risk factors, including frequency of migraine attacks, obesity, acute medication overuse, caffeine overuse, stressful life events, depression, and sleep disorders. We present the evidence for each risk factor and discuss possible interventions to address them.

Effects of ecological factors on secondary metabolites and inorganic elements of Scutellaria baicalensis and analysis of geoherblism.

PubMed

Guo, Lanping; Wang, Sheng; Zhang, Ji; Yang, Guang; Zhao, Manxi; Ma, Weifeng; Zhang, Xiaobo; Li, Xuan; Han, Bangxing; Chen, Naifu; Huang, Luqi

2013-11-01

This study analyzed the effects of ecological factors on secondary metabolites of Scutellaria baicalensis using two sources: 92 individual roots of S. baicalensis from all over China, and secondary metabolites, medicinal materials and inorganic element contents obtained from the testing of 92 S. baicalensis rhizosphere soil samples. The study used environmental data from the Genuine Medicinal Material Spatial Analysis Database. Most of the chemical constituents of S. baicalensis were negatively correlated to latitude and positively correlated to temperature; generally, the contents of 21 chemical constituents were higher at low latitudes than that at high latitudes. By gradual regression analysis, it was found that the content of baicalin in S. baicalensis was negatively correlated to latitude and generally the content of inorganic elements in soil was excessively high (excluding Mg and Ca), which has a negative effect on the accumulation of chemical constituents in S. baicalensis. Based on the cluster analysis of 21 constituents, S. baicalensis from different places of origin was divided into two groups, and S. baicalensis was not genuine only in a specific small region. Within the zone from Chifeng, Inner Mongolia to Taibai, Shaanxi is suitable for accumulation of secondary metabolites of S. baicalensis and such a zone represents a suitable distribution and potential genuine producing area.

Physical activity, sedentary behavior, and vitamin D metabolites.

PubMed

Hibler, Elizabeth A; Sardo Molmenti, Christine L; Dai, Qi; Kohler, Lindsay N; Warren Anderson, Shaneda; Jurutka, Peter W; Jacobs, Elizabeth T

2016-02-01

Physical activity is associated with circulating 25-hydroxyvitamin D (25(OH)D). However, the influence of activity and/or sedentary behavior on the biologically active, seco-steroid hormone 1α,25-dihydroxyvitamin D (1,25(OH)2D) is unknown. We conducted a cross-sectional analysis among ursodeoxycholic acid (UDCA) randomized trial participants (n=876) to evaluate associations between physical activity, sedentary behavior, and circulating vitamin D metabolite concentrations. Continuous vitamin D metabolite measurements and clinical thresholds were evaluated using multiple linear and logistic regression models, mutually adjusted for either 1,25(OH)2D or 25(OH)D and additional confounding factors. A statistically significant linear association between 1,25(OH)2D and moderate-vigorous physical activity per week was strongest among women (β (95% CI): 3.10 (1.51-6.35)) versus men (β (95% CI): 1.35 (0.79-2.29)) in the highest tertile of activity compared to the lowest (p-interaction=0.003). Furthermore, 25(OH)D was 1.54ng/ml (95% CI 1.09-1.98) higher per hour increase in moderate-vigorous activity (p=0.001) and odds of sufficient 25(OH)D status was higher among physically active participants (p=0.001). Sedentary behavior was not significantly associated with either metabolite in linear regression models, nor was a statistically significant interaction by sex identified. The current study identified novel associations between physical activity and serum 1,25(OH)2D levels, adjusted for 25(OH)D concentrations. These results identify the biologically active form of vitamin D as a potential physiologic mechanism related to observed population-level associations between moderate-vigorous physical activity with bone health and chronic disease risk. However, future longitudinal studies are needed to further evaluate the role of physical activity and vitamin D metabolites in chronic disease prevention. Copyright © 2015 Elsevier Inc. All rights reserved.

Toxicity assessment strategies, data requirements, and risk assessment approaches to derive health based guidance values for non-relevant metabolites of plant protection products.

PubMed

Dekant, Wolfgang; Melching-Kollmuss, Stephanie; Kalberlah, Fritz

2010-03-01

In Europe, limits for tolerable concentrations of "non-relevant metabolites" for active ingredients (AI) of plant protection products in drinking water between 0.1 and 10 microg/L are discussed depending on the toxicological information available. "Non-relevant metabolites" are degradation products of AIs, which do not or only partially retain the targeted toxicities of AIs. For "non-relevant metabolites" without genotoxicity (to be confirmed by testing in vitro), the application of the concept of "thresholds of toxicological concern" results in a health-based drinking water limit of 4.5 microg/L even for Cramer class III compounds, using the TTC threshold of 90 microg/person/day (divided by 10 and 2). Taking into account the thresholds derived from two reproduction toxicity data bases a drinking water limit of 3.0 microg/L is proposed. Therefore, for "non-relevant metabolites" whose drinking water concentration is below 3.0 microg/L, no toxicity testing is necessary. This work develops a toxicity assessment strategy as a basis to delineate health-based limits for "non-relevant metabolites" in ground and drinking water. Toxicological testing is recommended to investigate, whether the metabolites are relevant or not, based on the hazard properties of the parent AIs, as outlined in the SANCO Guidance document. Also, genotoxicity testing of the water metabolites is clearly recommended. In this publication, tiered testing strategies are proposed for non-relevant metabolites, when drinking water concentrations >3.0 microg/L will occur. Conclusions based on structure-activity relationships and the detailed toxicity database on the parent AI should be included. When testing in animals is required for risk assessment, key aspects are studies along OECD-testing guidelines with "enhanced" study designs addressing additional endpoints such as reproductive toxicity and a developmental screening test to derive health-based tolerable drinking water limits with a limited number

A breath fungal secondary metabolite signature to diagnose invasive aspergillosis.

PubMed

Koo, Sophia; Thomas, Horatio R; Daniels, S David; Lynch, Robert C; Fortier, Sean M; Shea, Margaret M; Rearden, Preshious; Comolli, James C; Baden, Lindsey R; Marty, Francisco M

2014-12-15

Invasive aspergillosis (IA) remains a leading cause of mortality in immunocompromised patients, in part due to the difficulty of diagnosing this infection. Using thermal desorption-gas chromatography/mass spectrometry, we characterized the in vitro volatile metabolite profile of Aspergillus fumigatus, the most common cause of IA, and other pathogenic aspergilli. We prospectively collected breath samples from patients with suspected invasive fungal pneumonia from 2011 to 2013, and assessed whether we could discriminate patients with proven or probable IA from patients without aspergillosis, as determined by European Organization for Research and Treatment of Cancer/Mycoses Study Group consensus definitions, by direct detection of fungal volatile metabolites in these breath samples. The monoterpenes camphene, α- and β-pinene, and limonene, and the sesquiterpene compounds α- and β-trans-bergamotene were distinctive volatile metabolites of A. fumigatus in vitro, distinguishing it from other pathogenic aspergilli. Of 64 patients with suspected invasive fungal pneumonia based on host risk factors, clinical symptoms, and radiologic findings, 34 were diagnosed with IA, whereas 30 were ultimately diagnosed with other causes of pneumonia, including other invasive mycoses. Detection of α-trans-bergamotene, β-trans-bergamotene, a β-vatirenene-like sesquiterpene, or trans-geranylacetone identified IA patients with 94% sensitivity (95% confidence interval [CI], 81%-98%) and 93% specificity (95% CI, 79%-98%). In patients with suspected fungal pneumonia, an Aspergillus secondary metabolite signature in breath can identify individuals with IA. These results provide proof-of-concept that direct detection of exogenous fungal metabolites in breath can be used as a novel, noninvasive, pathogen-specific approach to identifying the precise microbial cause of pneumonia. © The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America

Regulation and Role of Fungal Secondary Metabolites.

PubMed

Macheleidt, Juliane; Mattern, Derek J; Fischer, Juliane; Netzker, Tina; Weber, Jakob; Schroeckh, Volker; Valiante, Vito; Brakhage, Axel A

2016-11-23

Fungi have the capability to produce a tremendous number of so-called secondary metabolites, which possess a multitude of functions, e.g., communication signals during coexistence with other microorganisms, virulence factors during pathogenic interactions with plants and animals, and in medical applications. Therefore, research on this topic has intensified significantly during the past 10 years and thus knowledge of regulatory mechanisms and the understanding of the role of secondary metabolites have drastically increased. This review aims to depict the complexity of all the regulatory elements involved in controlling the expression of secondary metabolite gene clusters, ranging from epigenetic control and signal transduction pathways to global and specific transcriptional regulators. Furthermore, we give a short overview on the role of secondary metabolites, focusing on the interaction with other microorganisms in the environment as well as on pathogenic relationships.

Sociodemographic factors associated with multiple cardiovascular risk factors among Malaysian adults.

PubMed

Ghazali, Sumarni Mohd; Seman, Zamtira; Cheong, Kee Chee; Hock, Lim Kuang; Manickam, Mala; Kuay, Lim Kuang; Yusoff, Ahmad Faudzi; Mustafa, Feisul Idzwan; Mustafa, Amal Nasir

2015-01-31

To determine the prevalence and sociodemographic correlates of multiple risk factors for cardiovascular disease (CVD) among Malaysian adults. We analysed data on 1044 men and 1528 women, aged 24-64 years, participants in the Non Communicable Disease Surveillance 2005/2006, a nationally representative, population-based, cross-sectional study. Prevalence of obesity, high blood pressure, dyslipidaemia, hyperglycemia, physical inactivity, smoking, risky drinking, low vegetable and fruit intake were determined and multivariable logistic regression was used to identify sociodemographic factors associated with having ≥3 of these cardiovascular disease risk factors. The response rate was 84.6% (2572/3040). Overall, 68.4% (95% CI: 63.2, 73.1) had at least three risk factors. Among men, older age and Indian ethnicity were independently associated with having ≥3 CVD risk factors; while among women, older age, low education, and housewives were more likely to have ≥3 CVD risk factors. The prevalence of cardiovascular risk factors clustering among Malaysian adults is high, raising concerns that cardiovascular disease incidence will rise steeply in the near future if no immediate preventive measures are taken. The current national health education and promotion programmes pertaining to modifiable risk factors can be further improved by taking into account the sociodemographic variation in CVD risk factors clustering.

Quantifying cardiometabolic risk using modifiable non-self-reported risk factors.

PubMed

Marino, Miguel; Li, Yi; Pencina, Michael J; D'Agostino, Ralph B; Berkman, Lisa F; Buxton, Orfeu M

2014-08-01

Sensitive general cardiometabolic risk assessment tools of modifiable risk factors would be helpful and practical in a range of primary prevention interventions or for preventive health maintenance. To develop and validate a cumulative general cardiometabolic risk score that focuses on non-self-reported modifiable risk factors such as glycosylated hemoglobin (HbA1c) and BMI so as to be sensitive to small changes across a span of major modifiable risk factors, which may not individually cross clinical cut-off points for risk categories. We prospectively followed 2,359 cardiovascular disease (CVD)-free subjects from the Framingham offspring cohort over a 14-year follow-up. Baseline (fifth offspring examination cycle) included HbA1c and cholesterol measurements. Gender-specific Cox proportional hazards models were considered to evaluate the effects of non-self-reported modifiable risk factors (blood pressure, total cholesterol, high-density lipoprotein cholesterol, smoking, BMI, and HbA1c) on general CVD risk. We constructed 10-year general cardiometabolic risk score functions and evaluated its predictive performance in 2012-2013. HbA1c was significantly related to general CVD risk. The proposed cardiometabolic general CVD risk model showed good predictive performance as determined by cross-validated discrimination (male C-index=0.703, 95% CI=0.668, 0.734; female C-index=0.762, 95% CI=0.726, 0.801) and calibration (lack-of-fit chi-square=9.05 [p=0.338] and 12.54 [p=0.128] for men and women, respectively). This study presents a risk factor algorithm that provides a convenient and informative way to quantify cardiometabolic risk on the basis of modifiable risk factors that can motivate an individual's commitment to prevention and intervention. Copyright © 2014 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.

Quantifying Cardiometabolic Risk Using Modifiable Non–Self-Reported Risk Factors

PubMed Central

Marino, Miguel; Li, Yi; Pencina, Michael J.; D’Agostino, Ralph B.; Berkman, Lisa F.; Buxton, Orfeu M.

2014-01-01

Background Sensitive general cardiometabolic risk assessment tools of modifiable risk factors would be helpful and practical in a range of primary prevention interventions or for preventive health maintenance. Purpose To develop and validate a cumulative general cardiometabolic risk score that focuses on non–self-reported modifiable risk factors such as glycosylated hemoglobin (HbA1c) and BMI so as to be sensitive to small changes across a span of major modifiable risk factors, which may not individually cross clinical cut off points for risk categories. Methods We prospectively followed 2,359 cardiovascular disease (CVD)-free subjects from the Framingham offspring cohort over a 14–year follow-up. Baseline (fifth offspring examination cycle) included HbA1c and cholesterol measurements. Gender–specific Cox proportional hazards models were considered to evaluate the effects of non–self-reported modifiable risk factors (blood pressure, total cholesterol, high–density lipoprotein cholesterol, smoking, BMI, and HbA1c) on general CVD risk. We constructed 10–year general cardiometabolic risk score functions and evaluated its predictive performance in 2012–2013. Results HbA1c was significantly related to general CVD risk. The proposed cardiometabolic general CVD risk model showed good predictive performance as determined by cross-validated discrimination (male C-index=0.703, 95% CI=0.668, 0.734; female C-index=0.762, 95% CI=0.726, 0.801) and calibration (lack-of-fit χ2=9.05 [p=0.338] and 12.54 [p=0.128] for men and women, respectively). Conclusions This study presents a risk factor algorithm that provides a convenient and informative way to quantify cardiometabolic risk based on modifiable risk factors that can motivate an individual’s commitment to prevention and intervention. PMID:24951039

Chocolate Matrix Factors Modulate Pharmacokinetic Behavior of Cocoa Flavan-3-Ol Phase-II Metabolites Following Oral Consumption by Sprague-Dawley Rats

PubMed Central

Neilson, Andrew P.; Sapper, Teryn N.; Janle, Elsa M.; Rudolph, Ralf; Matusheski, Nathan V.; Ferruzzi, Mario G.

2010-01-01

The impact of carbohydrates and milk on the bioavailability of catechin (C) and epicatechin (EC) from chocolate has been previously studied. However, little data exists regarding potential modulation of the phase-II metabolism by these chocolate matrix factors. The objectives of this study were to assess the impact of matrix composition on qualitative and quantitative profiles of circulating catechins and their metabolites following administration of commercially relevant chocolate confections. Sprague-Dawley rats were fed 1.5 g of a confection (reference dark, high sucrose, or milk chocolate) by intragastric gavage, and plasma samples were collected over 8 h. HPLC-MS analysis was performed to quantify C, EC and their metabolites. The predominant metabolites were O-glucuronides (2 metabolites), and O-Me-O-glucuronides (3 metabolites). Plasma concentrations of metabolites were generally the highest for high sucrose treatment and lowest for milk treatment, while reference dark treatment generally resulted in intermediate concentrations. The O-Me-(±)-C/EC-O-β-glucuronide (peak 4) was significantly higher for the high sucrose treatment (2325 nM*h) versus the milk treatment (1300 nM*h). Additionally, CMAX values for (±)-C/EC-O-β-glucuronide (peak 3), and two O-Me-(±)-C/EC-O-β-glucuronides (peaks 4 and 6) were significantly higher for high sucrose treatment (4012, 518, and 2518 nM, respectively) versus the milk treatment (2590, 240, and 1670 nM, respectively). Milk and sucrose appear to modulate both metabolism and plasma pharmacokinetics, and to a lesser extent, the overall bioavailability of catechins from chocolate confections. PMID:20446738

Risk Factors and Causes of Syncope

MedlinePlus

... Risk Factors & Causes of Syncope Risk Factors for Cardiovascular Syncope The risk of cardiovascular syncope increases with ... Long QT syndrome and Brugada Syndrome Signs of Cardiovascular Syncope Cardiovascular syncope usually is sudden. There may ...

Vertigo and dizziness in adolescents: Risk factors and their population attributable risk.

PubMed

Filippopulos, Filipp M; Albers, Lucia; Straube, Andreas; Gerstl, Lucia; Blum, Bernhard; Langhagen, Thyra; Jahn, Klaus; Heinen, Florian; von Kries, Rüdiger; Landgraf, Mirjam N

2017-01-01

To assess potential risk factors for vertigo and dizziness in adolescents and to evaluate their variability by different vertigo types. The role of possible risk factors for vertigo and dizziness in adolescents and their population relevance needs to be addressed in order to design preventive strategies. The study population consisted of 1482 school-children between the age of 12 and 19 years, who were instructed to fill out a questionnaire on different vertigo types and related potential risk factors. The questionnaire specifically asked for any vertigo, spinning vertigo, swaying vertigo, orthostatic dizziness, and unspecified dizziness. Further a wide range of potential risk factors were addressed including gender, stress, muscular pain in the neck and shoulder region, sleep duration, migraine, coffee and alcohol consumption, physical activity and smoking. Gender, stress, muscular pain in the neck and shoulder region, sleep duration and migraine were identified as independent risk factors following mutual adjustment: The relative risk was 1.17 [1.10-1.25] for female sex, 1.07 [1.02-1.13] for stress, 1.24 [1.17-1.32] for muscular pain, and 1.09 [1.03-1.14] for migraine. The population attributable risk explained by these risk factors was 26%, with muscular pain, stress, and migraine accounting for 11%, 4%, and 3% respectively. Several established risk factors in adults were also identified in adolescents. Risk factors amenable to prevention accounted for 17% of the total population risk. Therefore, interventions targeting these risk factors may be warranted.

[Prevalence of cardiovascular risk factors in adolescents].

PubMed

Romanzini, Marcelo; Reichert, Felipe Fossati; Lopes, Adair da Silva; Petroski, Edio Luiz; de Farias Júnior, José Cazuza

2008-11-01

The aim of this study was to determine the prevalence of cardiovascular risk factors in adolescents and to verify its association with age and gender. 644 high school students from public schools in the city of Londrina, Paraná State, Brazil, participated in the study. A two-step sampling process was used. Behavioral risk factors (physical inactivity, inadequate consumption of fruits and vegetables, and smoking) and biological risk factors (overweight and high blood pressure) were investigated. Nearly 90% of adolescents showed at least one risk factor. Inadequate consumption of fruits (56.7%) and vegetables (43.9%) and physical inactivity (39.2%) were the most prevalent risk factors. Prevalence rates for high blood pressure and overweight were 18.6 and 12.7%, respectively. Cardiovascular risk factors were more frequent among boys (PR = 1.20; 95%CI = 1.01-1.42). In conclusion, cardiovascular risk factors are a prevalent health issue among students in the city of Londrina.

Activation of the Sigma-1 receptor by haloperidol metabolites facilitates brain-derived neurotrophic factor secretion from human astroglia

PubMed Central

Dalwadi, Dhwanil A.; Kim, Seongcheol; Schetz, John A.

2017-01-01

Glial cells play a critical role in neuronal support which includes the production and release of the neurotrophin brain-derived neurotrophic factor (BDNF). Activation of the sigma-1 receptor (S1R) has been shown to attenuate inflammatory stress-mediated brain injuries, and there is emerging evidence that this may involve a BDNF-dependent mechanism. In this report we studied S1R-mediated BDNF release from human astrocytic glial cells. Astrocytes express the S1R, which mediates BDNF release when stimulated with the prototypical S1R agonists 4-PPBP and (+)-SKF10047. This effect could be antagonized by a selective concentration of the S1R antagonist BD1063. Haloperidol is known to have high affinity interactions with the S1R, yet it was unable to facilitate BDNF release. Remarkably, however, two metabolites of haloperidol, haloperidol I and haloperidol II (reduced haloperidol), were discovered to facilitate BDNF secretion and this effect was antagonized by BD1063. Neither 4-PPBP, nor either of the haloperidol metabolites affected the level of BDNF mRNA as assessed by qPCR. These results demonstrate for the first time that haloperidol metabolites I and II facilitate the secretion of BDNF from astrocytes by acting as functionally selective S1R agonists. PMID:28188803

Vertigo and dizziness in adolescents: Risk factors and their population attributable risk

PubMed Central

Albers, Lucia; Straube, Andreas; Gerstl, Lucia; Blum, Bernhard; Langhagen, Thyra; Jahn, Klaus; Heinen, Florian; von Kries, Rüdiger; Landgraf, Mirjam N.

2017-01-01

Objectives To assess potential risk factors for vertigo and dizziness in adolescents and to evaluate their variability by different vertigo types. The role of possible risk factors for vertigo and dizziness in adolescents and their population relevance needs to be addressed in order to design preventive strategies. Study design The study population consisted of 1482 school-children between the age of 12 and 19 years, who were instructed to fill out a questionnaire on different vertigo types and related potential risk factors. The questionnaire specifically asked for any vertigo, spinning vertigo, swaying vertigo, orthostatic dizziness, and unspecified dizziness. Further a wide range of potential risk factors were addressed including gender, stress, muscular pain in the neck and shoulder region, sleep duration, migraine, coffee and alcohol consumption, physical activity and smoking. Results Gender, stress, muscular pain in the neck and shoulder region, sleep duration and migraine were identified as independent risk factors following mutual adjustment: The relative risk was 1.17 [1.10–1.25] for female sex, 1.07 [1.02–1.13] for stress, 1.24 [1.17–1.32] for muscular pain, and 1.09 [1.03–1.14] for migraine. The population attributable risk explained by these risk factors was 26%, with muscular pain, stress, and migraine accounting for 11%, 4%, and 3% respectively. Conclusion Several established risk factors in adults were also identified in adolescents. Risk factors amenable to prevention accounted for 17% of the total population risk. Therefore, interventions targeting these risk factors may be warranted. PMID:29131843

Chocolate matrix factors modulate the pharmacokinetic behavior of cocoa flavan-3-ol phase II metabolites following oral consumption by Sprague-Dawley rats.

PubMed

Neilson, Andrew P; Sapper, Teryn N; Janle, Elsa M; Rudolph, Ralf; Matusheski, Nathan V; Ferruzzi, Mario G

2010-06-09

The impact of carbohydrates and milk on the bioavailability of catechin (C) and epicatechin (EC) from chocolate has been previously studied. However, little data exist regarding potential modulation of the phase II metabolism by these chocolate matrix factors. The objectives of this study were to assess the impact of matrix composition on qualitative and quantitative profiles of circulating catechins and their metabolites following administration of commercially relevant chocolate confections. Sprague-Dawley rats were administered 1.5 g of a confection (reference dark, high sucrose, or milk chocolate) by intragastric gavage, and plasma samples were collected over 8 h. High-performance liquid chromatography-mass spectrometry analysis was performed to quantify C, EC, and their metabolites. The predominant metabolites were O-glucuronides (two metabolites) and O-Me-O-glucuronides (three metabolites). Plasma concentrations of metabolites were generally the highest for high sucrose treatment and lowest for milk treatment, while the reference dark treatment generally resulted in intermediate concentrations. The O-Me-(+/-)-C/EC-O-beta-glucuronide (peak 4) was significantly higher for the high sucrose treatment (2325 nM h) versus the milk treatment (1300 nM h). Additionally, C(MAX) values for (+/-)-C/EC-O-beta-glucuronide (peak 3) and two O-Me-(+/-)-C/EC-O-beta-glucuronides (peaks 4 and 6) were significantly higher for the high sucrose treatment (4012, 518, and 2518 nM, respectively) versus the milk treatment (2590, 240, and 1670 nM, respectively). Milk and sucrose appear to modulate both metabolism and plasma pharmacokinetics and, to a lesser extent, the overall bioavailability of catechins from chocolate confections.

Trichoderma secondary metabolites that affect plant metabolism.

PubMed

Vinale, Francesco; Sivasithamparam, Krishnapillai; Ghisalberti, Emilio L; Ruocco, Michelina; Wood, Sheridan; Lorito, Matteo

2012-11-01

Recently, there have been many exciting new developments relating to the use of Trichoderma spp. as agents for biocontrol of pathogens and as plant growth promoters. Several mechanisms have been proposed to explain the positive effects of these microorganisms on the plant host. One factor that contributes to their beneficial biological activities is related to the wide variety of metabolites that they produce. These metabolites have been found not only to directly inhibit the growth and pathogenic activities of the parasites, but also to increase disease resistance by triggering the system of defence in the plant host. In addition, these metabolites are also capable of enhancing plant growth, which enables the plant to counteract the disease with compensatory vegetative growth by the augmented production of root and shoot systems. This review takes into account the Trichoderma secondary metabolites that affect plant metabolism and that may play an important role in the complex interactions of this biocontrol agent with the plant and pathogens.

APOE genotype modulates proton magnetic resonance spectroscopy metabolites in the aging brain.

PubMed

Gomar, Jesus J; Gordon, Marc L; Dickinson, Dwight; Kingsley, Peter B; Uluğ, Aziz M; Keehlisen, Lynda; Huet, Sarah; Buthorn, Justin J; Koppel, Jeremy; Christen, Erica; Conejero-Goldberg, Concepcion; Davies, Peter; Goldberg, Terry E

2014-05-01

Proton magnetic resonance spectroscopy ((1)H-MRS) studies on healthy aging have reported inconsistent findings and have not systematically taken into account the possible modulatory effect of APOE genotype. We aimed to quantify brain metabolite changes in healthy subjects in relation to age and the presence of the APOE E4 genetic risk factor for Alzheimer's disease. Additionally, we examined these measures in relation to cognition. We studied a cohort of 112 normal adults between 50 and 86 years old who were genotyped for APOE genetic polymorphism. Measurements of (1)H-MRS metabolites were obtained in the posterior cingulate and precuneus region. Measures of general cognitive functioning, memory, executive function, semantic fluency, and speed of processing were also obtained. General linear model analysis demonstrated that older APOE E4 carriers had significantly higher choline/creatine and myo-inositol/creatine ratios than APOE E3 homozygotes. Structural equation modeling resulted in a model with an excellent goodness of fit and in which the APOE × age interaction and APOE status each had a significant effect on (1)H-MRS metabolites (choline/creatine and myo-inositol/creatine). Furthermore, the APOE × age variable modulation of cognition was mediated by (1)H-MRS metabolites. In a healthy aging normal population, choline/creatine and myo-inositol/creatine ratios were significantly increased in APOE E4 carriers, suggesting the presence of neuroinflammatory processes and greater membrane turnover in older carriers. Structural equation modeling analysis confirmed these possible neurodegenerative markers and also indicated the mediator role of these metabolites on cognitive performance among older APOE E4 carriers. Copyright © 2014 Society of Biological Psychiatry. All rights reserved.

APOE Genotype Modulates Proton Magnetic Resonance Spectroscopy Metabolites in the Aging Brain

PubMed Central

Gomar, Jesus J.; Gordon, Marc L.; Dickinson, Dwight; Kingsley, Peter B.; Uluğ, Aziz M.; Keehlisen, Lynda; Huet, Sarah; Buthorn, Justin J.; Koppel, Jeremy; Christen, Erica; Conejero-Goldberg, Concepcion; Davies, Peter; Goldberg, Terry E.

2013-01-01

Background Proton magnetic resonance spectroscopy (1H-MRS) studies on healthy aging have reported inconsistent findings and have not systematically taken into account the possible modulatory effect of APOE genotype. We aimed to quantify brain metabolite changes in healthy subjects in relation to age and the presence of the APOE E4 genetic risk factor for Alzheimer's disease. Additionally, we examined these measures in relation to cognition. Methods We studied a cohort of 112 normal adults between 50 and 86 years old who were genotyped for APOE genetic polymorphism. Measurements of 1H-MRS metabolites were obtained in the posterior cingulate and precuneus region. Measures of general cognitive functioning, memory, executive function, semantic fluency, and speed of processing were also obtained. Results General linear model analysis demonstrated that older APOE E4 carriers had significantly higher choline/creatine and myoinositol/creatine ratios than APOE E3 homozygotes. Structural equation modeling resulted in a model with an excellent goodness of fit and in which the APOE × age interaction and APOE status each had a significant effect on 1H-MRS metabolites (choline/creatine and myo-inositol/creatine). Furthermore, the APOE × age variable modulation of cognition was mediated by 1H-MRS metabolites. Conclusions In a healthy aging normal population, choline/creatine and myo-inositol/creatine ratios were significantly increased in APOE E4 carriers, suggesting the presence of neuroinflammatory processes and greater membrane turnover in older carriers. Structural equation modeling analysis confirmed these possible neurodegenerative markers and also indicated the mediator role of these metabolites on cognitive performance among older APOE E4 carriers. PMID:23831342

Variability in urinary phthalate metabolite levels across pregnancy and sensitive windows of exposure for the risk of preterm birth

PubMed Central

Ferguson, Kelly K.; McElrath, Thomas F.; Ko, Yi-An; Mukherjee, Bhramar; Meeker, John D.

2014-01-01

Background Preterm birth is a significant public health problem, affecting over 1 in 10 live births and contributing largely to infant mortality and morbidity. Everyday exposure to environmental chemicals such as phthalates could contribute, and may be modifiable. In the present study we examine variability in phthalate exposure across gestation and identify windows of susceptibility for the relationship with preterm birth. Methods Women were recruited early in pregnancy as part of a prospective, longitudinal birth cohort at the Brigham and Women’s Hospital in Boston, Massachusetts. Urine samples were collected at up to 4 time points during gestation for phthalate measurement, and birth outcomes were recorded at delivery. From this population we selected all 130 cases of preterm birth, defined as delivery before 37 weeks completed gestation, as well as 352 random controls. Results Urinary phthalate metabolite levels were moderately variable over pregnancy, but levels measured at multiple time points were associated with increased odds of preterm birth. Adjusted odds ratios (aOR) for spontaneous preterm birth were strongest in association with phthalate metabolite concentrations measured at the beginning of the third trimester (aOR for summed di-2-ethylhexyl phthalate metabolites [∑DEHP]=1.33, 95% confidence interval [CI]=1.02, 1.73). Odds ratios for placental preterm birth, defined as delivery with presentation of preeclampsia or intrauterine growth restriction, were slightly elevated in the first trimester for DEHP metabolites (aOR for ∑DEHP=1.33, 95% CI=0.99, 1.78). Conclusions Pregnant women with exposure to phthalates both early and late in pregnancy are at increased risk of delivering preterm, but mechanisms may differ based on etiology. PMID:24934852

Choline and its metabolites are differently associated with cardiometabolic risk factors, cardiovascular history and MRI documented cerebrovascular disease in older adults

USDA-ARS?s Scientific Manuscript database

Background: There is a potential role of choline in cardiovascular and cerebrovascular disease through its involvement in lipid and one-carbon metabolism. Objective: We evaluated the associations of plasma choline and choline-related compounds with cardiometabolic risk factors, history of cardiovas...

Associations between five-factor model of the Positive and Negative Syndrome Scale and plasma levels of monoamine metabolite in patients with schizophrenia.

PubMed

Watanabe, Kenya; Miura, Itaru; Kanno-Nozaki, Keiko; Horikoshi, Sho; Mashiko, Hirobumi; Niwa, Shin-Ichi; Yabe, Hirooki

2015-12-15

The five-factor model of the Positive and Negative Syndrome Scale (PANSS) for schizophrenia symptoms is the most common multiple-factor model used in analyses; its use may improve evaluation of symptoms in schizophrenia patients. Plasma monoamine metabolite levels are possible indicators of clinical symptoms or response to antipsychotics in schizophrenia. We investigated the association between five-factor model components and plasma monoamine metabolites levels to explore the model's biological basis. Plasma levels of homovanillic acid (HVA), 3-methoxy-4-hydroxyphenylglycol (MHPG), and 5-hydroxyindoleacetic acid (5-HIAA) were measured using high-performance liquid chromatography in 65 Japanese patients with schizophrenia. Significant negative correlation between plasma 5-HIAA levels and the depression/anxiety component was found. Furthermore, significant positive correlation was found between plasma MHPG levels and the excitement component. Plasma HVA levels were not correlated with any five-factor model component. These results suggest that the five-factor model of the PANSS may have a biological basis, and may be useful for elucidating the psychopathology of schizophrenia. Assessment using the five-factor model may enable understanding of monoaminergic dysfunction, possibly allowing more appropriate medication selection. Further studies of a larger number of first-episode schizophrenia patients are needed to confirm and extend these results. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Environmental Factors Correlated with the Metabolite Profile of Vitis vinifera cv. Pinot Noir Berry Skins along a European Latitudinal Gradient.

PubMed

Del-Castillo-Alonso, María Ángeles; Castagna, Antonella; Csepregi, Kristóf; Hideg, Éva; Jakab, Gabor; Jansen, Marcel A K; Jug, Tjaša; Llorens, Laura; Mátai, Anikó; Martínez-Lüscher, Johann; Monforte, Laura; Neugart, Susanne; Olejnickova, Julie; Ranieri, Annamaria; Schödl-Hummel, Katharina; Schreiner, Monika; Soriano, Gonzalo; Teszlák, Péter; Tittmann, Susanne; Urban, Otmar; Verdaguer, Dolors; Zipoli, Gaetano; Martínez-Abaigar, Javier; Núñez-Olivera, Encarnación

2016-11-23

Mature berries of Pinot Noir grapevines were sampled across a latitudinal gradient in Europe, from southern Spain to central Germany. Our aim was to study the influence of latitude-dependent environmental factors on the metabolite composition (mainly phenolic compounds) of berry skins. Solar radiation variables were positively correlated with flavonols and flavanonols and, to a lesser extent, with stilbenes and cinnamic acids. The daily means of global and erythematic UV solar radiation over long periods (bud break-veraison, bud break-harvest, and veraison-harvest), and the doses and daily means in shorter development periods (5-10 days before veraison and harvest) were the variables best correlated with the phenolic profile. The ratio between trihydroxylated and monohydroxylated flavonols, which was positively correlated with antioxidant capacity, was the berry skin variable best correlated with those radiation variables. Total flavanols and total anthocyanins did not show any correlation with radiation variables. Air temperature, degree days, rainfall, and aridity indices showed fewer correlations with metabolite contents than radiation. Moreover, the latter correlations were restricted to the period veraison-harvest, where radiation, temperature, and water availability variables were correlated, making it difficult to separate the possible individual effects of each type of variable. The data show that managing environmental factors, in particular global and UV radiation, through cultural practices during specific development periods, can be useful to promote the synthesis of valuable nutraceuticals and metabolites that influence wine quality.

Cytological effects of fungal metabolites produced by fungi isolated from Egyptian poultry feedstuffs.

PubMed

Abdou, R F; Megalla, S E; Moharram, A M; Abdel-Gawad, K M; Sherif, T H; el-Syed Mahmood, A L; Lottfy, A E

1989-01-01

The cytogenetic effects of fungal metabolites produced by 113 strains belonging to 36 fungal species and isolated form 5 substrates of commercial poultry feedstuffs were tested for their effect on the growing root meristems of Allium cepa. The fungal metabolites of Paecilomyces canescens, Aspergillus fumigatus, Syncephalastrum racemosum, Aspergillus terreus and Mucor hiemalis strongly suppressed cell division. Metabolites from other strains had less effect on cell division but permitted the appearance of several abnormalities through different mitotic stages. In general, chromosomal aberrations were more obvious with metabolites of Aspergillus species, Mucor circinelloides and Cladosporium cladosporioides. The mutagenic effects produced by these fungal metabolites reflect the risk that might take place through the consumption of these contaminated feedstuffs.

Adolescent Risk Factors for Child Maltreatment

PubMed Central

Matsuda, Mauri; Greenman, Sarah J.; Augustyn, Megan Bears; Henry, Kimberly L.; Smith, Carolyn A.; Ireland, Timothy O.

2014-01-01

We investigate adolescent risk factors, measured at both early and late adolescence, for involvement in child maltreatment during adulthood. Comprehensive assessments of risk factors for maltreatment that use representative samples with longitudinal data are scarce and can inform multilevel prevention. We use data from the Rochester Youth Development Study, a longitudinal study begun in 1988 with a sample of 1,000 seventh and eighth graders. Participants have been interviewed 14 times and, at the last assessment (age 31), 80% were retained. Risk factors represent 10 developmental domains: area characteristics, family background/structure, parent stressors, exposure to family violence, parent-child relationships, education, peer relationships, adolescent stressors, antisocial behaviors, and precocious transitions to adulthood. Maltreatment is measured by substantiated reports from Child Protective Services records. Many individual risk factors (20 at early adolescence and 14 at later adolescence) are significantly, albeit moderately, predictive of maltreatment. Several developmental domains stand out, including family background/structure, education, antisocial behaviors, and precocious transitions. In addition, there is a pronounced impact of cumulative risk on the likelihood of maltreatment. For example, only 3% of the youth with no risk domains in their background at early adolescence were involved in later maltreatment, but for those with risk in 9 developmental domains the rate was 45%. Prevention programs targeting youth at high risk for engaging in maltreatment should begin during early adolescence when risk factors are already at play. These programs need to be comprehensive, capable of addressing the multiple and interwoven nature of risk that is associated with maltreatment. PMID:24075569

Association of branched-chain amino acids and other circulating metabolites with risk of incident dementia and Alzheimer's disease: A prospective study in eight cohorts.

PubMed

Tynkkynen, Juho; Chouraki, Vincent; van der Lee, Sven J; Hernesniemi, Jussi; Yang, Qiong; Li, Shuo; Beiser, Alexa; Larson, Martin G; Sääksjärvi, Katri; Shipley, Martin J; Singh-Manoux, Archana; Gerszten, Robert E; Wang, Thomas J; Havulinna, Aki S; Würtz, Peter; Fischer, Krista; Demirkan, Ayse; Ikram, M Arfan; Amin, Najaf; Lehtimäki, Terho; Kähönen, Mika; Perola, Markus; Metspalu, Andres; Kangas, Antti J; Soininen, Pasi; Ala-Korpela, Mika; Vasan, Ramachandran S; Kivimäki, Mika; van Duijn, Cornelia M; Seshadri, Sudha; Salomaa, Veikko

2018-06-01

Metabolite, lipid, and lipoprotein lipid profiling can provide novel insights into mechanisms underlying incident dementia and Alzheimer's disease. We studied eight prospective cohorts with 22,623 participants profiled by nuclear magnetic resonance or mass spectrometry metabolomics. Four cohorts were used for discovery with replication undertaken in the other four to avoid false positives. For metabolites that survived replication, combined association results are presented. Over 246,698 person-years, 995 and 745 cases of incident dementia and Alzheimer's disease were detected, respectively. Three branched-chain amino acids (isoleucine, leucine, and valine), creatinine and two very low density lipoprotein (VLDL)-specific lipoprotein lipid subclasses were associated with lower dementia risk. One high density lipoprotein (HDL; the concentration of cholesterol esters relative to total lipids in large HDL) and one VLDL (total cholesterol to total lipids ratio in very large VLDL) lipoprotein lipid subclass was associated with increased dementia risk. Branched-chain amino acids were also associated with decreased Alzheimer's disease risk and the concentration of cholesterol esters relative to total lipids in large HDL with increased Alzheimer's disease risk. Further studies can clarify whether these molecules play a causal role in dementia pathogenesis or are merely markers of early pathology. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

Population-Attributable Risk Proportion of Clinical Risk Factors for Breast Cancer.

PubMed

Engmann, Natalie J; Golmakani, Marzieh K; Miglioretti, Diana L; Sprague, Brian L; Kerlikowske, Karla

2017-09-01

Many established breast cancer risk factors are used in clinical risk prediction models, although the proportion of breast cancers explained by these factors is unknown. To determine the population-attributable risk proportion (PARP) for breast cancer associated with clinical breast cancer risk factors among premenopausal and postmenopausal women. Case-control study with 1:10 matching on age, year of risk factor assessment, and Breast Cancer Surveillance Consortium (BCSC) registry. Risk factor data were collected prospectively from January 1, 1996, through October 31, 2012, from BCSC community-based breast imaging facilities. A total of 18 437 women with invasive breast cancer or ductal carcinoma in situ were enrolled as cases and matched to 184 309 women without breast cancer, with a total of 58 146 premenopausal and 144 600 postmenopausal women enrolled in the study. Breast Imaging Reporting and Data System (BI-RADS) breast density (heterogeneously or extremely dense vs scattered fibroglandular densities), first-degree family history of breast cancer, body mass index (>25 vs 18.5-25), history of benign breast biopsy, and nulliparity or age at first birth (≥30 years vs <30 years). Population-attributable risk proportion of breast cancer. Of the 18 437 women with breast cancer, the mean (SD) age was 46.3 (3.7) years among premenopausal women and 61.7 (7.2) years among the postmenopausal women. Overall, 4747 (89.8%) premenopausal and 12 502 (95.1%) postmenopausal women with breast cancer had at least 1 breast cancer risk factor. The combined PARP of all risk factors was 52.7% (95% CI, 49.1%-56.3%) among premenopausal women and 54.7% (95% CI, 46.5%-54.7%) among postmenopausal women. Breast density was the most prevalent risk factor for both premenopausal and postmenopausal women and had the largest effect on the PARP; 39.3% (95% CI, 36.6%-42.0%) of premenopausal and 26.2% (95% CI, 24.4%-28.0%) of postmenopausal breast cancers could potentially be

Implications for Metabolite Quantification by Mass Spectrometry in the Absence of Authentic Standards.

PubMed

Hatsis, Panos; Waters, Nigel J; Argikar, Upendra A

2017-05-01

Quantification of metabolites by mass spectrometry in the absence of authentic reference standards or without a radiolabel is often called "semiquantitative," which acknowledges that mass spectrometric responses are not truly quantitative. For many researchers, it is tempting to pursue this practice of semiquantification in early drug discovery and even preclinical development, when radiolabeled absorption, distribution, metabolism, and excretion studies are being deferred to later stages of drug development. The caveats of quantifying metabolites based on parent drug response are explored in this investigation. A set of 71 clinically relevant drugs/metabolites encompassing common biotransformation pathways was subjected to flow injection analysis coupled with electrospray ionization (ESI) mass spectrometry. The results revealed a large variation in ESI response even for structurally similar parent drug/metabolite pairs. The ESI response of each metabolite was normalized to that of the parent drug to generate an ESI relative response factor. Overall, relative response factors ranged from 0.014 (>70-fold lower response than parent) to 8.6 (8.6-fold higher response than parent). Various two-dimensional molecular descriptors were calculated that describe physicochemical, topological, and structural properties for each drug/metabolite. The molecular descriptors, along with the ESI response factors, were used in univariate analyses as well as a principal components analysis to ascertain which molecular descriptors best account for the observed discrepancies in drug/metabolite ESI response. This investigation has shown that the practice of using parent drug response to quantify metabolites should be used with caution. Copyright © 2017 by The American Society for Pharmacology and Experimental Therapeutics.

Risk factors for retained placenta.

PubMed

Coviello, Elizabeth M; Grantz, Katherine L; Huang, Chun-Chih; Kelly, Tara E; Landy, Helain J

2015-12-01

Retained placenta complicates 2-3% of vaginal deliveries and is a known cause of postpartum hemorrhage. Treatment includes manual or operative placental extraction, potentially increasing risks of hemorrhage, infections, and prolonged hospital stays. We sought to evaluate risk factors for retained placenta, defined as more than 30 minutes between the delivery of the fetus and placenta, in a large US obstetrical cohort. We included singleton, vaginal deliveries ≥24 weeks (n = 91,291) from the Consortium of Safe Labor from 12 US institutions (2002-2008). Multivariable logistic regression analyses estimated the adjusted odds ratios (OR) and 95% confidence intervals (CI) for potential risk factors for retained placenta stratified by parity, adjusting for relevant confounding factors. Characteristics such as stillbirth, maternal age, race, and admission body mass index were examined. Retained placenta complicated 1047 vaginal deliveries (1.12%). Regardless of parity, significant predictors of retained placenta included stillbirth (nulliparous adjusted OR, 5.67; 95% CI, 3.10-10.37; multiparous adjusted OR, 4.56; 95% CI, 2.08-9.94), maternal age ≥30 years, delivery at 24 0/7 to 27 6/7 compared with 34 weeks or later and delivery in a teaching hospital. In nulliparous women, additional risk factors were identified: longer first- or second-stage labor duration, whereas non-Hispanic black compared with non-Hispanic white race was found to be protective. Body mass index was not associated with an increased risk. Multiple risk factors for retained placenta were identified, particularly the strong association with stillbirth. It is plausible that there could be something intrinsic about stillbirth that causes a retained placenta, or perhaps there are shared pathways of certain etiologies of stillbirth and a risk of retained placenta. Copyright © 2015 Elsevier Inc. All rights reserved.

Metabolite Profiles of Diabetes Incidence and Intervention Response in the Diabetes Prevention Program

PubMed Central

Ma, Yong; Clish, Clary; Florez, Jose C.; Wang, Thomas J.; Gerszten, Robert E.

