Alpha-synuclein levels in patients with multiple system atrophy: a meta-analysis.
Yang, Fei; Li, Wan-Jun; Huang, Xu-Sheng
2018-05-01
This study evaluates the relationship between multiple system atrophy and α-synuclein levels in the cerebrospinal fluid, plasma and neural tissue. Literature search for relevant research articles was undertaken in electronic databases and study selection was based on a priori eligibility criteria. Random-effects meta-analyses of standardized mean differences in α-synuclein levels between multiple system atrophy patients and normal controls were conducted to obtain the overall and subgroup effect sizes. Meta-regression analyses were performed to evaluate the effect of age, gender and disease severity on standardized mean differences. Data were obtained from 11 studies involving 378 multiple system atrophy patients and 637 healthy controls (age: multiple system atrophy patients 64.14 [95% confidence interval 62.05, 66.23] years; controls 64.16 [60.06, 68.25] years; disease duration: 44.41 [26.44, 62.38] months). Cerebrospinal fluid α-synuclein levels were significantly lower in multiple system atrophy patients than in controls but in plasma and neural tissue, α-synuclein levels were significantly higher in multiple system atrophy patients (standardized mean difference: -0.99 [-1.65, -0.32]; p = 0.001). Percentage of male multiple system atrophy patients was significantly positively associated with the standardized mean differences of cerebrospinal fluid α-synuclein levels (p = 0.029) whereas the percentage of healthy males was not associated with the standardized mean differences of cerebrospinal fluid α-synuclein levels (p = 0.920). In multiple system atrophy patients, α-synuclein levels were significantly lower in the cerebrospinal fluid and were positively associated with the male gender.
Cheuk, Q Ky; Lo, T K; Wong, S F; Lee, C P
2016-02-01
Several studies have shown that women with pre-existing diabetes mellitus have significantly lower pregnancy-associated plasma protein-A levels than those without. This study aimed to evaluate whether first-trimester pregnancy-associated plasma protein-A multiple of median is associated with gestational diabetes mellitus in Chinese pregnant women. This prospectively collected case series was conducted in a regional hospital in Hong Kong. All consecutive Chinese women with a singleton pregnancy who attended the hospital for their first antenatal visit (before 14 weeks' gestation) from April to July 2014 were included. Pregnancy-associated plasma protein-A multiple of median was compared between the gestational diabetic (especially for early-onset gestational diabetes) and non-diabetic groups. The correlation between pregnancy-associated plasma protein-A level and glycosylated haemoglobin level in women with gestational diabetes was also examined. Of the 520 women recruited, gestational diabetes was diagnosed in 169 (32.5%). Among them, 43 (25.4%) had an early diagnosis, and 167 (98.8%) with the disease were managed by diet alone. The gestational diabetic group did not differ significantly to the non-diabetic group in pregnancy-associated plasma protein-A (0.97 vs 0.99, P=0.40) or free β-human chorionic gonadotrophin multiple of median (1.05 vs 1.02, P=0.29). Compared with the non-gestational diabetic group, women with early diagnosis of gestational diabetes had a non-significant reduction in pregnancy-associated plasma protein-A multiple of median (median, interquartile range: 0.86, 0.57-1.23 vs 0.99, 0.67-1.44; P=0.11). Pregnancy-associated plasma protein-A and glycosylated haemoglobin levels were not correlated in women with gestational diabetes (r=0.027; P=0.74). Chinese women with non-insulin-dependent gestational diabetes did not exhibit significant changes to pregnancy-associated plasma protein-A multiple of median nor a correlation between pregnancy-associated plasma protein-A with glycosylated haemoglobin levels. Pregnancy-associated plasma protein-A multiple of median was not predictive of non-insulin-dependent gestational diabetes or early onset of gestational diabetes. There was a high prevalence of gestational diabetes in the Chinese population.
The association of reproductive and lifestyle factors with a score of multiple endogenous hormones
Shafrir, Amy L.; Zhang, Xuehong; Poole, Elizabeth M.; Hankinson, Susan E.; Tworoger, Shelley S.
2014-01-01
Introduction We recently reported that high levels of multiple sex and growth hormones were associated with increased postmenopausal breast cancer risk. Limited research has explored the relationship between reproductive, anthropometric, and lifestyle factors and levels of multiple hormones simultaneously. Methods This cross-sectional analysis included 738 postmenopausal Nurses' Health Study participants who were controls in a breast cancer nested case-control study and had measured levels of estrone, estradiol, estrone sulfate, testosterone, androstenedione, dehydroepiandrosterone sulfate, prolactin and sex hormone binding globulin (SHBG). A score was created by summing the number of hormones a woman had above (below for SHBG) each hormone's age-adjusted geometric mean. The association between lifestyle, anthropometric, and reproductive exposures and the score was assessed using generalized linear models. Results The hormone score ranged from 0 to 8 with a mean of 4.0 (standard deviation=2.2). Body mass index (BMI) and alcohol consumption at blood draw were positively associated with the hormone score: a 5 unit increase in BMI was associated with a 0.79 (95%CI: 0.63, 0.95) unit increase in the score (p<0.0001) and each 15 grams/day increase in alcohol consumption was associated with a 0.41 (95%CI: 0.18, 0.63) unit increase in the score (p=0.0004). Family history of breast cancer, age at menarche, and physical activity were not associated with the score. Conclusions Reproductive breast cancer risk factors were not associated with elevated levels of multiple endogenous hormones, whereas anthropometric and lifestyle factors, particularly BMI and alcohol consumption, tended to be associated with higher levels of multiple hormones. PMID:25048255
The association of reproductive and lifestyle factors with a score of multiple endogenous hormones.