2016-01-01

Identifying novel biomarkers of type 2 diabetes risk may improve prediction and prevention among individuals at high risk of the disease and elucidate new biological pathways relevant to diabetes development. We performed plasma metabolite profiling in the Diabetes Prevention Program (DPP), a completed trial that randomized high-risk individuals to lifestyle, metformin, or placebo interventions. Previously reported markers, branched-chain and aromatic amino acids and glutamine/glutamate, were associated with incident diabetes (P < 0.05 for all), but these associations were attenuated upon adjustment for clinical and biochemical measures. By contrast, baseline levels of betaine, also known as glycine betaine (hazard ratio 0.84 per SD log metabolite level, P = 0.02), and three other metabolites were associated with incident diabetes even after adjustment. Moreover, betaine was increased by the lifestyle intervention, which was the most effective approach to preventing diabetes, and increases in betaine at 2 years were also associated with lower diabetes incidence (P = 0.01). Our findings indicate betaine is a marker of diabetes risk among high-risk individuals both at baseline and during preventive interventions and they complement animal models demonstrating a direct role for betaine in modulating metabolic health. PMID:26861782

Risk Factors for Internet Gaming Disorder: Psychological Factors and Internet Gaming Characteristics.

PubMed

Rho, Mi Jung; Lee, Hyeseon; Lee, Taek-Ho; Cho, Hyun; Jung, Dong Jin; Kim, Dai-Jin; Choi, In Young

2017-12-27

Background : Understanding the risk factors associated with Internet gaming disorder (IGD) is important to predict and diagnose the condition. The purpose of this study is to identify risk factors that predict IGD based on psychological factors and Internet gaming characteristics; Methods : Online surveys were conducted between 26 November and 26 December 2014. There were 3568 Korean Internet game users among a total of 5003 respondents. We identified 481 IGD gamers and 3087 normal Internet gamers, based on Diagnostic and Statistical Manual for Mental Disorders (DSM-5) criteria. Logistic regression analysis was applied to identify significant risk factors for IGD; Results : The following eight risk factors were found to be significantly associated with IGD: functional and dysfunctional impulsivity (odds ratio: 1.138), belief self-control (1.034), anxiety (1.086), pursuit of desired appetitive goals (1.105), money spent on gaming (1.005), weekday game time (1.081), offline community meeting attendance (2.060), and game community membership (1.393; p < 0.05 for all eight risk factors); Conclusions : These risk factors allow for the prediction and diagnosis of IGD. In the future, these risk factors could also be used to inform clinical services for IGD diagnosis and treatment.

Relationship Satisfaction and Risk Factors for Suicide.

PubMed

Till, Benedikt; Tran, Ulrich S; Niederkrotenthaler, Thomas

2017-01-01

Previous studies suggest that troubled romantic relationships are associated with higher risk factors for mental health. However, studies examining the role of relationship satisfaction in suicide risk factors are scarce. We investigated differences in risk factors for suicide between individuals with high relationship satisfaction, individuals with low relationship satisfaction, and singles. Furthermore, we explored patterns of experiencing, and dealing with, conflicts in the relationship and examined associations with suicide risk factors. In this cross-sectional study, we assessed relationship status, relationship satisfaction, specific types of relationship conflicts, and suicide risk factors (i.e., suicidal ideation, hopelessness, depression) with questionnaires among 382 individuals in Austria. Risk factors for suicide were higher among singles than among individuals in happy relationships, but highest among those with low relationship satisfaction [corrected]. Participants reporting a high number of unsolved conflicts in their relationship had higher levels of suicidal ideation, hopelessness, and depression than individuals who tend to solve issues with their partner amicably or report no conflicts. Relationship satisfaction and relationship conflicts reflect risk factors for suicide, with higher levels of suicidal ideation, hopelessness, and depression reported by individuals who mentioned unsolved conflicts with their partner and experienced low satisfaction with their relationship.

Risk factors for post-tonsillectomy hemorrhage.

PubMed

Ikoma, Ryo; Sakane, Sayaka; Niwa, Kazutomo; Kanetaka, Sayaka; Kawano, Toshiro; Oridate, Nobuhiko

2014-08-01

The aim of the present study was to investigate the rate of post-tonsillectomy hemorrhage (PTH) in a single institution and to evaluate the clinical risk factors for PTH. We reviewed the records of 692 patients who underwent tonsillectomy (TE) at Yokohama Minami Kyosai Hospital in Japan. PTH grades were grouped into three categories according to the severity of the hemorrhagic episode: (I) minimal hemorrhage that stopped after noninvasive treatment, (II) hemorrhage requiring treatment with local anesthesia, and (III) hemorrhage requiring reoperation under general anesthesia in the operating room. Clinical risk factors such as sex, age (adults vs. children), TE indication, surgeon's skill level, operative time, ligature type, and duration of antibiotic administration for PTH were investigated. Among the 692 patients, 80 (11.6%) showed PTH, with primary and secondary hemorrhage accounting for 1.6% and 10.0%, respectively. A category III PTH was observed in 18 patients; thus, the overall risk of reoperation was 2.6%. The PTH episode most frequently occurred on postoperative days 5 and 6. The frequency of PTH was significantly higher in male patients and in adults (P<0.01, for both factors). Surgeon's skill was also associated with PTH rate. A stepwise multivariate logistic regression revealed that adult age (odds ratio [OR]=18.9) and male gender (OR=3.78) were the clinical risk factors for PTH. It also revealed that male gender (OR=82065335), adult age (OR=10.6), and surgeon's skill level (OR=7.50) were the clinical risk factors for the category III PTH. The risk of PTH was higher in this report compared with previous reports, which may be associated with the definition of PTH. Clinical risk factors for PTH were adult age and male gender. The surgeon's skill level was an additional risk factor for category III PTH. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

[Risk factors of necrotizing enterocolitis].

PubMed

Tapia-Rombo, C A; Velasco-Lavín, M R; Nieto-Caldelas, A

1993-09-01

The purpose of the present study is to compare risk factors of necrotizing enterocolitis (NEC) between two group: group A, newborns with the disease and group B, newborns with other diseases different from NEC, in order to know if these risk factors are more frequent or not in the first group. We assessed the clinical records of all the patients hospitalized in the Neonatal Intensive Care Unit and Neonatology Service of the La Raza General Hospital between 1987 and 1991 with the diagnosis of NEC. They were compared with 65 clinical records chosen at random of patients hospitalized in the same Unit with other diagnosis at the same time, and who were discharged by improvement or deceased. In all of them were look for known risk factors for NEC generally accepted such as: prematurity, neonatal asphyxia, poliglobulia, cyanotic congenital heart disease, patent ductus arteriosus, respiratory distress syndrome, catheterization of umbilical vessels, early feeding of elevated formula increases, exchange exchange transfusion, hypoxic ischemic encephalopathy, infection, etc. Just 25 records of the possible 50 with the diagnosis of NEC full filled inclusion criteria. There were no statistically significant difference in weight, sex, mortality and known risk factors of NEC between both groups. Were concluded that NEC is a disease of unknown etiology that should be studied more thoroughly. The known risk factors must be avoided because the patient susceptibility probably play an important role.

Urinary Estrogen Metabolites, Active and Sedentary Behaviors, and Breast Cancer Risk

Cancer.gov

A cross-sectional study of approximately 600 postmenopausal controls in the Breast Cancer Case-Control Study in Poland to assess urinary estrogen metabolites in relation to accelerometer-based measures of active and sedentary behaviors

Configurations of Common Childhood Psychosocial Risk Factors

ERIC Educational Resources Information Center

Copeland, William; Shanahan, Lilly; Costello, E. Jane; Angold, Adrian

2009-01-01

Background: Co-occurrence of psychosocial risk factors is commonplace, but little is known about psychiatrically-predictive configurations of psychosocial risk factors. Methods: Latent class analysis (LCA) was applied to 17 putative psychosocial risk factors in a representative population sample of 920 children ages 9 to 17. The resultant class…

Metabolites in vertebrate Hedgehog signaling.

PubMed

Roberg-Larsen, Hanne; Strand, Martin Frank; Krauss, Stefan; Wilson, Steven Ray

2014-04-11

The Hedgehog (HH) signaling pathway is critical in embryonic development, stem cell biology, tissue homeostasis, chemoattraction and synapse formation. Irregular HH signaling is associated with a number of disease conditions including congenital disorders and cancer. In particular, deregulation of HH signaling has been linked to skin, brain, lung, colon and pancreatic cancers. Key mediators of the HH signaling pathway are the 12-pass membrane protein Patched (PTC), the 7-pass membrane protein Smoothened (SMO) and the GLI transcription factors. PTC shares homology with the RND family of small-molecule transporters and it has been proposed that it interferes with SMO through metabolites. Although a conclusive picture is lacking, substantial efforts are made to identify and understand natural metabolites/sterols, including cholesterol, vitamin D3, oxysterols and glucocorticoides, that may be affected by, or influence the HH signaling cascade at the level of PTC and SMO. In this review we will elaborate the role of metabolites in HH signaling with a focus on oxysterols, and discuss advancements in modern analytical approaches in the field. Copyright © 2014 Elsevier Inc. All rights reserved.

Skin Cancer: Biology, Risk Factors & Treatment

MedlinePlus

... turn Javascript on. Feature: Skin Cancer Skin Cancer: Biology, Risk Factors & Treatment Past Issues / Summer 2013 Table ... Articles Skin Cancer Can Strike Anyone / Skin Cancer: Biology, Risk Factors & Treatment / Timely Healthcare Checkup Catches Melanoma ...

Effect of Cultivar and Cultivation Year on the Metabolite Profile of Onion Bulbs ( Allium cepa L.).

PubMed

Böttcher, Christoph; Krähmer, Andrea; Stürtz, Melanie; Widder, Sabine; Schulz, Hartwig

2018-03-28

This study investigated the variation of metabolite profiles of onion bulbs ( Allium cepa L.) depending on genetic and environmental factors. Nine onion cultivars ("Corrado", "Cupido", "Forum", "Hytech", "Picador", "Redlight", "Snowpack", "Stardust", "Sturon") with different scale color and dry matter content were grown in a two-year field trial. Using a recently established metabolite profiling approach based on liquid chromatography-coupled electrospray ionization quadrupole time-of-flight mass spectrometry, 106 polar and semipolar metabolites which belong to compound classes determining nutritional, sensory, and technological quality of onion bulbs such as saccharides, flavonoids, S-substitued cysteine conjugates, amino acids, and derived γ-glutamyl peptides were relatively quantitated in parallel. Statistical analyses of the obtained data indicated that depending on the compound class genetic and environmental factors differently contributed to variation of metabolite levels. For saccharides and flavonoids the genetic factor was the major source of variation, whereas for cysteine sulfoxides, amino acids, and peptides both genetic and environmental factors had a significant impact on corresponding metabolite levels.

Managing Multiple Risk Factors.

DTIC Science & Technology

1998-09-01

to the racial differences in cardiovascular risk and events among women. High levels of socioeconomic stress, higher dietary fat intake and sedentary ... lifestyle are more prevalent among black than white women. The proposed study will address the issue of whether the cluster of risk factors for

Non-dietary environmental risk factors in prostate cancer

PubMed Central

Ferrís-i-Tortajada, J; Berbel-Tornero, O; Garcia-i-Castell, J; López-Andreu, J.A.; Sobrino-Najul, E; Ortega-García, J.A.

2016-01-01

Introduction The aim is to update and disclose the main environmental risk factors, excluding dietary factors, involved in the etiopathology of prostate cancer. Materials and methods Bibliographic review of the last 25 years of non-dietary environmental risk factors associated with prostate cancer between 1985 and 2010, obtained from MedLine, CancerLit, Science Citation Index and Embase. The search profiles were Environmental Risk Factors/Tobacco/Infectious-Inflammatory Factors/Pesticides/Vasectomy/Occupational Exposures/ Chemoprevention Agents/Radiation and Prostate Cancer. Results While some non-dietary environmental risk factors increase the risk of acquiring the disease, others decrease it. Of the former, it is worth mentioning exposal to tobacco smoke, chronic infectious-inflammatory prostatic processes and occupational exposure to cadmium, herbicides and pesticides. The first factors that reduce the risk are the use of chemopreventive drugs (Finasterida, Dutasteride) and exposure to ultraviolet solar radiation. With the current data, a vasectomy does not influence the risk of developing the disease. Conclusions The slow process of prostate carcinogenesis is the final result of the interaction of constitutional risk and environmental factors. Non-dietary environmental factors play an important role in the etiopathology of this disease. To appropriately assess the risk factors, extensive case studies that include all the possible variables must be analyzed. PMID:21439685

Global risk factor rankings: the importance of age-based health loss inequities caused by alcohol and other risk factors.

PubMed

Shield, Kevin D; Rehm, Jürgen

2015-06-09

Achieving health equity is a priority of the World Health Organization; however, there is a scant amount of literature on this topic. As the underlying influences that determine health loss caused by risk factors are age-dependent, the aim of this paper is to examine how the risk factor rankings for health loss differ by age. Rankings were based on data obtained from the 2010 Global Burden of Disease study. Health loss (as measured by Disability Adjusted Life Years lost) by risk factor was estimated using Population-Attributable Fractions, years of life lost due to premature mortality, and years lived with disability, which were calculated for 187 countries, 20 age groups and both sexes. Uncertainties of the risk factor rankings were estimated using 1,000 simulations taken from posterior distributions The top risk factors by age were: household air pollution for neonates 0-6 days of age [95% uncertainty interval (UI): 1 to 1]; suboptimal breast feeding for children 7-27 days of age (95% UI: 1-1); childhood underweight for children 28 days to less than 1 year of age and 1-4 years of age (95% UI: 1-2 and 1-1, respectively); iron deficiency for children and youth 5-14 years of age (95% UI: 1-1); alcohol use for people 15-49 years of age (95% UI: 1-2); and dietary risks for people 50 years of age and older (95% UI: 1-1). Rankings of risk factors varied by sex among the older age groups. Alcohol and smoking were the most important risk factors among men 15 years of age and older, and high body mass and intimate partner violence were some of the most important risk factors among women 15 years of age and older. Our analyses confirm that the relative importance of risk factors is age-dependent. Therefore, preventing harms caused by various modifiable risk factors using interventions that target people of different ages should be a priority, especially since easily implemented and cost-effective public health interventions exist.

Activation of the sigma-1 receptor by haloperidol metabolites facilitates brain-derived neurotrophic factor secretion from human astroglia.

PubMed

Dalwadi, Dhwanil A; Kim, Seongcheol; Schetz, John A

2017-05-01

Glial cells play a critical role in neuronal support which includes the production and release of the neurotrophin brain-derived neurotrophic factor (BDNF). Activation of the sigma-1 receptor (S1R) has been shown to attenuate inflammatory stress-mediated brain injuries, and there is emerging evidence that this may involve a BDNF-dependent mechanism. In this report we studied S1R-mediated BDNF release from human astrocytic glial cells. Astrocytes express the S1R, which mediates BDNF release when stimulated with the prototypical S1R agonists 4-PPBP and (+)-SKF10047. This effect could be antagonized by a selective concentration of the S1R antagonist BD1063. Haloperidol is known to have high affinity interactions with the S1R, yet it was unable to facilitate BDNF release. Remarkably, however, two metabolites of haloperidol, haloperidol I and haloperidol II (reduced haloperidol), were discovered to facilitate BDNF secretion and this effect was antagonized by BD1063. Neither 4-PPBP, nor either of the haloperidol metabolites affected the level of BDNF mRNA as assessed by qPCR. These results demonstrate for the first time that haloperidol metabolites I and II facilitate the secretion of BDNF from astrocytes by acting as functionally selective S1R agonists. Copyright © 2017 Elsevier Ltd. All rights reserved.

Suicide in developing countries (2): risk factors.

PubMed

Vijayakumar, Lakshmi; John, Sujit; Pirkis, Jane; Whiteford, Harvey

2005-01-01

The majority of studies on risk factors for suicide have been conducted in developed countries, and less work has been done to systematically profile risk factors in developing countries. The current paper presents a selective review of sociodemographic, clinical, and environmental/situational risk factors in developing countries. Taken together, the evidence suggests that the profiles of risk factors in developing countries demonstrate some differences from those in developed countries. In some developing countries, at least, being female, living in a rural area, and holding religious beliefs that sanction suicide may be of more relevance to suicide risk than these factors are in developed countries. Conversely, being single or having a history of mental illness may be of less relevance. Risk factors that appear to be universal include youth or old age, low socioeconomic standing, substance use, and previous suicide attempts. Recent stressful life events play a role in both developing and developed countries, although their nature may differ (e.g., social change may have more of an influence in the former). Likewise, access to means heightens risk in both, but the specific means may vary (e.g., access to pesticides is of more relevance in developing countries). These findings have clear implications for suicide prevention, suggesting that preventive efforts that have shown promise in developed countries may need to be tailored differently to address the risk factor profile of developing countries.

Risk Factors for Internet Gaming Disorder: Psychological Factors and Internet Gaming Characteristics

PubMed Central

Lee, Hyeseon; Lee, Taek-Ho; Cho, Hyun; Kim, Dai-Jin; Choi, In Young

2017-01-01

Background: Understanding the risk factors associated with Internet gaming disorder (IGD) is important to predict and diagnose the condition. The purpose of this study is to identify risk factors that predict IGD based on psychological factors and Internet gaming characteristics; Methods: Online surveys were conducted between 26 November and 26 December 2014. There were 3568 Korean Internet game users among a total of 5003 respondents. We identified 481 IGD gamers and 3087 normal Internet gamers, based on Diagnostic and Statistical Manual for Mental Disorders (DSM-5) criteria. Logistic regression analysis was applied to identify significant risk factors for IGD; Results: The following eight risk factors were found to be significantly associated with IGD: functional and dysfunctional impulsivity (odds ratio: 1.138), belief self-control (1.034), anxiety (1.086), pursuit of desired appetitive goals (1.105), money spent on gaming (1.005), weekday game time (1.081), offline community meeting attendance (2.060), and game community membership (1.393; p < 0.05 for all eight risk factors); Conclusions: These risk factors allow for the prediction and diagnosis of IGD. In the future, these risk factors could also be used to inform clinical services for IGD diagnosis and treatment. PMID:29280953

Phthalate metabolites related to infertile biomarkers and infertility in Chinese men.

PubMed

Liu, Liangpo; Wang, Heng; Tian, Meiping; Zhang, Jie; Panuwet, Parinya; D'Souza, Priya Esilda; Barr, Dana Boyd; Huang, Qingyu; Xia, Yankai; Shen, Heqing

2017-12-01

Although in vitro and in vivo laboratory studies have demonstrated androgen and anti-androgen effects on male reproduction from phthalate exposures, human studies still remain inconsistent. Therefore, a case-control study (n = 289) was conducted to evaluate the associations between phthalate exposures, male infertility risks, and changes in metabolomic biomarkers. Regional participants consisted of fertile (n = 150) and infertile (n = 139) males were recruited from Nanjing Medical University' affiliated hospitals. Seven urinary phthalate metabolites were measured using HPLC-MS/MS. Associations between levels of phthalate metabolites, infertility risks, and infertility-related biomarkers were statistically evaluated. MEHHP, one of the most abundant DEHP oxidative metabolites was significantly lower in cases than in controls (p = 0.039). When using the 1st quartile range as a reference, although statistically insignificant for odds ratios (ORs) of the 2nd, 3rd, and 4th quartiles (OR (95% CI) = 1.50 (0.34-6.48), 0.70 (0.14-3.52) and 0.42 (0.09-2.00), respectively), the MEHHP dose-dependent trend of infertility risk expressed as OR decreased significantly (p = 0.034). More interestingly, most of the phthalate metabolites, including MEHHP, were either positively associated with fertile prevention metabolic biomarkers or negatively associated with fertile hazard ones. Phthalate metabolism, along with their activated infertility-related biomarkers, may contribute to a decreased risk of male infertility at the subjects' ongoing exposure levels. Our results may be illustrated by the low-dose related androgen effect of phthalates and can improve our understanding of the controversial epidemiological results on this issue. Copyright © 2017 Elsevier Ltd. All rights reserved.

Risk factors for pulmonary tuberculosis in Estonia.

PubMed

Tekkel, M; Rahu, M; Loit, H M; Baburin, A

2002-10-01

To determine the risk factors for pulmonary tuberculosis incidence in Estonia. In a case-control study, the cases were 248 adult tuberculosis patients treated in a hospital in Tallinn between January 1999 and June 2000, and the controls were 248 persons sampled from the Population Registry and matched to cases by sex, year of birth and county of residence. A questionnaire was administered to collect information on potential risk factors. Logistic regression was used to calculate odds ratios and 95% confidence intervals. The main risk factors for tuberculosis were marital status other than married, educational level less than higher, low income, having been in prison, not having own place of residence, current unemployment, current smoking, alcohol consumption, shortage of food, and contact with tuberculosis patients. Place of birth was not a risk factor. Risk of tuberculosis decreased for overweight persons whose individual economic situation had improved during the last year. The pattern of risk factors for pulmonary tuberculosis in Estonia was somewhat different from that in Western European countries; a large percentage of the patients were men, but were not elderly, and immigration and drug abuse did not increase the risk. Major risk factors were related to poverty and low socio-economic status.

Hidden Risk Factors for Women

MedlinePlus

... risk factors are present. History of Preeclampsia/Eclampsia: Women with a history of preeclampsia/eclampsia have an increased risk of ... can increase the risk of stroke. Clotting disorders: Women who’ve ... can include previous history of clots in the legs (deep vein thrombosis) ...

Sexual harassment: identifying risk factors.

PubMed

O'Hare, E A; O'Donohue, W

1998-12-01

A new model of the etiology of sexual harassment, the four-factor model, is presented and compared with several models of sexual harassment including the biological model, the organizational model, the sociocultural model, and the sex role spillover model. A number of risk factors associated with sexually harassing behavior are examined within the framework of the four-factor model of sexual harassment. These include characteristics of the work environment (e.g., sexist attitudes among co-workers, unprofessional work environment, skewed sex ratios in the workplace, knowledge of grievance procedures for sexual harassment incidents) as well as personal characteristics of the subject (e.g., physical attractiveness, job status, sex-role). Subjects were 266 university female faculty, staff, and students who completed the Sexual Experience Questionnaire to assess the experience of sexual harassment and a questionnaire designed to assess the risk factors stated above. Results indicated that the four-factor model is a better predictor of sexual harassment than the alternative models. The risk factors most strongly associated with sexual harassment were an unprofessional environment in the workplace, sexist atmosphere, and lack of knowledge about the organization's formal grievance procedures.

Phthalate metabolite levels and menopausal hot flashes in midlife women.

PubMed

Ziv-Gal, Ayelet; Gallicchio, Lisa; Chiang, Catheryne; Ther, Sara N; Miller, Susan R; Zacur, Howard A; Dills, Russell L; Flaws, Jodi A

2016-04-01

During the menopausal transition, a woman's reproductive capacity declines, her hormone milieu changes, and her risk of hot flashes increases. Exposure to phthalates, which can be found in personal care products, can also result in altered reproductive function. Here, we investigated the associations between phthalate metabolite levels and midlife hot flashes. Eligible women (45-54 years of age) provided detailed information on hot flashes history and donated urine samples (n=195). Urinary phthalate metabolite levels were measured by HPLC-MS/MS. A higher total sum of phthalate metabolites commonly found in personal care products was associated with an increased risk of ever experiencing hot flashes (odds ratio (OR)=1.45; 95% confidence interval (CI)=1.07-1.96), hot flashes in the past 30days (OR=1.43; 95%CI=1.04-1.96), and more frequent hot flashes (OR=1.47; 95%CI=1.06-2.05). These data suggest that some phthalate exposures from personal care products are associated with menopausal hot flashes in women. Copyright © 2016 Elsevier Inc. All rights reserved.

Phthalate metabolite levels and menopausal hot flashes in midlife women

PubMed Central

Ziv-Gal, Ayelet; Gallicchio, Lisa; Chiang, Catheryne; Ther, Sara N.; Miller, Susan R.; Zacur, Howard A.; Dills, Russell L.; Flaws, Jodi A.

2016-01-01

During the menopausal transition, a woman’s reproductive capacity declines, her hormone milieu changes, and her risk of hot flashes increases. Exposure to phthalates, which can be found in personal-care products, can also result in altered reproductive function. Here, we investigated the associations between phthalate metabolite levels and midlife hot flashes. Eligible women (45–54 years of age) provided detailed information on hot flashes history and donated urine samples (n=195). Urinary phthalate metabolite levels were measured by HPLC-MS/MS. A higher total sum of phthalate metabolites commonly found in personal-care products was associated with an increased risk of ever experiencing hot flashes (odds ratio (OR)=1.45; 95% confidence interval (CI)= 1.07–1.96), hot flashes in the past 30 days (OR=1.43; 95%CI=1.04–1.96), and more frequent hot flashes (OR=1.47; 95%CI=1.06–2.05). These data suggest that some phthalate exposures from personal care products are associated with menopausal hot flashes in women. PMID:26867866

[Pathological gambling: risk factors].

PubMed

Bouju, G; Grall-Bronnec, M; Landreat-Guillou, M; Venisse, J-L

2011-09-01

In France, consumption of gambling games increased by 148% between 1960 and 2005. In 2004, gamblers lost approximately 0.9% of household income, compared to 0.4% in 1960. This represents approximately 134 Euros per year and per head. In spite of this important increase, the level remains lower than the European average (1%). However, gambling practices may continue to escalate in France in the next few years, particularly with the recent announce of the legalisation of online games and sports betting. With the spread of legalised gambling, pathological gambling rates may increase in France in the next years, in response to more widely available and more attractive gambling opportunities. In this context, there is a need for better understanding of the risk factors that are implicated in the development and maintenance of pathological gambling. This paper briefly describes the major risk factors for pathological gambling by examining the recent published literature available during the first quarter of 2008. This documentary basis was collected by Inserm for the collective expert report procedure on Gambling (contexts and addictions). Seventy-two articles focusing on risk factors for pathological gambling were considered in this review. Only 47 of them were taken into account for analysis. The selection of these 47 publications was based on the guide on literature analysis established by the French National Agency for Accreditation and Assessment in Health (ANAES, 2000). Some publications from more recent literature have also been added, mostly about Internet gambling. We identify three major types of risk factors implicated in gambling problems: some of them are related to the subject (individual factors), others are related to the object of the addiction, here the gambling activity by itself (structural factors), and the last are related to environment (contextual or situational factors). Thus, the development and maintenance of pathological gambling seems to be

Circulating metabolite predictors of glycemia in middle-aged men and women.

PubMed

Würtz, Peter; Tiainen, Mika; Mäkinen, Ville-Petteri; Kangas, Antti J; Soininen, Pasi; Saltevo, Juha; Keinänen-Kiukaanniemi, Sirkka; Mäntyselkä, Pekka; Lehtimäki, Terho; Laakso, Markku; Jula, Antti; Kähönen, Mika; Vanhala, Mauno; Ala-Korpela, Mika

2012-08-01

Metabolite predictors of deteriorating glucose tolerance may elucidate the pathogenesis of type 2 diabetes. We investigated associations of circulating metabolites from high-throughput profiling with fasting and postload glycemia cross-sectionally and prospectively on the population level. Oral glucose tolerance was assessed in two Finnish, population-based studies consisting of 1,873 individuals (mean age 52 years, 58% women) and reexamined after 6.5 years for 618 individuals in one of the cohorts. Metabolites were quantified by nuclear magnetic resonance spectroscopy from fasting serum samples. Associations were studied by linear regression models adjusted for established risk factors. Nineteen circulating metabolites, including amino acids, gluconeogenic substrates, and fatty acid measures, were cross-sectionally associated with fasting and/or postload glucose (P < 0.001). Among these metabolic intermediates, branched-chain amino acids, phenylalanine, and α1-acid glycoprotein were predictors of both fasting and 2-h glucose at 6.5-year follow-up (P < 0.05), whereas alanine, lactate, pyruvate, and tyrosine were uniquely associated with 6.5-year postload glucose (P = 0.003-0.04). None of the fatty acid measures were prospectively associated with glycemia. Changes in fatty acid concentrations were associated with changes in fasting and postload glycemia during follow-up; however, changes in branched-chain amino acids did not follow glucose dynamics, and gluconeogenic substrates only paralleled changes in fasting glucose. Alterations in branched-chain and aromatic amino acid metabolism precede hyperglycemia in the general population. Further, alanine, lactate, and pyruvate were predictive of postchallenge glucose exclusively. These gluconeogenic precursors are potential markers of long-term impaired insulin sensitivity that may relate to attenuated glucose tolerance later in life.

Urine phyto-oestrogen metabolites are not significantly associated with risk of type 2 diabetes: the Singapore Chinese health study.

PubMed

Talaei, Mohammad; Lee, Bee L; Ong, Choon N; van Dam, Rob M; Yuan, Jian M; Koh, Woon P; Pan, An

2016-05-01

We evaluated the relationship between urine concentrations of phyto-oestrogens (isoflavones and lignans) and risk of incident type 2 diabetes in middle-aged and elderly Chinese residing in Singapore. Urine metabolites of isoflavones and lignans were assayed by HPLC among 564 diabetes cases and 564 matched controls in a case-control study nested within the Singapore Chinese Health Study cohort. Participants were free of diagnosed diabetes, CVD and cancer at morning urine collections during 1999-2004. Cases were participants who reported to have physician-diagnosed diabetes at follow-up visits during 2006-2010, whereas controls were randomly selected among those who remained free of diabetes and were matched to the index cases by age, sex, dialect group and date of urine collection. Conditional logistic regression models were used to calculate OR and 95 % CI with adjustment for potential confounders. The mean age of the participants at the time of urine collection was 59·8 years, and the average interval between urine collection and diabetes diagnosis was 4·0 years. The multivariate-adjusted OR for diabetes were 1·00 (reference), 0·76 (95 % CI 0·52, 1·11), 0·78 (95 % CI 0·53, 1·14) and 0·79 (95 % CI 0·54, 1·15) across quartiles of urine isoflavones (P for trend=0·54), and were 1·00 (reference), 0·87 (95 % CI 0·60, 1·27), 1·10 (95 % CI 0·77, 1·56) and 0·93 (95 % CI 0·63, 1·37) for lignans (P for trend=0·93). The results were similar in men and women, as well as for individual metabolites of isoflavones (genistein, daidzein, glycitin and equol) or lignans (enterodiol and enterolactone). The present study did not find a significant association between urine phyto-oestrogen metabolites and risk of type 2 diabetes in Chinese adults.

Risk factors, health risks, and risk management for aircraft personnel and frequent flyers.

PubMed

Kim, Jeoum Nam; Lee, Byung Mu

2007-01-01

Health risks associated with long periods of time in flight are of concern to astronauts, crew members, and passengers. Many epidemiological studies showed that occupational and frequent flyers may be susceptible to ocular, cardiovascular, neurological, pulmonary, gastrointestinal, sensory, immunological, physiological, and even developmental disorders. In addition, the incidences of cancer and food poisoning are expected to be higher in such individuals. This article reviews health risks and risk factors associated with air travel, and discusses risk management strategies. To reduce adverse health risks, risk factors such as radiation, infection, stress, temperature, pressure, and circadian rhythm need to be avoided or reduced to levels that are as low as technologically achievable to protect flight personnel and passengers.

Biologically Active Metabolites Synthesized by Microalgae

PubMed Central

Costa, Jorge Alberto Vieira

2015-01-01

Microalgae are microorganisms that have different morphological, physiological, and genetic traits that confer the ability to produce different biologically active metabolites. Microalgal biotechnology has become a subject of study for various fields, due to the varied bioproducts that can be obtained from these microorganisms. When microalgal cultivation processes are better understood, microalgae can become an environmentally friendly and economically viable source of compounds of interest, because production can be optimized in a controlled culture. The bioactive compounds derived from microalgae have anti-inflammatory, antimicrobial, and antioxidant activities, among others. Furthermore, these microorganisms have the ability to promote health and reduce the risk of the development of degenerative diseases. In this context, the aim of this review is to discuss bioactive metabolites produced by microalgae for possible applications in the life sciences. PMID:26339647

Stroke - risk factors

MedlinePlus

... is cut off for longer than a few seconds, the brain cannot get nutrients and oxygen. Brain cells can die, causing lasting damage. Risk factors are things that increase your chance of getting a disease or condition. This article ...

Chemopreventive Activities of Sulforaphane and Its Metabolites in Human Hepatoma HepG2 Cells.

PubMed

Liu, Peng; Wang, Wei; Zhou, Zhigang; Smith, Andrew J O; Bowater, Richard P; Wormstone, Ian Michael; Chen, Yuqiong; Bao, Yongping

2018-05-09

Sulforaphane (SFN) exhibits chemopreventive effects through various mechanisms. However, few studies have focused on the bioactivities of its metabolites. Here, three metabolites derived from SFN were studied, known as sulforaphane glutathione, sulforaphane cysteine and sulforaphane- N -acetylcysteine. Their effects on cell viability, DNA damage, tumorigenicity, cell migration and adhesion were measured in human hepatoma HepG2 cells, and their anti-angiogenetic effects were determined in a 3D co-culture model of human umbilical vein endothelial cells (HUVECs) and pericytes. Results indicated that these metabolites at high doses decreased cancer cell viability, induced DNA damage and inhibited motility, and impaired endothelial cell migration and tube formation. Additionally, pre-treatment with low doses of SFN metabolites protected against H₂O₂ challenge. The activation of the nuclear factor E2-related factor 2 (Nrf2)-antioxidant response element (ARE) pathway and the induction of intracellular glutathione (GSH) played an important role in the cytoprotective effects of SFN metabolites. In conclusion, SFN metabolites exhibited similar cytotoxic and cytoprotective effects to SFN, which proves the necessity to study the mechanisms of action of not only SFN but also of its metabolites. Based on the different tissue distribution profiles of these metabolites, the most relevant chemical forms can be selected for targeted chemoprevention.

Epidemiology and risk factors of schizophrenia.

PubMed

Janoutová, Jana; Janácková, Petra; Serý, Omar; Zeman, Tomás; Ambroz, Petr; Kovalová, Martina; Varechová, Katerina; Hosák, Ladislav; Jirík, Vitezslav; Janout, Vladimír

2016-01-01

Schizophrenia is a severe mental disorder that affects approximately one percent of the general population. The pathogenesis of schizophrenia is influenced by many risk factors, both environmental and genetic. The environmental factors include the date of birth, place of birth and seasonal effects, infectious diseases, complications during pregnancy and delivery, substance abuse and stress. At the present time, in addition to environmental factors, genetic factors are assumed to play a role in the development of the schizophrenia. The heritability of schizo- phrenia is up to 80%. If one parent suffers from the condition, the probability that it will be passed down to the offspring is 13%. If it is present in both parents, the risk is more than 20%. The opinions are varied as to the risk factors affecting the development of schizophrenia. Knowing these factors may greatly contribute to prevention of the condition.

Risk Factor Intervention for Health Maintenance

ERIC Educational Resources Information Center

Breslow, Lester

1978-01-01

Risk factors for disease consist of personal habits such as cigarette smoking and excessive alcohol consumption, and bodily characteristics such as hypertension and high serum cholesterol. Progress in identifying, quantifying, and controlling risk factors is opening the way to the prevention of disease. (BB)

[Risk factors for preterm labor].

PubMed

Rodrigues, T; Barros, H

1998-10-01

Most studies investigating preterm risk factors include medically induced preterm labor due to fetal or maternal complications and do not distinguish preterm labor from preterm premature rupture of membranes. Thus, the objective of this study was to determine the proportion of the three types of preterm birth and identify risk factors for spontaneous preterm labor in a sample of pregnant women who delivered at two level III units. From January to October 1996, we interviewed 385 women with live preterm newborns and, as controls, 357 mothers of term newborns. Preterm births were classified as preterm labor, preterm premature rupture of membranes and iathrogenic preterm. Independent associations between maternal sociodemographic, constitutional, nutritional and obstetric characteristics and preterm labor were identified using logistic regression analysis. In this sample of preterm births, 29% corresponded to preterm labor, 49% to preterm premature rupture of the membranes and 22% were iathrogenic preterm. The identified risk factors for preterm labor were multiple gestation, no paid work during pregnancy, less than six prenatal care visits, arm circumference less than 26 cm and previous preterm or low birth-weight. Gestational bleeding during the first or third trimester was significantly associated with preterm labor. As previously recognized, multiple gestation, prior preterm or low birthweight and gestational bleeding are established risk factors for preterm labor. However, prenatal care, maternal work and nutritional status have also been revealed as important issues in preterm risk, deserving special interest since they are susceptible to preventive intervention.

Stroke Epidemiology and Risk Factor Management.

PubMed

Guzik, Amy; Bushnell, Cheryl

2017-02-01

Death from stroke has decreased over the past decade, with stroke now the fifth leading cause of death in the United States. In addition, the incidence of new and recurrent stroke is declining, likely because of the increased use of specific prevention medications, such as statins and antihypertensives. Despite these positive trends in incidence and mortality, many strokes remain preventable. The major modifiable risk factors are hypertension, diabetes mellitus, tobacco smoking, and hyperlipidemia, as well as lifestyle factors, such as obesity, poor diet/nutrition, and physical inactivity. This article reviews the current recommendations for the management of each of these modifiable risk factors. It has been documented that some blood pressure medications may increase variability of blood pressure and ultimately increase the risk for stroke. Stroke prevention typically includes antiplatelet therapy (unless an indication for anticoagulation exists), so the most recent evidence supporting use of these drugs is reviewed. In addition, emerging risk factors, such as obstructive sleep apnea, electronic cigarettes, and elevated lipoprotein (a), are discussed. Overall, secondary stroke prevention includes a multifactorial approach. This article incorporates evidence from guidelines and published studies and uses an illustrative case study throughout the article to provide examples of secondary prevention management of stroke risk factors.

A New Paradigm for Known Metabolite Identification in Metabonomics/Metabolomics: Metabolite Identification Efficiency

PubMed Central

Everett, Jeremy R.

2015-01-01

A new paradigm is proposed for assessing confidence in the identification of known metabolites in metabonomics studies using NMR spectroscopy approaches. This new paradigm is based upon the analysis of the amount of metabolite identification information retrieved from NMR spectra relative to the molecular size of the metabolite. Several new indices are proposed including: metabolite identification efficiency (MIE) and metabolite identification carbon efficiency (MICE), both of which can be easily calculated. These indices, together with some guidelines, can be used to provide a better indication of known metabolite identification confidence in metabonomics studies than existing methods. Since known metabolite identification in untargeted metabonomics studies is one of the key bottlenecks facing the science currently, it is hoped that these concepts based on molecular spectroscopic informatics, will find utility in the field. PMID:25750701

A new paradigm for known metabolite identification in metabonomics/metabolomics: metabolite identification efficiency.

PubMed

Everett, Jeremy R

2015-01-01

A new paradigm is proposed for assessing confidence in the identification of known metabolites in metabonomics studies using NMR spectroscopy approaches. This new paradigm is based upon the analysis of the amount of metabolite identification information retrieved from NMR spectra relative to the molecular size of the metabolite. Several new indices are proposed including: metabolite identification efficiency (MIE) and metabolite identification carbon efficiency (MICE), both of which can be easily calculated. These indices, together with some guidelines, can be used to provide a better indication of known metabolite identification confidence in metabonomics studies than existing methods. Since known metabolite identification in untargeted metabonomics studies is one of the key bottlenecks facing the science currently, it is hoped that these concepts based on molecular spectroscopic informatics, will find utility in the field.

Environmental risk factors for dementia: a systematic review.

PubMed

Killin, Lewis O J; Starr, John M; Shiue, Ivy J; Russ, Tom C

2016-10-12

Dementia risk reduction is a major and growing public health priority. While certain modifiable risk factors for dementia have been identified, there remains a substantial proportion of unexplained risk. There is evidence that environmental risk factors may explain some of this risk. Thus, we present the first comprehensive systematic review of environmental risk factors for dementia. We searched the PubMed and Web of Science databases from their inception to January 2016, bibliographies of review articles, and articles related to publically available environmental data. Articles were included if they examined the association between an environmental risk factor and dementia. Studies with another outcome (for example, cognition), a physiological measure of the exposure, case studies, animal studies, and studies of nutrition were excluded. Data were extracted from individual studies which were, in turn, appraised for methodological quality. The strength and consistency of the overall evidence for each risk factor identified was assessed. We screened 4784 studies and included 60 in the review. Risk factors were considered in six categories: air quality, toxic heavy metals, other metals, other trace elements, occupational-related exposures, and miscellaneous environmental factors. Few studies took a life course approach. There is at least moderate evidence implicating the following risk factors: air pollution; aluminium; silicon; selenium; pesticides; vitamin D deficiency; and electric and magnetic fields. Studies varied widely in size and quality and therefore we must be circumspect in our conclusions. Nevertheless, this extensive review suggests that future research could focus on a short list of environmental risk factors for dementia. Furthermore, further robust, longitudinal studies with repeated measures of environmental exposures are required to confirm these associations.

Risk factors affecting survival in heart transplant patients.

PubMed

Almenar, L; Cardo, M L; Martínez-Dolz, L; García-Palomar, C; Rueda, J; Zorio, E; Arnau, M A; Osa, A; Palencia, M

2005-11-01

Certain cardiovascular risk factors have been linked to morbidity and mortality in heart transplant (HT) patients. The sum of various risk factors may have a large cumulative negative effect, leading to a substantially worse prognosis and the need to consider whether HT is contraindicated. The objective of this study was to determine whether the risk factors usually available prior to HT result in an excess mortality in our setting that contraindicates transplantation. Consecutive patients who underwent heart transplantation from November 1987 to January 2004 were included. Heart-lung transplants, retransplants, and pediatric transplants were excluded. Of the 384 patients, 89% were men. Mean age was 52 years (range, 12 to 67). Underlying disease included ischemic heart disease (52%), idiopathic dilated cardiomyopathy (36%), valvular disease (8%), and other (4%). Variables considered risk factors were obesity (BMI >25), dyslipidemia, hypertension, prior thoracic surgery, diabetes, and history of ischemic heart disease. Survival curves by number of risk factors using Kaplan-Meier and log-rank for comparison of curves. Overall patient survival at 1, 5, 10, and 13 years was 76%, 68%, 54%, and 47%, respectively. Survival at 10 years, if fewer than two risk factors were present, was 69%; 59% if two or three factors were present; and 37% if more than three associated risk factors were present (P = .04). The presence of certain risk factors in patients undergoing HT resulted in lower survival rates. The combination of various risk factors clearly worsened outcomes. However, we do not believe this should be an absolute contraindication for transplantation.

Effect of Ramadan fasting on urinary risk factors for calculus formation.

PubMed

Miladipour, Amir Hossein; Shakhssalim, Nasser; Parvin, Mahmoud; Azadvari, Mohaddeseh

2012-01-01

Even though dehydration could aggravate formation of urinary calculi, the effects of fluid and food restriction on calculus formation is not thoroughly defined. The purpose of this study is to evaluate the effects of fluid and food restriction in Ramadan fasting on urinary factors in kidney and urinary calculus formation. Fifty-seven men aged 30 to 55 years old, including 37 recurrent calcium calculus formers and 20 with no history of kidney calculi were evaluated for blood tests, ultrasonography investigations, urinalysis, urine culture, and also 24-hour urine collection test. Metabolites including calcium, oxalate, citrate, uric acid, magnesium, phosphate, potassium, sodium, and creatinine were measured before and during Ramadan fasting. The values of calculus-precipitating solutes as well as inhibitory factors were documented thoroughly. Total excretion of calcium, phosphate, and magnesium in 24-hour urine and also urine volume during fasting were significantly lower than those in the nonfasting period. Urine concentration of calcium during fasting was significantly lower than nonfasting (P < .001). Urine concentrations of uric acid, citrate, phosphate, sodium, and potassium during fasting were significantly higher than nonfasting. Uric acid supersaturation was accentuated, and calcium phosphate supersaturation was decreased significantly during fasting. There was no significant increase in calcium oxalate supersaturation during the fasting period. Fasting during Ramadan has different effects on total excretion and concentrations of urinary precipitate and inhibitory factors contributing to calculus formation. We did not find enough evidence in favor of increased risks of calculus formation during Ramadan fasting.

[Risk factors associated to preclampsia].

PubMed

López-Carbajal, Mario Joaquín; Manríquez-Moreno, María Esther; Gálvez-Camargo, Daniela; Ramírez-Jiménez, Evelia

2012-01-01

preeclampsia constitutes one of the main causes of maternal and perinatal morbidity and mortality. The aim was to identify the risk factors associated to the developmental of preeclampsia mild-moderate and severe, as well as the force of association of these factors in a hospital of second-level medical care. study of cases and controls, a relation 1:1, in women withdrawn of the Service of Gynecology and Obstetrics during 2004 to 2007. Pregnant women with more than 20 weeks gestation were included. In the cases group we included patients with diagnosis of preeclampsia mild-moderate or severe (corroborated clinical and laboratory). In the controls group that had a normal childbirth without pathology during the pregnancy. 42 cases and 42 controls. The average age was of 27 years. The associated risk factors were overweight, obesity, irregular prenatal control, short or long intergenesic period, history of caesarean or preeclampsia in previous pregnancies. the knowledge of the risk factors will allow the accomplishment of preventive measures and decrease the fetal and maternal morbidity and mortality due to preeclampsia.

External risk factors affecting construction costs

NASA Astrophysics Data System (ADS)

Mubarak, Husin, Saiful; Oktaviati, Mutia

2017-11-01

Some risk factors can have impacts on the cost, time, and performance. Results of previous studies indicated that the external conditions are among the factors which give effect to the contractor in the completion of the project. The analysis in the study carried out by considering the conditions of the project in the last 15 years in Aceh province, divided into military conflict phase (2000-2004), post tsunami disaster rehabilitation and reconstruction phase (2005-2009), and post-rehabilitation and reconstruction phase (2010-present). This study intended to analyze the impact of external risk factors, primarily related to the impact on project costs and to investigate the influence of the risk factors and construction phases impacted the project cost. Data was collected by using a questionnaire distributed in 15 large companies qualification contractors in Aceh province. Factors analyzed consisted of socio-political, government policies, natural disasters, and monetary conditions. Data were analyzed using statistical application of severity index to measure the level of risk impact. The analysis results presented the tendency of impact on cost can generally be classified as low. There is only one variable classified as high-impact, variable `fuel price increases', which appear on the military conflict and post tsunami disaster rehabilitation and reconstruction periods. The risk impact on costs from the factors and variables classified with high intensity needs a serious attention, especially when the high level impact is followed by the high frequency of occurrences.

Cardiovascular risk factor investigation: a pediatric issue

PubMed Central

Rodrigues, Anabel N; Abreu, Glaucia R; Resende, Rogério S; Goncalves, Washington LS; Gouvea, Sonia Alves

2013-01-01

Objectives To correlate cardiovascular risk factors (e.g., hypertension, obesity, hypercholesterolemia, hypertriglyceridemia, hyperglycemia, sedentariness) in childhood and adolescence with the occurrence of cardiovascular disease. Sources A systematic review of books and selected articles from PubMed, SciELO and Cochrane from 1992 to 2012. Summary of findings Risk factors for atherosclerosis are present in childhood, although cardiovascular disease arises during adulthood. This article presents the main studies that describe the importance of investigating the risk factors for cardiovascular diseases in childhood and their associations. Significant rates of hypertension, obesity, dyslipidemia, and sedentariness occur in children and adolescents. Blood pressure needs to be measured in childhood. An increase in arterial blood pressure in young people predicts hypertension in adulthood. The death rate from cardiovascular disease is lowest in children with lower cholesterol levels and in individuals who exercise regularly. In addition, there is a high prevalence of sedentariness in children and adolescents. Conclusions Studies involving the analysis of cardiovascular risk factors should always report the prevalence of these factors and their correlations during childhood because these factors are indispensable for identifying an at-risk population. The identification of risk factors in asymptomatic children could contribute to a decrease in cardiovascular disease, preventing such diseases as hypertension, obesity, and dyslipidemia from becoming the epidemics of this century. PMID:23515212

Risk Factors for Homelessness Among US Veterans

PubMed Central

Tsai, Jack; Rosenheck, Robert A.

2015-01-01

Homelessness among US veterans has been a focus of research for over 3 decades. Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, this is the first systematic review to summarize research on risk factors for homelessness among US veterans and to evaluate the evidence for these risk factors. Thirty-one studies published from 1987 to 2014 were divided into 3 categories: more rigorous studies, less rigorous studies, and studies comparing homeless veterans with homeless nonveterans. The strongest and most consistent risk factors were substance use disorders and mental illness, followed by low income and other income-related factors. There was some evidence that social isolation, adverse childhood experiences, and past incarceration were also important risk factors. Veterans, especially those who served since the advent of the all-volunteer force, were at greater risk for homelessness than other adults. Homeless veterans were generally older, better educated, and more likely to be male, married/have been married, and to have health insurance coverage than other homeless adults. More studies simultaneously addressing premilitary, military, and postmilitary risk factors for veteran homelessness are needed. This review identifies substance use disorders, mental illness, and low income as targets for policies and programs in efforts to end homelessness among veterans. PMID:25595171

Developmental Risk Factors for Sexual Offending.

ERIC Educational Resources Information Center

Lee, Joseph K. P.; Jackson, Henry J.; Pattison, Pip; Ward, Tony

2002-01-01

A study involving 64 Australian sex offenders and 33 non-sex offenders found childhood emotional abuse and family dysfunction, childhood behavior problems, and childhood sexual abuse were developmental risk factors for paraphilia. Emotional abuse and family dysfunction was found to be a risk factor for pedophilia, exhibitionism, rape, or multiple…

Gambling Risk Groups are Not All the Same: Risk Factors Amongst Sports Bettors.

PubMed

Russell, Alex M T; Hing, Nerilee; Li, En; Vitartas, Peter

2018-03-20

Sports betting is increasing worldwide, with an associated increase in sports betting-related problems. Previous studies have examined risk factors for problem gambling amongst sports bettors and have identified demographic, behavioural, marketing, normative and impulsiveness factors. These studies have generally compared those in problem gambling, or a combination of moderate risk and problem gambling, groups to non-problem gamblers, often due to statistical power issues. However, recent evidence suggests that, at a population level, the bulk of gambling-related harm stems from low risk and moderate risk gamblers, rather than problem gamblers. Thus it is essential to understand the risk factors for each level of gambling-related problems (low risk, moderate risk, problem) separately. The present study used a large sample (N = 1813) to compare each gambling risk group to non-problem gamblers, first using bivariate and then multivariate statistical techniques. A range of demographic, behavioural, marketing, normative and impulsiveness variables were included as possible risk factors. The results indicated that some variables, such as gambling expenditure, number of accounts with different operators, number of different types of promotions used and impulsiveness were significantly higher for all risk groups, while others such as some normative factors, age, gender and particular sports betting variables only applied to those with the highest level of gambling-related problems. The results generally supported findings from previous literature for problem gamblers, and extended these findings to low risk and moderate risk groups. In the future, where statistical power allows, risk factors should be assessed separately for all levels of gambling problems.

[Environmental risk factors for schizophrenia: a review].

PubMed

Vilain, J; Galliot, A-M; Durand-Roger, J; Leboyer, M; Llorca, P-M; Schürhoff, F; Szöke, A

2013-02-01

Evidence of variations in schizophrenia incidence rates has been found in genetically homogenous populations, depending on changes within time or space of certain environmental characteristics. The consideration of the impact of environmental risk factors in etiopathogenic studies has put the environment in the forefront of research regarding psychotic illnesses. Various environmental factors such as urbanicity, migration, cannabis, childhood traumas, infectious agents, obstetrical complications and psychosocial factors have been associated with the risk of developing schizophrenia. These risk factors can be biological, physical, psychological as well as social and may operate at different times in an individual's life (fetal period, childhood, adolescence and early adulthood). Whilst some of these factors act on an individual level, others act on a populational level, modulating the individual risk. These factors can have a direct action on the development of schizophrenia, or on the other hand act as markers for directly implicated factors that have not yet been identified. This article summarizes the current knowledge on this subject. An extensive literature search was conducted via the search engine Pubmed. Eight risk factors were selected and developed in the following paper: urbanicity (or living in an urban area), cannabis, migration (and ethnic density), obstetrical complications, seasonality of birth, infectious agents (and inflammatory responses), socio-demographic factors and childhood traumas. For each of these factors, we provide information on the importance of the risk, the vulnerability period, hypotheses made on the possible mechanisms behind the factors and the level of proof the current research offers (good, medium, or insufficient) according to the amount, type, quality and concordance of the studies at hand. Some factors, such as cannabis, are "unique" in their influence on the development of schizophrenia since it labels only one risk factor

C-reactive protein and reactive oxygen metabolites in subjects with metabolic syndrome.

PubMed

Kotani, K; Sakane, N

2012-01-01

This cross-sectional study investigated the correlation between diacron reactive oxygen metabolites (d-ROMs) and high-sensitivity C-reactive protein (hs-CRP) in subjects with or without metabolic syndrome. Cardiometabolic risk factors, d-ROMs and hs-CRP were determined in 457 women: 123 with metabolic syndrome and 334 without metabolic syndrome. The correlation between d-ROMs and hs-CRP levels was compared between the two groups. The group with metabolic syndrome had significantly higher d-ROMs and hs-CRP levels than the group without metabolic syndrome. While the d-ROMs level was significantly and positively correlated with the hs-CRP level in both groups, the correlation level between the two groups was significantly different. Multiple linear regression analysis adjusted for other cardiometabolic risk factors also showed significant positive correlation between dROMs and hs-CRP levels in both groups. Subjects with metabolic syndrome may have a closer relationship between inflammation and oxidative stress than subjects without metabolic syndrome, possibly reflecting their increased predisposition to atherosclerosis. Further studies are necessary to confirm the observed relationship.

Risk factors for cryptorchidism

PubMed Central

Gurney, Jason K.; McGlynn, Katherine A.; Stanley, James; Merriman, Tony; Signal, Virginia; Shaw, Caroline; Edwards, Richard; Richiardi, Lorenzo; Hutson, John; Sarfati, Diana

2018-01-01

The condition known as cryptorchidism – undescended testis – is one of the most common congenital abnormalities found among males, and is one of the few known risk factors for testicular cancer (TC). Like testicular cancer, the key exposures in the occurrence of cryptorchidism remain elusive. Testicular descent is thought to occur during two hormonally-controlled phases – between 8–15 weeks and 25–35 weeks gestation – and while it is clear that a failure of testes to descend permanently is likely due to disruptions to one or both of these phases, the cause(s) and mechanism(s) of such disruption are still unclear. In this manuscript, we review the broad range of putative risk factors that have been evaluated in relation to the development of cryptorchidism to date, discuss their plausibility, and make suggestions regarding further approaches to understand aetiology. There are few exposures for which there is consistent evidence of an association with cryptorchidism; and in those cases where evidence appears unequivocal – for example, the relationship between cryptorchidism and gestational measures such as low birth weight – the measured exposure is likely to be a surrogate for the true causal exposure. The relative importance of each risk factor may vary considerably between mother/son pairs depending on an array of genetic, maternal, placental and foetal factors – all of which could vary between regions. PMID:28654092

Bioactive Androgens and Glucuronidated Androgen Metabolites are Associated with Subcutaneous and Ectopic Skeletal Muscle Adiposity among Older Black Men

PubMed Central

Miljkovic, Iva; Cauley, Jane A; Dressen, Amy S; Gordon, Christopher L; Goodpaster, Bret H; Kuller, Lewis H; Bunker, Clareann H; Patrick, Alan L; Wheeler, Victor W; Orwoll, Eric S; Zmuda, Joseph M

2011-01-01

Aging is associated with declining serum levels of androgenic hormones and with increased skeletal muscle fat infiltration, an emerging risk factor for type 2 diabetes mellitus (T2DM). Androgens regulate fat mass and glucose homeostasis, but the effect of androgenic hormones on skeletal muscle fat infiltration is largely unknown. Thus, the aim of the current study was to examine the association of serum androgens and their precursors and metabolites with skeletal muscle fat infiltration and T2DM in a black male population group at high risk of T2DM. Serum androgens, estrogens, and androgen precursors and metabolites were measured using mass spectrometry, and calf skeletal muscle fat distribution [subcutaneous and intermuscular fat; skeletal muscle density] were measured using quantitative computed tomography in 472 Afro-Caribbean men aged 65 and older. Bioactive androgens, testosterone, free testosterone and dihydrotestosterone, were associated with less skeletal muscle fat infiltration (r=−0.14 to −0.18, P<0.05) and increased skeletal muscle density (r=0.10 to 0.14, P<0.05), independent of total adiposity. Additionally, glucuronidated androgen metabolites were associated with less subcutaneous fat (r=−0.11 to −0.15, P<0.05). Multivariate logistic regression analysis identified an increased level of 3α-diol-3 glucuronide (OR=1.38, P<0.01) and a decreased level of dihydrotestosterone (OR=0.66, P<0.01) to be significantly associated with T2DM. Our findings suggest that in elderly black men, independent of total adiposity, bioactive androgens and glucuronidated androgen metabolites may play previously unrecognized role in skeletal muscle fat distribution. Longitudinal studies are needed to further evaluate the relationship between androgens and androgen metabolites with changes in skeletal muscle fat distribution with aging and the incidence of T2DM. PMID:21353258

The pharmacokinetics of anthocyanins and their metabolites in humans.

PubMed

de Ferrars, R M; Czank, C; Zhang, Q; Botting, N P; Kroon, P A; Cassidy, A; Kay, C D

2014-07-01

Anthocyanins are phytochemicals with reported vasoactive bioactivity. However, given their instability at neutral pH, they are presumed to undergo significant degradation and subsequent biotransformation. The aim of the present study was to establish the pharmacokinetics of the metabolites of cyanidin-3-glucoside (C3G), a widely consumed dietary phytochemical with potential cardioprotective properties. A 500 mg oral bolus dose of 6,8,10,3',5'-(13)C5-C3G was fed to eight healthy male participants, followed by a 48 h collection (0, 0.5, 1, 2, 4, 6, 24, 48 h) of blood, urine and faecal samples. Samples were analysed by HPLC-ESI-MS/MS with elimination kinetics established using non-compartmental pharmacokinetic modelling. Seventeen (13)C-labelled compounds were identified in the serum, including (13)C5-C3G, its degradation products, protocatechuic acid (PCA) and phloroglucinaldehyde (PGA), 13 metabolites of PCA and 1 metabolite derived from PGA. The maximal concentrations of the phenolic metabolites (Cmax ) ranged from 10 to 2000 nM, between 2 and 30 h (tmax) post-consumption, with half-lives of elimination observed between 0.5 and 96 h. The major phenolic metabolites identified were hippuric acid and ferulic acid, which peaked in the serum at approximately 16 and 8 h respectively. Anthocyanins are metabolized to a structurally diverse range of metabolites that exhibit dynamic kinetic profiles. Understanding the elimination kinetics of these metabolites is key to the design of future studies examining their utility in dietary interventions or as therapeutics for disease risk reduction. © 2014 The Authors. British Journal of Pharmacology published by John Wiley & Sons Ltd on behalf of The British Pharmacological Society.

Family Factors Predicting Categories of Suicide Risk

ERIC Educational Resources Information Center

Randell, Brooke P.; Wang, Wen-Ling; Herting, Jerald R.; Eggert, Leona L.

2006-01-01

We compared family risk and protective factors among potential high school dropouts with and without suicide-risk behaviors (SRB) and examined the extent to which these factors predict categories of SRB. Subjects were randomly selected from among potential dropouts in 14 high schools. Based upon suicide-risk status, 1,083 potential high school…

Metabolite Profiles of Diabetes Incidence and Intervention Response in the Diabetes Prevention Program.

PubMed

Walford, Geoffrey A; Ma, Yong; Clish, Clary; Florez, Jose C; Wang, Thomas J; Gerszten, Robert E

2016-05-01

Identifying novel biomarkers of type 2 diabetes risk may improve prediction and prevention among individuals at high risk of the disease and elucidate new biological pathways relevant to diabetes development. We performed plasma metabolite profiling in the Diabetes Prevention Program (DPP), a completed trial that randomized high-risk individuals to lifestyle, metformin, or placebo interventions. Previously reported markers, branched-chain and aromatic amino acids and glutamine/glutamate, were associated with incident diabetes (P < 0.05 for all), but these associations were attenuated upon adjustment for clinical and biochemical measures. By contrast, baseline levels of betaine, also known as glycine betaine (hazard ratio 0.84 per SD log metabolite level, P = 0.02), and three other metabolites were associated with incident diabetes even after adjustment. Moreover, betaine was increased by the lifestyle intervention, which was the most effective approach to preventing diabetes, and increases in betaine at 2 years were also associated with lower diabetes incidence (P = 0.01). Our findings indicate betaine is a marker of diabetes risk among high-risk individuals both at baseline and during preventive interventions and they complement animal models demonstrating a direct role for betaine in modulating metabolic health. © 2016 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

Environmental risk factors for osteoporosis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Goyer, R.A.; Korach, K.S.; Epstein, S.

Environmental risk factors for osteoporosis were reviewed at a conference held at the National Institute for Environmental Health Sciences 8-9 November 1993. The conference was co-sponsored by the National Institute of Arthritis and Musculoskeletal and Skin Disease and the NIH Office of Research in Women's Health. The objective of the conference was to review what is known about risk factors for osteoporosis and to identify gaps in the present state of knowledge that might be addressed by future research. The conference was divided into two broad themes. The first session focused on current knowledge regarding etiology, risk factors, and approachesmore » to clinical and laboratory diagnosis. This was followed by three sessions in which various environmental pollutants were discussed. Topics selected for review included environmental agents that interfere with bone and calcium metabolism, such as the toxic metals lead, cadmium, aluminum, and fluoride, natural and antiestrogens, calcium, and vitamin D.« less

Microbial secondary metabolites in homes in association with moisture damage and asthma.

PubMed

Kirjavainen, P V; Täubel, M; Karvonen, A M; Sulyok, M; Tiittanen, P; Krska, R; Hyvärinen, A; Pekkanen, J

2016-06-01

We aimed to characterize the presence of microbial secondary metabolites in homes and their association with moisture damage, mold, and asthma development. Living room floor dust was analyzed by LC-MS/MS for 333 secondary metabolites from 93 homes of 1-year-old children. Moisture damage was present in 15 living rooms. At 6 years, 8 children had active and 15 lifetime doctor-diagnosed asthma. The median number of different metabolites per house was 17 (range 8-29) and median sum load 65 (4-865) ng/m(2) . Overall 42 different metabolites were detected. The number of metabolites present tended to be higher in homes with mold odor or moisture damage. The higher sum loads and number of metabolites with loads over 10 ng/m(2) were associated with lower prevalence of active asthma at 6 years (aOR 0.06 (95% CI <0.001-0.96) and 0.05 (<0.001-0.56), respectively). None of the individual metabolites, which presence tended (P < 0.2) to be increased by moisture damage or mold, were associated with increased risk of asthma. Microbial secondary metabolites are ubiquitously present in home floor dust. Moisture damage and mold tend to increase their numbers and amount. There was no evidence indicating that the secondary metabolites determined would explain the association between moisture damage, mold, and the development of asthma. © 2015 The Authors. Indoor Air published by John Wiley & Sons Ltd.

Analysis of Particulate and Dissolved Metabolite Pools at Station ALOHA

NASA Astrophysics Data System (ADS)

Boysen, A.; Carlson, L.; Hmelo, L.; Ingalls, A. E.

2016-02-01

Metabolomic studies focus on identifying and quantifying the small organic molecules that are the currency by which an organism lives and dies. Metabolite profiles of microorganisms have the potential to elucidate mechanisms of chemically mediated interactions that influence the success of microbial groups living in a complex environment. However, the chemical diversity of metabolites makes resolving a wide range of compounds analytically challenging. As such, metabolomics has lagged behind other genomic analyses. Here we conduct targeted analysis of over 200 primary and secondary metabolites present in the intracellular and extracellular metabolite pools at Station ALOHA using both reverse phase and hydrophilic interaction liquid chromatography coupled with tandem mass spectrometry. We selected the metabolites in our method due to their known importance in primary metabolism, secondary metabolism, and interactions between marine microorganisms such as nutrient exchange, growth promotion, and cell signaling. Through these analyses we obtain a snapshot of microbial community status that, blended with other forms of genomic data, can further our understanding of microbial dynamics. We hypothesize that monitoring a large suite of important metabolites across environmental gradients and diurnal cycles can elucidate factors controlling the distribution and activity of important microbial groups.

Dissipation, residues and risk assessment of spirotetramat and its four metabolites in citrus and soil under field conditions by LC-MS/MS.

PubMed

Zhang, Qingtao; Chen, Yuling; Wang, Shouyi; Yu, Yurong; Lu, Ping; Hu, Deyu; Yang, Zaihui

2018-04-01

A modified Quick, Easy, Cheap, Effective, Rugged and Safe (QuEChERS) method for the simultaneous determination of spirotetramat and its four metabolite residues in citrus, peel, pulp and soil was developed and validated by liquid chromatography with tandem mass spectrometry (LC-MS/MS). The samples were extracted with acetonitrile (1%, glacial acetic acid, v/v) and purified using primary secondary amine and octadecylsilane. The limit of detection was 0.01-0.13 mg/kg, whereas that of quantification was 0.02-0.40 mg/kg for spirotetramat and its metabolites. The average recoveries of spirotetramat, spirotetramat-enol, spirotetramat-mono-hydroxy, spirotetramat-enol-glucoside and spirotetramat-ketohydroxy in all matrices were 73.33-107.91%, 75.93-114.85%, 76.44-100.78%, 71.46-103.19% and 73.08-105.27%, respectively, with relative standard deviations < 12.32%. The dissipation dynamics of spirotetramat in citrus and soil followed first-order kinetics, with half-lives of 2.3-8.5 days in the three sampling locations. The terminal residues of spirotetramat in four matrices at the three locations were measured below the 1.0 mg/kg maximum residue limit set by China, and residues were found to be concentrated on the peel. The risk assessment of citrus was evaluated using risk quotients. The risk quotient values were found to be significantly <1, suggesting that the risk to human health was negligible when using the recommended doses of spirotetramat in citrus. These results could provide guidance for the safe and proper application of spirotetramat in citrus in China. Copyright © 2017 John Wiley & Sons, Ltd.

Effects of metformin on metabolite profiles and LDL cholesterol in patients with type 2 diabetes.

PubMed

Xu, Tao; Brandmaier, Stefan; Messias, Ana C; Herder, Christian; Draisma, Harmen H M; Demirkan, Ayse; Yu, Zhonghao; Ried, Janina S; Haller, Toomas; Heier, Margit; Campillos, Monica; Fobo, Gisela; Stark, Renee; Holzapfel, Christina; Adam, Jonathan; Chi, Shen; Rotter, Markus; Panni, Tommaso; Quante, Anne S; He, Ying; Prehn, Cornelia; Roemisch-Margl, Werner; Kastenmüller, Gabi; Willemsen, Gonneke; Pool, René; Kasa, Katarina; van Dijk, Ko Willems; Hankemeier, Thomas; Meisinger, Christa; Thorand, Barbara; Ruepp, Andreas; Hrabé de Angelis, Martin; Li, Yixue; Wichmann, H-Erich; Stratmann, Bernd; Strauch, Konstantin; Metspalu, Andres; Gieger, Christian; Suhre, Karsten; Adamski, Jerzy; Illig, Thomas; Rathmann, Wolfgang; Roden, Michael; Peters, Annette; van Duijn, Cornelia M; Boomsma, Dorret I; Meitinger, Thomas; Wang-Sattler, Rui

2015-10-01

Metformin is used as a first-line oral treatment for type 2 diabetes (T2D). However, the underlying mechanism is not fully understood. Here, we aimed to comprehensively investigate the pleiotropic effects of metformin. We analyzed both metabolomic and genomic data of the population-based KORA cohort. To evaluate the effect of metformin treatment on metabolite concentrations, we quantified 131 metabolites in fasting serum samples and used multivariable linear regression models in three independent cross-sectional studies (n = 151 patients with T2D treated with metformin [mt-T2D]). Additionally, we used linear mixed-effect models to study the longitudinal KORA samples (n = 912) and performed mediation analyses to investigate the effects of metformin intake on blood lipid profiles. We combined genotyping data with the identified metformin-associated metabolites in KORA individuals (n = 1,809) and explored the underlying pathways. We found significantly lower (P < 5.0E-06) concentrations of three metabolites (acyl-alkyl phosphatidylcholines [PCs]) when comparing mt-T2D with four control groups who were not using glucose-lowering oral medication. These findings were controlled for conventional risk factors of T2D and replicated in two independent studies. Furthermore, we observed that the levels of these metabolites decreased significantly in patients after they started metformin treatment during 7 years' follow-up. The reduction of these metabolites was also associated with a lowered blood level of LDL cholesterol (LDL-C). Variations of these three metabolites were significantly associated with 17 genes (including FADS1 and FADS2) and controlled by AMPK, a metformin target. Our results indicate that metformin intake activates AMPK and consequently suppresses FADS, which leads to reduced levels of the three acyl-alkyl PCs and LDL-C. Our findings suggest potential beneficial effects of metformin in the prevention of cardiovascular disease. © 2015 by the American

Risk factors in neuroleptic malignant syndrome.

PubMed

Gupta, Vinay; Magon, Rakesh; Mishra, B P; Sidhu, G B S; Mahajan, Ranjiv

2003-01-01

Neuroleptic malignant syndrome (NMS) is an uncommon but potentially serious idiosyncratic response to neuroleptic antipsychotics. It usually affects young males, but the risk has been seen to increase with certain factors including the administration practices of antipsychotic neuroleptics in these individuals. Even though no predictors for NMS are yet known, this article highlights the findings on certain risk factors as seen from a series of fifteen patients who developed NMS. Cautious use of neuroleptics in those at risk, early recognition and institution of immediate management is important.

(1)H-NMR-based metabolomic analysis of the effect of moderate wine consumption on subjects with cardiovascular risk factors.

PubMed

Vázquez-Fresno, Rosa; Llorach, Rafael; Alcaro, Francesca; Rodríguez, Miguel Ángel; Vinaixa, Maria; Chiva-Blanch, Gemma; Estruch, Ramon; Correig, Xavier; Andrés-Lacueva, Cristina

2012-08-01

Moderate wine consumption is associated with health-promoting activities. An H-NMR-based metabolomic approach was used to identify urinary metabolomic differences of moderate wine intake in the setting of a prospective, randomized, crossover, and controlled trial. Sixty-one male volunteers with high cardiovascular risk factors followed three dietary interventions (28 days): dealcoholized red wine (RWD) (272mL/day, polyphenol control), alcoholized red wine (RWA) (272mL/day) and gin (GIN) (100mL/day, alcohol control). After each period, 24-h urine samples were collected and analyzed by (1) H-NMR. According to the results of a one-way ANOVA, significant markers were grouped in four categories: alcohol-related markers (ethanol); gin-related markers; wine-related markers; and gut microbiota markers (hippurate and 4-hydroxphenylacetic acid). Wine metabolites were classified into two groups; first, metabolites of food metabolome: tartrate (RWA and RWD), ethanol, and mannitol (RWA); and second, biomarkers that relates to endogenous modifications after wine consumption, comprising branched-chain amino acid (BCAA) metabolite (3-methyl-oxovalerate). Additionally, a possible interaction between alcohol and gut-related biomarkers has been identified. To our knowledge, this is the first time that this approach has been applied in a nutritional intervention with red wine. The results show the capacity of this approach to obtain a comprehensive metabolome picture including food metabolome and endogenous biomarkers of moderate wine intake. © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Obesity-related metabolite profiles of black women spanning the epidemiologic transition.

PubMed

Dugas, Lara R; Chorell, Elin; Plange-Rhule, Jacob; Lambert, Estelle V; Cao, Guichan; Cooper, Richard S; Layden, Brian T; Scholten, Denise; Olsson, Tommy; Luke, Amy; Goedecke, Julia H

2016-03-01

In developed countries, specific metabolites have been associated with obesity and metabolic diseases, e.g. type 2 diabetes. It is unknown whether a similar profile persists across populations of African-origin, at increased risk for obesity and related diseases. In a cross-sectional study of normal-weight and obese black women (33.3 ± 6.3 years) from the US ( N = 69, 65 % obese), South Africa (SA, N = 97, 49 % obese) and Ghana ( N = 82, 33 % obese) serum metabolite profiles were characterized via gas chromatography-time of flight/mass spectrometry. In US and SA women, BMI correlated with branched-chain and aromatic amino acids, as well as dopamine and aminoadipic acid. The relationship between BMI and lipid metabolites differed by site; BMI correlated positively with palmitoleic acid (16:1) in the US; negatively with stearic acid (18:0) in SA, and positively with arachidonic acid (20:4) in Ghana. BMI was also positively associated with sugar-related metabolites in the US; i.e. uric acid, and mannitol, and with glucosamine, glucoronic acid and mannitol in SA. While we identified a common amino acid metabolite profile associated with obesity in black women from the US and SA, we also found site-specific obesity-related metabolites suggesting that the local environment is a key moderator of obesity.

Ethnicity-related variation in breast cancer risk factors.

PubMed

Bernstein, Leslie; Teal, Cayla R; Joslyn, Sue; Wilson, Jerome

2003-01-01

A variety of factors are predictors of breast cancer risk. However, the studies conducted to establish these risk factors have rarely included African American women. The few studies with sufficient numbers of African-American women suggest that risk factors for breast cancer among African-American women are similar to those of white women. Although risk factors may be similar for African-American and white women, differences in the prevalence of risk factors may explain the differences in patterns of incidence. The authors reviewed the epidemiologic studies of breast cancer among African-American women and identified resources with information regarding the prevalence of risk factors among African American and white women. Considerable variation exists in the studies of breast cancer risk factors among African American women. Because few studies have included sufficient numbers of African-American women, no firm conclusions can be drawn regarding whether risk estimates for African American women differ from those of white women. Estimates of the prevalence of breast cancer risk factors indicate that African American and white women differ in terms of their ages at menarche, menstrual cycle patterns, birth rates, lactation histories, patterns of oral contraceptive use, levels of obesity, frequency of menopausal hormone use, physical activity patterns, and alcohol intake. The risk factor profile of African-American women appears to differ from that of white women. This may explain in part, the higher incidence rates for African Americans before age 45 years and the lower incidence rates at older ages. Discussions of these data at a workshop highlighted the need for future research on breast cancer risk among African Americans. This research should acknowledge the heterogeneous heritage, cultural beliefs, and cultural knowledge of African-American women. Studies conducted in collaboration with the African-American community of women and with the breast cancer

Does area deprivation modify the association between exposure to a nitrate and low-dose atrazine metabolite mixture in drinking water and small for gestational age? A historic cohort study.

PubMed

Limousi, F; Albouy-Llaty, M; Carles, C; Dupuis, A; Rabouan, S; Migeot, V

2014-04-01

Birth weight may be influenced by environmental and socio-economic factors that could interact. The main objective of our research was to investigate whether area deprivation may modify the association between drinking water exposure to a mixture of atrazine metabolites and nitrates during the second trimester of pregnancy and prevalence of small for gestational age (SGA) neonates. We conducted a historic cohort study in Deux-Sèvres, France between 2005 and 2010, using birth records, population census and regularly performed drinking water withdrawals at community water systems. Exposure to an atrazine metabolite/nitrate mixture in drinking water was divided into six classes according to the presence or absence of atrazine metabolites and to the terciles of nitrate concentrations in each trimester of pregnancy. We used a logistic regression to model the association between SGA and mixture exposure at the second trimester while taking into account the area deprivation measured by the Townsend index as an effect modifier and controlling for the usual confounders. We included 10,784 woman-neonate couples. The risk of SGA when exposed to second tercile of nitrate without atrazine metabolites was significantly greater in women living in less deprived areas (OR = 2.99; 95 % CI (1.14, 7.89)), whereas it was not significant in moderately and more deprived areas. One of the arguments used to explain this result is the presence of competing risk factors in poorer districts.

[Risk factors for developing tuberculosis].

PubMed

Skodrić-Trifunović, Vesna

2004-01-01

Application of modern achievements in the field of medicine such as organ transplantation, long-term immunosuppressive therapy in treatment of numerous diseases, dialysis, successful treatment of malignant diseases prolonged duration of life and consequential continuation of long-term immunodeficiency. HIV infection currently represents a major risk factor for reactivation of tuberculosis with its associated relative risk being 30-170 times higher in comparison to the control group, in regard to the number of CD4 T-lymphocytes. Malignant diseases (hematological, lung and breast carcinomas) are important immunocompromising conditions affecting reactivation of tuberculosis, whereas the relative risk is 16. Development of tuberculosis among diabetics is considerably more frequent in comparison to general population (relative risk 2-4). Prominent glycoregulation disorders point to greater liability to development of tuberculosis. Alcoholism is characterized by general reduction of resistance, resulting from alcohol intoxication, malnutrition, irregular life style, etc. In malabsorption, immunosuppression is induced by deficiency of nutritive components and thus, relative risk for reactivation of tuberculosis is 5-12 in gastrectomy and 27-63 in jejunoileal bypass. In patients with chronic renal failur the relative risk ranges from 10 (nephropathies) to 37 (transplantation). Numerous patients use long-term immunosuppressive therapy that contributes to increased risk for developing tuberculosis (relative risk 12) as early as one month after application of a dose above 15 mg/day. There are numerous of risk factors that have frequently combined effects responsible for immunologic imbalance and development of tuberculosis.

Risk Factors in Neuroleptic Malignant Syndrome

PubMed Central

Gupta, Vinay; Magon, Rakesh; Mishra, B.P.; Sidhu, G.B.S.; Mahajan, Ranjiv

2003-01-01

Neuroleptic malignant syndrome (NMS) is an uncommon but potentially serious idiosyncratic response to neuroleptic antipsychotics. It usually affects young males, but the risk has been seen to increase with certain factors including the administration practices of antipsychotic neuroleptics in these individuals. Even though no predictors for NMS are yet known, this article highlights the findings on certain risk factors as seen from a series of fifteen patients who developed NMS. Cautious use of neuroleptics in those at risk, early recognition and institution of immediate management is important. PMID:21206810

Stereoselective Inhibition of CYP2C19 and CYP3A4 by Fluoxetine and Its Metabolite: Implications for Risk Assessment of Multiple Time-Dependent Inhibitor Systems

PubMed Central

Lutz, Justin D.; VandenBrink, Brooke M.; Babu, Katipudi N.; Nelson, Wendel L.; Kunze, Kent L.

2013-01-01

Recent guidance on drug-drug interaction (DDI) testing recommends evaluation of circulating metabolites. However, there is little consensus on how to quantitatively predict and/or assess the risk of in vivo DDIs by multiple time-dependent inhibitors (TDIs) including metabolites from in vitro data. Fluoxetine was chosen as the model drug to evaluate the role of TDI metabolites in DDI prediction because it is a TDI of both CYP3A4 and CYP2C19 with a circulating N-dealkylated inhibitory metabolite, norfluoxetine. In pooled human liver microsomes, both enantiomers of fluoxetine and norfluoxetine were TDIs of CYP2C19, (S)-norfluoxetine was the most potent inhibitor with time-dependent inhibition affinity constant (KI) of 7 μM, and apparent maximum time-dependent inhibition rate (kinact,app) of 0.059 min−1. Only (S)-fluoxetine and (R)-norfluoxetine were TDIs of CYP3A4, with (R)-norfluoxetine being the most potent (KI = 8 μM, and kinact,app = 0.011 min−1). Based on in-vitro-to-in-vivo predictions, (S)-norfluoxetine plays the most important role in in vivo CYP2C19 DDIs, whereas (R)-norfluoxetine is most important in CYP3A4 DDIs. Comparison of two multiple TDI prediction models demonstrated significant differences between them in in-vitro-to-in-vitro predictions but not in in-vitro-to-in-vivo predictions. Inclusion of all four inhibitors predicted an in vivo decrease in CYP2C19 (95%) and CYP3A4 (60–62%) activity. The results of this study suggest that adequate worst-case risk assessment for in vivo DDIs by multiple TDI systems can be achieved by incorporating time-dependent inhibition by both parent and metabolite via simple addition of the in vivo time-dependent inhibition rate/cytochrome P450 degradation rate constant (λ/kdeg) values, but quantitative DDI predictions will require a more thorough understanding of TDI mechanisms. PMID:23785064

Psychological Factors Linked to Risk Perception

NASA Astrophysics Data System (ADS)

Armaş, I.; Creãu, R. Z.; Stǎnciugelu, I.

2012-04-01

Risks are mental models, which allow people to cope with dangerous phenomena (Renn, 2008; Jasanoff, 1998). The term "risk" refers to the likelihood of an adverse effect resulting from an event. The aim of the present study is to identify the psychological factors that are most predictive of risk perception in relation with age, gender, educational level and socio-economical status. Earthquake hazard was considered, because it is an emerging danger for Bucharest. 80% of the laypeople sample are waiting for this event to happen in the next three years. By integrating all the research data, it was attempted to build a risk profile of the investigated population, which could be used by institutions responsible for earthquake risk mitigation situations in Bucharest. This research appealed to the social learning Rotter (1966), auto-effectiveness Bandura (1977; 1983), and anxiety and stress theories. We used psychological variables that measured stress, personal effectiveness and the belief in personal control. The multi-modal risk perception questionnaire was structured on a 49 items sequence. The sample was composed of 1.376 participants recruited on a voluntary basis. The characteristics of risk (like probability and magnitude, time scales) are perceived differently according to psychological factors that play a role also in biases in people's ability to draw inferences from probabilistic information (like cognitive dissonance). Since the 1970's, it has been argued that those who perceive life's events as being beyond their locus of control (external locus of control) are significantly more anxious and less adapted. In this research, strongest associations and significant differences were obtained between sex, age and income categories with Stress vulnerability factor and the External Locus of Control factor. The profile of the low risk perceiver is that of a young, more educated, male individual with a higher self- efficacy level and an internal locus of control.

Risk factors for homelessness among US veterans.

PubMed

Tsai, Jack; Rosenheck, Robert A

2015-01-01

Homelessness among US veterans has been a focus of research for over 3 decades. Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, this is the first systematic review to summarize research on risk factors for homelessness among US veterans and to evaluate the evidence for these risk factors. Thirty-one studies published from 1987 to 2014 were divided into 3 categories: more rigorous studies, less rigorous studies, and studies comparing homeless veterans with homeless nonveterans. The strongest and most consistent risk factors were substance use disorders and mental illness, followed by low income and other income-related factors. There was some evidence that social isolation, adverse childhood experiences, and past incarceration were also important risk factors. Veterans, especially those who served since the advent of the all-volunteer force, were at greater risk for homelessness than other adults. Homeless veterans were generally older, better educated, and more likely to be male, married/have been married, and to have health insurance coverage than other homeless adults. More studies simultaneously addressing premilitary, military, and postmilitary risk factors for veteran homelessness are needed. This review identifies substance use disorders, mental illness, and low income as targets for policies and programs in efforts to end homelessness among veterans. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health 2015. This work is written by (a) US Government employee(s) and is in the public domain in the US.

Risk factors identified for certain lymphoma subtypes

Cancer.gov

In a large international collaborative analysis of risk factors for non-Hodgkin lymphoma (NHL), scientists were able to quantify risk associated with medical history, lifestyle factors, family history of blood or lymph-borne cancers, and occupation for 11

[Risk factors found in suicide attempters].

PubMed

Villa-Manzano, Alberto Iram; Robles-Romero, Miguel Angel; Gutiérrez-Román, Elsa Armida; Martínez-Arriaga, María Guadalupe; Valadez-Toscano, Francisco Javier; Cabrera-Pivaral, Carlos E

2009-01-01

A better understanding of risk factors for suicide in general population is crucial for the design of suicide prevention programs. Our objective was to identify personal and family risk factors in suicide attempters. Case-control design. We searched in patients with an acute intoxication, those subjects with and intoxication attributable to suicide attempt. These patients were matched with controls by gender and the date of intoxication. We use a structured questionnaire to identify personal characteristics, family features and network support. Odds ratio (OR) and 95 % confidence interval were obtained. 25 cases and 25 controls were evaluated. The risk factors associated with suicide attempt adjusted by age, were being a student and smoking habits. Family violence background showed OR = 3.8 (IC 95 % = 1.1-13), family disintegration a OR = 8.5 (IC 95 % = 2.1-35), critical events background OR = 8.8 (IC 95 % = 2.1-36), poor self-esteem OR = 8.2 (IC 95 % 2-35), depression OR = 22 (IC 95 % = 3-190), anxiety OR = 9 (IC 95 % = 2-47), family dysfunction OR = 25 (IC 95 % = 4-151). The principal risk factor for suicide attempt was family dysfunction and psychological traits.

Heart Disease Risk Factors You Can't Control

MedlinePlus

... Submit Heart disease risk factors you can't control Some factors you can't control, like pregnancy ... 2018. Heart disease risk factors you can't control Age and menopause As you get older, your ...

Improved profiling of estrogen metabolites by orbitrap LC/MS

PubMed Central

Li, Xingnan; Franke, Adrian A.

2015-01-01

Estrogen metabolites are important biomarkers to evaluate cancer risks and metabolic diseases. Due to their low physiological levels, a sensitive and accurate method is required, especially for the quantitation of unconjugated forms of endogenous steroids and their metabolites in humans. Here, we evaluated various derivatives of estrogens for improved analysis by orbitrap LC/MS in human serum samples. A new chemical derivatization reagent was applied modifying phenolic steroids to form 1-methylimidazole-2-sulfonyl adducts. The method significantly improves the sensitivity 2–100 fold by full scan MS and targeted selected ion monitoring MS over other derivatization methods including, dansyl, picolinoyl, and pyridine-3-sulfonyl products. PMID:25543003

The Ecological Role of Volatile and Soluble Secondary Metabolites Produced by Soil Bacteria.

PubMed

Tyc, Olaf; Song, Chunxu; Dickschat, Jeroen S; Vos, Michiel; Garbeva, Paolina

2017-04-01

The rich diversity of secondary metabolites produced by soil bacteria has been appreciated for over a century, and advances in chemical analysis and genome sequencing continue to greatly advance our understanding of this biochemical complexity. However, we are just at the beginning of understanding the physicochemical properties of bacterial metabolites, the factors that govern their production and ecological roles. Interspecific interactions and competitor sensing are among the main biotic factors affecting the production of bacterial secondary metabolites. Many soil bacteria produce both volatile and soluble compounds. In contrast to soluble compounds, volatile organic compounds can diffuse easily through air- and gas-filled pores in the soil and likely play an important role in long-distance microbial interactions. In this review we provide an overview of the most important soluble and volatile classes of secondary metabolites produced by soil bacteria, their ecological roles, and their possible synergistic effects. Copyright © 2016 Elsevier Ltd. All rights reserved.

Trespass event risk factors.

DOT National Transportation Integrated Search

2014-11-12

The Volpe Center has used three sources of datathe Federal Railroad Administrations required accident reports, locomotive video, and U.S. Census datato investigate common risk factors for railroad trespassing incidents, the leading cause of ...

[Chronic renal disease as cardiovascular risk factor].

PubMed

Hermans, M M H; Kooman, J P; Stehouwer, C D A

2008-07-19

A lowering of the glomerular filtration rate (GFR) and/or the presence of albuminuria are signs of chronic renal disease. Both variables are for the most part independently associated with an increased risk of cardiovascular morbidity and mortality. Albuminuria is a marker of endothelial dysfunction. A decrease of the GFR is associated with non-traditional risk factors, e.g. renal anaemia, uraemic toxins due to a decrease of the renal clearance, hyperhomocysteinaemia caused by a diminished homocysteine metabolism, excessive activation of the sympathetic nervous system which is related to sleep apnoea syndrome, oxidative stress and dyslipidaemia associated with the formation of vasotoxic, oxidised LDL cholesterol. These non-traditional risk factors may, alone or in combination with traditional atherogenic risk factors (e.g. age, male gender, smoking, hypercholesterolaemia, hypertension, obesity, positive family history and diabetes mellitus), partially via endothelial dysfunction, result in harmful effects on arterial function, increasing cardiovascular morbidity and mortality. Different stages of chronic kidney disease are associated with specific risk factors, making a specific therapeutic approach essential.

Exploring Risk Factors for Follicular Lymphoma

PubMed Central

Ambinder, Alexander J.; Shenoy, Pareen J.; Malik, Neha; Maggioncalda, Alison; Nastoupil, Loretta J.; Flowers, Christopher R.

2012-01-01

Follicular lymphoma (FL) is an indolent malignancy of germinal center B cells with varied incidence across racial groups and geographic regions. Improvements in the classification of non-Hodgkin lymphoma subtypes provide an opportunity to explore associations between environmental exposures and FL incidence. Our paper found that aspects of Western lifestyle including sedentary lifestyle, obesity, and diets high in meat and milk are associated with an increased risk of FL. Diets rich in fruits and vegetables, polyunsaturated fatty acids, vitamin D, and certain antioxidants are inversely associated with FL risk. A medical history of Sjogren's syndrome, influenza vaccination, and heart disease may be associated with FL incidence. Associations between FL and exposure to pesticides, industrial solvents, hair dyes, and alcohol/tobacco were inconsistent. Genetic risk factors include variants at the 6p21.32 region of the MHC II locus, polymorphisms of the DNA repair gene XRCC3, and UV exposure in individuals with certain polymorphisms of the vitamin D receptor. Increasing our understanding of risk factors for FL must involve integrating epidemiological studies of genetics and exposures to allow for the examination of risk factors and interactions between genes and environment. PMID:23028387

Risk Factors for Progression of Chronic Kidney Disease

PubMed Central

Staples, Amy; Wong, Craig

2010-01-01

Purpose of Review Provides an overview of the identified risk factors for chronic kidney disease (CKD) progression emphasizing the pediatric population. Recent findings Over the past ten years, there have been significant changes to our understanding and study of pre-terminal kidney failure. Recent refinements in the measurement of glomerular filtration rate (GFR) and GFR estimating equations are important tools for identification and association of risk factors for CKD progression in children. In pediatric CKD, lower level of kidney function at presentation, higher levels of proteinuria, and hypertension are known markers for a more rapid decline in GFR. Anemia and other reported risk factors from the pre-genomic era have need for further study and validation. Genome-wide association studies have identified genetic loci which have provided novel genetic risk factors for CKD progression. Summary With cohort studies of children with CKD becoming mature, they have started to yield important refinements to the assessment of CKD progression. While many of the traditional risk factors for renal progression will certainly be assessed, such cohorts will be important for evaluating novel risk factors identified by genome-wide studies. PMID:20090523

Risk factors for postoperative hypocalcemia.

PubMed

Docimo, Giovanni; Ruggiero, Roberto; Casalino, Giuseppina; Del Genio, Gianmattia; Docimo, Ludovico; Tolone, Salvatore

2017-06-01

Hypocalcaemia is one of the most common complications after thyroidectomy; however, it is still unclear what preoperative factors could predict this event. The aim of this study was to evaluate the role of risk factors for hypocalcaemia after total thyroidectomy (TT). Consecutive patients who underwent total thyroidectomyat our institution between January 2014 and January 2016 were enrolled. The clinical and pathologic characteristics and surgical details of normocalcemic and hypocalcemic patients were compared. Univariate and multivariate analyses to estimate risk ratio were assessed. A total of 328 patients underwent TT; histology revealed benign and malignant disease in 83 and 17% of cases, respectively. Central-compartment neck dissection (CCND) was performed in 36 subjects (10.9%). Parathyroid glands were observed in 23% (76) of specimens. Laboratory asymptomatic hypocalcaemia was observed in 92 (28%) patients; symptomatic hypocalcaemia occurred in 26 (7.9%). Transient hypocalcaemia has been observed in 48 (14.6%) patients; permanent hypocalcaemia occurred in two subjects (0.6%). On univariate analysis, malignant pathology (p < 0.001), CCND (p < 0.05), female gender (p < 0.001), presence of at least two parathyroid glands in specimens (p < 0.002), and operative time longer than 120 min (p < 0.05) were factors that significantly increased the risk of developing asymptomatic and transient hypocalcaemia. After logistic regression analysis, malignant pathology (p < 0.000; p < 0.001) and CCND (p < 0.005; p = 0.013) were the significant factors that affected the development of symptomatic and transient hypocalcaemia. The presence of malignant pathology and CCND was found to be significant risks factors for postoperative hypocalcaemia. In patients in whom this pathological features are present, attention should be paid to rapidly start an adequate therapy.

Factors Influencing Cancer Risk Perception in High Risk Populations: A Systematic Review

PubMed Central

2011-01-01

Background Patients at higher than average risk of heritable cancer may process risk information differently than the general population. However, little is known about clinical, demographic, or psychosocial predictors that may impact risk perception in these groups. The objective of this study was to characterize factors associated with perceived risk of developing cancer in groups at high risk for cancer based on genetics or family history. Methods We searched Ovid MEDLINE, Ovid Embase, Ovid PsycInfo, and Scopus from inception through April 2009 for English-language, original investigations in humans using core concepts of "risk" and "cancer." We abstracted key information and then further restricted articles dealing with perceived risk of developing cancer due to inherited risk. Results Of 1028 titles identified, 53 articles met our criteria. Most (92%) used an observational design and focused on women (70%) with a family history of or contemplating genetic testing for breast cancer. Of the 53 studies, 36 focused on patients who had not had genetic testing for cancer risk, 17 included studies of patients who had undergone genetic testing for cancer risk. Family history of cancer, previous prophylactic tests and treatments, and younger age were associated with cancer risk perception. In addition, beliefs about the preventability and severity of cancer, personality factors such as "monitoring" personality, the ability to process numerical information, as well as distress/worry also were associated with cancer risk perception. Few studies addressed non-breast cancer or risk perception in specific demographic groups (e.g. elderly or minority groups) and few employed theory-driven analytic strategies to decipher interrelationships of factors. Conclusions Several factors influence cancer risk perception in patients at elevated risk for cancer. The science of characterizing and improving risk perception in cancer for high risk groups, although evolving, is still

Assessing osteoporosis risk factors in Spanish menopausal women.

PubMed

Martínez Pérez, José Antonio; Palacios, Santiago; García, Felipe Chavida; Pérez, Maite

2011-10-01

(1) To assess the prevalence of osteoporosis risk factors in Spanish menopausal women; (2) to detect medical and lifestyle risk factor differences between perimenopausal and postmenopausal women; (3) and to identify the main factors responsible for osteoporosis. Cross-sectional descriptive study encompassing women aged 45-65 across Spain. The study population sample was collected through random sampling and a total of 10,514 women were included. Socio-demographic, medical history, and lifestyle data were assessed. The prevalence of osteoporosis risk factors was 67.6%. The most common risk factors were physical inactivity (53.6%), use of medication related to osteoporosis risk (45.9%), and low calcium intake (30.1%). There were statistically significant differences between peri- and postmenopausal women in terms of smoking status, alcohol intake, personal history, poor dairy product intake, and medication use that could increase risk. Logistic regression analysis showed that osteoporosis was significantly associated with age, family history, age at onset of menopause, Kupperman Index, prolonged immobilization, weight loss, and other diseases that increase the probability of developing osteoporosis. A high prevalence of women taking osteoporosis risk-related medication was observed in our study. There was correlation between the menopausal symptoms' degree of severity and the risk of suffering from osteoporosis.

Modifying Risk Factors for Total Joint Arthroplasty: Strategies That Work Nicotine.

PubMed

Springer, Bryan D

2016-08-01

Smoking and nicotine use remain a major health care crisis in the United States. Although rates have dropped dramatically over the last 50 years, approximately 18% of the US adult population still smokes. The musculoskeletal effects of nicotine and other byproducts of smoking place patients at increased risk for perioperative complications including medical complication, wound healing problems, infection, and death. A comprehensive behavioral modification program with or without the use of nicotine replacement therapy has been shown to be most effective at smoking cessation around the time of planned surgery. Although literature suggests that smoking cessation 4-6 weeks before surgery can diminish risk, both current and former smokers are at increased risk for perioperative complications compared with those that have never smoked. Cotinine, a metabolite of nicotine, can be used to monitor smoking cessation before surgery. Copyright © 2016 Elsevier Inc. All rights reserved.

Quantitative influence of risk factors on blood glucose level.

PubMed

Chen, Songjing; Luo, Senlin; Pan, Limin; Zhang, Tiemei; Han, Longfei; Zhao, Haixiu

2014-01-01

The aim of this study is to quantitatively analyze the influence of risk factors on the blood glucose level, and to provide theory basis for understanding the characteristics of blood glucose change and confirming the intervention index for type 2 diabetes. The quantitative method is proposed to analyze the influence of risk factors on blood glucose using back propagation (BP) neural network. Ten risk factors are screened first. Then the cohort is divided into nine groups by gender and age. According to the minimum error principle, nine BP models are trained respectively. The quantitative values of the influence of different risk factors on the blood glucose change can be obtained by sensitivity calculation. The experiment results indicate that weight is the leading cause of blood glucose change (0.2449). The second factors are cholesterol, age and triglyceride. The total ratio of these four factors reaches to 77% of the nine screened risk factors. And the sensitivity sequences can provide judgment method for individual intervention. This method can be applied to risk factors quantitative analysis of other diseases and potentially used for clinical practitioners to identify high risk populations for type 2 diabetes as well as other disease.

Contribution of the Nurses’ Health Studies to Uncovering Risk Factors for Type 2 Diabetes: Diet, Lifestyle, Biomarkers, and Genetics

PubMed Central

Ley, Sylvia H.; Ardisson Korat, Andres V.; Sun, Qi; Tobias, Deirdre K.; Zhang, Cuilin; Qi, Lu; Willett, Walter C.; Manson, JoAnn E.

2016-01-01

Objectives. To review the contribution of the Nurses’ Health Study (NHS) and the NHS II to addressing hypotheses regarding risk factors for type 2 diabetes. Methods. We carried out a narrative review of 1976 to 2016 NHS and NHS II publications. Results. The NHS and NHS II have uncovered important roles in type 2 diabetes for individual nutrients, foods, dietary patterns, and physical activity independent of excess body weight. Up to 90% of type 2 diabetes cases are potentially preventable if individuals follow a healthy diet and lifestyle. The NHS investigations have also identified novel biomarkers for diabetes, including adipokines, inflammatory cytokines, nutrition metabolites, and environmental pollutants, offering new insights into the pathophysiology of the disease. Global collaborative efforts have uncovered many common genetic variants associated with type 2 diabetes and improved our understanding of gene–environment interactions. Continued efforts to identify epigenetic, metagenomic, and metabolomic risk factors for type 2 diabetes have the potential to reveal new pathways and improve prediction and prevention. Conclusions. Over the past several decades, the NHS and NHS II have made major contributions to public health recommendations and strategies designed to reduce the global burden of diabetes. PMID:27459454

Contribution of the Nurses' Health Studies to Uncovering Risk Factors for Type 2 Diabetes: Diet, Lifestyle, Biomarkers, and Genetics.

PubMed

Ley, Sylvia H; Ardisson Korat, Andres V; Sun, Qi; Tobias, Deirdre K; Zhang, Cuilin; Qi, Lu; Willett, Walter C; Manson, JoAnn E; Hu, Frank B

2016-09-01

To review the contribution of the Nurses' Health Study (NHS) and the NHS II to addressing hypotheses regarding risk factors for type 2 diabetes. We carried out a narrative review of 1976 to 2016 NHS and NHS II publications. The NHS and NHS II have uncovered important roles in type 2 diabetes for individual nutrients, foods, dietary patterns, and physical activity independent of excess body weight. Up to 90% of type 2 diabetes cases are potentially preventable if individuals follow a healthy diet and lifestyle. The NHS investigations have also identified novel biomarkers for diabetes, including adipokines, inflammatory cytokines, nutrition metabolites, and environmental pollutants, offering new insights into the pathophysiology of the disease. Global collaborative efforts have uncovered many common genetic variants associated with type 2 diabetes and improved our understanding of gene-environment interactions. Continued efforts to identify epigenetic, metagenomic, and metabolomic risk factors for type 2 diabetes have the potential to reveal new pathways and improve prediction and prevention. Over the past several decades, the NHS and NHS II have made major contributions to public health recommendations and strategies designed to reduce the global burden of diabetes.

Risk factors for persistent gestational trophoblastic neoplasia.

PubMed

Kuyumcuoglu, Umur; Guzel, Ali Irfan; Erdemoglu, Mahmut; Celik, Yusuf

2011-01-01

This retrospective study evaluated the risk factors for persistent gestational trophoblastic disease (GTN) and determined their odds ratios. This study included 100 cases with GTN admitted to our clinic. Possible risk factors recorded were age, gravidity, parity, size of the neoplasia, and beta-human chorionic gonadotropin levels (beta-hCG) before and after the procedure. Statistical analyses consisted of the independent sample t-test and logistic regression using the statistical package SPSS ver. 15.0 for Windows (SPSS, Chicago, IL, USA). Twenty of the cases had persistent GTN, and the differences between these and the others cases were evaluated. The size of the neoplasia and histopathological type of GTN had no statistical relationship with persistence, whereas age, gravidity, and beta-hCG levels were significant risk factors for persistent GTN (p < 0.05). The odds ratios (95% confidence interval (CI)) for age, gravidity, and pre- and post-evacuation beta-hCG levels determined using logistic regression were 4.678 (0.97-22.44), 7.315 (1.16-46.16), 2.637 (1.41-4.94), and 2.339 (1.52-3.60), respectively. Patient age, gravidity, and beta-hCG levels were risk factors for persistent GTN, whereas the size of the neoplasia and histopathological type of GTN were not significant risk factors.

Obesity-related metabolite profiles of black women spanning the epidemiologic transition

PubMed Central

Plange-Rhule, Jacob; Lambert, Estelle V.; Cao, Guichan; Cooper, Richard S.; Layden, Brian T.; Scholten, Denise; Olsson, Tommy; Luke, Amy; Goedecke, Julia H.

2016-01-01

In developed countries, specific metabolites have been associated with obesity and metabolic diseases, e.g. type 2 diabetes. It is unknown whether a similar profile persists across populations of African-origin, at increased risk for obesity and related diseases. In a cross-sectional study of normal-weight and obese black women (33.3 ± 6.3 years) from the US (N = 69, 65 % obese), South Africa (SA, N = 97, 49 % obese) and Ghana (N = 82, 33 % obese) serum metabolite profiles were characterized via gas chromatography-time of flight/mass spectrometry. In US and SA women, BMI correlated with branched-chain and aromatic amino acids, as well as dopamine and aminoadipic acid. The relationship between BMI and lipid metabolites differed by site; BMI correlated positively with palmitoleic acid (16:1) in the US; negatively with stearic acid (18:0) in SA, and positively with arachidonic acid (20:4) in Ghana. BMI was also positively associated with sugar-related metabolites in the US; i.e. uric acid, and mannitol, and with glucosamine, glucoronic acid and mannitol in SA. While we identified a common amino acid metabolite profile associated with obesity in black women from the US and SA, we also found site-specific obesity-related metabolites suggesting that the local environment is a key moderator of obesity. PMID:27346989

Circulating estrogens and postmenopausal ovarian cancer risk in the Women’s Health Initiative Observational Study

PubMed Central

Trabert, Britton; Brinton, Louise A.; Anderson, Garnet L.; Pfeiffer, Ruth M.; Falk, Roni T.; Strickler, Howard D.; Sliesoraitis, Sarunas; Kuller, Lewis H.; Gass, Margery L.; Fuhrman, Barbara J.; Xu, Xia; Wentzensen, Nicolas

2016-01-01

Background Hormonal and reproductive factors contribute to the development of ovarian cancer, but few studies have examined associations between circulating estrogens and estrogen metabolites and ovarian cancer risk. We evaluated whether serum estrogens and estrogen metabolite levels are associated with ovarian cancer risk among postmenopausal women in a nested case-control study in the Women’s Health Initiative (WHI) Observational Study (OS). Methods We selected all 169 eligible epithelial ovarian cancer cases and 412 matched controls from women enrolled in WHI-OS who were not using menopausal hormones at baseline. Baseline levels of 15 estrogens and estrogen metabolites were measured via LC-MS/MS. Associations with ovarian cancer risk overall and stratified by histologic subtype (serous/non-serous) were analyzed using logistic regression. The mean time from serum collection to cancer diagnosis was 6.9 years. Results Overall we observed modest ovarian cancer risk associations among women with higher levels of estrone [Odds Ratio (95% Confidence Interval) quintile (Q)5 vs. Q1: 1.54 (0.82–2.90), p-trend=0.05], as well as 2- and 4-methoxyestrone metabolites [2.03 (1.06–3.88), p-trend=0.02; 1.86 (0.98–3.56), p-trend=0.01, respectively]. Associations of estrogens and estrogen metabolites varied substantially by histologic subtype. Associations with serous tumors were universally null, while estrone (2.65 (1.09–6.45), p-trend=0.01, p-heterogeneity=0.04), unconjugated estradiol (2.72 (1.04–7.14), p-trend=0.03, p-heterogeneity=0.02) and many of the 2-, 4-, and 16-pathway metabolites were positively associated with non-serous tumors. Conclusions Our study provides novel molecular data showing an association of the parent estrogens and several estrogen metabolites with non-serous ovarian cancers. Impact These findings further support the heterogeneous etiology of ovarian cancer. PMID:26908437

Urine and plasma metabolites predict the development of diabetic nephropathy in individuals with Type 2 diabetes mellitus.

PubMed

Pena, M J; Lambers Heerspink, H J; Hellemons, M E; Friedrich, T; Dallmann, G; Lajer, M; Bakker, S J L; Gansevoort, R T; Rossing, P; de Zeeuw, D; Roscioni, S S

2014-09-01

Early detection of individuals with Type 2 diabetes mellitus or hypertension at risk for micro- or macroalbuminuria may facilitate prevention and treatment of renal disease. We aimed to discover plasma and urine metabolites that predict the development of micro- or macroalbuminuria. Patients with Type 2 diabetes (n = 90) and hypertension (n = 150) were selected from the community-cohort 'Prevention of REnal and Vascular End-stage Disease' (PREVEND) and the Steno Diabetes Center for this case-control study. Cases transitioned in albuminuria stage (from normo- to microalbuminuria or micro- to macroalbuminuria). Controls, matched for age, gender, and baseline albuminuria stage, remained in normo- or microalbuminuria stage during follow-up. Median follow-up was 2.9 years. Metabolomics were performed on plasma and urine. The predictive performance of a metabolite for albuminuria transition was assessed by the integrated discrimination index. In patients with Type 2 diabetes with normoalbuminuria, no metabolites discriminated cases from controls. In patients with Type 2 diabetes with microalbuminuria, plasma histidine was lower (fold change = 0.87, P = 0.02) and butenoylcarnitine was higher (fold change = 1.17, P = 0.007) in cases vs. controls. In urine, hexose, glutamine and tyrosine were lower in cases vs. controls (fold change = 0.20, P < 0.001; 0.32, P < 0.001; 0.51, P = 0.006, respectively). Adding the metabolites to a model of baseline albuminuria and estimated glomerular filtration rate metabolites improved risk prediction for macroalbuminuria transition (plasma integrated discrimination index = 0.28, P < 0.001; urine integrated discrimination index = 0.43, P < 0.001). These metabolites did not differ between hypertensive cases and controls without Type 2 diabetes. Type 2 diabetes-specific plasma and urine metabolites were discovered that predict the development of macroalbuminuria beyond established renal risk markers. These results should be confirmed in a large

Review on risk factors related to lower back disorders at workplace

NASA Astrophysics Data System (ADS)

A' Tifah Jaffar, Nur; Nasrull Abdol Rahman, Mohd

2017-08-01

This review examines the evidence of the occurrence of risk exposure on work-related lower back disorders in the workplace. This review also investigates potential interactions between the risk factors in the workplace which include heavy physical work risk factor, static work postures risk factor, frequent bending and twisting risk factor, lifting risk factor, pushing and pulling risk factor, repetitive work risk factor, vibration risk factor, psychological and psychosocial risk factor that may be associated with symptoms of musculoskeletal disorders of lower back. These risk factors can reinforce each other and their influence can also be mediated by cultural or social factors. A systematic review of the literature was carried out by searching using databases and the searching strategy was used combined keyword for risk factors, work-related lower back disorders, heavy physical work, static work postures, frequent bending and twisting, lifting, pushing and pulling, repetitive work, vibration, psychological and psychosocial risk factor. A total of 67 articles were identified and reviewed. The risk factors identified that related for low back disorder are seven which are heavy physical work, static work postures, frequent bending and twisting, lifting, pushing and pulling, repetitive work, vibration, psychological and psychosocial risk factor and the level of evidence supporting the relationship with lower back disorders also described such as strong, moderate, insufficient, limited and no evidence. This result confirms that, existing of higher physical and psychosocial demand related to reported risk factors of low back disorders. The result also showed that previous reviews had evaluated relationship between risk factors of low back disorders and specific types of musculoskeletal disorders. This review also highlights the scarves evidence regarding some of the frequently reported risk factors for work related lower back disorders.

Associations of anthropometric markers with serum metabolites using a targeted metabolomics approach: results of the EPIC-potsdam study

PubMed Central

Bachlechner, U; Floegel, A; Steffen, A; Prehn, C; Adamski, J; Pischon, T; Boeing, H

2016-01-01

Background/Objectives: The metabolic consequences of type of body shape need further exploration. Whereas accumulation of body mass in the abdominal area is a well-established metabolic risk factor, accumulation in the gluteofemoral area is controversially debated. We evaluated the associations of anthropometric markers of overall body mass and body shape with 127 serum metabolites within a sub-sample of the European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam cohort. Subjects/Methods: The cross-sectional analysis was conducted in 2270 participants, randomly drawn from the EPIC-Potsdam cohort. Metabolites were measured by targeted metabolomics. To select metabolites related with both waist circumference (WC) (abdominal subcutaneous and visceral fat) and hip circumference (HC) (gluteofemoral fat, muscles and bone structure) correlations (r) with body mass index (BMI) as aggregating marker of body mass (lean and fat mass) were calculated. Relations with body shape were assessed by median metabolite concentrations across tertiles of WC and HC, mutually adjusted to each other. Results: Correlations revealed 23 metabolites related to BMI (r⩾I0.20 I). Metabolites showing relations with BMI were showing similar relations with HC adjusted WC (WCHC). In contrast, relations with WC adjusted HC (HCWC) were less concordant with relations of BMI and WCHC. In both sexes, metabolites with concordant relations regarding WCHC and HCWC included tyrosine, diacyl-phosphatidylcholine C38:3, C38:4, lyso-phosphatidylcholine C18:1, C18:2 and sphingomyelin C18:1; metabolites with opposite relations included isoleucine, diacyl-phosphatidylcholine C42:0, acyl–alkyl-phosphatidylcholine C34:3, C42:4, C42:5, C44:4 and C44:6. Metabolites specifically related to HCWC included acyl–alkyl-phosphatidylcholine C34:2, C36:2, C38:2 and C40:4, and were solely observed in men. Other metabolites were related to WCHC only. Conclusions: The study revealed specific metabolic

The urban risk and migration risk factors for schizophrenia: are cats the answer?

PubMed

Torrey, E Fuller; Yolken, Robert H

2014-11-01

Being born in and/or raised in an urban area is a proven risk factor for developing schizophrenia. Migrating from countries such as Jamaica or Morocco to countries such as England or the Netherlands is also a proven risk factor for developing schizophrenia. The transmission of Toxoplasma gondii oocysts to children is reviewed and proposed as a partial explanation for both of these risk factors. Copyright © 2014 Elsevier B.V. All rights reserved.

Biological risk factors for deep vein trombosis.

PubMed

Vayá, Amparo; Mira, Yolanda; Martínez, Marcial; Villa, Piedad; Ferrando, Fernando; Estellés, Amparo; Corella, Dolores; Aznar, Justo

2002-01-01

Hypercoagulable states due either to inherited or acquired thrombotic risk factors are only present in approximately half of cases of DVT, but the causes in the other half, remain unknown. The importance of biological risk factors such as hyperlipidemia, hypofibrinolysis and hemorheological alterations in the pathogenesis of DVT has not been well established. In order to ascertain whether the above mentioned biological factors are associated with DVT and could constitute independent risk factors, we carried out a case-control study in 109 first DVT patients in whom inherited or acquired thrombophilic risk factors had been ruled out and 121 healthy controls age (42+/-15 years) and sex matched. From all the biological variables analyzed (cholesterol, triglycerides, glucose, fibrinogen, erythrocyte aggregation, hematocrit, plasma viscosity and PAI-1) only fibrinogen concentration reached a statistically significant difference on the comparison of means (290+/-73 mg/dl in cases vs 268+/-58 mg/dl in controls, p<0.05). After this continuous variables were dichotomized according to our reference values, the percentage of cases with cholesterolemia >220 mg/dl, hematocrit >45% and fibrinogen >300 mg/dl was higher in cases than in controls: 38% vs 22%; p<0.01; 43% vs 27%; p<0.05; 36% vs 23%; p<0.05, respectively. The percentage of cases with PAI-1 values >30 ng/ml, 37% vs 25% was borderline significant; p=0.055. Multivariate logistic regression analysis showed that cholesterolemia >220 mg/dl and fibrinogen >300 mg/dl constitute independent predictors of venous thrombotic risk. The adjusted OR's were 2.03 (95% CI; 1.12-3.70) for cholesterolemia and 1.94 (95% CI; 1.07-3.55) for fibrinogen. When these two variables combined DVT risk rose about fourfold (3.96; p<0.05). Our results suggest that hypercholesterolemia and hyperfibrinogenemia should be added to the list of known DVT risk factors and we recommend adopting measures to decrease these variables in the population with a

Prognostic Metabolite Biomarkers for Soft Tissue Sarcomas Discovered by Mass Spectrometry Imaging

NASA Astrophysics Data System (ADS)

Lou, Sha; Balluff, Benjamin; Cleven, Arjen H. G.; Bovée, Judith V. M. G.; McDonnell, Liam A.

2017-02-01

Metabolites can be an important read-out of disease. The identification and validation of biomarkers in the cancer metabolome that can stratify high-risk patients is one of the main current research aspects. Mass spectrometry has become the technique of choice for metabolomics studies, and mass spectrometry imaging (MSI) enables their visualization in patient tissues. In this study, we used MSI to identify prognostic metabolite biomarkers in high grade sarcomas; 33 high grade sarcoma patients, comprising osteosarcoma, leiomyosarcoma, myxofibrosarcoma, and undifferentiated pleomorphic sarcoma were analyzed. Metabolite MSI data were obtained from sections of fresh frozen tissue specimens with matrix-assisted laser/desorption ionization (MALDI) MSI in negative polarity using 9-aminoarcridine as matrix. Subsequent annotation of tumor regions by expert pathologists resulted in tumor-specific metabolite signatures, which were then tested for association with patient survival. Metabolite signals with significant clinical value were further validated and identified by high mass resolution Fourier transform ion cyclotron resonance (FTICR) MSI. Three metabolite signals were found to correlate with overall survival ( m/z 180.9436 and 241.0118) and metastasis-free survival ( m/z 160.8417). FTICR-MSI identified m/z 241.0118 as inositol cyclic phosphate and m/z 160.8417 as carnitine.

Risk factors for suicide in bipolar disorder: a systematic review.

PubMed

Costa, Lucas da Silva; Alencar, Átila Pereira; Nascimento Neto, Pedro Januário; dos Santos, Maria do Socorro Vieira; da Silva, Cláudio Gleidiston Lima; Pinheiro, Sally de França Lacerda; Silveira, Regiane Teixeira; Bianco, Bianca Alves Vieira; Pinheiro, Roberto Flávio Fontenelle; de Lima, Marcos Antonio Pereira; Reis, Alberto Olavo Advincula; Rolim Neto, Modesto Leite

2015-01-01

Bipolar disorder confers the highest risk of suicide among major psychological disorders. The risk factors associated with bipolar disorder and suicide exist and are relevant to clinicians and researchers. The aim of the present study was to conduct a systematic review of articles regarding the suicide risk factors in bipolar disorder. A systematic review of articles on suicide risk factors in bipolar disorder, published from January 1, 2010 to April 05, 2014, on SCOPUS and PUBMED databases was carried out. Search terms were "Suicide" (medical subject headings [MeSH]), "Risk factors" (MeSH), and "Bipolar" (keyword). Of the 220 retrieved studies, 42 met the eligibility criteria. Bipolar disorder is associated with an increased rate death by suicide which contributes to overall mortality rates. Studies covered a wide range of aspects regarding suicide risk factors in bipolar disorder, such as risk factors associated to Sociodemographic conditions, Biological characteristics, Drugs Relationships, Psychological Factors, Genetic Compound, Religious and Spirituals conditions. Recent scientific literature regarding the suicide risk factors in bipolar disorder converge to, directly or indirectly, highlight the negative impacts of risk factors to the affected population quality of life. This review demonstrated that Bipolar disorders commonly leads to other psychiatric disorders and co-morbidities involving risk of suicide. Thus the risk factors are relevant to have a better diagnosis and prognosis of BD cases involving risk of suicide. Copyright © 2014 Elsevier B.V. All rights reserved.

[Perception of health risks: psychological and social factors].

PubMed

Kurzenhäuser, S; Epp, A

2009-12-01

This article reviews central findings and current developments of psychological and sociological research on the perception of health risks. Risk perception is influenced by numerous psychological, social, political, and cultural factors. These factors can be categorized into (a) risk characteristics, (b) characteristics of the risk perceiving person and his/her situation, and (c) characteristics of risk communication. Thus, besides individual cognitive and affective processing of risk information, social processes of risk amplification (e.g., media effects) are also involved in the construction of individual risk perceptions. We discuss the recommendations for health risk communication that follow from these findings with regard to different communication goals.

Factors influencing naproxen metabolite interference in total bilirubin assays.

PubMed

Saifee, Nabiha Huq; Ranjitkar, Pratistha; Greene, Dina N

2016-04-01

The factors influencing naproxen metabolite O-desmethylnaproxen (ODMN) positive interference in diazo-based Jendrassik and Grof (JG) total bilirubin (Tbil) assays and lack of interference in direct bilirubin (Dbil) assays have not been resolved. The objective of this study was to understand the conditions causing this interference pattern. Pooled normal and ultra-filtered plasma samples spiked with ODMN and naproxen were measured on the Beckman Coulter DxC and AU instruments. Absorbance spectra were obtained for ODMN mixed with Dbil reagent at original and adjusted pH. Absorbance spectra were also obtained for ODMN and bilirubin samples mixed with Tbil assay reagents. ODMN produces a positive interference in the DxC JG Tbil assays, but not the AU Tbil or Dbil assays or the DxC Dbil assay. Neutralizing the acidic pH of AU and DxC Dbil reagents allows ODMN to react with diazo salts. ODMN samples mixed with DxC and AU Tbil reagents produce broad peaks from 450 to 560nm and 400 to 540nm, respectively. The DxC JG Tbil assay monitors a change in absorbance at 520nm close to peak absorbance wavelength of diazo-reacted ODMN, whereas the AU Tbil assay monitors a change in absorbance at 570/660nm, beyond the peak absorbance wavelengths of diazo-reacted ODMN. The acidic pH of diazo-based Dbil assay reagents inhibits the reaction of ODMN with diazo salts. The AU JG Tbil assay is a reliable method to measure Tbil in the setting of naproxen overdose. Copyright © 2015 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

Cardiovascular Risk Factors in Severely Obese Adolescents

PubMed Central

Michalsky, Marc P.; Inge, Thomas H.; Simmons, Mark; Jenkins, Todd M.; Buncher, Ralph; Helmrath, Michael; Brandt, Mary L.; Harmon, Carroll M.; Courcoulas, Anita; Chen, Michael; Horlick, Mary; Daniels, Stephen R.; Urbina, Elaine M.

2015-01-01

IMPORTANCE Severe obesity is increasingly common in the adolescent population but, as of yet, very little information exists regarding cardiovascular disease (CVD) risks in this group. OBJECTIVE To assess the baseline prevalence and predictors of CVD risks among severely obese adolescents undergoing weight-loss surgery. DESIGN, SETTING, AND PARTICIPANTS A prospective cohort study was conducted from February 28, 2007, to December 30, 2011, at the following 5 adolescent weight-loss surgery centers in the United States: Nationwide Children’s Hospital in Columbus, Ohio; Cincinnati Children’s Hospital Medical Center in Cincinnati, Ohio; Texas Children’s Hospital in Houston; University of Pittsburgh Medical Center in Pittsburgh, Pennsylvania; and Children’s Hospital of Alabama in Birmingham. Consecutive patients aged 19 years or younger were offered enrollment in a long-term outcome study; the final analysis cohort consisted of 242 participants. MAIN OUTCOMES AND MEASURES This report examined the preoperative prevalence of CVD risk factors (ie, fasting hyperinsulinemia, elevated high-sensitivity C-reactive protein levels, impaired fasting glucose levels, dyslipidemia, elevated blood pressure, and diabetes mellitus) and associations between risk factors and body mass index (calculated as weight in kilograms divided by height in meters squared), age, sex, and race/ethnicity. Preoperative data were collected within 30 days preceding bariatric surgery. RESULTS The mean (SD) age was 17 (1.6) years and median body mass index was 50.5. Cardiovascular disease risk factor prevalence was fasting hyperinsulinemia (74%), elevated high-sensitivity C-reactive protein levels (75%), dyslipidemia (50%), elevated blood pressure (49%), impaired fasting glucose levels (26%), and diabetes mellitus (14%). The risk of impaired fasting glucose levels, elevated blood pressure, and elevated high-sensitivity C-reactive protein levels increased by 15%, 10%, and 6%, respectively, per 5-unit

Environmental and lifestyle risk factors of gastric cancer.

PubMed

Lee, Yeong Yeh; Derakhshan, Mohammad H

2013-06-01

Effective prevention and early diagnostic strategies are the most important public health interventions in gastric cancer, which remains a common malignancy worldwide. Preventive strategies require identification and understanding of environmental risk factors that lead to carcinogenesis. Helicobacter pylori (H. pylori) is the primary carcinogen as this ancient bacterium has a complex ability to interact with its human host. Smoking and salt are strong independent risk factors for gastric cancer whereas alcohol is only a risk when it is heavily consumed. Red meat and high fat increase the risk of gastric cancer however fresh fruits, vegetables (allium family) and certain micronutrients (selenium, vitamin C) reduce the risk, with evidence lacking for fish, coffee and tea. Foods that inhibit H. pylori viability, colonization and infection may reduce cancer risk. Obesity is increasingly recognized as a contributory factor in gastric cardia carcinogenesis. Therefore, modest daily physical activities can be protective against cancer. Foundry workers are at risk for developing gastric cancer with dust iron being an important cause. Other risk factors include Epstein-Barr virus (EBV), possibly JC virus and radiation but the effects of these are likely to remain small.

Risk Factors of Periodontal Disease: Review of the Literature

PubMed Central

AlJehani, Yousef A.

2014-01-01

Objectives. This paper aims to review the evidence on the potential roles of modifiable and nonmodifiable risk factors associated with periodontal disease. Data. Original articles that reported on the risk factors for periodontal disease were included. Sources. MEDLINE (1980 to Jan 2014), PubMed (using medical subject headings), and Google Scholar were searched using the following terms in different combinations: “periodontal disease,” “periodontitis,” “risk factors,” and “causal.” This was supplemented by hand-searching in peer-reviewed journals and cross-referenced with the articles accessed. Conclusions. It is important to understand the etiological factors and the pathogenesis of periodontal disease to recognize and appreciate the associated risk factors. As periodontal disease is multifactorial, effective disease management requires a clear understanding of all the associated risk factors. PMID:24963294

Evaluation of community health screening participants' knowledge of cardiovascular risk factors.

PubMed

Mooney, Leslie A; Franks, Amy M

2009-01-01

To assess knowledge of cardiovascular disease (CVD) risk factors among a group of health screening participants and to compare knowledge between participants with high and low CVD risk. Cross-sectional pilot study. Jonesboro, AR, during June 2007. 121 adult volunteers participating in a community health screening. 34-item self-administered written questionnaire. Ability to identify CVD risk factors and healthy values for CVD risk factors and the differences in these abilities between participants with high and low CVD risk. Participants demonstrated good knowledge of traditional CVD risk factors such as high blood pressure, high cholesterol, lack of exercise, and overweight or obese status. Knowledge of other CVD risk factors and healthy values for major CVD risk factors was limited. Participants with high CVD risk were significantly more likely to correctly identify high triglycerides as a CVD risk factor and to identify healthy values for fasting blood glucose and total cholesterol compared with participants with low CVD risk. Overall, participants lacked knowledge of the risk factor status and healthy values for many CVD risk factors. Participants with high CVD risk may have better knowledge of some CVD risk factors than participants with low CVD risk. These findings highlight the need for more education to improve knowledge in both risk groups.

Patient-specific risk factors for infection in arthroplasty procedure.

PubMed

Marmor, S; Kerroumi, Y

2016-02-01

All patients are not equally at risk when it comes to postoperative infections, whether the risks are related to the environment or the patient. Patient-specific infection risk factors for arthroplasty should be a focal point during the preoperative consultation as they impact the treatment decision. Eighty percent of patients have at least one modifiable infection risk factor. These risk factors must be corrected preoperatively whenever possible so that the patient is operated under the best possible conditions, with the lowest possible infection risk. The screenings and preoperative preparations are multidisciplinary but must also involve the patient. The information provided to the patient must match the patient's infectious risk profile. This lecture will review every infection risk factor, whether it is modifiable or not, and then suggest how the treatment decision should be adapted to each patient's infection risk. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Risk factors for sciatica leading to hospitalization.

PubMed

Euro, Ulla; Knekt, P; Rissanen, H; Aromaa, A; Karppinen, J; Heliövaara, M

2017-06-13

To study the known or suspected risk factors for sciatica: Tallness, overweight, smoking, leisure-time physical exercise, self-reported health and occupation, and how they predict hospitalizations due to sciatica. Only a few cohort studies have previously focused on the risk factors for sciatica. The 13,095 subjects, free from low back disorders at the baseline in 1973-1976 were followed up to the end of 2011 via the Care Register for Health Care. Along with an invitation to the health examination, a basic questionnaire concerning lifestyle factors was sent to participants. The outcome measure was incident sciatica leading to hospitalization. Altogether 702 incident sciatica cases occurred. Among men, the adjusted hazard ratio (HR) with 95% confidence interval (CI) was 2.57 (95% CI 1.47-4.50) in metal or machine work, and 1.44 (1.06-1.95) in other industrial work, compared to that in white-collar occupations. Among women, the corresponding risk estimates were 1.81 (1.18-2.78) for nurses and related occupations, 1.56 (1.05-2.31) for sales workers, and 1.46 (1.03-2.08) for industrial workers. Among men, physical exercise during leisure predicted a decrease in the risk of sciatica (0.74; 0.55-1.00); this association was significantly pronounced in white-collar occupations (0.38; 0.18-0.88). Among women, the association between body mass index and the risk of sciatica was only modest, but varied greatly between different occupations. Physically demanding work is a strong risk factor for sciatica. Leisure-time physical activity seems to protect men against sciatica, while overweight is a risk factor among women. However, occupation substantially modifies these associations.

Cardiovascular disease risk factors and cognitive impairment.

PubMed

Nash, David T; Fillit, Howard

2006-04-15

The role of cardiovascular disease risk factors in the occurrence and progression of cognitive impairment has been the subject of a significant number of publications but has not achieved widespread recognition among many physicians and educated laymen. It is apparent that the active treatment of certain of these cardiovascular disease risk factors is accompanied by a reduced risk for cognitive impairment. Patients with hypertension who are treated experience fewer cardiovascular disease events as well as less cognitive impairment than similar untreated patients. Patients who exercise may present with less cognitive impairment, and obesity may increase the risk for cognitive impairment. Lipid abnormalities and genetic markers are associated with an increased risk for cardiovascular disease and cognitive impairment. Autopsy studies have demonstrated a correlation between elevated levels of cholesterol and amyloid deposition in the brain. Research has demonstrated a relation between atherosclerotic obstruction lesions in the circle of Willis and dementia. Diabetes mellitus is associated with an increased risk for cardiovascular disease and cognitive impairment. A number of nonpharmacologic factors have a role in reducing the risk for cognitive impairment. Antioxidants, fatty acids, and micronutrients may have a role, and diets rich in fruits and vegetables and other dietary approaches may improve the outlook for patients considered at risk for cognitive impairment.

Risk Factors for Complications of Traumatic Injuries.

PubMed

de Aguiar Júnior, Wagner; Saleh, Carmen Mohamad Rida; Whitaker, Iveth Yamaguchi

2016-01-01

Complications in hospitalized trauma patients are major causes of morbidity and mortality. The aims of this study were to identify the in-hospital trauma patients' complications and identify the risk factors for complications in this population. A retrospective analysis was conducted in a sample from a Brazilian hospital. The sample consisted of 407 patients, 194 (47.66%) of whom had records of complications. The most common complications were infections (41.80%). The risk factors related to the complications were age, length of hospital stay, external causes, and injury severity. The complications were frequent in this sample, and the risk for complications was characterized by multiple factors.

[Analysis of risk factors associated with professional drivers’ work].

PubMed

Czerwińska, Maja; Hołowko, Joanna; Stachowska, Ewa

Professional driver is an occupation associated with high health risk. The factors which increase the risk of developing lifestyle diseases are closely related to working conditions. The aim of this study was to analyse the risk factors which are associated with professional drivers’ lifestyle. The material consisted of 23 articles from PubMed.gov. Risk factors related to drivers’ work have a signiicant impact on their health.

New Methodology for Known Metabolite Identification in Metabonomics/Metabolomics: Topological Metabolite Identification Carbon Efficiency (tMICE).

PubMed

Sanchon-Lopez, Beatriz; Everett, Jeremy R

2016-09-02

A new, simple-to-implement and quantitative approach to assessing the confidence in NMR-based identification of known metabolites is introduced. The approach is based on a topological analysis of metabolite identification information available from NMR spectroscopy studies and is a development of the metabolite identification carbon efficiency (MICE) method. New topological metabolite identification indices are introduced, analyzed, and proposed for general use, including topological metabolite identification carbon efficiency (tMICE). Because known metabolite identification is one of the key bottlenecks in either NMR-spectroscopy- or mass spectrometry-based metabonomics/metabolomics studies, and given the fact that there is no current consensus on how to assess metabolite identification confidence, it is hoped that these new approaches and the topological indices will find utility.

Sudden cardiac death: epidemiology and risk factors

PubMed Central

Adabag, A. Selcuk; Luepker, Russell V.; Roger, Véronique L.; Gersh, Bernard J.

2016-01-01

Sudden cardiac death (SCD) is an important public-health problem with multiple etiologies, risk factors, and changing temporal trends. Substantial progress has been made over the past few decades in identifying markers that confer increased SCD risk at the population level. However, the quest for predicting the high-risk individual who could be a candidate for an implantable cardioverter-defibrillator, or other therapy, continues. In this article, we review the incidence, temporal trends, and triggers of SCD, and its demographic, clinical, and genetic risk factors. We also discuss the available evidence supporting the use of public-access defibrillators. PMID:20142817

Metabolomic determinants of metabolic risk in Mexican adolescents

PubMed Central

Perng, Wei; Hector, Emily C.; Song, Peter X.K.; Rojo, Martha Maria Tellez; Raskind, Sasha; Kachman, Maureen; Cantoral, Alejandra; Burant, Charles F.; Peterson, Karen E.

2017-01-01

Objective To identify metabolites associated with metabolic risk, separately by sex, in Mexican adolescents. Methods We carried out untargeted metabolomic profiling on fasting serum of 238 youth age 8–14 years, and identified metabolites associated with a metabolic syndrome risk z-score (MetRisk z-score), separately for boys and girls using the simulation and extrapolation (SIMEX) algorithm. We examined associations of each metabolite with MetRisk z-score using linear regression models that accounted for maternal education, child’s age, and pubertal status. Results Of the 938 features identified in metabolomics analysis, 7 named compounds (of 27 identified metabolites) were associated with MetRisk z-score in girls, and 3 named compounds (of 14 identified) were associated with MetRisk z-score in boys. In girls, diacylglycerol (DG) 16:0/16:0, 1,3-dielaidin, myo-inositol, and urate corresponded with higher MetRisk z-score, whereas N-acetylglycine, thymine, and dodecenedioic acid were associated with lower MetRisk z-score. For example, each z-score increment in DG 16:0/16:0 corresponded with 0.60 (0.47, 0.74). In boys, we found positive associations of DG 16:0/16:0, tyrosine, and 5′-methylthioadenosine with MetRisk z-score. Conclusions Metabolites on lipid, amino acid, and carbohydrate metabolism pathways are associated with metabolic risk in girls. Compounds on lipid and DNA pathways correspond with metabolic risk in boys. PMID:28758362

Risk Factors for Smoking in Rural Women

PubMed Central

Salsberry, Pamela J.; Ferketich, Amy K.; Ahijevych, Karen L.; Hood, Nancy E.; Paskett, Electra D.

2012-01-01

Abstract Background This study examined the association between social, demographic, and psychologic factors and smoking status among Appalachian Ohio women. A secondary aim examined whether specific factors could be identified and segmented for future tailored treatment of tobacco dependence. Methods A cross-sectional survey (n=570) obtained information about social, demographic, and psychologic factors and smoking. Logistic regression described associations between these characteristics and smoking status. Chi-square automatic interaction detection (CHAID) analyses identified subgroups at risk for smoking. Results Fifty-two percent never smoked, with 20.5% and 27.5% categorized as former and current smokers, respectively. Women with low adult socioeconomic position (SEP) were more likely to smoke (odds ratio [OR] 3.05, 95% confidence interval [CI] 1.74-5.34) compared to high SEP women. Other factors associated with current smoking included age 31–50 (OR 2.30, 95% CI 1.22-4.33), age 18–30 (OR 3.29, 95% CI 1.72-5.34), Center for Epidemiologic Studies Depression scale (CES-D) score≥16 (OR 1.99, 95% CI 1.31-3.05), and first pregnancy at age<20 (OR 1.74, 95% CI 1.14-2.66). The prevalence of smoking was 50% among those with four or more risk factors compared to 10% for those reporting no risk factors. CHAID analyses identified low adult SEP and depressive symptoms as the combination of risk factors most strongly associated with smoking; 49.3% of women in this subgroup currently smoked. Conclusions Low SEP in adulthood, maternal circumstances, and depressive symptoms are associated with current smoking. Tailored cessation interventions that address these risk factors should be developed and further evaluated in an attempt to reduce disparities in smoking prevalence among this vulnerable group of women. PMID:22360694

Risk Factors Associated with Overdose among Bahraini Youth.

ERIC Educational Resources Information Center

Al Ansari, Ahmed M.; Hamadeh, Randah R.; Matar, Ali M.; Marhoon, Huda; Buzaboon, Bana Y.; Raees, Ahmed G.

2001-01-01

Study aimed to identify risk factors, such as family pathology and psychosocial stress, of overdose suicide attempts among Bahraini youth. Stresses from living in a non-intact family; interpersonal relationships mainly with the opposite sex; unemployment; and school performance emerged as main risk factors. Previously identified factors, such as…

[Secondary Metabolites from Marine Microorganisms. I. Secondary Metabolites from Marine Actinomycetes].

PubMed

Orlova, T I; Bulgakova, V G; Polin, A N

2015-01-01

Review represents data on new active metabolites isolated from marine actinomycetes published in 2007 to 2014. Marine actinomycetes are an unlimited source of novel secondary metabolites with various biological activities. Among them there are antibiotics, anticancer compounds, inhibitors of biochemical processes.

Validation of the association between a branched chain amino acid metabolite profile and extremes of coronary artery disease in patients referred for cardiac catheterization.

PubMed

Bhattacharya, Sayanti; Granger, Christopher B; Craig, Damian; Haynes, Carol; Bain, James; Stevens, Robert D; Hauser, Elizabeth R; Newgard, Christopher B; Kraus, William E; Newby, L Kristin; Shah, Svati H

2014-01-01

To validate independent associations between branched-chain amino acids (BCAA) and other metabolites with coronary artery disease (CAD). We conducted mass-spectrometry-based profiling of 63 metabolites in fasting plasma from 1983 sequential patients undergoing cardiac catheterization. Significant CAD was defined as CADindex ≥ 32 (at least one vessel with ≥ 95% stenosis; N = 995) and no CAD as CADindex ≤ 23 and no previous cardiac events (N = 610). Individuals (N = 378) with CAD severity between these extremes were excluded. Principal components analysis (PCA) reduced large numbers of correlated metabolites into uncorrelated factors. Association between metabolite factors and significant CAD vs. no CAD was tested using logistic regression; and between metabolite factors and severity of CAD was tested using linear regression. Of twelve PCA-derived metabolite factors, two were associated with CAD in multivariable models: factor 10, composed of BCAA (adjusted odds ratio, OR, 1.20; 95% CI 1.05-1.35, p = 0.005) and factor 7, composed of short-chain acylcarnitines, which include byproducts of BCAA metabolism (adjusted OR 1.30; 95% CI 1.14-1.48, p = 0.001). After adjustment for glycated albumin (marker of insulin resistance [IR]) both factors 7 (p = 0.0001) and 10 (p = 0.004) remained associated with CAD. Severity of CAD as a continuous variable (including patients with non-obstructive disease) was associated with metabolite factors 2, 3, 6, 7, 8 and 9; only factors 7 and 10 were associated in multivariable models. We validated the independent association of metabolites involved in BCAA metabolism with CAD extremes. These metabolites may be reporting on novel mechanisms of CAD pathogenesis that are independent of IR and diabetes. Copyright © 2013. Published by Elsevier Ireland Ltd.

Voice disorders in teachers: occupational risk factors and psycho-emotional factors.

PubMed

van Houtte, Evelyne; Claeys, Sofie; Wuyts, Floris; van Lierde, Kristiane

2012-10-01

Teaching is a high-risk occupation for developing voice disorders. The purpose of this study was to investigate previously described vocal risk factors as well as to identify new risk factors related to both the personal life of the teacher (fluid intake, voice-demanding activities, family history of voice disorders, and children at home) and to environmental factors (temperature changes, chalk use, presence of curtains, carpet, or air-conditioning, acoustics in the classroom, and noise in and outside the classroom). The study group comprised 994 teachers (response rate 46.6%). All participants completed a questionnaire. Chi-square tests and logistic regression analyses were performed. A total of 51.2% (509/994) of the teachers presented with voice disorders. Women reported more voice disorders compared to men (56.4% versus 40.4%, P < 0.001). Vocal risk factors were a family history of voice disorders (P = 0.005), temperature changes in the classroom (P = 0.017), the number of pupils per classroom (P = 0.001), and noise level inside the classroom (P = 0.001). Teachers with voice disorders presented a higher level of psychological distress (P < 0.001) compared to teachers without voice problems. Voice disorders are frequent among teachers, especially in female teachers. The results of this study emphasize that multiple factors are involved in the development of voice disorders.

Serum metabolites are associated with all-cause mortality in chronic kidney disease.

PubMed

Hu, Jiun-Ruey; Coresh, Josef; Inker, Lesley A; Levey, Andrew S; Zheng, Zihe; Rebholz, Casey M; Tin, Adrienne; Appel, Lawrence J; Chen, Jingsha; Sarnak, Mark J; Grams, Morgan E

2018-06-02

Chronic kidney disease (CKD) involves significant metabolic abnormalities and has a high mortality rate. Because the levels of serum metabolites in patients with CKD might provide insight into subclinical disease states and risk for future mortality, we determined which serum metabolites reproducibly associate with mortality in CKD using a discovery and replication design. Metabolite levels were quantified via untargeted liquid chromatography and mass spectroscopy from serum samples of 299 patients with CKD in the Modification of Diet in Renal Disease (MDRD) study as a discovery cohort. Six among 622 metabolites were significantly associated with mortality over a median follow-up of 17 years after adjustment for demographic and clinical covariates, including urine protein and measured glomerular filtration rate. We then replicated associations with mortality in 963 patients with CKD from the African American Study of Kidney Disease and Hypertension (AASK) cohort over a median follow-up of ten years. Three of the six metabolites identified in the MDRD cohort replicated in the AASK cohort: fumarate, allantoin, and ribonate, belonging to energy, nucleotide, and carbohydrate pathways, respectively. Point estimates were similar in both studies and in meta-analysis (adjusted hazard ratios 1.63, 1.59, and 1.61, respectively, per doubling of the metabolite). Thus, selected serum metabolites were reproducibly associated with long-term mortality in CKD beyond markers of kidney function in two well characterized cohorts, providing targets for investigation. Copyright © 2018 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

Fate of cyanobacteria and their metabolites during water treatment sludge management processes.

PubMed

Ho, Lionel; Dreyfus, Jennifer; Boyer, Justine; Lowe, Todd; Bustamante, Heriberto; Duker, Phil; Meli, Tass; Newcombe, Gayle

2012-05-01

Cyanobacteria and their metabolites are an issue for water authorities; however, little is known as to the fate of coagulated cyanobacterial-laden sludge during waste management processes in water treatment plants (WTPs). This paper provides information on the cell integrity of Anabaena circinalis and Cylindrospermopsis raciborskii during: laboratory-scale coagulation/sedimentation processes; direct filtration and backwashing procedures; and cyanobacterial-laden sludge management practices. In addition, the metabolites produced by A. circinalis (geosmin and saxitoxins) and C. raciborskii (cylindrospermopsin) were investigated with respect to their release (and possible degradation) during each of the studied processes. Where sedimentation was used, coagulation effectively removed cyanobacteria (and intracellular metabolites) without any considerable exertion on coagulant demand. During direct filtration experiments, cyanobacteria released intracellular metabolites through a stagnation period, suggesting that more frequent backwashing of filters may be required to prevent floc build-up and metabolite release. Cyanobacteria appeared to be protected within the flocs, with minimal damage during backwashing of the filters. Within coagulant sludge, cyanobacteria released intracellular metabolites into the supernatant after 3d, even though cells remained viable up to 7d. This work has improved the understanding of cyanobacterial metabolite risks associated with management of backwash water and sludge and is likely to facilitate improvements at WTPs, including increased monitoring and the application of treatment strategies and operational practices, with respect to cyanobacterial-laden sludge and/or supernatant recycle management. Copyright © 2012 Elsevier B.V. All rights reserved.

Risk factors for Staphylococcus aureus postpartum breast abscess.

PubMed

Branch-Elliman, Westyn; Golen, Toni H; Gold, Howard S; Yassa, David S; Baldini, Linda M; Wright, Sharon B

2012-01-01

Staphylococcus aureus (SA) breast abscesses are a complication of the postpartum period. Risk factors for postpartum SA breast abscesses are poorly defined, and literature is conflicting. Whether risk factors for methicillin-resistant SA (MRSA) and methicillin-susceptible SA (MSSA) infections differ is unknown. We describe novel risk factors associated with postpartum breast abscesses and the changing epidemiology of this infection. We conducted a cohort study with a nested case-control study (n = 216) involving all patients with culture-confirmed SA breast abscess among >30 000 deliveries at our academic tertiary care center from 2003 through 2010. Data were collected from hospital databases and through abstraction from medical records. All SA cases were compared with both nested controls and full cohort controls. A subanalysis was completed to determine whether risk factors for MSSA and MRSA breast abscess differ. Univariate analysis was completed using Student's t test, Wilcoxon rank-sum test, and analysis of variance, as appropriate. A multivariable stepwise logistic regression was used to determine final adjusted results for both the case-control and the cohort analyses. Fifty-four cases of culture-confirmed abscess were identified: 30 MRSA and 24 MSSA. Risk factors for postpartum SA breast abscess in multivariable analysis include in-hospital identification of a mother having difficulty breastfeeding (odds ratio, 5.00) and being a mother employed outside the home (odds ratio, 2.74). Risk factors did not differ between patients who developed MRSA and MSSA infections. MRSA is an increasingly important pathogen in postpartum women; risk factors for postpartum SA breast abscess have not changed with the advent of community-associated MRSA.

Child sexual assault: risk factors for girls.

PubMed

Butler, Amy C

2013-09-01

To identify prospectively measured risk factors of sexual assault (SA) among girls age 17 and younger. The data come from the Panel Study of Income Dynamics and are derived from interviews with 1,087 girls, their primary caregivers, and household heads. The data were collected from the girls' first year of life through their early twenties. Factors measured during childhood were used to predict whether the girls experienced a subsequent first sexual assault before the age of 18. Prospectively measured risk factors associated with subsequent child SA included the absence of one or both parents, maternal education less than college, family income below 400% of the federal poverty threshold, low caregiver warmth, child internalizing and externalizing behaviors, impulsivity, low achievement scores, and having been classified by their school as needing special education. Girls with behavioral health problems and learning challenges are at heightened risk for sexual assault. Research on behavioral health consequences of SA should control for preexisting SA risk factors to more accurately estimate the impact of child SA on subsequent behavioral health. Copyright © 2013 Elsevier Ltd. All rights reserved.

Personal and couple level risk factors: Maternal and paternal parent-child aggression risk.

PubMed

Tucker, Meagan C; Rodriguez, Christina M; Baker, Levi R

2017-07-01

Previous literature examining parent-child aggression (PCA) risk has relied heavily upon mothers, limiting our understanding of paternal risk factors. Moreover, the extent to which factors in the couple relationship work in tandem with personal vulnerabilities to impact PCA risk is unclear. The current study examined whether personal stress and distress predicted PCA risk (child abuse potential, over-reactive discipline style, harsh discipline practices) for fathers as well as mothers and whether couple functioning mediated versus moderated the relation between personal stress and PCA risk in a sample of 81 couples. Additionally, the potential for risk factors in one partner to cross over and affect their partner's PCA risk was considered. Findings indicated higher personal stress predicted elevated maternal and paternal PCA risk. Better couple functioning did not moderate this relationship but partially mediated stress and PCA risk for both mothers and fathers. In addition, maternal stress evidenced a cross-over effect, wherein mothers' personal stress linked to fathers' couple functioning. Findings support the role of stress and couple functioning in maternal and paternal PCA risk, including potential cross-over effects that warrant further inquiry. Copyright © 2017 Elsevier Ltd. All rights reserved.

Improvement of reverse-phase high pressure liquid chromatographic resolution of benzo(a)pyrene metabolites using organic amines: application to metabolites produced by fish

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tjessum, K.; Stegeman, J.J.

1979-10-15

Addition of primary organic amines, such as n-butylamine, to the mobile phase altered the capacity factors and selectivity of benzo(a)pyrene metabolites obtained with reverse-phase high pressure liquid chromatography on an ODS column. Separation of benzo(a)pyrene phenols in particular was improved with 8 of the 10 available metabolites resolved, including those known to be biologically produced. The method offers sufficiently improved resolution or convenience that it should prove useful in comparative studies of metabolism of benzo(a)-pyrene and other polynuclear aromatic hydrocarbons. Applying the method to analysis of benzo(a)pyrene metabolites produced in vitro by hepatic microsomes from the marine fish Stenotomus versicolormore » indicated the principal phenolic derivatives produced by this fish were 1-hydroxy-, 3-hydroxy-, 7-hydroxy-, and 9-hydroxybenzo(a)pyrene.« less

[Risk factors associated with dystocic delivery].

PubMed

Romero Gutiérrez, Gustavo; Ríos López, Juan Carlos; Cortés Salim, Patricia; Ponce Ponce de León, Ana Lilia

2007-09-01

the dystocic delivery is a frequent complication and its perinatal repercussions vary from minor lesions to severe brain damage. It has been reported diverse factors associated with this medical complication. to identify the risk factors with significant association with dystocic delivery. a case-control study was carried out. There were included 750 patients, divided into 250 women with dystocic deliveries (cases) and 500 women with eutocic deliveries (controls). Demographic and clinical variables were registered. The statistical analysis was performed with percentages, arithmetic media, standard deviation, Student t test, chi2 and logistic regression analysis. An alpha value was set at 0.05. the factors with statistical significance were: advanced age (p < 0.001), major patient's height (p < 0.001), major new born's weight (p = 0.009), lower parity (p < 0.001), and prolonged duration of labor (p = 0.04). Other variables such as number of pregnancies, previous cesarean sections, spontaneous abortions, weight of the patient, weight earned during pregnancy, number of medical appointments during antenatal care, previous dystocic delivery, and premature rupture of the membranes, were not significant. there are clinical and demographic risk factors associated with dystocic delivery. To identify this risk factors during the antenatal care could diminish the frequency of dystocic deliveries and therefore to avoid the associated maternal-fetal complications.

Engineering Microbial Metabolite Dynamics and Heterogeneity.

PubMed

Schmitz, Alexander C; Hartline, Christopher J; Zhang, Fuzhong

2017-10-01

As yields for biological chemical production in microorganisms approach their theoretical maximum, metabolic engineering requires new tools, and approaches for improvements beyond what traditional strategies can achieve. Engineering metabolite dynamics and metabolite heterogeneity is necessary to achieve further improvements in product titers, productivities, and yields. Metabolite dynamics, the ensemble change in metabolite concentration over time, arise from the need for microbes to adapt their metabolism in response to the extracellular environment and are important for controlling growth and productivity in industrial fermentations. Metabolite heterogeneity, the cell-to-cell variation in a metabolite concentration in an isoclonal population, has a significant impact on ensemble productivity. Recent advances in single cell analysis enable a more complete understanding of the processes driving metabolite heterogeneity and reveal metabolic engineering targets. The authors present an overview of the mechanistic origins of metabolite dynamics and heterogeneity, why they are important, their potential effects in chemical production processes, and tools and strategies for engineering metabolite dynamics and heterogeneity. The authors emphasize that the ability to control metabolite dynamics and heterogeneity will bring new avenues of engineering to increase productivity of microbial strains. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Degradation in soil and water and ecotoxicity of rimsulfuron and its metabolites.

PubMed

Martins, J M; Chevre, N; Spack, L; Tarradellas, J; Mermoud, A

2001-11-01

The degradation and ecotoxicity of sulfonylurea herbicide rimsulfuron and its major metabolites were examined in batch samples of an alluvial sandy loam and in freshwater. An HPLC-DAD method was adapted to simultaneously identify and quantify rimsulfuron and its metabolites, which was successfully validated by GC-MS analysis. In aqueous solutions, pure rimsulfuron was rapidly hydrolyzed into metabolite 1 (N-(4,6-dimethoxypyrimidin-2-yl)-N-(3-(ethylsulfonyl)-2-pyridinylurea)), which itself was transformed into the more stable metabolite 2 (N-((3-(ethylsulfonyl)-2-pyridinyl)-4,6-dimethoxy-2-pyrimidineamine)), with half-life (t(1/2)) values of 2 and 2.5 days, respectively. Hydrolysis was instantaneous under alkaline conditions (pH = 10). In aqueous suspensions of the alluvial soil (pH = 8), formulated rimsulfuron had a half-life of 7 days, whereas that of metabolite 1 was similar to that in water (about 3.5 days). The degradation of the two major metabolites was also studied in soil suspensions with the pure compounds at concentrations ranging from 1 to 10 mg l(-1). The half-life of metabolite 1 ranged from 3.9 to 5 days, close to the previous values. Metabolite 2 was more persistent and its degradation is strongly dependent on the initial concentration (C0): half-life values ranged from 8.1 to 55 days at 2-10 mg l(-1), respectively. These values are higher than those determined from the kinetics of metabolite 1 transformation into metabolite 2 (t(1/2) = 8-19 days). The ecotoxicity of the three chemicals was evaluated through their effect on Daphnia magna and Vibrio fischeri (Microtox bioassay). No effect was observed on D. magna with 24 and 48 h acute toxicity tests. Similarly, no toxic effect was observed with the Microtox test for the three chemicals in the range of concentrations tested that included the field application dose. Thus, being of low persistence and lacking acute toxicity, these chemicals present a low environmental risk. However, chronic effects

Risk factors for age-related maculopathy.

PubMed

Connell, Paul P; Keane, Pearse A; O'Neill, Evelyn C; Altaie, Rasha W; Loane, Edward; Neelam, Kumari; Nolan, John M; Beatty, Stephen

2009-01-01

Age-related maculopathy (ARM) is the leading cause of blindness in the elderly. Although beneficial therapeutic strategies have recently begun to emerge, much remains unclear regarding the etiopathogenesis of this disorder. Epidemiologic studies have enhanced our understanding of ARM, but the data, often conflicting, has led to difficulties with drawing firm conclusions with respect to risk for this condition. As a consequence, we saw a need to assimilate the published findings with respect to risk factors for ARM, through a review of the literature appraising results from published cross-sectional studies, prospective cohort studies, case series, and case control studies investigating risk for this condition. Our review shows that, to date, and across a spectrum of epidemiologic study designs, only age, cigarette smoking, and family history of ARM have been consistently demonstrated to represent risk for this condition. In addition, genetic studies have recently implicated many genes in the pathogenesis of age-related maculopathy, including Complement Factor H, PLEKHA 1, and LOC387715/HTRA1, demonstrating that environmental and genetic factors are important for the development of ARM suggesting that gene-environment interaction plays an important role in the pathogenesis of this condition.

Marine-Derived Metabolites of S-Adenosylmethionine as Templates for New Anti-Infectives

PubMed Central

Sufrin, Janice R.; Finckbeiner, Steven; Oliver, Colin M.

2009-01-01

S-Adenosylmethionine (AdoMet) is a key biochemical co-factor whose proximate metabolites include methylated macromolecules (e.g., nucleic acids, proteins, phospholipids), methylated small molecules (e.g., sterols, biogenic amines), polyamines (e.g., spermidine, spermine), ethylene, and N-acyl-homoserine lactones. Marine organisms produce numerous AdoMet metabolites whose novel structures can be regarded as lead compounds for anti-infective drug design. PMID:19841722

Low bone density risk is higher in exercising women with multiple triad risk factors.

PubMed

Gibbs, Jenna C; Nattiv, Aurelia; Barrack, Michelle T; Williams, Nancy I; Rauh, Mitchell J; Nichols, Jeanne F; De Souza, Mary Jane

2014-01-01

The cumulative effect of the female athlete triad (Triad) risk factors on the likelihood of low bone mineral density (BMD) in exercising women is unclear. This study aimed to determine the risk of low BMD in exercising women with multiple Triad risk factors. We retrospectively examined cross-sectional data from 437 exercising women (mean ± SD age of 18.0 ± 3.5 yr, weighed 57.5 ± 7.1 kg with 24.5% ± 6.1% body fat) obtained at baseline from 4 prospective cohort studies examining Triad risk factors. Questionnaires were completed to obtain information on demographic characteristics, self-reported eating attitudes/behaviors, menstrual function, sport/activity participation, and medication use. Height and body weight were measured. BMD was measured using dual energy x-ray absorptiometry. Low BMD was defined as z-scores of <-1 and ≤-2. Chi-square tests were performed to determine the percentage of women with low BMD who met the criteria for individual (current oligo/amenorrhea, late menarche, low body mass index (BMI), elevated dietary restraint, lean sport/activity participation) or multiple (2, 3, 4, or 5) Triad risk factors. Late menarche and low BMI were associated with the highest percentage of low BMD (z-score < -1), 55% and 54%, respectively, and low BMD (z-score ≤-2), 14% and 16%, respectively. The percentage of participants with low BMD (z-score < -1 and ≤-2) increased from 10% to 62% and from 2% to 18%, respectively, as women met the criteria for an increasing number of Triad risk factors. A cumulative number of Triad risk factors were associated with an increased risk of low BMD, suggesting a dose-response association between the number of Triad risk factors and BMD in exercising women. Further research should be conducted to develop a user-friendly algorithm integrating these indicators of risk for low BMD in exercising women (particularly factors associated with low BMI/body weight, menstrual dysfunction, lean sport/activity participation, and

Towards microbial fermentation metabolites as markers for health benefits of prebiotics.

PubMed

Verbeke, Kristin A; Boobis, Alan R; Chiodini, Alessandro; Edwards, Christine A; Franck, Anne; Kleerebezem, Michiel; Nauta, Arjen; Raes, Jeroen; van Tol, Eric A F; Tuohy, Kieran M

2015-06-01

Available evidence on the bioactive, nutritional and putative detrimental properties of gut microbial metabolites has been evaluated to support a more integrated view of how prebiotics might affect host health throughout life. The present literature inventory targeted evidence for the physiological and nutritional effects of metabolites, for example, SCFA, the potential toxicity of other metabolites and attempted to determine normal concentration ranges. Furthermore, the biological relevance of more holistic approaches like faecal water toxicity assays and metabolomics and the limitations of faecal measurements were addressed. Existing literature indicates that protein fermentation metabolites (phenol, p-cresol, indole, ammonia), typically considered as potentially harmful, occur at concentration ranges in the colon such that no toxic effects are expected either locally or following systemic absorption. The endproducts of saccharolytic fermentation, SCFA, may have effects on colonic health, host physiology, immunity, lipid and protein metabolism and appetite control. However, measuring SCFA concentrations in faeces is insufficient to assess the dynamic processes of their nutrikinetics. Existing literature on the usefulness of faecal water toxicity measures as indicators of cancer risk seems limited. In conclusion, at present there is insufficient evidence to use changes in faecal bacterial metabolite concentrations as markers of prebiotic effectiveness. Integration of results from metabolomics and metagenomics holds promise for understanding the health implications of prebiotic microbiome modulation but adequate tools for data integration and interpretation are currently lacking. Similarly, studies measuring metabolite fluxes in different body compartments to provide a more accurate picture of their nutrikinetics are needed.

Women's Heart Disease: Heart Disease Risk Factors

MedlinePlus

... this page please turn JavaScript on. Feature: Women's Heart Disease Heart Disease Risk Factors Past Issues / Winter 2014 Table ... or habits may raise your risk for coronary heart disease (CHD). These conditions are known as risk ...

Risk factors for tornado injuries.

PubMed

Eidson, M; Lybarger, J A; Parsons, J E; MacCormack, J N; Freeman, J I

1990-12-01

Tornadoes in North and South Carolina on 28 March 1984 caused 252 people to be injured seriously enough to require hospitalization and 59 to be killed. To evaluate risk factors, we gathered information on 238 (94%) of those hospitalized and 46 (78%) of those killed. Those hospitalized or deceased had statistically significantly more deep cuts, concussions, unconsciousness and broken bones than those with them at the time of the tornado who were not hospitalized or killed. People living in mobile homes were more likely to be hospitalized or die than people occupying conventional houses. Other risk factors for hospitalization or death included advanced age (60+ years), no physical protection (not having been covered with a blanket or other object), having been struck by broken window glass or other falling objects, home lifted off its foundation, collapsed ceiling or floor, or walls blown away. More awareness of the tornado risk before it strikes and better adherence to tornado protection guidelines could reduce injuries and deaths in the future.

Human Microdosing with Carcinogenic Polycyclic Aromatic Hydrocarbons: In Vivo Pharmacokinetics of Dibenzo[ def,p ]chrysene and Metabolites by UPLC Accelerator Mass Spectrometry

DOE Office of Scientific and Technical Information (OSTI.GOV)

Madeen, Erin P.; Ognibene, Ted J.; Corley, Richard A.

Metabolism is a key health risk factor following exposures to pro-carcinogenic polycyclic aromatic hydrocarbons (PAHs) such as dibenzo[def,p]chrysene (DBC), an IARC classified 2A probable human carcinogen. Human exposure to PAHs occurs primarily from the diet in non-smokers. However, little data is available on the metabolism and pharmacokinetics in humans of high molecular weight PAHs (≥4 aromatic rings), including DBC. We previously determined the pharmacokinetics of DBC in human volunteers orally administered a micro-dose (29 ng; 5 nCi) of [14C]-DBC by accelerator mass spectrometry (AMS) analysis of total [14C] in plasma and urine. In the current study, we utilized a novelmore » “moving wire” interface between ultra-performance liquid chromatography (UPLC) and AMS to detect and quantify parent DBC and its major metabolites. The major [14C] product identified in plasma was unmetabolized [14C]-DBC itself, (Cmax= 18.5 ± 15.9 fg/mL, Tmax= 2.1 ± 1.0 h), whereas the major metabolite was identified as [14C]-(+/-)-DBC-11,12-diol (Cmax= 2.5 ± 1.3 fg/mL, Tmax= 1.8 h). Several minor species of [14C]-DBC metabolites were also detected for which no reference standards were available. Free and conjugated metabolites were detected in urine with [14C]-(+/-)-DBC-11,12,13,14-tetraol isomers identified as the major metabolites, 56.3% of which were conjugated (Cmax= 35.8 ± 23.0 pg/pool, Tmax= 6-12 h pool). [14C]-DBC-11,12-diol, of which 97.5% was conjugated, was also identified in urine (Cmax= 29.4 ± 11.6 pg/pool, Tmax= 6-12 h pool). Parent [14C]-DBC was not detected in urine. This is the first dataset to assess metabolite profiles and associated pharmacokinetics of a carcinogenic PAH in human volunteers at an environmentally relevant dose, providing the data necessary for translation of high dose animal models to humans for translation of environmental health risk assessment.« less

Trends in selected chronic conditions and behavioral risk factors among women of reproductive age, behavioral risk factor surveillance system, 2001-2009.

PubMed

Hayes, Donald K; Fan, Amy Z; Smith, Ruben A; Bombard, Jennifer M

2011-11-01

Some potentially modifiable risk factors and chronic conditions cause significant disease and death during pregnancy and promote the development of chronic disease. This study describes recent trends of modifiable risk factors and controllable chronic conditions among reproductive-aged women. Data from the 2001 to 2009 Behavioral Risk Factor Surveillance System, a representative state-based telephone survey of health behavior in US adults, was analyzed for 327,917 women of reproductive age, 18 to 44 years. We calculated prevalence ratios over time to assess trends for 4 selected risk factors and 4 chronic conditions, accounting for age, race/ethnicity, education, health care coverage, and individual states. From 2001 to 2009, estimates of 2 risk factors improved: smoking declined from 25.9% to 18.8%, and physical inactivity declined from 25.0% to 23.0%. One risk factor, heavy drinking, did not change. From 2003 to 2009, the estimates for 1 risk factor and 4 chronic conditions worsened: obesity increased from 18.3% to 24.7%, diabetes increased from 2.1% to 2.9%, high cholesterol increased from 10.3% to 13.6%, asthma increased from 13.5% to 16.2%, and high blood pressure increased from 9.0% to 10.1%. All trends were significant after adjustment, except that for heavy drinking. Among women of reproductive age, prevalence of smoking and physical inactivity improved, but prevalence of obesity and all 4 chronic conditions worsened. Understanding reasons for the improvements in smoking and physical activity may support the development of targeted interventions to reverse the trends and help prevent chronic disease and adverse reproductive outcomes among women in this age group.

Risk factors for occupational acute mountain sickness.

PubMed

Vinnikov, D; Brimkulov, N; Krasotski, V; Redding-Jones, R; Blanc, P D

2014-10-01

Studies of occupational acute mountain sickness (AMS) have not focused on the more severe end of the spectrum to date. To examine risk factors associated with the development of occupational AMS severe enough to receive treatment in a compression chamber. A nested case referent study in a cohort of high-altitude (4000 m) mine workers, comparing cases of severe, chamber-treated AMS to matched referents. Using logistic regression, we tested potential risk factors based on premorbid surveillance examinations, including cigarette smoking (current smoking, smoking intensity and exhaled carbon monoxide [CO]). There were 15 cases and 30 controls. In multivariate analysis including age, sex and place of residence, current smoking was associated with increased risk of severe AMS (odds ratio [OR] 10.0; 95% confidence interval [CI] 1.5-67.4), taking into account any prior, less severe AMS event, which was also a potent risk factor (OR 33.3; 95% CI 2.8-390). Smoking intensity (cigarettes per day) and exhaled CO were also statistically significantly associated with severe AMS. Cigarette smoking is a strong, previously under-appreciated risk factor for severe AMS. Because this is a modifiable factor, these findings suggest that workplace-based smoking cessation should be tested as an intervention to prevent such morbidity. © The Author 2014. Published by Oxford University Press on behalf of the Society of Occupational Medicine. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

In vitro toxicological characterization of two arsenosugars and their metabolites.

PubMed

Leffers, Larissa; Ebert, Franziska; Taleshi, Mojtaba S; Francesconi, Kevin A; Schwerdtle, Tanja

2013-07-01

In their recently published Scientific Opinion on Arsenic in Food, the European Food Safety Authority concluded that a risk assessment for arsenosugars is currently not possible, largely because of the lack of relevant toxicological data. To address this issue, we carried out a toxicological in vitro characterization of two arsenosugars and six arsenosugar metabolites. The highly pure synthesized arsenosugars, DMA(V) -sugar-glycerol and DMA(V) -sugar-sulfate, investigated in this study, as well as four metabolites, oxo-dimethylarsenoacetic acid (oxo-DMAA(V) ), oxo-dimethylarsenoethanol (oxo-DMAE(V) ), thio-DMAA(V) and thio-DMAE(V) , exerted neither cytotoxicity nor genotoxicity up to 500 μM exposure in cultured human bladder cells. However, two arsenosugar metabolites, namely dimethyl-arsinic acid (DMA(V) ) and thio-dimethylarsinic acid (thio-DMA(V) ), were toxic to the cells; thio-DMA(V) was even slightly more cytotoxic than arsenite. Additionally, intestinal bioavailability of the arsenosugars was assessed applying the Caco-2 intestinal barrier model. The observed low, but significant transfer rates of the arsenosugars across the barrier model provide further evidence that arsenosugars are intestinally bioavailable. In a cellular system that metabolizes arsenosugars, cellular toxicity likely arises. Thus, in strong contrast to arsenobetaine, arsenosugars cannot be categorized as nontoxic for humans and a risk to human health cannot be excluded. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Enhanced photo(geno)toxicity of demethylated chlorpromazine metabolites

DOE Office of Scientific and Technical Information (OSTI.GOV)

Palumbo, Fabrizio

Chlorpromazine (CPZ) is an anti-psychotic drug widely used to treat disorders such as schizophrenia or manic-depression. Unfortunately, CPZ exhibits undesirable side effects such as phototoxic and photoallergic reactions in humans. In general, the influence of drug metabolism on this type of reactions has not been previously considered in photosafety testing. Thus, the present work aims to investigate the possible photo(geno)toxic potential of drug metabolites, using CPZ as an established reference compound. In this case, the metabolites selected for the study are demethylchlorpromazine (DMCPZ), didemethylchlorpromazine (DDMCPZ) and chlorpromazine sulfoxide (CPZSO). The demethylated CPZ metabolites DMCPZ and DDMCPZ maintain identical chromophore tomore » the parent drug. In this work, it has been found that the nature of the aminoalkyl side chain modulates the hydrophobicity and the photochemical properties (for instance, the excited state lifetimes), but it does not change the photoreactivity pattern, which is characterized by reductive photodehalogenation, triggered by homolytic carbon-chlorine bond cleavage with formation of highly reactive aryl radical intermediates. Accordingly, these metabolites are phototoxic to cells, as revealed by the 3T3 NRU assay; their photo-irritation factors are even higher than that of CPZ. The same trend is observed in photogenotoxicity studies, both with isolated and with cellular DNA, where DMCPZ and DDMCPZ are more active than CPZ itself. In summary, side-chain demethylation of CPZ, as a consequence of Phase I biotransformation, does not result a photodetoxification. Instead, it leads to metabolites that exhibit in an even enhanced photo(geno)toxicity. - Highlights: • Demethylated CPZ metabolites are phototoxic to cells, as revealed by the NRU assay. • Single cell electrophoresis (Comet Assay) confirms the photodamage to cellular DNA. • DNA single strand breaks formation is observed on agarose gel electrophoresis. �

Selected environmental risk factors and congenital heart defects.

PubMed

Kuciene, Renata; Dulskiene, Virginija

2008-01-01

The aim of the article is to review the published scientific literature and epidemiological studies about the effect of selected environmental risk factors on congenital heart defects in infants. According to recent reports, the prevalence of congenital heart defects is around 1% of live births. Congenital heart malformations are the leading cause of infant mortality. Unfortunately, the majority of the causes of heart defects remain unknown. These malformations are caused by interaction of genetic and environmental factors. The article reviews selected environmental risk factors: maternal illnesses and conditions associated with metabolic disorder (maternal diabetes, obesity, phenylketonuria), maternal lifestyle factors (alcohol use, smoking), which may increase the risk of congenital heart defects.

MetabolitePredict: A de novo human metabolomics prediction system and its applications in rheumatoid arthritis.

PubMed

Wang, QuanQiu; Xu, Rong

2017-07-01

Human metabolomics has great potential in disease mechanism understanding, early diagnosis, and therapy. Existing metabolomics studies are often based on profiling patient biofluids and tissue samples and are difficult owing to the challenges of sample collection and data processing. Here, we report an alternative approach and developed a computation-based prediction system, MetabolitePredict, for disease metabolomics biomarker prediction. We applied MetabolitePredict to identify metabolite biomarkers and metabolite targeting therapies for rheumatoid arthritis (RA), a last-lasting complex disease with multiple genetic and environmental factors involved. MetabolitePredict is a de novo prediction system. It first constructs a disease-specific genetic profile using genes and pathways data associated with an input disease. It then constructs genetic profiles for a total of 259,170 chemicals/metabolites using known chemical genetics and human metabolomic data. MetabolitePredict prioritizes metabolites for a given disease based on the genetic profile similarities between disease and metabolites. We evaluated MetabolitePredict using 63 known RA-associated metabolites. MetabolitePredict found 24 of the 63 metabolites (recall: 0.38) and ranked them highly (mean ranking: top 4.13%, median ranking: top 1.10%, P-value: 5.08E-19). MetabolitePredict performed better than an existing metabolite prediction system, PROFANCY, in predicting RA-associated metabolites (PROFANCY: recall: 0.31, mean ranking: 20.91%, median ranking: 16.47%, P-value: 3.78E-7). Short-chain fatty acids (SCFAs), the abundant metabolites of gut microbiota in the fermentation of fiber, ranked highly (butyrate, 0.03%; acetate, 0.05%; propionate, 0.38%). Finally, we established MetabolitePredict's potential in novel metabolite targeting for disease treatment: MetabolitePredict ranked highly three known metabolite inhibitors for RA treatments (methotrexate:0.25%; leflunomide: 0.56%; sulfasalazine: 0

Achilles tendon injury risk factors associated with running.

PubMed

Lorimer, Anna V; Hume, Patria A

2014-10-01

Research into the nature of overuse Achilles tendon injuries is extensive, yet uncertainty remains around how to identify athletes susceptible to Achilles tendon injury. To identify the strength of evidence for biomechanical risk factors associated with Achilles tendon injuries. SPORTDiscus, CINAHL, Web of Science and PubMed were searched for Achilles tendon injury risk factors and biomechanical measures which are altered in runners with Achilles tendon injuries, excluding ruptures. Fifteen articles were included in the analysis. Two variables, high vertical forces and high arch, showed strong evidence for reduced injury risk. High propulsive forces and running on stiffer surfaces may also be protective. Only one biomechanical variable, high braking force, showed clear evidence for increasing Achilles injury risk. Gait retraining to direct the centre of mass further forward to reduce high braking force could be useful in decreasing the risk of Achilles injury. The majority of biomechanical risk factors examined showed unclear results, which is likely due to the multifactorial nature of Achilles overuse injuries. Many risk factors are related to how the athlete's body interacts with the environment during gait, including ground reaction forces, muscle activity both prior to landing and immediately post ground contact, and joint motion throughout stance. Multiple risk factors have been associated with the development of Achilles tendon injuries in running athletes but most effects remain unclear. Advice for athletes recovering from Achilles tendon injuries could include avoiding soft surfaces and reducing the pace of recovery runs. Orthotic intervention could assist athletes with low arches but modification of pronation should be viewed with caution. Strength training and gait retraining could be beneficial for reducing injury risk.

Mass spectrometric characterization of the hypoxia-inducible factor (HIF) stabilizer drug candidate BAY 85-3934 (molidustat) and its glucuronidated metabolite BAY-348, and their implementation into routine doping controls.

PubMed

Dib, Josef; Mongongu, Cynthia; Buisson, Corinne; Molina, Adeline; Schänzer, Wilhelm; Thuss, Uwe; Thevis, Mario

2017-01-01

The development of new therapeutics potentially exhibiting performance-enhancing properties implicates the risk of their misuse by athletes in amateur and elite sports. Such drugs necessitate preventive anti-doping research for consideration in sports drug testing programmes. Hypoxia-inducible factor (HIF) stabilizers represent an emerging class of therapeutics that allows for increasing erythropoiesis in patients. BAY 85-3934 is a novel HIF stabilizer, which is currently undergoing phase-2 clinical trials. Consequently, the comprehensive characterization of BAY 85-3934 and human urinary metabolites as well as the implementation of these analytes into routine doping controls is of great importance. The mass spectrometric behaviour of the HIF stabilizer drug candidate BAY 85-3934 and a glucuronidated metabolite (BAY-348) were characterized by electrospray ionization-(tandem) mass spectrometry (ESI-MS(/MS)) and multiple-stage mass spectrometry (MS n ). Subsequently, two different laboratories established different analytical approaches (one each) enabling urine sample analyses by employing either direct urine injection or solid-phase extraction. The methods were cross-validated for the metabolite BAY-348 that is expected to represent an appropriate target analyte for human urine analysis. Two test methods allowing for the detection of BAY-348 in human urine were applied and cross-validated concerning the validation parameters specificity, linearity, lower limit of detection (LLOD; 1-5 ng/mL), ion suppression/enhancement (up to 78%), intra- and inter-day precision (3-21%), recovery (29-48%), and carryover. By means of ten spiked test urine samples sent blinded to one of the participating laboratories, the fitness-for-purpose of both assays was provided as all specimens were correctly identified applying both testing methods. As no post-administration study samples were available, analyses of authentic urine specimens remain desirable. Copyright © 2016 John Wiley

Polo pony injuries: player-owner reported risk, perception, mitigation and risk factors.

PubMed

Inness, C M; Morgan, K L

2015-07-01

Polo, one of the world's oldest sports, is unique in merging human skill and balance with animal agility and performance in a contact sport. These modern-day 'centaurs' offer medical, dental and veterinary scientists an unrivalled, if quirky, opportunity to collaborate. Collection of epidemiological data on injuries to UK polo riders and ponies is the first step. To measure the reported risk and risk factors for injuries to UK polo ponies, their perception and mitigation by player-owners. A retrospective cohort design and telephone interviews were used. Data on equine injuries, preseason training and risk perception were collected from a random sample of player-owners using a structured questionnaire. Injuries were defined as requiring veterinary treatment. Frequencies were represented as percentages and 95% confidence intervals (CIs). Risk factors for injuries were identified by univariable and multivariable analyses. The cumulative incidence of player-owner-reported injury was 10.6% (95% CI 8.4-12.7). Tendon injuries were most common (4.3%; 95% CI 2.9-5.7), followed by wounds and splints. The only risk factor was stabling all season (odds ratio 4.79; 95% CI 1.46-15.73). Tendon injuries were perceived as the major risk and hard ground the most important risk factor. Risk mitigation practices were bandaging before exercise (45.7%; 95% CI 34.8-56.5), checking tendons (84.0%; 95% CI 76.0-91.9), cold hosing (40.7%; 95% CI 30.0-51.4), bandaging (38.3%; 95% CI 27.7-48.9) and using clays and coolants after exercise (24.7%; 15.3-34.1). Cuts and wounds were considered most frequent by only 2.5% (95% CI 0.0-3.6) of players but were the second most common injury, accounting for 21.6% of veterinary treatments. Splints accounted for 12.5% of injuries. The risk of injury to polo ponies is similar to that in the general horse population; musculoskeletal injuries, particularly tendon injuries, are most common, followed by wounds and splints. The association between stabling and

XENOBIOTIC METABOLISM RESEARCH AND ITS APPLICATION TO HUMAN AND ECOLOGICAL EXPOSURE AND RISK ASSESSMENT

EPA Science Inventory

A major uncertainty in risk assessment is determining the exposure of a target organism to a chemical stressor, and a confounding factor is the transformation of the chemical to a toxic metabolite inside the target organism. Physiologically-based pharmacokinetic (PBPK) models are...

Use of Metabolomics as a Complementary Omic Approach to Implement Risk Criteria for First-Degree Relatives of Gastric Cancer Patients

PubMed Central

Miolo, Gianmaria; Caggiari, Laura; De Zorzi, Mariangela; Steffan, Agostino

2018-01-01

A positive family history is a strong and consistently reported risk factor for gastric cancer (GC). So far, it has been demonstrated that serum pepsinogens (PGs), and gastrin 17 (G17) are useful for screening individuals at elevated risk to develop atrophic gastritis but they are suboptimal biomarkers to screen individuals for GC. The main purpose of this study was to investigate serum metabolomic profiles to find additional biomarkers that could be integrated with serum PGs and G17 to improve the diagnosis of GC and the selection of first-degree relatives (FDR) at higher risk of GC development. Serum metabolomic profiles included 188 serum metabolites, covering amino acids, biogenic amines, acylcarnitines, phosphatidylcholines, sphingomyelins and hexoses. Serum metabolomic profiles were performed with tandem mass spectrometry using the Biocrates AbsoluteIDQ p180 kit. The initial cohort (training set) consisted of n = 49 GC patients and n = 37 FDR. Differential metabolomic signatures among the two groups were investigated by univariate and multivariate partial least square differential analysis. The most significant metabolites were further selected and validated in an independent group of n = 22 GC patients and n = 17 FDR (validation set). Receiver operating characteristic (ROC) curves were used to evaluate the diagnostic power and the optimal cut-off for each of the discriminant markers. Multivariate analysis was applied to associate the selected serum metabolites, PGs, G17 and risk factors such as age, gender and Helicobacter pylori (H. pylori) infection with the GC and FDR has been performed and an integrative risk prediction algorithm was developed. In the training set, 40 metabolites mainly belonging to phospholipids and acylcarnitines classes were differentially expressed between GC and FDR. Out of these 40 metabolites, 9 were further confirmed in the validation set. Compared with FDR, GC patients were characterized by lower levels of hydroxylated

[Clinical risk factors for progressive myopia].

PubMed

Schaeffel, F

2012-08-01

The average worldwide frequency of myopia is approximately 30 % and is traditionally subdivided into school myopia and pathological myopia. A further distinction is made between progressive myopia and stationary myopia. There is a high correlation between the frequency of myopia and urbanization and training. Risk factors for development of myopia are close-up work, lack of outdoor activity, biometrical variables of the eye and genetic risk factors. Development of myopia can be positively influenced by peripheral focusing, increased exposure to light and in the future possibly pharmacologically.

A modular modulation method for achieving increases in metabolite production.

PubMed

Acerenza, Luis; Monzon, Pablo; Ortega, Fernando

2015-01-01

Increasing the production of overproducing strains represents a great challenge. Here, we develop a modular modulation method to determine the key steps for genetic manipulation to increase metabolite production. The method consists of three steps: (i) modularization of the metabolic network into two modules connected by linking metabolites, (ii) change in the activity of the modules using auxiliary rates producing or consuming the linking metabolites in appropriate proportions and (iii) determination of the key modules and steps to increase production. The mathematical formulation of the method in matrix form shows that it may be applied to metabolic networks of any structure and size, with reactions showing any kind of rate laws. The results are valid for any type of conservation relationships in the metabolite concentrations or interactions between modules. The activity of the module may, in principle, be changed by any large factor. The method may be applied recursively or combined with other methods devised to perform fine searches in smaller regions. In practice, it is implemented by integrating to the producer strain heterologous reactions or synthetic pathways producing or consuming the linking metabolites. The new procedure may contribute to develop metabolic engineering into a more systematic practice. © 2015 American Institute of Chemical Engineers.

Smoking is underrecognized as a risk factor for chronic pancreatitis.

PubMed

Yadav, Dhiraj; Slivka, Adam; Sherman, Stuart; Hawes, Robert H; Anderson, Michelle A; Burton, Frank R; Brand, Randall E; Lewis, Michele D; Gardner, Timothy B; Gelrud, Andres; Disario, James; Amann, Stephen T; Baillie, John; Lawrence, Christopher; O'Connell, Michael; Lowenfels, Albert B; Banks, Peter A; Whitcomb, David C

2010-01-01

Smoking is an established risk factor for chronic pancreatitis (CP). We sought to identify how often and in which CP patients physicians consider smoking to be a risk factor. We analyzed data on CP patients and controls prospectively enrolled from 19 US centers in the North American Pancreatitis Study-2. We noted each subject's self-reported smoking status and quantified the amount and duration of smoking. We noted whether the enrolling physician (gastroenterologist with specific interest in pancreatology) classified alcohol as the etiology for CP and selected smoking as a risk factor. Among 382/535 (71.4%) CP patients who were self-reported ever smokers, physicians cited smoking as a risk factor in only 173/382 (45.3%). Physicians cited smoking as a risk factor more often among current smokers, when classifying alcohol as CP etiology, and with higher amount and duration of smoking. We observed a wide variability in physician decision to cite smoking as a risk factor. Multivariable regression analysis however confirmed that the association of CP with smoking was independent of physician decision to cite smoking as a risk factor. Physicians often underrecognize smoking as a CP risk factor. Efforts are needed to raise awareness of the association between smoking and CP. and IAP. Copyright © 2011 S. Karger AG, Basel.

To what extent is the familial risk of rheumatoid arthritis explained by established rheumatoid arthritis risk factors?

PubMed

Jiang, Xia; Frisell, Thomas; Askling, Johan; Karlson, Elizabeth W; Klareskog, Lars; Alfredsson, Lars; Källberg, Henrik

2015-02-01

Family history of rheumatoid arthritis (RA) is one of the strongest risk factors for developing RA, and information on family history is, therefore, routinely collected in clinical practice. However, as more genetic and environmental risk factors shared by relatives are identified, the importance of family history may diminish. The aim of this study was to determine how much of the familial risk of RA can be explained by established genetic and nongenetic risk factors. History of RA among first-degree relatives of individuals in the Epidemiological Investigation of Rheumatoid Arthritis case-control study was assessed through linkage to the Swedish Multigeneration Register and the Swedish Patient Register. We used logistic regression models to investigate the decrease in familial risk after successive adjustment for combinations of nongenetic risk factors (smoking, alcohol intake, parity, silica exposure, body mass index, fatty fish consumption, and education), and genetic risk factors (shared epitope [SE] and 76 single-nucleotide polymorphisms [SNPs]). Established nongenetic risk factors did not explain familial risk of either seropositive or seronegative RA to any significant degree. Genetic risk factors accounted for a limited proportion of the familial risk of seropositive RA (unadjusted odds ratio [OR] 4.10, SE-adjusted OR 3.72, SNP-adjusted OR 3.46, and SE and SNP-adjusted OR 3.35). Established risk factors only provided an explanation for familial risk of RA in minor part, suggesting that many (familial) risk factors remain to be identified, in particular for seronegative RA. Family history of RA therefore remains an important clinical risk factor for RA, the value of which has not yet been superseded by other information. There is thus a need for further etiologic studies of both seropositive and seronegative RA. Copyright © 2015 by the American College of Rheumatology.

Risk factors of hepatocellular carcinoma--current status and perspectives.

PubMed

Gao, Jing; Xie, Li; Yang, Wan-Shui; Zhang, Wei; Gao, Shan; Wang, Jing; Xiang, Yong-Bing

2012-01-01

Hepatocellular carcinoma is a common disorder worldwide which ranks 5th and 7th most common cancer among men and women. In recent years, different incidence trends have been observed in various regions, but the reasons are not completely understood. However, due to the great public efforts in HCC prevention and alternation of lifestyle, the roles of some well documented risk factors played in hepatocarcinogenesis might have changed. This paper summarizes both the environmental and host related risk factors of hepatocellular carcinoma including well established risk factors such as hepatitis virus infection, aflatoxin and alcohol, as well as possible risk factors such as coffee drinking and other dietary agents.

Changing risk factors for fluorosis among South Australian children.

PubMed

Spencer, A John; Do, Loc G

2008-06-01

Research in the last decade has shown changing exposure patterns to discretionary fluorides and declining prevalence of fluorosis among South Australian children, raising the question of how risk factors for fluorosis have changed. To examine and compare risk factors for fluorosis among representative samples of South Australian children in 1992/1993 and 2002/2003. Similar sampling strategies and data collection methods were employed in the Child Fluoride Study (CFS) Marks 1 (1992/1993) and 2 (2002/2003). Participants in each CFS round were examined for fluorosis using the Thylstrup and Fejerskov (TF) Index. Exposure history was collected for fluoride in water, toothpaste, fluoride supplements and infant formula, allowing for a fluorosis risk assessment analysis. Data were re-weighted to represent the child population at each time. Changes in prevalence of fluorosis, defined as having a TF score of 1+ on maxillary central incisors, fluoride exposure and risk factors between the two rounds were evaluated. A total of 375 and 677 children participated in the 1992/1993 and 2002/2003 rounds respectively. Prevalence of fluorosis declined significantly from 45.3% to 25.9%. Reduced use of fluoride supplements and increased use of 400-550-ppm children F toothpaste were the most substantial fluoride exposure changes. Early toothpaste use, residence in fluoridated areas and fluoride supplement use were the risk factors in 1992/1993. Early toothpaste use and fluoride supplement use were not risk factors, leaving fluoridated water as the only risk factor among the common variables in 2002/2003. In an analysis stratified by the type of fluoridated toothpaste in 2002/2003, the large amount of toothpaste used was a risk factor in those who used 1000-ppm fluoridated toothpaste, and eating/licking toothpaste when toothpaste use started was a risk factor among children who used either 1000-ppm or 400-550-ppm fluoridated toothpaste. Introduction of the 400-550-ppm F toothpaste and use

Estimation of caffeine intake from analysis of caffeine metabolites in wastewater.

PubMed

Gracia-Lor, Emma; Rousis, Nikolaos I; Zuccato, Ettore; Bade, Richard; Baz-Lomba, Jose Antonio; Castrignanò, Erika; Causanilles, Ana; Hernández, Félix; Kasprzyk-Hordern, Barbara; Kinyua, Juliet; McCall, Ann-Kathrin; van Nuijs, Alexander L N; Plósz, Benedek G; Ramin, Pedram; Ryu, Yeonsuk; Santos, Miguel M; Thomas, Kevin; de Voogt, Pim; Yang, Zhugen; Castiglioni, Sara

2017-12-31

Caffeine metabolites in wastewater were investigated as potential biomarkers for assessing caffeine intake in a population. The main human urinary metabolites of caffeine were measured in the urban wastewater of ten European cities and the metabolic profiles in wastewater were compared with the human urinary excretion profile. A good match was found for 1,7-dimethyluric acid, an exclusive caffeine metabolite, suggesting that might be a suitable biomarker in wastewater for assessing population-level caffeine consumption. A correction factor was developed considering the percentage of excretion of this metabolite in humans, according to published pharmacokinetic studies. Daily caffeine intake estimated from wastewater analysis was compared with the average daily intake calculated from the average amount of coffee consumed by country per capita. Good agreement was found in some cities but further information is needed to standardize this approach. Wastewater analysis proved useful to providing additional local information on caffeine use. Copyright © 2017 Elsevier B.V. All rights reserved.

Surgical risk factors associated with lung transplantation.

PubMed

Paradela, M; González, D; Parente, I; Fernández, R; De La Torre, M M; Delgado, M; García, J A; Fieira, E; Bonhome, C; Maté, J M B

2009-01-01

Despite years of experience with lung transplantation, perioperative morbidity rates remain high. The objective of this study was to analyze our series of lung transplant recipients, seeking to identify possible intra- and postoperative risk factors associated with mortality. We performed a descriptive, retrospective study of 224 consecutive patients undergoing lung transplantation over a period of 112 months; we excluded retransplant procedures. We gathered details of the surgical procedure and postoperative period in the recovery unit. Univariate analysis using the chi-square test identified variables associated with the incidence of mortality. From 1999 to 2008, we performed 224 lung transplants, including 66% in men and 34% in women. Their overall mean age was 49.9 +/- 13.5 years. The conditions that led to transplantation were pulmonary fibrosis (38.4%); chronic obstructive pulmonary disease emphysema (29%); cystic fibrosis (10.7%); bronchiectasis (8.9%); pulmonary hypertension (3.1%); and other diseases (9.9%). A total of 124 (55.4%) patients underwent single and 100 (44.6%) received sequential bilateral lung transplantations. Surgical risk factors were identified in 51.3% of the cases, the most frequent being hemorrhage (25.3%), followed by severe pulmonary hypertension (14.7%) and cardiopulmonary bypass (12.1%). Greater perioperative mortality was detected among patients with surgical risk factors, namely, significantly related to cardiopulmonary bypass, pulmonary hypertension, and air leak. A higher frequency of surgical risk factors was observed among patients with bilateral lung transplantations and longer procedures, but they were not associated with greater perioperative mortality. Reoperation was necessary in 16 patients (7.2%), mainly owing to bleeding, it was not significantly related to mortality risk. The incidence of surgical risk factors in lung transplantation was high, especially in bilateral lung transplantations and prolonged procedures

Domestic Environmental Risk Factors Associated with Falling in Elderly

PubMed Central

LÖK, Neslihan; AKIN, Belgin

2013-01-01

Background: This is a cross-sectional study aiming at analyzing the relation between falling and domestic environmental –risk factors in community-dwelling elderly. Methods: The study consisted of 243 randomly chosen community-dwelling elderly over 65 years of age living around a health care center in Central Selcuklu, Konya. Data were collected with a questionnaire form including socio-demographic and other characteristics, with the Rivermead Mobility Index for evaluating mobility condition and an Evaluation Form of Domestic Environmental Risk Factors of Falling (EFDERF), which is developed by the researcher to assess domestic environmental risk factors of falling. Results: Based on (EFDERF) high number of problems lived in bathroom/restroom, kitchen, bedroom, sitting room/saloon and in all other areas was a risk factor in terms of domestic falling characteristics while the number of problems lived in hall and stairs was not a significant risk factor. Conclusion: EFDERF may be used by the nurses and health professionals to evaluate risk of falling and collecting data after visits in primary-care of elderly. PMID:23515204

Human Micro-Dosing with Carcinogenic Polycyclic Aromatic Hydrocarbons: In Vivo Pharmacokinetics of Dibenzo[def,p]chrysene and Metabolites by UPLC Accelerator Mass Spectrometry

PubMed Central

Madeen, Erin P.; Ognibene, Ted J.; Corley, Richard A.; McQuistan, Tammie J.; Baird, William M.; Bench, Graham; Turteltaub, Ken W.; Williams, David E.

2017-01-01

Metabolism is a key health risk factor for exposures to pro-carcinogenic polycyclic aromatic hydrocarbons (PAHs) such as dibenzo[def,p]chrysene (DBC), an IARC classified 2A probable human carcinogen. Human exposure to PAHs occurs primarily from the diet in non-smokers. However, little data is available on the metabolism and pharmacokinetics in humans of high molecular weight PAHs (≥4 aromatic rings), including DBC. We previously determined the pharmacokinetics of DBC in human volunteers orally administered a micro-dose (29 ng; 5 nCi) of [14C]-DBC by accelerator mass spectrometry (AMS) analysis of total [14C] in plasma and urine. In the current study, we utilized a novel “moving wire” interface between ultra-performance liquid chromatography (UPLC) and the AMS to detect and quantify parent DBC and its major metabolites. The major [14C] product identified in plasma was unmetabolized [14C]-DBC itself, (Cmax= 18.5 ± 15.9 fg/mL, Tmax= 2.1 ± 1.0 h), whereas the major metabolite was identified as [14C]-(+/−)-DBC-11,12-diol (Cmax= 2.5 ± 1.3 fg/mL, Tmax= 1.8 h). Several minor species of [14C]-DBC metabolites were also detected for which no reference standards were available. Deconjugated and conjugated metabolites were detected in urine with [14C]-(+/−)-DBC-tetraol identified as the major metabolite, 88.7% of which was detected upon enzymatic deconjugation (Cmax= 35.8 ± 23.0 pg/pool, Tmax= 6–12 h pool). [14C]-DBC-11,12-diol, of which 94.4% was conjugated and identified in urine (Cmax= 29.4 ± 11.6 pg/pool, Tmax= 6–12 h pool). Parent [14C]-DBC was not detected in the urine. This is the first dataset to assess metabolite profiles and associated pharmacokinetics of a carcinogenic PAH in human volunteers at an environmentally relevant dose, providing the data necessary for translation of high dose laboratory animal models to human translation for environmental health risk assessment. PMID:27494294

Risk Factors of Sudden Infant Death Syndrome and Risk Factors for Sleep Disturbances

ERIC Educational Resources Information Center

Kelmanson, Igor A.

2011-01-01

Relationship between major risk factors of sudden infant death syndrome (SIDS) and sleep disorders in the infants is the subject of review and discussion. Improper micro-environmental characteristics (especially poor environmental organisation and lack of developmental stimulation), pre-term delivery and/or infant low birth weight, prone sleep…

Bisphenol-A alters microbiota metabolites derived from aromatic amino acids and worsens disease activity during colitis.

PubMed

DeLuca, Jennifer Aa; Allred, Kimberly F; Menon, Rani; Riordan, Rebekah; Weeks, Brad R; Jayaraman, Arul; Allred, Clinton D

2018-06-01

Inflammatory bowel disease is a complex collection of disorders. Microbial dysbiosis as well as exposure to toxins including xenoestrogens are thought to be risk factors for inflammatory bowel disease development and relapse. Bisphenol-A has been shown to exert estrogenic activity in the colon and alter intestinal function, but the role that xenoestrogens, such as bisphenol-A , play in colonic inflammation has been previously described but with conflicting results. We investigated the ability of bisphenol-A to exacerbate colonic inflammation and alter microbiota metabolites derived from aromatic amino acids in an acute dextran sulfate sodium-induced colitis model. Female C57BL/6 mice were ovariectomized and exposed to bisphenol-A daily for 15 days. Disease activity measures include body weight, fecal consistency, and rectal bleeding. Colons were scored for inflammation, injury, and nodularity. Alterations in the levels of microbiota metabolites derived from aromatic amino acids known to reflect phenotypic changes in the gut microbiome were analyzed. Bisphenol-A exposure increased mortality and worsened disease activity as well as inflammation and nodularity scores in the middle colon region following dextran sulfate sodium exposure. Unique patterns of metabolites were associated with bisphenol-A consumption. Regardless of dextran sulfate sodium treatment, bisphenol-A reduced levels of tryptophan and several metabolites associated with decreased inflammation in the colon. This is the first study to show that bisphenol-A treatment alone can reduce microbiota metabolites derived from aromatic amino acids in the colon which may be associated with increased colonic inflammation and inflammatory bowel disease. Impact statement As rates of inflammatory bowel disease rise, discovery of the mechanisms related to the development of these conditions is important. Environmental exposure is hypothesized to play a role in etiology of the disease, as are alterations in the gut

Flow rate of transport network controls uniform metabolite supply to tissue

PubMed Central

Meigel, Felix J.

2018-01-01

Life and functioning of higher organisms depends on the continuous supply of metabolites to tissues and organs. What are the requirements on the transport network pervading a tissue to provide a uniform supply of nutrients, minerals or hormones? To theoretically answer this question, we present an analytical scaling argument and numerical simulations on how flow dynamics and network architecture control active spread and uniform supply of metabolites by studying the example of xylem vessels in plants. We identify the fluid inflow rate as the key factor for uniform supply. While at low inflow rates metabolites are already exhausted close to flow inlets, too high inflow flushes metabolites through the network and deprives tissue close to inlets of supply. In between these two regimes, there exists an optimal inflow rate that yields a uniform supply of metabolites. We determine this optimal inflow analytically in quantitative agreement with numerical results. Optimizing network architecture by reducing the supply variance over all network tubes, we identify patterns of tube dilation or contraction that compensate sub-optimal supply for the case of too low or too high inflow rate. PMID:29720455

Environmental risk factors for attention-deficit hyperactivity disorder.

PubMed

Banerjee, Tania Das; Middleton, Frank; Faraone, Stephen V

2007-09-01

Attention-deficit hyperactivity disorder (ADHD) is the most common cognitive and behavioural disorder diagnosed among school children. It is characterized by deficient attention and problem solving, along with hyperactivity and difficulty withholding incorrect responses. This highly prevalent disorder is estimated to affect 5-10% of children and in many cases, persists into adulthood, leading to 4% prevalence among adults. Converging evidence from epidemiologic, neuropsychology, neuroimaging, genetic and treatment studies shows that ADHD is a valid medical disorder. The majority of studies performed to assess genetic risk factors in ADHD have supported a strong familial nature of this disorder. Family studies have identified a 2- to 8-fold increase in the risk for ADHD in parents and siblings of children with ADHD. Various twin and adoption studies have also highlighted the highly genetic nature of ADHD. In fact the mean heritability of ADHD was shown to be 0.77, which is comparable to other neuropsychiatric disorders such as schizophrenia or bipolar disorder. However, several biological and environmental factors have also been proposed as risk factors for ADHD, including food additives/diet, lead contamination, cigarette and alcohol exposure, maternal smoking during pregnancy, and low birth weight. Many recent studies have specifically examined the relationships between ADHD and these extraneous factors. This review describes some of these possible risk factors. Although a substantial fraction of the aetiology of ADHD is due to genes, the studies reviewed in this article show that many environmental risk factors and potential gene-environment interactions also increase the risk for the disorder.

Risk factors for serious injury in Finnish agriculture.

PubMed

Rautiainen, Risto H; Ledolter, Johannes; Donham, Kelley J; Ohsfeldt, Robert L; Zwerling, Craig

2009-05-01

Previous studies indicate 20% of injuries represent 80% of injury costs in agriculture. To help prevent the most costly injuries, we aimed to identify characteristics and risk factors associated with serious injuries. We analyzed insurance records of 93,550 self-employed Finnish farmers. We ranked injury causes by claim cost and used multiple logistic regressions to identify risk factors for (any) injury and serious injury (injuries exceeding claim costs of 2000 euros). A total of 5,507 compensated injuries occurred in 2002 (rate 5.9/100 person-years), and 1,167 or 21% of them (rate 1.25/100 person-years) were serious. The causes/sources resulting in highest average claim costs were motor vehicles; stairs, scaffoldings, and ladders; trailers and wagons; floors, walkways, and steps; other structures and obstacles; augers, mills, and grain handling equipment; horses; combines and harvesting equipment; tractor steps; and uneven and slippery terrain. Older age, male gender, higher income level, greater field size, residing on the farm, Finnish language (vs. Swedish), occupational health service (OHS) membership, and animal production were risk factors for injury. The risk factors for serious injury were similar; however, the effects of age, income level, and the raising of horses were more prominent. Language, residence, ownership status, and OHS membership were not risk factors for serious injury. Cost-effective prevention efforts should address the following risk factors: older age, male gender, larger income and operation size, livestock production (particularly dairy, swine, and horses), motor vehicle incidents, falls from elevation, and slips, trips and falls. Copyright 2009 Wiley-Liss, Inc.

Chronic disease risk factors among hotel workers.

PubMed

Gawde, Nilesh Chandrakant; Kurlikar, Prashika R

2016-01-01

Non-communicable diseases have emerged as a global health issue. Role of occupation in pathogenesis of non-communicable diseases has not been explored much especially in the hospitality industry. Objectives of this study include finding risk factor prevalence among hotel workers and studying relationship between occupational group and chronic disease risk factors chiefly high body mass index. A cross-sectional study was conducted among non-managerial employees from classified hotels in India. The study participants self-administered pre-designed pilot-tested questionnaires. The risk factor prevalence rates were expressed as percentages. Chi-square test was used for bi-variate analysis. Overweight was chosen as 'outcome' variable of interest and binary multi-logistic regression analysis was used to identify determinants. The prevalence rates of tobacco use, alcohol use, inadequate physical activity and inadequate intake of fruits and vegetables were 32%, 49%, 24% and 92% respectively among hotel employees. Tobacco use was significantly common among those in food preparation and service, alcohol use among those in food service and security and leisure time physical activity among front office workers. More than two-fifths (42.7%) were overweight. Among the hotel workers, those employed in food preparation and security had higher odds of 1.650 (CI: 1.025 - 2.655) and 3.245 (CI: 1.296 - 8.129) respectively of being overweight. Prevalence of chronic disease risk factors is high among hotel workers. Risk of overweight is significantly high in food preparation and security departments and workplace interventions are necessary to address these risks.

Metabolomics for secondary metabolite research.

PubMed

Breitling, Rainer; Ceniceros, Ana; Jankevics, Andris; Takano, Eriko

2013-11-11

Metabolomics, the global characterization of metabolite profiles, is becoming an increasingly powerful tool for research on secondary metabolite discovery and production. In this review we discuss examples of recent technological advances and biological applications of metabolomics in the search for chemical novelty and the engineered production of bioactive secondary metabolites.

Endometrial Cancer Risk Factors by 2 Main Histologic Subtypes

PubMed Central

Yang, Hannah P.; Wentzensen, Nicolas; Trabert, Britton; Gierach, Gretchen L.; Felix, Ashley S.; Gunter, Marc J.; Hollenbeck, Albert; Park, Yikyung; Sherman, Mark E.; Brinton, Louise A.

2013-01-01

On the basis of clinical and pathologic criteria, endometrial carcinoma has been distinguished as Types I (mainly endometrioid) and II (nonendometrioid). Limited data suggest that these subtypes have different risk factor profiles. The authors prospectively evaluated risk factors for Types I (n = 1,312) and II (n = 138) incident endometrial carcinoma among 114,409 women in the National Institutes of Health (NIH)-AARP Diet and Health Study (1995–2006). For individual risk factors, relative risks were estimated with Cox regression by subtype, and Pheterogeneity was assessed in case-case comparisons with Type I as the referent. Stronger relations for Type I versus Type II tumors were seen for menopausal hormone therapy use (relative risk (RR) of 1.18 vs. 0.84; Pheterogeneity = 0.01) and body mass index of ≥30 vs. <30 kg/m2 (RR of 2.93 vs. 1.83; Pheterogeneity = 0.001). Stronger relations for Type II versus Type I tumors were observed for being black versus white (RR of 2.18 vs. 0.66; Pheterogeneity = 0.0004) and having a family history of breast cancer (RR of 1.93 vs. 0.80; Pheterogeneity = 0.002). Other risk factor associations were similar by subtype. In conclusion, the authors noted different risk factor associations for Types I and II endometrial carcinomas, supporting the etiologic heterogeneity of these tumors. Because of the limited number of Type II cancers, additional evaluation of risk factors will benefit from consortial efforts. PMID:23171881

Breast Cancer Risk From Modifiable and Nonmodifiable Risk Factors Among White Women in the United States

PubMed Central

Maas, Paige; Barrdahl, Myrto; Joshi, Amit D.; Auer, Paul L.; Gaudet, Mia M.; Milne, Roger L.; Schumacher, Fredrick R.; Anderson, William F.; Check, David; Chattopadhyay, Subham; Baglietto, Laura; Berg, Christine D.; Chanock, Stephen J.; Cox, David G.; Figueroa, Jonine D.; Gail, Mitchell H.; Graubard, Barry I.; Haiman, Christopher A.; Hankinson, Susan E.; Hoover, Robert N.; Isaacs, Claudine; Kolonel, Laurence N.; Le Marchand, Loic; Lee, I-Min; Lindström, Sara; Overvad, Kim; Romieu, Isabelle; Sanchez, Maria-Jose; Southey, Melissa C.; Stram, Daniel O.; Tumino, Rosario; VanderWeele, Tyler J.; Willett, Walter C.; Zhang, Shumin; Buring, Julie E.; Canzian, Federico; Gapstur, Susan M.; Henderson, Brian E.; Hunter, David J.; Giles, Graham G; Prentice, Ross L.; Ziegler, Regina G.; Kraft, Peter; Garcia-Closas, Montse; Chatterjee, Nilanjan

2017-01-01

IMPORTANCE An improved model for risk stratification can be useful for guiding public health strategies of breast cancer prevention. OBJECTIVE To evaluate combined risk stratification utility of common low penetrant single nucleotide polymorphisms (SNPs) and epidemiologic risk factors. DESIGN, SETTING, AND PARTICIPANTS Using a total of 17 171 cases and 19 862 controls sampled from the Breast and Prostate Cancer Cohort Consortium (BPC3) and 5879 women participating in the 2010 National Health Interview Survey, a model for predicting absolute risk of breast cancer was developed combining information on individual level data on epidemiologic risk factors and 24 genotyped SNPs from prospective cohort studies, published estimate of odds ratios for 68 additional SNPs, population incidence rate from the National Cancer Institute-Surveillance, Epidemiology, and End Results Program cancer registry and data on risk factor distribution from nationally representative health survey. The model is used to project the distribution of absolute risk for the population of white women in the United States after adjustment for competing cause of mortality. EXPOSURES Single nucleotide polymorphisms, family history, anthropometric factors, menstrual and/or reproductive factors, and lifestyle factors. MAIN OUTCOMES AND MEASURES Degree of stratification of absolute risk owing to nonmodifiable (SNPs, family history, height, and some components of menstrual and/or reproductive history) and modifiable factors (body mass index [BMI; calculated as weight in kilograms divided by height in meters squared], menopausal hormone therapy [MHT], alcohol, and smoking). RESULTS The average absolute risk for a 30-year-old white woman in the United States developing invasive breast cancer by age 80 years is 11.3%. A model that includes all risk factors provided a range of average absolute risk from 4.4% to 23.5% for women in the bottom and top deciles of the risk distribution, respectively. For women who

Risk Factors and Levels of Risk for High School Dropouts

ERIC Educational Resources Information Center

Suh, Suhyun; Suh, Jingyo

2007-01-01

The study in this article identifies three major risk categories of high school dropouts and evaluates the impact of possible prevention strategies. As students accumulate these risks, they became more likely to drop out and prevention programs become less effective. Additionally, it was found that factors influencing the decision to drop out vary…

The hidden risk of deep vein thrombosis--the need for risk factor assessment: case reviews.

PubMed

Race, Tara Kay; Collier, Paul E

2007-01-01

Deep vein thrombosis (DVT) is a very serious, potentially fatal, and very preventable medical condition. It is important for all patients admitted to the hospital to be screened for the risk of developing a DVT. This could be easily accomplished by performing a risk factor assessment-screening tool on all patients. It is also important to educate the medical and nursing staff on the fact that all patients are at risk for developing DVT, not just surgical patients who are often believed to be at the highest risk of DVT. The implementation of the risk factor assessment could potentially save lives and reduce the hospital costs of treating and managing the complications of DVT and venous thromboembolic disease. The cases chosen for review in this article will demonstrate many risk factors that often go overlooked in nonsurgical patients. The implementation of a risk factor assessment tool could potentially aid in the recognition and appropriate prophylaxis of those patients who are at extremely high risk for DVT. Without appropriate recognition of the risk for DVT, patients may be placed at risk for DVT and the potentially fatal and/or debilitating complications associated with the development of DVT.

Risk factor assessment of endoscopically removed malignant colorectal polyps.

PubMed

Netzer, P; Forster, C; Biral, R; Ruchti, C; Neuweiler, J; Stauffer, E; Schönegg, R; Maurer, C; Hüsler, J; Halter, F; Schmassmann, A

1998-11-01

Malignant colorectal polyps are defined as endoscopically removed polyps with cancerous tissue which has invaded the submucosa. Various histological criteria exist for managing these patients. To determine the significance of histological findings of patients with malignant polyps. Five pathologists reviewed the specimens of 85 patients initially diagnosed with malignant polyps. High risk malignant polyps were defined as having one of the following: incomplete polypectomy, a margin not clearly cancer-free, lymphatic or venous invasion, or grade III carcinoma. Adverse outcome was defined as residual cancer in a resection specimen and local or metastatic recurrence in the follow up period (mean 67 months). Malignant polyps were confirmed in 70 cases. In the 32 low risk malignant polyps, no adverse outcomes occurred; 16 (42%) of the 38 patients with high risk polyps had adverse outcomes (p<0.001). Independent adverse risk factors were incomplete polypectomy and a resected margin not clearly cancer-free; all other risk factors were only associated with adverse outcome when in combination. As no patients with low risk malignant polyps had adverse outcomes, polypectomy alone seems sufficient for these cases. In the high risk group, surgery is recommended when either of the two independent risk factors, incomplete polypectomy or a resection margin not clearly cancer-free, is present or if there is a combination of other risk factors. As lymphatic or venous invasion or grade III cancer did not have an adverse outcome when the sole risk factor, operations in such cases should be individually assessed on the basis of surgical risk.

[Tuberculosis recurrence and its risk factors].

PubMed

de Oliveira, H B; Moreira Filho, D de C

2000-04-01

The persistence of tuberculosis bacilli in patients who are cured, thus causing recurrence, is an important issue. This case-control study investigated individual and institutional risk factors for relapse by analyzing independent variables related to the patient, the use of antituberculosis drugs, and the service delivered at health care institutions; 56 cases and 105 controls were interviewed. Recurrence was defined as a new tuberculosis episode after the patient had been successfully treated. Controls were selected from among patients who were treated and cured of pulmonary tuberculosis and who did not experience a relapse. Regression models were proposed to control confounding factors or effect modifiers. The variables identified as risk factors for relapse were those related to erratic patient behavior (missing medical appointments and therefore not picking up the medication, not taking the medication, taking the wrong dosage), age, and stress from life events; adverse reactions to antituberculosis drugs; and problems in the organization of health care services that resulted in patients receiving insufficient dosages or amounts of antituberculosis drugs. Receiving information regarding treatment duration provided protection against recurrence. The knowledge regarding these risk factors should result in more intensive follow-up and in more use of directly observed treatment of tuberculosis in order to prevent relapse.

Media Violence and Other Aggression Risk Factors in Seven Nations.

PubMed

Anderson, Craig A; Suzuki, Kanae; Swing, Edward L; Groves, Christopher L; Gentile, Douglas A; Prot, Sara; Lam, Chun Pan; Sakamoto, Akira; Horiuchi, Yukiko; Krahé, Barbara; Jelic, Margareta; Liuqing, Wei; Toma, Roxana; Warburton, Wayne A; Zhang, Xue-Min; Tajima, Sachi; Qing, Feng; Petrescu, Poesis

2017-07-01

Cultural generality versus specificity of media violence effects on aggression was examined in seven countries (Australia, China, Croatia, Germany, Japan, Romania, the United States). Participants reported aggressive behaviors, media use habits, and several other known risk and protective factors for aggression. Across nations, exposure to violent screen media was positively associated with aggression. This effect was partially mediated by aggressive cognitions and empathy. The media violence effect on aggression remained significant even after statistically controlling a number of relevant risk and protective factors (e.g., abusive parenting, peer delinquency), and was similar in magnitude to effects of other risk factors. In support of the cumulative risk model, joint effects of different risk factors on aggressive behavior in each culture were larger than effects of any individual risk factor.

Cardiovascular Disease Prevalence and Risk Factors of Persons with Mental Retardation

ERIC Educational Resources Information Center

Draheim, Christopher C.

2006-01-01

This paper reviews the recent literature on cardiovascular disease (CVD) prevalence, CVD-related mortality, physiological CVD risk factors, and behavioral CVD risk factors in adults with mental retardation (MR). The literature on the potential influences of modifiable behavioral CVD risk factors and the physiological CVD risk factors are also…

Stillbirth risk factors according to timing of exposure.

PubMed

Dodds, Linda; King, Will D; Fell, Deshayne B; Armson, B Anthony; Allen, Alexander; Nimrod, Carl

2006-08-01

The purpose of the present study is to identify risk factors for stillbirth and explore hypotheses about the cause of stillbirth based on the time in gestation when exposures occur. Relationships between lifestyle factors, pregnancy conditions, medication use, and occupation on risk for stillbirth were examined within a population-based case-control study. Women who had a stillbirth and a random sample of women who had a live birth between 1999 and 2001 were identified through perinatal databases in Nova Scotia and Eastern Ontario, Canada. Exposure data were collected for each month of pregnancy and analyzed within trimesters. Case-control data were converted to case-cohort data, and hazard ratios (HRs) and 95% confidence intervals (CIs) were determined from Cox proportional hazards models. This study included 105 stillbirth cases and 389 live-birth controls. Fertility treatment in the present pregnancy was associated with increased risk for stillbirth (adjusted HR, 4.0; 95% CI, 1.4-11.6). Smoking during the first trimester also was associated with increased risk for stillbirth (adjusted HR, 2.4; 95% CI, 1.2-4.9). Other risk factors included antiemetic use during the first trimester, second-trimester antibiotic use, low family income, and age older than 35 years. Risk factors identified in this study concur with findings of previous studies and support the importance of early pregnancy exposures on stillbirth risk.

Risk Factors for Hispanic Male Intimate Partner Violence Perpetration.

PubMed

Mancera, Bibiana M; Dorgo, Sandor; Provencio-Vasquez, Elias

2017-07-01

The literature review analyzed 24 studies that explored male intimate partner violence (IPV) perpetration risk factors among men, in particular Hispanics, using the socioecological model framework composed of four socioecological levels for violence prevention. Six databases were reviewed within the EBSCO search engine for articles published from 2000 to 2014. Articles reviewed were specific to risk factors for IPV perpetration among Hispanic men, focusing particularly on Mexican American men. Many key factors have previously been associated with risk for IPV perpetration; however, certain determinants are unique to Hispanics such as acculturation, acculturation stress, and delineated gender roles that include Machismo and Marianismo. These risk factors should be incorporated in future targeted prevention strategies and efforts and capitalize on the positive aspects of each to serve as protective factors.

Risk Factors for Hispanic Male Intimate Partner Violence Perpetration

PubMed Central

Mancera, Bibiana M.; Dorgo, Sandor; Provencio-Vasquez, Elias

2015-01-01

The literature review analyzed 24 studies that explored male intimate partner violence (IPV) perpetration risk factors among men, in particular Hispanics, using the socioecological model framework composed of four socioecological levels for violence prevention. Six databases were reviewed within the EBSCO search engine for articles published from 2000 to 2014. Articles reviewed were specific to risk factors for IPV perpetration among Hispanic men, focusing particularly on Mexican American men. Many key factors have previously been associated with risk for IPV perpetration; however, certain determinants are unique to Hispanics such as acculturation, acculturation stress, and delineated gender roles that include Machismo and Marianismo. These risk factors should be incorporated in future targeted prevention strategies and efforts and capitalize on the positive aspects of each to serve as protective factors. PMID:25891392

Korean immigrants' knowledge of heart attack symptoms and risk factors.

PubMed

Hwang, Seon Y; Ryan, Catherine J; Zerwic, Julie Johnson

2008-02-01

This study assessed the knowledge of heart attack symptoms and risk factors in a convenience sample of Korean immigrants. A total of 116 Korean immigrants in a Midwestern metropolitan area were recruited through Korean churches and markets. Knowledge was assessed using both open-ended questions and a structured questionnaire. Latent class cluster analysis and Chi-square tests were used to analyze the data. About 76% of the sample had at least one self-reported risk factor for cardiovascular disease. Using an open-ended question, the majority of subjects could only identify one symptom. In the structured questionnaire, subjects identified a mean of 5 out of 10 heart attack symptoms and a mean of 5 out of 9 heart attack risk factors. Latent class cluster analysis showed that subjects clustered into two groups for both risk factors and symptoms: a high knowledge group and a low knowledge group. Subjects who clustered into the risk factor low knowledge group (48%) were more likely than the risk factor high knowledge group to be older than 65 years, to have lower education, to not know to use 911 when a heart attack occurred, and to not have a family history of heart attack. Korean immigrants' knowledge of heart attack symptoms and risk factors was variable, ranging from high to very low. Education should be focused on those at highest risk for a heart attack, which includes the elderly and those with risk factors.

Risk factors for in-hospital post-hip fracture mortality.

PubMed

Frost, Steven A; Nguyen, Nguyen D; Black, Deborah A; Eisman, John A; Nguyen, Tuan V

2011-09-01

Approximately 10% of hip fracture patients die during hospitalization; however, it is not clear what risk factors contribute to the excess mortality. This study sought to examine risk factors of, and to develop prognostic model for, predicting in-hospital mortality among hip fracture patients. We studied outcomes among 410 men and 1094 women with a hip fracture who were admitted to a major-teaching-hospital in Sydney (Australia) between 1997 and 2007. Clinical data, including concomitant illnesses, were obtained from inpatient data. The primary outcome of the study was in-hospital mortality regardless of length of stay. A Log-binomial regression model was used to identify risk factors for in-hospital mortality. Using the identified risk factors, prognostic nomograms were developed for predicting short term risk of mortality for an individual. The median duration of hospitalization was 9 days. During hospitalization, the risk of mortality was higher in men (9%) than in women (4%). After adjusting for multiple risk factors, increased risk of in-hospital mortality was associated with advancing age (rate ratio [RR] for each 10-year increase in age: 1.91 95% confidence interval [CI]: 1.47 to 2.49), in men (RR 2.13; 95% CI 1.41 to 3.22), and the presence of comorbid conditions on admission (RR for one or more comorbid conditions vs. none: 2.30; 95% CI 1.52 to 3.48). Specifically, the risk of mortality was increased in patients with a pre-existing congestive heart failure (RR 3.02; 95% CI: 1.65 to 5.54), and liver disease (RR 4.75; 95% CI: 1.87 to 12.1). These factors collectively accounted for 69% of the risk for in-hospital mortality. A nomogram was developed from these risk factors to individualize the risk of in-hospital death following a hip fracture. The area under the receiver operating characteristic curve of the final model containing age, sex and comorbid conditions was 0.76. These data suggest that among hip fracture patients, advancing age, gender (men), and

Determination of candidate metabolite biomarkers associated with recurrence of HCV-related hepatocellular carcinoma

PubMed Central

Liu, Zhicheng; Nahon, Pierre; Li, Zaifang; Yin, Peiyuan; Li, Yanli; Amathieu, Roland; Ganne-Carrié, Nathalie; Ziol, Marianne; Sellier, Nicolas; Seror, Olivier; Le Moyec, Laurence; Savarin, Philippe; Xu, Guowang

2018-01-01

Hepatitis C virus (HCV) infection is associated with a high risk of developing hepatocellular carcinoma (HCC) and HCC recurrence remains the primary threat to outcomes after curative therapy. In this study, we compared recurrent and non-recurrent HCC patients treated with radiofrequency ablation (RFA) in order to identify characteristic metabolic profile variations associated with HCC recurrence. Gas chromatography-mass spectrometry (GC-MS) -based metabolomic analyses were conducted on serum samples obtained before and after RFA therapy. Significant variations were observed in metabolites in the glycerolipid, tricarboxylic acid (TCA) cycle, fatty acid, and amino acid pathways between recurrent and non-recurrent patients. Observed differences in metabolites associated with recurrence did not coincide before and after treatment except for fatty acids. Based on the comparison of serum metabolomes between recurrent and non-recurrent patients, key discriminatory metabolites were defined by a random forest (RF) test. Two combinations of these metabolites before and after RFA treatment showed outstanding performance in predicting HCV-related HCC recurrence, they were further confirmed by an external validation set. Our study showed that the determined combination of metabolites may be potential biomarkers for the prediction of HCC recurrence before and after RFA treatment. PMID:29464069

The "polyenviromic risk score": Aggregating environmental risk factors predicts conversion to psychosis in familial high-risk subjects.

PubMed

Padmanabhan, Jaya L; Shah, Jai L; Tandon, Neeraj; Keshavan, Matcheri S

2017-03-01

Young relatives of individuals with schizophrenia (i.e. youth at familial high-risk, FHR) are at increased risk of developing psychotic disorders, and show higher rates of psychiatric symptoms, cognitive and neurobiological abnormalities than non-relatives. It is not known whether overall exposure to environmental risk factors increases risk of conversion to psychosis in FHR subjects. Subjects consisted of a pilot longitudinal sample of 83 young FHR subjects. As a proof of principle, we examined whether an aggregate score of exposure to environmental risk factors, which we term a 'polyenviromic risk score' (PERS), could predict conversion to psychosis. The PERS combines known environmental risk factors including cannabis use, urbanicity, season of birth, paternal age, obstetric and perinatal complications, and various types of childhood adversity, each weighted by its odds ratio for association with psychosis in the literature. A higher PERS was significantly associated with conversion to psychosis in young, familial high-risk subjects (OR=1.97, p=0.009). A model combining the PERS and clinical predictors had a sensitivity of 27% and specificity of 96%. An aggregate index of environmental risk may help predict conversion to psychosis in FHR subjects. Copyright © 2016 Elsevier B.V. All rights reserved.

Environmental risk factors for chronic pancreatitis and pancreatic cancer.

PubMed

Nitsche, Claudia; Simon, Peter; Weiss, F Ulrich; Fluhr, Gabriele; Weber, Eckhard; Gärtner, Simone; Behn, Claas O; Kraft, Matthias; Ringel, Jörg; Aghdassi, Ali; Mayerle, Julia; Lerch, Markus M

2011-01-01

Chronic pancreatitis has long been thought to be mainly associated with immoderate alcohol consumption. The observation that only ∼10% of heavy drinkers develop chronic pancreatitis not only suggests that other environmental factors, such as tobacco smoke, are potent additional risk factors, but also that the genetic component of pancreatitis is more common than previously presumed. Either disease-causing or protective traits have been indentified for mutations in different trypsinogen genes, the gene for the trypsin inhibitor SPINK1, chymotrypsinogen C, and the cystic fibrosis transmembane conductance regulator (CFTR). Other factors that have been proposed to contribute to pancreatitis are obesity, diets high in animal protein and fat, as well as antioxidant deficiencies. For the development of pancreatic cancer, preexisting chronic pancreatitis, more prominently hereditary pancreatitis, is a risk factor. The data on environmental risk factors for pancreatic cancer are, with the notable exception of tobacco smoke, either sparse, unconfirmed or controversial. Obesity appears to increase the risk of pancreatic cancer in the West but not in Japan. Diets high in processed or red meat, diets low in fruits and vegetables, phytochemicals such as lycopene and flavonols, have been proposed and refuted as risk or protective factors in different trials. The best established and single most important risk factor for cancer as well as pancreatitis and the one to clearly avoid is tobacco smoke. Copyright © 2011 S. Karger AG, Basel.

Risk Factors for Social Isolation in Older Korean Americans.

PubMed

Jang, Yuri; Park, Nan Sook; Chiriboga, David A; Yoon, Hyunwoo; Ko, Jisook; Lee, Juyoung; Kim, Miyong T

2016-02-01

Given the importance of social ties and connectedness in the lives of older ethnic immigrants, the present study examined the prevalence of social isolation and its risk factors in older Korean Americans. Using survey data from 1,301 participants (Mage = 70.5, SD = 7.24), risk groups for marginal social ties with family and friends were identified and predictors of each type of social isolation explored. Male gender and poorer rating of health were identified as common risk factors for marginal ties to both family and friends. Findings also present specific risk factors for each type of social isolation. For example, an increased risk of having marginal ties with friends was observed among individuals with perceived financial strain, greater functional impairment, and a shorter stay in the United States. The common and specific risk factors should be incorporated in programs to reduce social isolation in older immigrant populations. © The Author(s) 2015.

Childhood Risk Factors in Dually Diagnosed Homeless Adults.

ERIC Educational Resources Information Center

Blankertz, Laura E.; And Others

1993-01-01

Examined prevalence of five childhood risk factors (sexual abuse, physical abuse, parental mental illness, substance abuse, out-of-home placement) among dually diagnosed (mentally ill and substance abusing) homeless adults (n=156) in rehabilitation programs. Findings suggest that childhood risk factors, whether single or multiple, are very…

Is isomerism a risk factor for intestinal volvulus?

PubMed

Landisch, Rachel M; Loomba, Rohit S; Salazar, Jose H; Buelow, Matthew W; Frommelt, Michele; Anderson, Robert H; Wagner, Amy J

2018-03-06

Isomerism, or heterotaxy syndrome, affects many organ systems anatomically and functionally. Intestinal malrotation is common in patients with isomerism. Despite a low reported risk of volvulus, some physicians perform routine screening and prophylactic Ladd procedures on asymptomatic patients with isomerism who are found to have intestinal malrotation. The primary aim of this study was to determine if isomerism is an independent risk factor for volvulus. Kid's Inpatient Database data from 1997 to 2012 was utilized for this study. Characteristics of admissions with and without isomerism were compared with a particular focus on intestinal malrotation, volvulus, and Ladd procedure. A logistic regression was conducted to determine independent risk factors for volvulus with respect to isomerism. 15,962,403 inpatient admissions were included in the analysis, of which 7970 (0.05%) patients had isomerism, and 6 patients (0.1%) developed volvulus. Isomerism was associated with a 52-fold increase in the odds of intestinal malrotation by univariate analysis. Of 251 with isomerism and intestinal malrotation, only 2.4% experienced volvulus. Logistic regression demonstrated that isomerism was not an independent risk factor for volvulus. Isomerism is associated with an increased risk of intestinal malrotation but is not an independent risk factor for volvulus. Prognosis study. Level III. Copyright © 2018 Elsevier Inc. All rights reserved.

[Cardiovascular risk factors in a group of health care workers].

PubMed

Kramer, Verónica; Adasme, Marcela; Bustamante, M José; Jalil, Jorge; Navarrete, Carlos; Acevedo, Mónica

2012-05-01

Health promotion can be carried out at work places. To assess cardiovascular risk factors among workers of a University hospital. Cross sectional study of 888 participants (aged 41 ± 11 years, 76% women), who answered a survey about cardiovascular risk factors. Body mass index, waist, blood pressure and total cholesterol (TC) by capillary method were determined. Self reported prevalence of risk factors were as follows: 19% of participants had high blood pressure, 30% hypercholesterolemia, 6% diabetes, 41% smoked, 88% were sedentary and 26% had a family history of cardiovascular diseases. Five percent of participants did not have any risk factor, 20% had one risk factor, 32% had two and 43% had three or more. The highest frequency of lack of awareness was about blood glucose values. A high blood cholesterol level was found in 27% of those reporting normal cholesterol levels. Likewise, a high body mass index was found in 18% of those reporting a normal weight. The prevalence of cardiovascular risk factors in this group of participants is similar to that found in the last national health survey in Chile. Noteworthy is the lack of awareness about these risk factors.

Parkinson disease and Alzheimer disease: environmental risk factors.

PubMed

Campdelacreu, J

2014-01-01

The purpose of this review is to update and summarise available evidence on environmental risk factors that have been associated with risk of Parkinson disease (PD) or Alzheimer disease (AD) and discuss their potential mechanisms. Evidence consistently suggests that a higher risk of PD is associated with pesticides and that a higher risk of AD is associated with pesticides, hypertension and high cholesterol levels in middle age, hyperhomocysteinaemia, smoking, traumatic brain injury and depression. There is weak evidence suggesting that higher risk of PD is associated with high milk consumption in men, high iron intake, chronic anaemia and traumatic brain injury. Weak evidence also suggests that a higher risk of AD is associated with high aluminium intake through drinking water, excessive exposure to electromagnetic fields from electrical grids, DM and hyperinsulinaemia, obesity in middle age, excessive alcohol consumption and chronic anaemia. Evidence consistently suggests that a lower risk of PD is associated with hyperuricaemia, tobacco and coffee use, while a lower risk of AD is associated with moderate alcohol consumption, physical exercise, perimenopausal hormone replacement therapy and good cognitive reserve. Weak evidence suggests that lower risk of PD is associated with increased vitamin E intake, alcohol, tea, NSAIDs, and vigorous physical exercise, and that lower risk of AD is associated with the Mediterranean diet, coffee and habitual NSAID consumption. Several environmental factors contribute significantly to risk of PD and AD. Some may already be active in the early stages of life, and some may interact with other genetic factors. Population-based strategies to modify such factors could potentially result in fewer cases of PD or AD. Copyright © 2012 Sociedad Española de Neurología. Published by Elsevier Espana. All rights reserved.

Secondary metabolites from marine microorganisms.

PubMed

Kelecom, Alphonse

2002-03-01

After 40 years of intensive research, chemistry of marine natural products has become a mature field. Since 1995, there are signals of decreased interest in the search of new metabolites from traditional sources such as macroalgae and octocorals, and the number of annual reports on marine sponges stabilized. On the contrary, metabolites from microorganisms is a rapidly growing field, due, at least in part, to the suspicion that a number of metabolites obtained from algae and invertebrates may be produced by associated microorganisms. Studies are concerned with bacteria and fungi, isolated from seawater, sediments, algae, fish and mainly from marine invertebrates such as sponges, mollusks, tunicates, coelenterates and crustaceans. Although it is still to early to define tendencies, it may be stated that the metabolites from microorganisms are in most cases quite different from those produced by the invertebrate hosts. Nitrogenated metabolites predominate over acetate derivatives, and terpenes are uncommon. Among the latter, sesquiterpenes, diterpenes and carotenes have been isolated; among nitrogenated metabolites, amides, cyclic peptides and indole alkaloids predominate.

Gout: a review of non-modifiable and modifiable risk factors

PubMed Central

MacFarlane, Lindsey A.; Kim, Seoyoung C.

2014-01-01

Gout is a common inflammatory arthritis triggered by the crystallization of uric acid within the joints. Gout affects millions worldwide and has an increasing prevalence. Recent research has been carried out to better qualify and quantify the risk factors predisposing individuals to gout. These can largely be broken into non-modifiable risk factors such as sex, age, race, and genetics, and modifiable risk factors such as diet and lifestyle. Increasing knowledge of factors predisposing certain individuals to gout could potentially lead to improved preventive practices. This review summarizes the non-modifiable and modifiable risk factors associated with development of gout. PMID:25437279

Identification of drug metabolites in human plasma or serum integrating metabolite prediction, LC-HRMS and untargeted data processing.

PubMed

Jacobs, Peter L; Ridder, Lars; Ruijken, Marco; Rosing, Hilde; Jager, Nynke Gl; Beijnen, Jos H; Bas, Richard R; van Dongen, William D

2013-09-01

Comprehensive identification of human drug metabolites in first-in-man studies is crucial to avoid delays in later stages of drug development. We developed an efficient workflow for systematic identification of human metabolites in plasma or serum that combines metabolite prediction, high-resolution accurate mass LC-MS and MS vendor independent data processing. Retrospective evaluation of predictions for 14 (14)C-ADME studies published in the period 2007-January 2012 indicates that on average 90% of the major metabolites in human plasma can be identified by searching for accurate masses of predicted metabolites. Furthermore, the workflow can identify unexpected metabolites in the same processing run, by differential analysis of samples of drug-dosed subjects and (placebo-dosed, pre-dose or otherwise blank) control samples. To demonstrate the utility of the workflow we applied it to identify tamoxifen metabolites in serum of a breast cancer patient treated with tamoxifen. Previously published metabolites were confirmed in this study and additional metabolites were identified, two of which are discussed to illustrate the advantages of the workflow.

Developing a pressure ulcer risk factor minimum data set and risk assessment framework.

PubMed

Coleman, Susanne; Nelson, E Andrea; Keen, Justin; Wilson, Lyn; McGinnis, Elizabeth; Dealey, Carol; Stubbs, Nikki; Muir, Delia; Farrin, Amanda; Dowding, Dawn; Schols, Jos M G A; Cuddigan, Janet; Berlowitz, Dan; Jude, Edward; Vowden, Peter; Bader, Dan L; Gefen, Amit; Oomens, Cees W J; Schoonhoven, Lisette; Nixon, Jane

2014-10-01

To agree a draft pressure ulcer risk factor Minimum Data Set to underpin the development of a new evidenced-based Risk Assessment Framework. A recent systematic review identified the need for a pressure ulcer risk factor Minimum Data Set and development and validation of an evidenced-based pressure ulcer Risk Assessment Framework. This was undertaken through the Pressure UlceR Programme Of reSEarch (RP-PG-0407-10056), funded by the National Institute for Health Research and incorporates five phases. This article reports phase two, a consensus study. Consensus study. A modified nominal group technique based on the Research and Development/University of California at Los Angeles appropriateness method. This incorporated an expert group, review of the evidence and the views of a Patient and Public Involvement service user group. Data were collected December 2010-December 2011. The risk factors and assessment items of the Minimum Data Set (including immobility, pressure ulcer and skin status, perfusion, diabetes, skin moisture, sensory perception and nutrition) were agreed. In addition, a draft Risk Assessment Framework incorporating all Minimum Data Set items was developed, comprising a two stage assessment process (screening and detailed full assessment) and decision pathways. The draft Risk Assessment Framework will undergo further design and pre-testing with clinical nurses to assess and improve its usability. It will then be evaluated in clinical practice to assess its validity and reliability. The Minimum Data Set could be used in future for large scale risk factor studies informing refinement of the Risk Assessment Framework. © 2014 The Authors. Journal of Advanced Nursing Published by John Wiley & Sons Ltd.

[Risk factors for changes in glucose metabolism in pregnancy].

PubMed

Esparza, L; Tavano, L; Breña, H; Avila, H; Karchmer, S

1989-02-01

Eighty women were studied having between 20-25 weeks of gestation at the National Institute of Perinatology. Weight and height were taken, and they were questioned about the risk factors (positive family history of diabetes mellitus, age, overweight and number of gestations). Two hours postprandial glucose tests were carried out using 100 g glucose load. Plasma glucose values were determinated according to the glucose-oxidase technique. Results showed that 36% of the population had at least glucose metabolism alteration (GMA) (glucose value 120 mg/dL). No significant difference was found for the weeks of gestation, nor number of gestations to define any cut point. On the other hand, significant values were found for the other risk factors, such as being 35 years or older, having 119% and 103% or more of pregestational and gestational weight for height respectively and having positive maternal family history of diabetes mellitus. The risk factor that is more capable to identify the subjects with an GMA is age 35 years followed by positive maternal family history of diabetes mellitus; when the combination of 4 risk factors is observed (gestas factor is excluded because it is a confusion element), the pregestational and pregestational and gestational weights work more like secondary supplementary risk factors than like determinants of the metabolic process. In view of these facts, it was found that positive maternal history of diabetes mellitus and the age less than or equal to 35 years individually and the presence of 3-4 risk factors can be considered high risk characteristics to develop GMA.

Risk Factors for Increased Severity of Paediatric Medication Administration Errors

PubMed Central

Sears, Kim; Goodman, William M.

2012-01-01

Patients' risks from medication errors are widely acknowledged. Yet not all errors, if they occur, have the same risks for severe consequences. Facing resource constraints, policy makers could prioritize factors having the greatest severe–outcome risks. This study assists such prioritization by identifying work-related risk factors most clearly associated with more severe consequences. Data from three Canadian paediatric centres were collected, without identifiers, on actual or potential errors that occurred. Three hundred seventy-two errors were reported, with outcome severities ranging from time delays up to fatalities. Four factors correlated significantly with increased risk for more severe outcomes: insufficient training; overtime; precepting a student; and off-service patient. Factors' impacts on severity also vary with error class: for wrong-time errors, the factors precepting a student or working overtime significantly increase severe-outcomes risk. For other types, caring for an off-service patient has greatest severity risk. To expand such research, better standardization is needed for categorizing outcome severities. PMID:23968607

Bioanalytical methods for determination of tamoxifen and its phase I metabolites: a review.

PubMed

Teunissen, S F; Rosing, H; Schinkel, A H; Schellens, J H M; Beijnen, J H

2010-12-17

The selective estrogen receptor modulator tamoxifen is used in the treatment of early and advanced breast cancer and in selected cases for breast cancer prevention in high-risk subjects. The cytochrome P450 enzyme system and flavin-containing monooxygenase are responsible for the extensive metabolism of tamoxifen into several phase I metabolites that vary in toxicity and potencies towards estrogen receptor (ER) alpha and ER beta. An extensive overview of publications on the determination of tamoxifen and its phase I metabolites in biological samples is presented. In these publications techniques were used such as capillary electrophoresis, liquid, gas and thin layer chromatography coupled with various detection techniques (mass spectrometry, ultraviolet or fluorescence detection, liquid scintillation counting and nuclear magnetic resonance spectroscopy). A trend is seen towards the use of liquid chromatography coupled to mass spectrometry (LC-MS). State-of-the-art LC-MS equipment allowed for identification of unknown metabolites and quantification of known metabolites reaching lower limit of quantification levels in the sub pg mL(-1) range. Although tamoxifen is also metabolized into phase II metabolites, the number of publications reporting on phase II metabolism of tamoxifen is scarce. Therefore the focus of this review is on phase I metabolites of tamoxifen. We conclude that in the past decades tamoxifen metabolism has been studied extensively and numerous metabolites have been identified. Assays have been developed for both the identification and quantification of tamoxifen and its metabolites in an array of biological samples. This review can be used as a resource for method transfer and development of analytical methods used to support pharmacokinetic and pharmacodynamic studies of tamoxifen and its phase I metabolites. Copyright © 2010 Elsevier B.V. All rights reserved.

Cardiovascular disease risk factors: a childhood perspective.

PubMed

Praveen, Pradeep A; Roy, Ambuj; Prabhakaran, Dorairaj

2013-03-01

Atherosclerotic cardiovascular disease (CVD) is one of the leading causes of death and disability worldwide including in developing countries like India. Indians are known to be predisposed to CVD, which occur almost a decade earlier in them. Though these diseases manifest in the middle age and beyond, it is now clear that the roots of CVD lie in childhood and adolescence. Many of the conventional risk factors of CVD such as high blood pressure, dyslipidemia, tobacco use, unhealthy diet and obesity have their beginnings in childhood and then track overtime. It is thus important to screen and identify these risk factors early and treat them to prevent onset of CVD. Similarly community based strategies to prevent onset of these risk factors is imperative to tackle this burgeoning public health crisis especially in countries like ours with limited resources.

Risk Factors for Brachial Plexus Birth Injury

PubMed Central

Louden, Emily; Marcotte, Michael; Mehlman, Charles; Lippert, William; Huang, Bin; Paulson, Andrea

2018-01-01

Over the course of decades, the incidence of brachial plexus birth injury (BPBI) has increased despite advances in healthcare which would seem to assist in decreasing the rate. The aim of this study is to identify previously unknown risk factors for BPBI and the risk factors with potential to guide preventative measures. A case control study of 52 mothers who had delivered a child with a BPBI injury and 132 mothers who had delivered without BPBI injury was conducted. Univariate, multivariable and logistic regressions identified risk factors and their combinations. The odds of BPBI were 2.5 times higher when oxytocin was used and 3.7 times higher when tachysystole occurred. The odds of BPBI injury are increased when tachysystole and oxytocin occur during the mother’s labor. Logistic regression identified a higher risk for BPBI when more than three of the following variables (>30 lbs gained during the pregnancy, stage 2 labor >61.5 min, mother’s age >26.4 years, tachysystole, or fetal malpresentation) were present in any combination. PMID:29596309

Modifiable cardiovascular risk factors among adults in Aleppo, Syria.

PubMed

Al Ali, Radwan; Rastam, Samer; Fouad, Fouad M; Mzayek, Fawaz; Maziak, Wasim

2011-12-01

This report provides the first comprehensive and standardized assessment of the distribution of cardiovascular disease (CVD) risk factors in Syria, where such data are still scarce. A population-based household survey was conducted in Aleppo (population >2.5 million), involving 1,168 subjects ≥25 years old (47.7% men; mean age 44.7 ± 12.7 years). Information about socio-demographics, personal behavior, and other CVD risk factors was collected. Anthropometric measurements and fasting blood samples were obtained. The prevalence of clinical risk factors of CVD (ClinRFs) was 45.6% for hypertension, 43.2% for obesity, 21.9% for hypercholesterolemia and 15.6% for diabetes. The prevalence of behavioral risk factors (BehRFs) was 82.3% for physical inactivity, 39.0% for smoking, and 33.4% for unhealthy diet. All ClinRFs increased with age, while gender was associated only with obesity and smoking. Education was associated with obesity and diabetes (P < 0.05 for all). Adults in Syria have some of the world's highest prevalence of CVD risk factors. Unhealthy behaviors and social norms unfavorable to women may explain some of such risk profiles.

Risk Factors for Opioid-Use Disorder and Overdose.

PubMed

Webster, Lynn R

2017-11-01

Opioid analgesics are recognized as a legitimate medical therapy for selected patients with severe chronic pain that does not respond to other therapies. However, opioids are associated with risks for patients and society that include misuse, abuse, diversion, addiction, and overdose deaths. Therapeutic success depends on proper candidate selection, assessment before administering opioid therapy, and close monitoring throughout the course of treatment. Risk assessment and prevention include knowledge of patient factors that may contribute to misuse, abuse, addiction, suicide, and respiratory depression. Risk factors for opioid misuse or addiction include past or current substance abuse, untreated psychiatric disorders, younger age, and social or family environments that encourage misuse. Opioid mortality prevalence is higher in people who are middle aged and have substance abuse and psychiatric comorbidities. Suicides are probably undercounted or frequently misclassified in reports of opioid-related poisoning deaths. Greater understanding and better assessment are needed of the risk associated with suicide risk in patients with pain. Clinical tools and an evolving evidence base are available to assist clinicians with identifying patients whose risk factors put them at risk for adverse outcomes with opioids.

Risk factors of carotid plaque and carotid common artery intima-media thickening in a high-stroke-risk population.

PubMed

Wang, ChunFang; Lv, GaoPeng; Zang, DaWei

2017-11-01

To analyze the risk factors of carotid plaque (CP) and carotid common artery intima-media thickening (CCAIMT) and the association between the risk factors and CP numbers and the side of the CCAIMT in a high-stroke-risk population. Carotid ultrasonography was conducted in 2025 participants with high stroke risk. Participants were divided into different groups according to the results of the ultrasound. The risk factors and blood biochemical indices were recorded. The presence of CP and CCAIMT were 38.9% and 24.8% respectively. Multivariate logistic regression indicated that the risk factors of CP were age, high LDL-C and FBG levels, male gender, stroke, diabetes, hypertension, and tobacco use. Compared with participants without CPs, the participants who were male, and older in age, with risk factors of tobacco use, diabetes, high LDL-C levels, and a family history of hypertension were likely to have a single CP, whereas the participants with risk factors of tobacco use, diabetes, hypertension, male gender, older age, high LDL-C levels, stroke and AF or valvulopathy were prone to have multiple CPs. The risk factors of CCAIMT were male gender, stroke, hypertension, diabetes, AF or valvulopathy, tobacco use and age. Compared with the N-CCAIMT subgroup, the risk factors of left CCAIMT were tobacco use, diabetes, male gender, and age. The risk factors of right CCAIMT were male gender, high FBG levels, age, AF or valvulopathy. The risk factors of dual CCAIMT were high frequency of drinking milk, tobacco use, male gender, age, stroke, and hypertension. These findings revealed the risk factors of CP and CCAIMT, and an association between the risk factors and the CP numbers and the side of the CCAIMT.

Risk factor assessment of endoscopically removed malignant colorectal polyps

PubMed Central

Netzer, P; Forster, C; Biral, R; Ruchti, C; Neuweiler, J; Stauffer, E; Schonegg, R; Maurer, C; Husler, J; Halter, F; Schmassmann, A

1998-01-01

Background—Malignant colorectal polyps are defined as endoscopically removed polyps with cancerous tissue which has invaded the submucosa. Various histological criteria exist for managing these patients. 
Aims—To determine the significance of histological findings of patients with malignant polyps. 
Methods—Five pathologists reviewed the specimens of 85 patients initially diagnosed with malignant polyps. High risk malignant polyps were defined as having one of the following: incomplete polypectomy, a margin not clearly cancer-free, lymphatic or venous invasion, or grade III carcinoma. Adverse outcome was defined as residual cancer in a resection specimen and local or metastatic recurrence in the follow up period (mean 67months). 
Results—Malignant polyps were confirmed in 70 cases. In the 32 low risk malignant polyps, no adverse outcomes occurred; 16(42%) of the 38 patients with high risk polyps had adverse outcomes (p<0.001). Independent adverse risk factors were incomplete polypectomy and a resected margin not clearly cancer-free; all other risk factors were only associated with adverse outcome when in combination. 
Conclusion—As no patients with low risk malignant polyps had adverse outcomes, polypectomy alone seems sufficient for these cases. In the high risk group, surgery is recommended when either of the two independent risk factors, incomplete polypectomy or a resection margin not clearly cancer-free, is present or if there is a combination of other risk factors. As lymphatic or venous invasion or grade III cancer did not have an adverse outcome when the sole risk factor, operations in such cases should be individually assessed on the basis of surgical risk. 

 Keywords: malignant polyps; colon cancer; colonoscopy; polypectomy; histology PMID:9824349

Meat consumption as a risk factor for type 2 diabetes.

PubMed

Barnard, Neal; Levin, Susan; Trapp, Caroline

2014-02-21

Disease risk factors identified in epidemiological studies serve as important public health tools, helping clinicians identify individuals who may benefit from more aggressive screening or risk-modification procedures, allowing policymakers to prioritize intervention programs, and encouraging at-risk individuals to modify behavior and improve their health. These factors have been based primarily on evidence from cross-sectional and prospective studies, as most do not lend themselves to randomized trials. While some risk factors are not modifiable, eating habits are subject to change through both individual action and broader policy initiatives. Meat consumption has been frequently investigated as a variable associated with diabetes risk, but it has not yet been described as a diabetes risk factor. In this article, we evaluate the evidence supporting the use of meat consumption as a clinically useful risk factor for type 2 diabetes, based on studies evaluating the risks associated with meat consumption as a categorical dietary characteristic (i.e., meat consumption versus no meat consumption), as a scalar variable (i.e., gradations of meat consumption), or as part of a broader dietary pattern.

Meat Consumption as a Risk Factor for Type 2 Diabetes

PubMed Central

Barnard, Neal; Levin, Susan; Trapp, Caroline

2014-01-01

Disease risk factors identified in epidemiological studies serve as important public health tools, helping clinicians identify individuals who may benefit from more aggressive screening or risk-modification procedures, allowing policymakers to prioritize intervention programs, and encouraging at-risk individuals to modify behavior and improve their health. These factors have been based primarily on evidence from cross-sectional and prospective studies, as most do not lend themselves to randomized trials. While some risk factors are not modifiable, eating habits are subject to change through both individual action and broader policy initiatives. Meat consumption has been frequently investigated as a variable associated with diabetes risk, but it has not yet been described as a diabetes risk factor. In this article, we evaluate the evidence supporting the use of meat consumption as a clinically useful risk factor for type 2 diabetes, based on studies evaluating the risks associated with meat consumption as a categorical dietary characteristic (i.e., meat consumption versus no meat consumption), as a scalar variable (i.e., gradations of meat consumption), or as part of a broader dietary pattern. PMID:24566443

The role of exogenous risk factors of antituberculosis treatment failure.

PubMed

Lesnic, Evelina; Ustian, Aurelia; Pop, Carmen Monica

2016-01-01

The Republic of Moldova reports the highest incidence of tuberculosis and the lowest treatment success rate among European region countries. In most of the patients the antituberculosis treatment failure is correlated with social risk factors (low socio-economical state, epidemiological danger characteristics) and biological factors (young age, male sex, physiological conditions, associated diseases). Clinical factors (advanced forms of tuberculosis, chronic evolution, immune disturbances), therapeutic factors (treatment errors and interruptions, individualized regimens) and administrative factors (drug interruption in supply, suboptimal treatment quality) prevail in regions with defficient in health care delivery. The association of risk factors has a higher impact than the severity of one risk factor. The risk factor assessment is very important before initiation of the treatment, for establishing the plan of risk reduction measures for increasing the success rate. The aim of the study was to determine the impact of exogenous risk factors on antituberculosis treatment failure. The study was conducted on 201 patients with pulmonary tuberculosis and treatment failure and 105 patients with pulmonary tuberculosis who successfully finished the antituberculosis treatment. Selected cases were investigated according national standards. The treatment failure occurred in patients belonging to socially disadvantaged groups, patients with harmful habits (alcohol abuse, drug use, active smoking), patients from infectious clusters. Migration, homelessness and detention releasing imperil the quality of treatment, thus predisposing to the treatment failure. Social, educational support and the substitutive therapy and withdrawal techniques (tobacco, alcohol, psycho-active substances) must be implemented in the high risk groups in order to diminish the risk of treatment failure and to increase the treatment success rate. The study of exogenous risk factors in vulnerable groups

Chronic disease risk factors among hotel workers

PubMed Central

Gawde, Nilesh Chandrakant; Kurlikar, Prashika R.

2016-01-01

Context: Non-communicable diseases have emerged as a global health issue. Role of occupation in pathogenesis of non-communicable diseases has not been explored much especially in the hospitality industry. Aims: Objectives of this study include finding risk factor prevalence among hotel workers and studying relationship between occupational group and chronic disease risk factors chiefly high body mass index. Settings and Design: A cross-sectional study was conducted among non-managerial employees from classified hotels in India. Materials and Methods: The study participants self-administered pre-designed pilot-tested questionnaires. Statistical analysis used: The risk factor prevalence rates were expressed as percentages. Chi-square test was used for bi-variate analysis. Overweight was chosen as ‘outcome’ variable of interest and binary multi-logistic regression analysis was used to identify determinants. Results: The prevalence rates of tobacco use, alcohol use, inadequate physical activity and inadequate intake of fruits and vegetables were 32%, 49%, 24% and 92% respectively among hotel employees. Tobacco use was significantly common among those in food preparation and service, alcohol use among those in food service and security and leisure time physical activity among front office workers. More than two-fifths (42.7%) were overweight. Among the hotel workers, those employed in food preparation and security had higher odds of 1.650 (CI: 1.025 – 2.655) and 3.245 (CI: 1.296 – 8.129) respectively of being overweight. Conclusions: Prevalence of chronic disease risk factors is high among hotel workers. Risk of overweight is significantly high in food preparation and security departments and workplace interventions are necessary to address these risks PMID:27390474

Metabolite monitoring to guide thiopurine therapy in systemic autoimmune diseases.

PubMed

Chapdelaine, Aurélie; Mansour, Anne-Marie; Troyanov, Yves; Williamson, David R; Doré, Maxime

2017-06-01

6-Thioguanine nucleotide (6-TGN) is the active metabolite of thiopurine drugs azathioprine and 6-mercaptopurine. 6-Methylmercaptopurine (6-MMP) is an inactive and potentially hepatotoxic metabolite. A subgroup of patients (shunters) preferentially produce 6-MMP instead of 6-TGN, therefore displaying thiopurine resistance and risk for hepatotoxicity. Outside inflammatory bowel disease literature, few data exist regarding individualized thiopurine therapy based on metabolite monitoring. This study sought to describe metabolite monitoring in patients receiving weight-based thiopurine for systemic autoimmune diseases. Patients were enrolled using a laboratory database, and data were retrospectively collected. The correlation between the highest thiopurine dose (mg/kg) and the 6-TGN concentration (pmol/8 × 10 8 erythrocytes) was estimated with Pearson's correlation coefficient. Seventy-one patients with various systemic autoimmune conditions were enrolled. The correlation between the thiopurine dose and the 6-TGN level was weak for the overall patient sample (r = 0.201, p = 0.092) and for the subgroup of non-shunters (r = 0.278, p = 0.053). Subjects with 6-MMP levels >5700 pmol/8 × 10 8 erythrocytes had more hepatic cytolysis compared to subjects with 6-MMP <5700, OR = 4.36 (CI 95% 1.18-16.13, p = 0.027). Twenty-two patients (31%) were identified as shunters. Six shunters developed hepatotoxicity, five of which had 6-MMP concentration >5700. Eleven non-shunters had hepatotoxicity, one of which had 6-MMP >5700. Thiopurine metabolite monitoring shows wide variability in 6-TGN levels among patients treated with weight-based thiopurine for systemic autoimmune diseases. Thirty-one percent of the patients in our series fulfilled the shunter definition. Thiopurine metabolite monitoring and dose adjustment to improve maintenance of remission and avoid hepatotoxicity should be studied prospectively.

Substantial contribution of extrinsic risk factors to cancer development

PubMed Central

Wu, Song; Powers, Scott; Zhu, Wei; Hannun, Yusuf A

2015-01-01

Summary Recent research has highlighted a strong correlation between tissue-specific cancer risk and the lifetime number of tissue-specific stem cell divisions. Whether such correlation implies a high unavoidable intrinsic cancer risk has become a key public health debate with dissemination of the ‘bad luck’ hypothesis. Here we provide evidence that intrinsic risk factors contribute only modestly (<10~30%) to cancer development. First, we demonstrate that the correlation between stem-cell division and cancer risk does not distinguish between the effects of intrinsic and extrinsic factors. Next, we show that intrinsic risk is better estimated by the lower bound risk controlling for total stem cell divisions. Finally, we show that the rates of endogenous mutation accumulation by intrinsic processes are not sufficient to account for the observed cancer risks. Collectively, we conclude that cancer risk is heavily influenced by extrinsic factors. These results carry immense consequences for strategizing cancer prevention, research, and public health. PMID:26675728

Pneumococcal Disease: Risk Factors and Transmission

MedlinePlus

... Vaccination For Clinicians Streptococcus pneumoniae Transmission Clinical Features Risk Factors Diagnosis & Management Prevention For Laboratorians Drug Resistance Surveillance & Reporting Global ...

Capsaicinoids Modulating Cardiometabolic Syndrome Risk Factors: Current Perspectives

PubMed Central

2016-01-01

Capsaicinoids are bioactive nutrients present within red hot peppers reported to cut ad libitum food intake, to increase energy expenditure (thermogenesis) and lipolysis, and to result in weight loss over time. In addition it has shown more benefits such as improvement in reducing oxidative stress and inflammation, improving vascular health, improving endothelial function, lowering blood pressure, reducing endothelial cytokines, cholesterol lowering effects, reducing blood glucose, improving insulin sensitivity, and reducing inflammatory risk factors. All these beneficial effects together help to modulate cardiometabolic syndrome risk factors. The early identification of cardiometabolic risk factors can help try to prevent obesity, hypertension, diabetes, and cardiovascular disease. PMID:27313880

Key Issues in the Modes of Action and Effects of Trichloroethylene Metabolites for Liver and Kidney Tumorigenesis

PubMed Central

Caldwell, Jane C.; Keshava, Nagalakshmi

2006-01-01

Trichloroethylene (TCE) exposure has been associated with increased risk of liver and kidney cancer in both laboratory animal and epidemiologic studies. The U.S. Environmental Protection Agency 2001 draft TCE risk assessment concluded that it is difficult to determine which TCE metabolites may be responsible for these effects, the key events involved in their modes of action (MOAs), and the relevance of these MOAs to humans. In this article, which is part of a mini-monograph on key issues in the health risk assessment of TCE, we present a review of recently published scientific literature examining the effects of TCE metabolites in the context of the preceding questions. Studies of the TCE metabolites dichloroacetic acid (DCA), trichloroacetic acid (TCA), and chloral hydrate suggest that both DCA and TCA are involved in TCE-induced liver tumorigenesis and that many DCA effects are consistent with conditions that increase the risk of liver cancer in humans. Studies of S-(1,2-dichlorovinyl)-l-cysteine have revealed a number of different possible cell signaling effects that may be related to kidney tumorigenesis at lower concentrations than those leading to cytotoxicity. Recent studies of trichloroethanol exploring an alternative hypothesis for kidney tumorigenesis have failed to establish the formation of formate as a key event for TCE-induced kidney tumors. Overall, although MOAs and key events for TCE-induced liver and kidney tumors have yet to be definitively established, these results support the likelihood that toxicity is due to multiple metabolites through several MOAs, none of which appear to be irrelevant to humans. PMID:16966105

Identification of Early Risk Factors for Developmental Delay

ERIC Educational Resources Information Center

Delgado, Christine E. F.; Vagi, Sara J.; Scott, Keith G.

2007-01-01

Statewide birth certificate and preschool exceptionality records were integrated to identify risk factors for developmental delay (DD). Epidemiological methods were used to investigate both individual-level and population-level risk for DD associated with a number of child and maternal factors. Infants born with very low birth weight were at the…

Metabolites as novel biomarkers for childhood obesity-related traits in Mexican-American children.

PubMed

Farook, V S; Reddivari, L; Chittoor, G; Puppala, S; Arya, R; Fowler, S P; Hunt, K J; Curran, J E; Comuzzie, A G; Lehman, D M; Jenkinson, C P; Lynch, J L; DeFronzo, R A; Blangero, J; Hale, D E; Duggirala, R; Vanamala, J

2015-08-01

Although newer approaches have identified several metabolites associated with obesity, there is paucity of such information in paediatric populations, especially among Mexican-Americans (MAs) who are at high risk of obesity. Therefore, we performed a global serum metabolite screening in MA children to identify biomarkers of childhood obesity. We selected 15 normal-weight, 13 overweight and 14 obese MA children (6-17 years) and performed global serum metabolite screening using ultra-performance liquid chromatography/quadruple orthogonal acceleration time of flight tandem micro mass spectrometer. Metabolite values were analysed to assess mean differences among groups using one-way analysis of variance, to test for linear trend across groups and to examine Pearson's correlations between them and seven cardiometabolic traits (CMTs): body mass index, waist circumference, systolic blood pressure, diastolic blood pressure, homeostasis model of assessment-insulin resistance, triglycerides and high-density lipoprotein cholesterol. We identified 14 metabolites exhibiting differences between groups as well as linear trend across groups with nominal statistical significance. After adjustment for multiple testing, mean differences and linear trends across groups remained significant (P < 5.9 × 10(-5) ) for L-thyronine, bradykinin and naringenin. Of the examined metabolite-CMT trait pairs, all metabolites except for 2-methylbutyroylcarnitine were nominally associated with two or more CMTs, some exhibiting significance even after accounting for multiple testing (P < 3.6 × 10(-3) ). To our knowledge, this study - albeit pilot in nature - is the first study to identify these metabolites as novel biomarkers of childhood obesity and its correlates. These findings signify the need for future systematic investigations of metabolic pathways underlying childhood obesity. © 2014 World Obesity.

Gender differences in risk factors for coronary heart disease.

PubMed

Tan, Yen Y; Gast, Gerrie-Cor M; van der Schouw, Yvonne T

2010-02-01

Coronary heart disease (CHD), traditionally considered a male disease, is also a major threat to women. This review article addresses independent risk factors for CHD that are specific for women as well as non-gender-specific risk factors and how their effects differ between men and women. Although polycystic ovary syndrome (PCOS) in women is associated with an adverse metabolic risk profile, current evidence regarding future risk of CHD is conflicting. Preeclampsia is consistently associated with higher risk of CHD later in life. Menopause is associated with an increased risk of CHD, and the earlier the onset of menopause, the larger the risk. Existing data on postmenopausal hormone therapy (HT) was inconclusive with regard to possible protection when HT is initiated close to menopause in young peri- or postmenopausal women. Evidence on use of low-dose oral contraceptives strongly suggests no increased risk of CHD. Although levels of physical inactivity are similar for men and women, the higher prevalences of hypertension, diabetes, and obesity in older women portends a greater risk in women than in men. Additionally, risk factors like smoking, hypertriglyceridemia and low high-density lipoprotein cholesterol levels have greater impact in women than in men. This review indicates that acknowledgement of non-gender-specific risk factors in addition to those that are unique to women would help optimize diagnosis, treatment and earlier prevention of CHD in women. Further research is needed to ascertain if incorporating these gender-specific risks into a clinically used risk stratification model would change outcome in women. Copyright 2009 Elsevier Ireland Ltd. All rights reserved.

[Risk factors for tardive movement disorders in schizophrenia].

PubMed

Tenback, D E; Bakker, P R; van Harten, P N

2015-01-01

Tardive movement disorders are common among patients with schizophrenia. Risk factors for movement disorders are of the utmost importance in the context of preventive strategies. To achieve clearer classification of movement disorders in schizophrenia, to identify the risk factors involved and thereby develop strategies to prevent movement disorders. We searched PubMed for prospective studies which had been performed in homogeneous target populations with schizophrenia and which contained well-defined definitions of the movement disorders. From these we selected studies in which risk factors were repeatedly identified. Tardive dyskinesia is well documented. Risk factors for developing tardive dyskinesia are use of antipsychotics, particularly those belonging to the first generation, 'not belonging to the Caucasian race', early extrapyramidal symptoms and older age. So far, there is very little conclusive evidence regarding the genetics of tardive movement disorders. With regard to tardive dyskinesia, not belonging to the Caucasian race and old age are two risk factors that can be quickly determined for the purpose of prevention. In this case it leads to the choice of medication with a low D2 affinity. Furthermore, it is advisable, after commencing treatment with an antipsychotic drug, to evaluate on a regular basis if the patient is showing (early) signs of TD. If TD does occur, there is a choice between medication with a low D-2 affinity or clozapine.

Risk factors for hypospadias in China

PubMed Central

Xu, Ling-Fan; Liang, Chao-Zhao; Lipianskaya, Julia; Chen, Xian-Guo; Fan, Song; Zhang, Li; Zhou, Jun; Tai, Sheng; Jiang, Chang-Qin

2014-01-01

This case-controlled study was designed to evaluate the association between various baseline parental factors and the risk of hypospadias in China. Patients were selected from tertiary referral hospitals in Anhui, a province in mid-eastern China. A questionnaire was given to the parents of each patient. The final database included 193 cases and 835 controls. The incidence of additional coexistent anomalies was 13.0%, primarily cryptorchidism (9.8%). Ten patients (5.1%) were from families with genital anomaly, including five families (2.6%) with hypospadias. The risks of hypospadias was higher for children of mothers > 35 (odds ratio [OR] =1.47) and < 18 (OR = 2.95) years of age, and in mothers who had consumed alcohol (OR = 2.67), used drugs (OR = 1.53) and had an infection (OR = 1.87) during pregnancy. The risk of hypospadias was also higher when mothers (OR = 1.68) and fathers (OR = 1.74) were engaged in agriculture. Other factors assessed were not associated with the risk of hypospadias. PMID:24875823

Cancer risk factors in Korean news media: a content analysis.

PubMed

Kye, Su Yeon; Kwon, Jeong Hyun; Kim, Yong-Chan; Shim, Minsun; Kim, Jee Hyun; Cho, Hyunsoon; Jung, Kyu Won; Park, Keeho

2015-01-01

Little is known about the news coverage of cancer risk factors in Korea. This study aimed to examine how the news media encompasses a wide array of content regarding cancer risk factors and related cancer sites, and investigate whether news coverage of cancer risk factors is congruent with the actual prevalence of the disease. A content analysis was conducted on 1,138 news stories covered during a 5-year period between 2008 and 2012. The news stories were selected from nationally representative media in Korea. Information was collected about cancer risk factors and cancer sites. Of various cancer risk factors, occupational and environmental exposures appeared most frequently in the news. Breast cancer was mentioned the most in relation to cancer sites. Breast, cervical, prostate, and skin cancer were overrepresented in the media in comparison to incidence and mortality cases, whereas lung, thyroid, liver, and stomach cancer were underrepresented. To our knowledge, this research is the first investigation dealing with news coverage about cancer risk factors in Korea. The study findings show occupational and environmental exposures are emphasized more than personal lifestyle factors; further, more prevalent cancers in developed countries have greater media coverage, not reflecting the realities of the disease. The findings may help health journalists and other health storytellers to develop effective ways to communicate cancer risk factors.

Kynurenine pathway metabolites and enzymes involved in redox reactions.

PubMed

González Esquivel, D; Ramírez-Ortega, D; Pineda, B; Castro, N; Ríos, C; Pérez de la Cruz, V

2017-01-01

Oxido-reduction reactions are a fundamental part of the life due to support many vital biological processes as cellular respiration and glucose oxidation. In the redox reactions, one substance transfers one or more electrons to another substance. An important electron carrier is the coenzyme NAD + , which is involved in many metabolic pathways. De novo biosynthesis of NAD + is through the kynurenine pathway, the major route of tryptophan catabolism, which is sensitive to redox environment and produces metabolites with redox capacity, able to alter biological functions that are controlled by redox-responsive signaling pathways. Kynurenine pathway metabolites have been implicated in the physiology process and in the physiopathology of many diseases; processes that also share others factors as dysregulation of calcium homeostasis, mitochondrial dysfunction, oxidative stress, inflammation and cell death, which impact the redox environment. This review examines in detail the available evidence in which kynurenine pathway metabolites participate in redox reactions and their effect on cellular redox homeostasis, since the knowledge of the main factors and mechanisms that lead to cell death in many neurodegenative disorders and other pathologies, such as mitochondrial dysfunction, oxidative stress and kynurenines imbalance, will allow to develop therapies using them as targets. This article is part of the Special Issue entitled 'The Kynurenine Pathway in Health and Disease'. Copyright © 2016 Elsevier Ltd. All rights reserved.

Risk factors for depression in community-treated epilepsy: systematic review.

PubMed

Lacey, Cameron J; Salzberg, Michael R; D'Souza, Wendyl J

2015-02-01

Depression is one of the most common psychiatric comorbidities in epilepsy; however, the factors contributing to this association remain unclear. There is a growing consensus that methodological limitations, particularly selection bias, affect many of the original studies. A systematic review focussed on community-based studies offers an alternative approach for the identification of the risk factors for depression. Searches were performed in MEDLINE (Ovid), 2000 to 31 December 2013, EMBASE, and Google Scholar to identify studies examining risk factors for depression in epilepsy. Community-based studies of adults with epilepsy that reported at least one risk factor for depression were included. The search identified 17 studies that met selection criteria, representing a combined total of 12,212 people with epilepsy with a mean sample size of 718. The most consistent risk factors for depression were sociodemographic factors, despite the fact that most studies focus on epilepsy-related factors. Most studies lacked a systematic conceptual approach to investigating depression, and few risk factors were consistently well studied. Future community-based studies require a detailed systematic approach to improve the ability to detect risk factors for depression in epilepsy. Psychological factors were rarely studied in community-based samples with epilepsy, although the consistent association with depression in the few studies that did suggests this warrants further examination. Copyright © 2014 Elsevier Inc. All rights reserved.

Bariatric surgery modulates circulating and cardiac metabolites.

PubMed

Ashrafian, Hutan; Li, Jia V; Spagou, Konstantina; Harling, Leanne; Masson, Perrine; Darzi, Ara; Nicholson, Jeremy K; Holmes, Elaine; Athanasiou, Thanos

2014-02-07

Bariatric procedures such as the Roux-en-Y gastric bypass (RYGB) operation offer profound metabolic enhancement in addition to their well-recognized weight loss effects. They are associated with significant reduction in cardiovascular disease risk and mortality, which suggests a surgical modification on cardiac metabolism. Metabolic phenotyping of the cardiac tissue and plasma postsurgery may give insight into cardioprotective mechanisms. The aim of the study was to compare the metabolic profiles of plasma and heart tissue extracts from RYGB- and sham-operated Wistar rats to identify the systemic and cardiac signature of metabolic surgery. A total of 27 male Wistar rats were housed individually for a week and subsequently underwent RYGB (n = 13) or sham (n = 14) operation. At week 8 postoperation, a total of 27 plasma samples and 16 heart tissue samples (8 RYGB; 8 Sham) were collected from animals and analyzed using (1)H nuclear magnetic resonance (NMR) spectroscopy and ultra performance liquid chromatography (UPLC-MS) to characterize the global metabolite perturbation induced by RYGB operation. Plasma bile acids, phosphocholines, amino acids, energy-related metabolites, nucleosides and amine metabolites, and cardiac glycogen and amino acids were found to be altered in the RYGB operated group. Correlation networks were used to identify metabolite association. The metabolic phenotype of this bariatric surgical model inferred systematic change in both myocardial and systemic activity post surgery. The altered metabolic profile following bariatric surgery reflects an enhancement of cardiac energy metabolism through TCA cycle intermediates, cardiorenal protective activity, and biochemical caloric restriction. These surgically induced metabolic shifts identify some of the potential mechanisms that contribute toward bariatric cardioprotection through gut microbiota ecological fluxes and an enterocardiac axis to shield against metabolic syndrome of cardiac dysfunction.

Risk Factors for Peer Sexual Harassment in Schools

ERIC Educational Resources Information Center

Fineran, Susan; Bolen, Rebecca M.

2006-01-01

This study introduces potential risk factors for victimization and perpetration of sexual harassment among teens not previously studied. The first set of analyses compared histories of perpetration and victimization by gender, as well as the relationship between risk factors and perpetration or victimization. For girls (r = 0.544) and boys (r =…

[Risk factors for anorexia in children].

PubMed

Liu, Wei-Xiao; Lang, Jun-Feng; Zhang, Qin-Feng

2016-11-01

To investigate the risk factors for anorexia in children, and to reduce the prevalence of anorexia in children. A questionnaire survey and a case-control study were used to collect the general information of 150 children with anorexia (case group) and 150 normal children (control group). Univariate analysis and multivariate logistic stepwise regression analysis were performed to identify the risk factors for anorexia in children. The results of the univariate analysis showed significant differences between the case and control groups in the age in months when supplementary food were added, feeding pattern, whether they liked meat, vegetables and salty food, whether they often took snacks and beverages, whether they liked to play while eating, and whether their parents asked them to eat food on time (P<0.05). The results of the multivariate logistic regression analysis showed that late addition of supplementary food (OR=5.408), high frequency of taking snacks and/or drinks (OR=11.813), and eating while playing (OR=6.654) were major risk factors for anorexia in children. Liking of meat (OR=0.093) and vegetables (OR=0.272) and eating on time required by parents (OR=0.079) were protective factors against anorexia in children. Timely addition of supplementary food, a proper diet, and development of children's proper eating and living habits can reduce the incidence of anorexia in children.

Modifications of coronary risk factors.

PubMed

Albu, Jeanine; Gottlieb, Sheldon H; August, Phyllis; Nesto, Richard W; Orchard, Trevor J

2006-06-19

In addition to the revascularization and glycemic management interventions assigned at random, the Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) design includes the uniform control of major coronary artery disease risk factors, including dyslipidemia, hypertension, smoking, central obesity, and sedentary lifestyle. Target levels for risk factors were adjusted throughout the trial to comply with changes in recommended clinical practice guidelines. At present, the goals are low-density lipoprotein cholesterol <2.59 mmol/L (<100 mg/dL) with an optional goal of <1.81 mmol/L (<70 mg/dL); plasma triglyceride level <1.70 mmol/L (<150 mg/dL); blood pressure level <130 mm Hg systolic and <80 mm Hg diastolic; and smoking cessation treatment for all active smokers. Algorithms were developed for the pharmacologic management of dyslipidemia and hypertension. Dietary prescriptions for the management of glycemia, plasma lipid profiles, and blood pressure levels were adapted from existing clinical practice guidelines. Patients with a body mass index >25 were prescribed moderate caloric restriction; after the trial was under way, a lifestyle weight-management program was instituted. All patients were formally prescribed both endurance and resistance/flexibility exercises, individually adapted to their level of disability and fitness. Pedometers were distributed as a biofeedback strategy. Strategies to achieve the goals for risk factors were designed by BARI 2D working groups (lipid, cardiovascular and hypertension, and nonpharmacologic intervention) and the ongoing implementation of the strategies is monitored by lipid, hypertension, and lifestyle intervention management centers.

Knowledge of oral cancer risk factors amongst high-risk Australians: findings from the LESIONS programme.

PubMed

Dost, F; Do, L; Farah, C S

2016-12-01

Patient awareness of risk factors associated with cancer has been shown to increase patient presentation for screening and early detection. This study aimed to identify the level of awareness of oral cancer risk factors in a high risk Australian population. Participants were recruited from the LESIONS programme between April 2012 and April 2014. Demographics were collected via semi-structured interview. A self-administered questionnaire was provided, listing a number of possible oral cancer risk factors. Participants were requested to indicate their level of agreement on a three-point scale. Bivariate and multivariable analysis was performed. A total of 1498 participants took part in the LESIONS programme and were invited to complete the questionnaire. The most common risk factors thought to be associated with oral cancer were smoking (87.5%), poor oral hygiene (67.9%) and family history (61.1%). Only 50.2% of respondents were aware of alcohol consumption as a risk factor. While most participants were aware of the association between smoking and oral cancer, only half were aware of the significant risk alcohol consumption poses. A significant portion of participants also held a number of inaccurate beliefs in relation to oral cancer risk. These findings can benefit both clinicians and public health policy makers in targeting oral cancer education. © 2016 Australian Dental Association.

Epidemiological risk factors associated with inflammatory breast cancer subtypes.

PubMed

Atkinson, Rachel L; El-Zein, Randa; Valero, Vicente; Lucci, Anthony; Bevers, Therese B; Fouad, Tamer; Liao, Weiqin; Ueno, Naoto T; Woodward, Wendy A; Brewster, Abenaa M

2016-03-01

In this single-institution case-control study, we identified risk factors associated with inflammatory breast cancer (IBC) subtypes based on staining of estrogen receptor (ER), progesterone receptor (PR) and expression of human epidermal growth factor 2 (HER2neu) to determine distinct etiologic pathways. We identified 224 women with IBC and 396 cancer-free women seen at the MD Anderson Cancer Center. Multinomial logistic regression was used to estimate odds ratios (ORs) and 95 % confidence intervals (CIs) for associations between breast cancer risk factors and the IBC tumor subtypes: luminal (ER+ and/or PR+/HER2neu-), HER2neu+ (any ER and PR, HER2neu+), and triple-negative (ER-/PR-/HER2neu-). In multivariable analysis, compared with women age ≥26 at first pregnancy, women age <26 had a higher risk of triple-negative IBC (OR 3.32, 95% CI 1.37-8.05). Women with a history of breast-feeding had a lower risk of triple-negative (OR 0.30; 95% CI 0.15-0.62) and luminal IBC (OR 0.35, 95% CI 0.18-0.68). A history of smoking was associated with an increased risk of luminal IBC (OR 2.37; 95% CI 1.24-4.52). Compared with normal-weight women, those who were overweight or obese (body mass index ≥25 kg/m(2)) had a higher risk of all three tumor subtypes (p < 0.01 for all subtypes). Overweight or obese status is important modifiable risk factor for IBC of any subtype. Modifiable risk factors, age at first pregnancy (≥26), breast-feeding, and smoking may be associated with specific IBC subtypes. These results highlight the importance of evaluating epidemiologic risk factors for IBC for the identification of subtype-specific prevention strategies.

Disruption of dopamine transport by DDT and its metabolites

PubMed Central

Hatcher, Jaime M.; Delea, Kristin C.; Richardson, Jason R.; Pennell, Kurt D.; Miller, Gary W.

2016-01-01

Epidemiological studies suggest a link between pesticide exposure and an increased risk of developing Parkinson’s disease (PD). Although studies have been unable to clearly identify specific pesticides that contribute to PD, a few human studies have reported higher levels of the organochlorine pesticides dieldrin and DDE (a metabolite of DDT) in post-mortem PD brains. Previously, we found that exposure of mice to dieldrin caused perturbations in the nigrostriatal dopamine system consistent with those seen in PD. Given the concern over the environmental persistence and reintroduction of DDT for the control of malaria-carrying mosquitoes and other pests, we sought to determine whether DDT and its two major metabolites, DDD and DDE, could damage the dopamine system. In vitro analyses in mouse synaptosomes and vesicles demonstrated that DDT and its metabolites inhibit the plasma membrane dopamine transporter (DAT) and the vesicular monoamine transporter (VMAT2). However, exposure of mice to either DDT or DDE failed to show evidence of nigrostriatal damage or behavioral abnormalities in any of the measures examined. Thus, we report that in vitro effects of DDT and its metabolites on components of the dopamine system do not translate into neurotoxicological outcomes in orally exposed mice and DDT appears to have less dopamine toxicity when compared to dieldrin. These data suggest elevated DDE levels in PD patients may represent a measure of general pesticide exposure and that other pesticides may be responsible for the association between pesticide exposure and PD. PMID:18533268

Pancreatic ductal adenocarcinoma: Risk factors, screening, and early detection

PubMed Central

Becker, Andrew E; Hernandez, Yasmin G; Frucht, Harold; Lucas, Aimee L

2014-01-01

Pancreatic cancer is the fourth most common cause of cancer-related deaths in the United States, with over 38000 deaths in 2013. The opportunity to detect pancreatic cancer while it is still curable is dependent on our ability to identify and screen high-risk populations before their symptoms arise. Risk factors for developing pancreatic cancer include multiple genetic syndromes as well as modifiable risk factors. Genetic conditions include hereditary breast and ovarian cancer syndrome, Lynch Syndrome, familial adenomatous polyposis, Peutz-Jeghers Syndrome, familial atypical multiple mole melanoma syndrome, hereditary pancreatitis, cystic fibrosis, and ataxia-telangiectasia; having a genetic predisposition can raise the risk of developing pancreatic cancer up to 132-fold over the general population. Modifiable risk factors, which include tobacco exposure, alcohol use, chronic pancreatitis, diet, obesity, diabetes mellitus, as well as certain abdominal surgeries and infections, have also been shown to increase the risk of pancreatic cancer development. Several large-volume centers have initiated such screening protocols, and consensus-based guidelines for screening high-risk groups have recently been published. The focus of this review will be both the genetic and modifiable risk factors implicated in pancreatic cancer, as well as a review of screening strategies and their diagnostic yields. PMID:25170203

On the use of sibling recurrence risks to select environmental factors liable to interact with genetic risk factors.

PubMed

Kazma, Rémi; Bonaïti-Pellié, Catherine; Norris, Jill M; Génin, Emmanuelle

2010-01-01

Gene-environment interactions are likely to be involved in the susceptibility to multifactorial diseases but are difficult to detect. Available methods usually concentrate on some particular genetic and environmental factors. In this paper, we propose a new method to determine whether a given exposure is susceptible to interact with unknown genetic factors. Rather than focusing on a specific genetic factor, the degree of familial aggregation is used as a surrogate for genetic factors. A test comparing the recurrence risks in sibs according to the exposure of indexes is proposed and its power is studied for varying values of model parameters. The Exposed versus Unexposed Recurrence Analysis (EURECA) is valuable for common diseases with moderate familial aggregation, only when the role of exposure has been clearly outlined. Interestingly, accounting for a sibling correlation for the exposure increases the power of EURECA. An application on a sample ascertained through one index affected with type 2 diabetes is presented where gene-environment interactions involving obesity and physical inactivity are investigated. Association of obesity with type 2 diabetes is clearly evidenced and a potential interaction involving this factor is suggested in Hispanics (P=0.045), whereas a clear gene-environment interaction is evidenced involving physical inactivity only in non-Hispanic whites (P=0.028). The proposed method might be of particular interest before genetic studies to help determine the environmental risk factors that will need to be accounted for to increase the power to detect genetic risk factors and to select the most appropriate samples to genotype.

Risk factors for community-acquired bacterial meningitis.

PubMed

Lundbo, Lene Fogt; Benfield, Thomas

2017-06-01

Bacterial meningitis is a significant burden of disease and mortality in all age groups worldwide despite the development of effective conjugated vaccines. The pathogenesis of bacterial meningitis is based on complex and incompletely understood host-pathogen interactions. Some of these are pathogen-specific, while some are shared between different bacteria. We searched the database PubMed to identify host risk factors for bacterial meningitis caused by the pathogens Streptococcus pneumoniae, Neisseria meningitidis and Haemophilus influenzae type b, because they are three most common causative bacteria beyond the neonatal period. We describe a number of risk factors; including socioeconomic factors, age, genetic variation of the host and underlying medical conditions associated with increased susceptibility to invasive bacterial infections in both children and adults. As conjugated vaccines are available for these infections, it is of utmost importance to identify high risk patients to be able to prevent invasive disease.

What are the main risk factors for running-related injuries?

PubMed

Saragiotto, Bruno Tirotti; Yamato, Tiê Parma; Hespanhol Junior, Luiz Carlos; Rainbow, Michael J; Davis, Irene S; Lopes, Alexandre Dias

2014-08-01

Despite several studies that have been conducted on running injuries, the risk factors for running-related injuries are still not clear in the literature. The aim of this study was to systematically review prospective cohort studies that investigated the risk factors for running injuries in general. We conducted electronic searches without restriction of language on EMBASE (1980 to Dec 2012), PUBMED (1946 to Dec 2012), CINAHL (1988 to Dec 2012) SPORTDiscus (1977 to Dec 2012), Latin American and Caribbean Centre on Health Sciences Information (1985 to Dec 2012) and Scientific Electronic Library Online (1998 to Dec 2012) databases, using subject headings, synonyms, relevant terms and variant spellings for each database. Only prospective cohort studies investigating the risk factors for running-related musculoskeletal injuries were included in this review. Two independent reviewers screened each article and, if they did not reach a consensus, a third reviewer decided whether or not the article should be included. Year of publication, type of runners, sample size, definition of running-related musculoskeletal injury, baseline characteristics, reported risk factors and the statistical measurement of risk or protection association were extracted from the articles. A scale adapted by the authors evaluated the risk of bias of the articles. A total of 11 articles were considered eligible in this systematic review. A total of 4,671 pooled participants were analysed and 60 different predictive factors were investigated. The main risk factor reported was previous injury (last 12 months), reported in 5 of the 8 studies that investigated previous injuries as a risk factor. Only one article met the criteria for random selection of the sample and only six articles included a follow-up of 6 months or more. There was no association between gender and running injuries in most of the studies. It is possible that eligible articles for this review were published in journals that were

Anesthesia patient risk: a quantitative approach to organizational factors and risk management options.

PubMed

Paté-Cornell, M E; Lakats, L M; Murphy, D M; Gaba, D M

1997-08-01

The risk of death or brain damage to anesthesia patients is relatively low, particularly for healthy patients in modern hospitals. When an accident does occur, its cause is usually an error made by the anesthesiologist, either in triggering the accident sequence, or failing to take timely corrective measures. This paper presents a pilot study which explores the feasibility of extending probabilistic risk analysis (PRA) of anesthesia accidents to assess the effects of human and management components on the patient risk. We develop first a classic PRA model for the patient risk per operation. We then link the probabilities of the different accident types to their root causes using a probabilistic analysis of the performance shaping factors. These factors are described here as the "state of the anesthesiologist" characterized both in terms of alertness and competence. We then analyze the effects of different management factors that affect the state of the anesthesiologist and we compute the risk reduction benefits of several risk management policies. Our data sources include the published version of the Australian Incident Monitoring Study as well as expert opinions. We conclude that patient risk could be reduced substantially by closer supervision of residents, the use of anesthesia simulators both in training and for periodic recertification, and regular medical examinations for all anesthesiologists.

The Relationship Between Socioeconomic Status and CV Risk Factors

PubMed Central

Quispe, Renato; Benziger, Catherine P.; Bazo-Alvarez, Juan Carlos; Howe, Laura D.; Checkley, William; Gilman, Robert H.; Smeeth, Liam; Bernabé-Ortiz, Antonio; Miranda, J. Jaime; Bernabé-Ortiz, Antonio; Casas, Juan P.; Smith, George Davey; Ebrahim, Shah; García, Héctor H.; Gilman, Robert H.; Huicho, Luis; Málaga, Germán; Miranda, J. Jaime; Montori, Víctor M.; Smeeth, Liam; Checkley, William; Diette, Gregory B.; Gilman, Robert H.; Huicho, Luis; León-Velarde, Fabiola; Rivera, María; Wise, Robert A.; Checkley, William; García, Héctor H.; Gilman, Robert H.; Miranda, J. Jaime; Sacksteder, Katherine

2016-01-01

Background Variations in the distribution of cardiovascular disease and risk factors by socioeconomic status (SES) have been described in affluent societies, yet a better understanding of these patterns is needed for most low- and middle-income countries. Objective This study sought to describe the relationship between cardiovascular risk factors and SES using monthly family income, educational attainment, and assets index, in 4 Peruvian sites. Methods Baseline data from an age- and sex-stratified random sample of participants, ages ≥35 years, from 4 Peruvian sites (CRONICAS Cohort Study, 2010) were used. The SES indicators considered were monthly family income (n = 3,220), educational attainment (n = 3,598), and assets index (n = 3,601). Behavioral risk factors included current tobacco use, alcohol drinking, physical activity, daily intake of fruits and vegetables, and no control of salt intake. Cardiometabolic risk factors included obesity, elevated waist circumference, hypertension, insulin resistance, diabetes mellitus, low high-density lipoprotein cholesterol, and high triglyceride levels. Results In the overall population, 41.6% reported a monthly family income risk of obesity, whereas higher levels of education were associated with lower risk of obesity. In contrast, higher SES according to all 3 indicators was associated with higher levels of triglycerides. Conclusions The association between SES and cardiometabolic risk factors varies depending on the SES indicator used. These results highlight the need to contextualize risk factors by socioeconomic groups in Latin American settings. PMID:27102029

Cardiovascular Risk Factors among College Students: Knowledge, Perception, and Risk Assessment

ERIC Educational Resources Information Center

Tran, Dieu-My T.; Zimmerman, Lani M.; Kupzyk, Kevin A.; Shurmur, Scott W.; Pullen, Carol H.; Yates, Bernice C.

2017-01-01

Objective: To assess college students' knowledge and perception of cardiovascular risk factors and to screen for their cardiovascular risks. Participants: The final sample that responded to recruitment consisted of 158 college students from a midwestern university. Methods: A cross-sectional, descriptive study was performed using convenience…

Semen quality in Peruvian pesticide applicators: association between urinary organophosphate metabolites and semen parameters

PubMed Central

Yucra, Sandra; Gasco, Manuel; Rubio, Julio; Gonzales, Gustavo F

2008-01-01

Background Organophosphates are broad class of chemicals widely used as pesticides throughout the world. We performed a cross-sectional study of associations between dialkylphosphate metabolites of organophosphates and semen quality among pesticide applicators in Majes (Arequipa), Peru. Methods Thirty-one men exposed to organophosphate (OP) pesticides and 31 non-exposed were recruited (age, 20–60 years). In exposed subjects, semen and a blood sample were obtained one day after the last pesticide application. Subjects were grouped according to levels of OP metabolites in urine. Semen samples were analyzed for sperm concentration, percentage of sperm motility, percentage of normal morphology, semen leucocytes and concentrations of fructose and zinc. Exposure to OP was assessed by measuring six urinary OP metabolites (dimethyl and diethyl phosphates and thiophosphates) by gas chromatography using a single flame photometric detector. Results Diethyldithiophosphate (p = 0.04) and diethylthiophosphate (p = 0.02) better reflected occupational pesticide exposure than other OP metabolites. Semen analysis revealed a significant reduction of semen volume and an increase in semen pH in men with OP metabolites. Multiple regression analysis showed that both occupational exposure to pesticides and the time of exposure to pesticides were more closely related to alterations in semen quality parameters than the single measurement of OP metabolites in urine. Conclusion The study demonstrated that occupational exposure to OP pesticides was more closely related to alterations in semen quality than a single measurement of urine OP metabolites. Current measurement of OP metabolites in urine may not reflect the full risk. PMID:19014632

Colonic Absorption of Low-Molecular-Weight Metabolites Influenced by the Intestinal Microbiome: A Pilot Study.

PubMed

Matsumoto, Mitsuharu; Ooga, Takushi; Kibe, Ryoko; Aiba, Yuji; Koga, Yasuhiro; Benno, Yoshimi

2017-01-01

Low-molecular-weight metabolites produced by the intestinal microbiome play a direct role in health and disease. However, little is known about the ability of the colon to absorb these metabolites. It is also unclear whether these metabolites are bioavailable. Here, metabolomics techniques (capillary electrophoresis with time-of-flight mass spectrometry, CE-TOFMS), germ-free (GF) mice, and colonized (Ex-GF) mice were used to identify the colonic luminal metabolites transported to colonic tissue and/or blood. We focused on the differences in each metabolite between GF and Ex-GF mice to determine the identities of metabolites that are transported to the colon and/or blood. CE-TOFMS identified 170, 246, 166, and 193 metabolites in the colonic feces, colonic tissue, portal plasma, and cardiac plasma, respectively. We classified the metabolites according to the following influencing factors: (i) the membrane transport system of the colonocytes, (ii) metabolism during transcellular transport, and (iii) hepatic metabolism based on the similarity in the ratio of each metabolite between GF and Ex-GF mice and found 62 and 22 metabolites that appeared to be absorbed from the colonic lumen to colonocytes and blood, respectively. For example, 11 basic amino acids were transported to the systemic circulation from the colonic lumen. Furthermore, many low-molecular-weight metabolites influenced by the intestinal microbiome are bioavailable. The present study is the first to report the transportation of metabolites from the colonic lumen to colonocytes and somatic blood in vivo, and the present findings are critical for clarifying host-intestinal bacterial interactions.

Microsomal metabolism of trenbolone acetate metabolites ...

EPA Pesticide Factsheets

Trenbolone acetate (TBA) is a synthetic growth promoter widely used in animal agriculture, and its metabolites are suspected endocrine disrupting compounds in agriculturally impacted receiving waters. However, beyond the three widely recognized TBA metabolites (17-trenbolone, 17-trenbolone and trendione), little is known about other metabolites formed in vivo and subsequently discharged into the environment, with some evidence suggesting these unknown metabolites comprise a majority of the TBA mass dosed to the animal. Here, we explored the metabolism of the three known TBA metabolites using rat liver microsome studies. All TBA metabolites are transformed into a complex mixture of monohydroxylated products. Based on product characterization, the majority are more polar than the parent metabolites but maintain their characteristic trienone backbone. A minor degree of interconversion between known metabolites was also observed, as were higher order hydroxylated products with a greater extent of reaction. Notably, the distribution and yield of products were generally comparable across a series of variably induced rat liver microsomes, as well as during additional studies with human and bovine liver microsomes. Bioassays conducted with mixtures of these transformation products suggest that androgen receptor (AR) binding activity is diminished as a result of the microsomal treatment, suggesting that the transformation products are generally less potent than

Obesity and Cardiovascular Disease: a Risk Factor or a Risk Marker?

PubMed

Mandviwala, Taher; Khalid, Umair; Deswal, Anita

2016-05-01

In the USA, 69 % of adults are either overweight or obese and 35 % are obese. Obesity is associated with an increased incidence of various cardiovascular disorders. Obesity is a risk marker for cardiovascular disease, in that it is associated with a much higher prevalence of comorbidities such as diabetes, hypertension, and metabolic syndrome, which then increase the risk for cardiovascular disease. However, in addition, obesity may also be an independent risk factor for the development of cardiovascular disease. Furthermore, although obesity has been shown to be an independent risk factor for several cardiovascular diseases, it is often associated with improved survival once the diagnosis of the cardiovascular disease has been made, leading to the term "obesity paradox." Several pathways linking obesity and cardiovascular disease have been described. In this review, we attempt to summarize the complex relationship between obesity and cardiovascular disorders, in particular coronary atherosclerosis, heart failure, and atrial fibrillation.

Risk Factors for Attempting Suicide in Heroin Addicts

ERIC Educational Resources Information Center

Roy, Alec

2010-01-01

In order to examine risk factors for attempting suicide in heroin dependent patients, a group of 527 abstinent opiate dependent patients had a psychiatric interview and completed the Childhood Trauma Questionnaire. Patients who had or had never attempted suicide were compared on putative suicide risk factors. It was found that 207 of the 527…

Risk Factors for Osteoporosis Among Middle-Aged Women

ERIC Educational Resources Information Center

Turner, Lori W.; Wallace, Lorraine Silver; Perry, Blake Allen; Bleeker, Jeanne

2004-01-01

Objective: To investigate the risk factors for osteoporosis among a sample of middle-aged women. Methods: Adipose tissue and bone mineral density levels at the left femur, lumbar spine, and total body were assessed using dual-energy x-ray absorptiometry (DXA). Subjects (n=342) were surveyed regarding a variety of osteoporosis-related risk factors.…

Bioactivation of tamoxifen to metabolite E quinone methide: reaction with glutathione and DNA.

PubMed

Fan, P W; Bolton, J L

2001-06-01

Despite the beneficial effects of tamoxifen in the treatment and prevention of breast cancer, long-term usage of this popular antiestrogen has been linked to an increased risk of developing endometrial cancer in women. One of the suggested pathways leading to the potential toxicity of tamoxifen involves its oxidative metabolism to 4-hydroxytamoxifen, which may be further oxidized to an electrophilic quinone methide. Alternatively, tamoxifen could undergo O-dealkylation to give cis/trans-1,2-diphenyl-1-(4-hydroxyphenyl)-but-1-ene, which is commonly known as metabolite E. Because of its structural similarity to 4-hydroxytamoxifen, metabolite E could also be biotransformed to a quinone methide, which has the potential to alkylate DNA and may contribute to the genotoxic effects of tamoxifen. To further probe the chemical reactivity/toxicity of such an electrophilic species, we have prepared metabolite E quinone methide chemically and enzymatically and examined its reactivity with glutathione (GSH) and DNA. Like 4-hydroxytamoxifen quinone methide, metabolite E quinone methide is quite stable; its half-life under physiological conditions is around 4 h, and its half-life in the presence of GSH is approximately 4 min. However, unlike the unstable GSH adducts of 4-hydroxytamoxifen quinone methide, metabolite E GSH adducts are stable enough to be isolated and characterized by NMR and liquid chromatography/tandem mass spectrometry (LC/MS/MS). Reaction of metabolite E quinone methide with DNA generated exclusively deoxyguanosine adducts, which were characterized by LC/MS/MS. These data suggest that metabolite E has the potential to cause cytotoxicity/genotoxicity through the formation of a quinone methide.

Tubal Factor Infertility and Perinatal Risk After Assisted Reproductive Technology

PubMed Central

Kawwass, Jennifer F.; Crawford, Sara; Kissin, Dmitry M.; Session, Donna R.; Boulet, Sheree; Jamieson, Denise J.

2014-01-01

OBJECTIVE To assess trends of tubal factor infertility and to evaluate risk of miscarriage and delivery of preterm or low birth weight (LBW) neonates among women with tubal factor infertility using assisted reproductive technology (ART). METHODS We assessed trends of tubal factor infertility among all fresh and frozen, donor, and nondonor ART cycles performed annually in the United States between 2000 and 2010 (N=1,418,774) using the National ART Surveillance System. The data set was then limited to fresh, nondonor in vitro fertilization cycles resulting in pregnancy to compare perinatal outcomes for cycles associated with tubal compared with male factor infertility. We performed bivariate and multivariable analyses controlling for maternal characteristics and calculated adjusted risk ratios (RRs) and 95% confidence intervals (CI). RESULTS The percentage of ART cycles associated with tubal factor infertility diagnoses decreased from 2000 to 2010 (26.02–14.81%). Compared with male factor infertility, tubal factor portended an increased risk of miscarriage (14.0% compared with 12.7%, adjusted RR 1.08, 95% CI 1.04–1.12); risk was increased for both early and late miscarriage. Singleton neonates born to women with tubal factor infertility had an increased risk of pre-term birth (15.8% compared with 11.6%, adjusted RR 1.27, 95% CI 1.20–1.34) and LBW (10.9% compared with 8.5%, adjusted RR 1.28, 95% CI 1.20–1.36). Significant increases in risk persisted for early and late preterm delivery and very low and moderately LBW delivery. A significantly elevated risk was also detected for twin, but not triplet, pregnancies. CONCLUSION Tubal factor infertility, which is decreasing in prevalence in the United States, is associated with an increased risk of miscarriage, preterm birth, and LBW delivery as compared with couples with male factor infertility using ART. PMID:23812461

Population attributable risks of patient, child and organizational risk factors for perinatal mortality in hospital births.

PubMed

Poeran, Jashvant; Borsboom, Gerard J J M; de Graaf, Johanna P; Birnie, Erwin; Steegers, Eric A P; Bonsel, Gouke J

2015-04-01

The main objective of this study was to estimate the contributing role of maternal, child, and organizational risk factors in perinatal mortality by calculating their population attributable risks (PAR). The primary dataset comprised 1,020,749 singleton hospital births from ≥22 weeks' gestation (The Netherlands Perinatal Registry 2000-2008). PARs for single and grouped risk factors were estimated in four stages: (1) creating a duplicate dataset for each PAR analysis in which risk factors of interest were set to the most favorable value (e.g., all women assigned 'Western' for PAR calculation of ethnicity); (2) in the primary dataset an elaborate multilevel logistic regression model was fitted from which (3) the obtained coefficients were used to predict perinatal mortality in each duplicate dataset; (4) PARs were then estimated as the proportional change of predicted- compared to observed perinatal mortality. Additionally, PARs for grouped risk factors were estimated by using sequential values in two orders: after PAR estimation of grouped maternal risk factors, the resulting PARs for grouped child, and grouped organizational factors were estimated, and vice versa. The combined PAR of maternal, child and organizational factors is 94.4 %, i.e., when all factors are set to the most favorable value perinatal mortality is expected to be reduced with 94.4 %. Depending on the order of analysis, the PAR of maternal risk factors varies from 1.4 to 13.1 %, and for child- and organizational factors 58.7-74.0 and 7.3-34.3 %, respectively. In conclusion, the PAR of maternal-, child- and organizational factors combined is 94.4 %. Optimization of organizational factors may achieve a 34.3 % decrease in perinatal mortality.

Characterization of Urinary Phthalate Metabolites Among Custodians

PubMed Central

Cavallari, Jennifer M.; Simcox, Nancy J.; Wakai, Sara; Lu, Chensheng; Garza, Jennifer L.; Cherniack, Martin

2015-01-01

Phthalates, a ubiquitous class of chemicals found in consumer, personal care, and cleaning products, have been linked to adverse health effects. Our goal was to characterize urinary phthalate metabolite concentrations and to identify work and nonwork sources among custodians using traditional cleaning chemicals and ‘green’ or environmentally preferable products (EPP). Sixty-eight custodians provided four urine samples on a workday (first void, before shift, end of shift, and before bedtime) and trained observers recorded cleaning tasks and types of products used (traditional, EPP, or disinfectant) hourly over the work shifts. Questionnaires were used to assess personal care product use. Four different phthalate metabolites [monoethyl phthalate (MEP), monomethyl phthalate (MMP), mono (2-ethylhexyl) phthalate (MEHP), and monobenzyl phthalate (MBzP)] were quantified using liquid chromatography mass spectrometry. Geometric means (GM) and 95% confidence intervals (95% CI) were calculated for creatinine-adjusted urinary phthalate concentrations. Mixed effects univariate and multivariate modeling, using a random intercept for each individual, was performed to identify predictors of phthalate metabolites including demographics, workplace factors, and personal care product use. Creatinine-adjusted urinary concentrations [GM (95% CI)] of MEP, MMP, MEHP, and MBzP were 107 (91.0–126), 2.69 (2.18–3.30), 6.93 (6.00–7.99), 8.79 (7.84–9.86) µg g−1, respectively. An increasing trend in phthalate concentrations from before to after shift was not observed. Creatinine-adjusted urinary MEP was significantly associated with frequency of traditional cleaning chemical intensity in the multivariate model after adjusting for potential confounding by demographics, workplace factors, and personal care product use. While numerous demographics, workplace factors, and personal care products were statistically significant univariate predictors of MMP, MEHP, and MBzP, few

[Association between urinary polycyclic aromatic hydrocarbon metabolites and elevated serum uric acid levels in coke oven workers].

PubMed

Deng, Siyun; Deng, Qifei; Hu, Die; Li, Jun; Zhu, Xiaoyan; Guo, Huan; Wu, Tangchun

2014-06-01

To analyze the relationship between metabolites of polycyclic aromatic hydrocarbons (PAHs) and serum uric acid levels in coke oven workers and to provide new clues to the pathogenic mechanism of PAHs. A total of 1302 coke oven workers were divided into four groups, namely control group and low-, intermediate-, and high-dose exposure groups. The concentrations of ambient PAHs at each workplace were determined by high-performance liquid chromatography. The detailed information on the occupational history and health of workers was collected by questionnaire survey and physical examination, and so were their blood and urine samples. Serum uric acid and creatinine levels were measured using a Hitachi 7020 automatic biochemical analyzer. Ten urinary PAH metabolites were detected by gas chromatography-mass spectrometry. Serum uric acid levels were the highest in the high-dose exposure group, followed by the intermediate- and low-dose exposure groups, and were the lowest in the control group. There were significant correlations between serum uric acid levels and the quartiles of 1-hydroxynaphthalene and 1-hydroxyphenanthrene (P < 0.05). After adjustment for PAH metabolite-related relationship, only urinary 1-hydroxyphenanthrene was significantly correlated with serum uric acid levels (P = 0.001). After adjustment for confounding factors and using the 1st quartile of 1-hydroxyphenanthrene as a reference, the odds ratio for hyperuricemia in subjects with the 2nd, 3rd, and 4th quartiles of 1-hydroxyphenanthrene were 1.55, 1.57, and 2.35, respectively. Urinary 1-hydroxyphenanthrene is associated with a dose-response increase in serum uric acid levels in coke oven workers, and exposure to phenanthrene in PAHs may be a risk factor for hyperuricemia.

Risk factors for amyotrophic lateral sclerosis

PubMed Central

Ingre, Caroline; Roos, Per M; Piehl, Fredrik; Kamel, Freya; Fang, Fang

2015-01-01

Amyotrophic lateral sclerosis (ALS) is the most common motor neuron disease. It is typically fatal within 2–5 years of symptom onset. The incidence of ALS is largely uniform across most parts of the world, but an increasing ALS incidence during the last decades has been suggested. Although recent genetic studies have substantially improved our understanding of the causes of ALS, especially familial ALS, an important role of non-genetic factors in ALS is recognized and needs further study. In this review, we briefly discuss several major genetic contributors to ALS identified to date, followed by a more focused discussion on the most commonly examined non-genetic risk factors for ALS. We first review factors related to lifestyle choices, including smoking, intake of antioxidants, physical fitness, body mass index, and physical exercise, followed by factors related to occupational and environmental exposures, including electromagnetic fields, metals, pesticides, β-methylamino-L-alanine, and viral infection. Potential links between ALS and other medical conditions, including head trauma, metabolic diseases, cancer, and inflammatory diseases, are also discussed. Finally, we outline several future directions aiming to more efficiently examine the role of non-genetic risk factors in ALS. PMID:25709501

Risk factors for sensorineural hearing loss in children.

PubMed

Núñez-Batalla, Faustino; Trinidad-Ramos, Germán; Sequí-Canet, José Miguel; Alzina De Aguilar, Valentín; Jáudenes-Casaubón, Carmen

2012-01-01

In the last decade, tremendous progress has been made very rapidly in the development of Early Hearing Detection and Intervention (EHDI) systems as a major public health initiative. The percentage of infants screened annually in Spain has increased significantly since the EHDI systems have expanded to all autonomic regions. Historically, high risk indicators have been used for the identification of infants who should receive audiological evaluation but who live in geographic locations where universal hearing screening is not yet available, to help identify infants who pass neonatal screening but are at risk of developing delayed-onset hearing loss and to identify infants who may have passed neonatal screening but have mild forms of permanent hearing loss. In this review, the standard risk factors for hearing loss are analysed and the risk factors known to be associated with late onset or progressive hearing loss are identified. The recommendation for infants with a risk factor that may be considered as low risk is to perform at least one audiology assessment by 24-30 months. In contrast, for an infant with risk factors known to be associated with late onset or progressive hearing loss (such as cytomegalovirus infection or family history), early and more frequent assessment is appropriate. All infants should have an objective standardised screening of global development with a validated assessment tool at 9, 18 and 24-30 months of age or at any time if the health care professional or the family is concerned. Copyright © 2011 Elsevier España, S.L. All rights reserved.

The significance of cholesterol and its metabolite, 27-hydroxycholesterol in breast cancer.

PubMed

Nelson, Erik R

2018-05-05

Although significant advances in the treatment of breast cancer have been made, in particular in the use of endocrine therapy, de novo and aquired resistance to therapy, and metastatic recurrence continue to be major clinical problems. Given the high prevalence of breast cancer, new life-style or chemotherapeutic approaches are required. In this regard, cholesterol has emerged as a risk factor for the onset of breast cancer, and elevated cholesterol is associated with a poor prognosis. While treatment with cholesterol lowering medication is not associated with breast cancer risk, it does appear to be protective against recurrence. Importantly, the cholesterol axis represents a potential target for both life-style and pharmacological intervention. This review will outline the clinical and preclinical data supporting a role for cholesterol in breast cancer pathophysiology. Specific focus is given to 27-hydroxycholesterol (27-OHC; (3β,25R)-Cholest-5-ene-3,26-diol)), a primary metabolite of cholesterol that has recently been defined as an endogenous Selective Estrogen Receptor Modulator. Future perspectives and directions are discussed. Copyright © 2017 Elsevier B.V. All rights reserved.

The role of exogenous risk factors of antituberculosis treatment failure

PubMed Central

LESNIC, EVELINA; USTIAN, AURELIA; POP, CARMEN MONICA

2016-01-01

Background and aim The Republic of Moldova reports the highest incidence of tuberculosis and the lowest treatment success rate among European region countries. In most of the patients the antituberculosis treatment failure is correlated with social risk factors (low socio-economical state, epidemiological danger characteristics) and biological factors (young age, male sex, physiological conditions, associated diseases). Clinical factors (advanced forms of tuberculosis, chronic evolution, immune disturbances), therapeutic factors (treatment errors and interruptions, individualized regimens) and administrative factors (drug interruption in supply, suboptimal treatment quality) prevail in regions with defficient in health care delivery. The association of risk factors has a higher impact than the severity of one risk factor. The risk factor assessment is very important before initiation of the treatment, for establishing the plan of risk reduction measures for increasing the success rate. The aim of the study was to determine the impact of exogenous risk factors on antituberculosis treatment failure. Methods The study was conducted on 201 patients with pulmonary tuberculosis and treatment failure and 105 patients with pulmonary tuberculosis who successfully finished the antituberculosis treatment. Selected cases were investigated according national standards. Results The treatment failure occurred in patients belonging to socially disadvantaged groups, patients with harmful habits (alcohol abuse, drug use, active smoking), patients from infectious clusters. Migration, homelessness and detention releasing imperil the quality of treatment, thus predisposing to the treatment failure. Social, educational support and the substitutive therapy and withdrawal techniques (tobacco, alcohol, psycho-active substances) must be implemented in the high risk groups in order to diminish the risk of treatment failure and to increase the treatment success rate. Conclusions The study of

Shared Risk Factors in Cardiovascular Disease and Cancer.

PubMed

Koene, Ryan J; Prizment, Anna E; Blaes, Anne; Konety, Suma H

2016-03-15

Cardiovascular disease (CVD) and cancer are the 2 leading causes of death worldwide. Although commonly thought of as 2 separate disease entities, CVD and cancer possess various similarities and possible interactions, including a number of similar risk factors (eg, obesity, diabetes mellitus), suggesting a shared biology for which there is emerging evidence. Although chronic inflammation is an indispensable feature of the pathogenesis and progression of both CVD and cancer, additional mechanisms can be found at their intersection. Therapeutic advances, despite improving longevity, have increased the overlap between these diseases, with millions of cancer survivors now at risk of developing CVD. Cardiac risk factors have a major impact on subsequent treatment-related cardiotoxicity. In this review, we explore the risk factors common to both CVD and cancer, highlighting the major epidemiological studies and potential biological mechanisms that account for them. © 2016 American Heart Association, Inc.

Modifiable risk factors associated with bronchiolitis

PubMed Central

Nenna, Raffaella; Cutrera, Renato; Frassanito, Antonella; Alessandroni, Claudia; Nicolai, Ambra; Cangiano, Giulia; Petrarca, Laura; Arima, Serena; Caggiano, Serena; Ullmann, Nicola; Papoff, Paola; Bonci, Enea; Moretti, Corrado; Midulla, Fabio

2017-01-01

Background: We sought to clarify possibly modifiable risk factors related to pollution responsible for acute bronchiolitis in hospitalized infants. Methods: For this observational study, we recruited 213 consecutive infants with bronchiolitis (cases: median age: 2 months; age range: 0.5–12 months; boys: 55.4%) and 213 children aged <3 years (controls: median age: 12 months; age range: 0.5–36 months; boys: 54.5%) with a negative medical history for lower respiratory tract diseases hospitalized at ‘Sapienza’ University Rome and IRCCS Bambino Gesù Hospital. Infants’ parents completed a standardized 53-item questionnaire seeking information on social-demographic and clinical characteristics, indoor pollution, eating habits and outdoor air pollution. Multivariate logistic regression analyses were run to assess the independent effect of risk factors, accounting for confounders and effect modifiers. Results: In the 213 hospitalized infants the questionnaire identified the following risk factors for acute bronchiolitis: breastfeeding ⩾3 months (OR: 2.1, 95% confidence interval [CI]: 1.2–3.6), presence of older siblings (OR: 2.8, 95% CI: 1.7–4.7), ⩾4 cohabitants (OR: 1.5, 95% CI: 1.1–2.1), and using seed oil for cooking (OR: 1.7, 95% CI: 1.2–2.6). Having renovated their home in the past 12 months and concurrently being exposed daily to smoking, involving more than 11 cigarettes and two or more smoking cohabitants, were more frequent factors in cases than in controls (p = 0.021 and 0.05), whereas self-estimated proximity to road and traffic was similar in the two groups. Conclusions: We identified several risk factors for acute bronchiolitis related to indoor and outdoor pollution, including inhaling cooking oil fumes. Having this information would help public health authorities draw up effective preventive measures – for example, teach mothers to avoid handling their child when they have a cold and eliminate exposure to second-hand tobacco smoke

LC-MS/MS-based approach for obtaining exposure estimates of metabolites in early clinical trials using radioactive metabolites as reference standards.

PubMed

Zhang, Donglu; Raghavan, Nirmala; Chando, Theodore; Gambardella, Janice; Fu, Yunlin; Zhang, Duxi; Unger, Steve E; Humphreys, W Griffith

2007-12-01

An LC-MS/MS-based approach that employs authentic radioactive metabolites as reference standards was developed to estimate metabolite exposures in early drug development studies. This method is useful to estimate metabolite levels in studies done with non-radiolabeled compounds where metabolite standards are not available to allow standard LC-MS/MS assay development. A metabolite mixture obtained from an in vivo source treated with a radiolabeled compound was partially purified, quantified, and spiked into human plasma to provide metabolite standard curves. Metabolites were analyzed by LC-MS/MS using the specific mass transitions and an internal standard. The metabolite concentrations determined by this approach were found to be comparable to those determined by valid LC-MS/MS assays. This approach does not requires synthesis of authentic metabolites or the knowledge of exact structures of metabolites, and therefore should provide a useful method to obtain early estimates of circulating metabolites in early clinical or toxicological studies.

New Pioglitazone Metabolites and Absence of Opened-Ring Metabolites in New N-Substituted Thiazolidinedione.

PubMed

Campos, Michel Leandro; Cerqueira, Letícia Bonancio; Silva, Bruna Cristina Ulian; Franchin, Taísa Busaranho; Galdino-Pitta, Marina Rocha; Pitta, Ivan Rocha; Peccinini, Rosângela Gonçalves; Pontarolo, Roberto

2018-06-01

Thiazolidinediones (TZDs) are drugs used to treat type 2 diabetes mellitus; however, several safety concerns remain regarding the available drugs in this class. Therefore, the search for new TZD candidates is ongoing; metabolism studies play a crucial step in the development of new candidates. Pioglitazone, one of the most commonly used TZDs, and GQ-11, a new N -substituted TZD, were investigated in terms of their metabolic activity in rat and human liver microsomes to assess their metabolic stability and investigate their metabolites. Methods for preparation of samples were based on liquid-liquid extraction and protein precipitation. Quantitation was performed using liquid chromatography (LC)-tandem mass spectrometry, and the metabolite investigation was performed using ultraperformance LC coupled to a hybrid quadrupole-time of flight mass spectrometer. The predicted intrinsic clearance of GQ-11 was 70.3 and 46.1 ml/kg per minute for rats and humans, respectively. The predicted intrinsic clearance of pioglitazone was 24.1 and 15.9 ml/kg per minute for rats and humans, respectively. The pioglitazone metabolite investigation revealed two unpublished metabolites (M-D and M-A). M-A is a hydration product and may be related to the mechanism of ring opening and the toxicity of pioglitazone. The metabolites of GQ-11 are products of oxidation; no ring-opening metabolite was observed for GQ-11. In conclusion, under the same experimental conditions, a ring-opening metabolite was observed only for pioglitazone. The resistance of GQ-11 to the ring opening is probably related to N -substitution in the TZD ring. Copyright © 2018 by The American Society for Pharmacology and Experimental Therapeutics.

Risk factors for tuberculosis in Greenland: case-control study.

PubMed

Ladefoged, K; Rendal, T; Skifte, T; Andersson, M; Søborg, B; Koch, A

2011-01-01

Despite several efforts aiming at disease control, the incidence of tuberculosis (TB) remains high in Greenland, averaging 131 per 100,000 population during the period 1998-2007. The purpose of the present study was to disclose risk factors for TB. A case-control study was performed among 146 patients diagnosed with TB in the period 2004-2006. For each patient, four healthy age- and sex-matched control persons living in the same district were included. All participants completed a questionnaire regarding socio-demographic and lifestyle factors. Risk factor analyses were carried out using logistic regression models. Factors associated with TB were Inuit ethnicity, living in a small settlement, unemployment, no access to tap water, no bathroom or flushing toilet, underweight, smoking, frequent intake of alcohol and immunosuppressive treatment. The multivariate model showed that Inuit ethnicity (OR 15.3), living in a settlement (OR 5.1), being unemployed (OR 4.1) and frequent alcohol use (OR 3.1) were independent determinants of risk. Unemployment was associated with the highest population-attributable risk (29%). Risk factors associated with living in a settlement should be further explored and an investigation of genetic susceptibility is warranted.