Shafrir, Amy L; Zhang, Xuehong; Poole, Elizabeth M; Hankinson, Susan E; Tworoger, Shelley S
2014-10-01
We recently reported that high levels of multiple sex and growth hormones were associated with increased postmenopausal breast cancer risk. Limited research has explored the relationship between reproductive, anthropometric, and lifestyle factors and levels of multiple hormones simultaneously. This cross-sectional analysis included 738 postmenopausal Nurses' Health Study participants who were controls in a breast cancer nested case-control study and had measured levels of estrone, estradiol, estrone sulfate, testosterone, androstenedione, dehydroepiandrosterone sulfate, prolactin, and sex hormone binding globulin (SHBG). A score was created by summing the number of hormones a woman had above (below for SHBG) each hormone's age-adjusted geometric mean. The association between lifestyle, anthropometric, and reproductive exposures and the score was assessed using generalized linear models. The hormone score ranged from 0 to 8 with a mean of 4.0 (standard deviation = 2.2). Body mass index (BMI) and alcohol consumption at blood draw were positively associated with the hormone score: a 5 unit increase in BMI was associated with a 0.79 (95%CI: 0.63, 0.95) unit increase in the score (p < 0.0001) and each 15 g/day increase in alcohol consumption was associated with a 0.41 (95%CI: 0.18, 0.63) unit increase in the score (p = 0.0004). Family history of breast cancer, age at menarche, and physical activity were not associated with the score. Reproductive breast cancer risk factors were not associated with elevated levels of multiple endogenous hormones, whereas anthropometric and lifestyle factors, particularly BMI and alcohol consumption, tended to be associated with higher levels of multiple hormones.
Motl, Robert W; McAuley, Edward; Wynn, Daniel; Sandroff, Brian; Suh, Yoojin
2013-03-01
Physical activity and self-efficacy represent behavioral and psychological factors, respectively, that are compromised in persons with multiple sclerosis (MS), but might be modifiable through intervention and result in better health-related quality of life (HRQOL). The present study adopted a panel research design and examined the associations between individual-level changes in physical activity, self-efficacy, and HRQOL over a one-year period in persons with MS. The sample consisted of 269 persons with relapsing-remitting MS who completed the Godin Leisure-Time Questionnaire (GLTEQ), Multiple Sclerosis Self-Efficacy (MSSE) Scale, and Multiple Sclerosis Quality of Life-29 (MSIS-29) Scale on two occasions that were separated by 1 year. The data were analyzed using panel analysis in Mplus 3.0. The initial panel analysis indicated that individual-level change in physical activity was associated with individual-level change in both physical and psychological HRQOL. The subsequent panel analysis indicated that (a) individual-level change in self-efficacy for functioning with MS was associated with individual-level change in physical HRQOL, whereas individual-level change in self-efficacy for control was associated with individual-level change in psychological HRQOL; (b) individual-level change in self-efficacy for functioning with MS, but not self-efficacy for control, mediated the association between individual-level change in physical activity and physical HRQOL; and (c) individual-level change in self-efficacy for controlling MS was the strongest predictor of individual-level change in HRQOL. Physical activity and self-efficacy both might be important targets of subsequent behavioral and self-management interventions for improving the HRQOL of persons with MS, although self-efficacy is seemingly more important than physical activity.
Schiff, Miriam; Pat-Horenczyk, Ruth; Ziv, Yuval; Brom, Danny
2017-09-01
This study examined whether maternal depression, mother-child relationships, and maternal perceived social support mediate the associations between child's exposure to multiple traumatic events and behavioral problems. We recruited a representative sample of 904 Israeli (Jewish and Arab) mothers and their 2- to 6-year-old children. Data collection was conducted through structured face-to-face interviews with the mothers between July and November 2011. All measures were completed by the mothers. We used the child's and mother's exposure to political violence questionnaires, Child Behavior Checklist (CBCL), a short version of the Parental Acceptance-Rejection Questionnaire (PARQ), the Center for Epidemiologic Studies Depression Scale (CES-D), and the Medical Outcomes Study (MOS) Social Support Survey. The research study model was tested using path analysis. The model showed a very good fit to the data, suggesting that maternal rejection, maternal depression, and social support play an important role in child's behavioral problems in the context of multiple traumatic events. Higher levels of maternal rejection were significantly associated with greater children behavior problems. Maternal rejection mediated the associations between maternal depressive symptoms and child's behavioral problems. Maternal perceived social support mediated the associations between child's exposure to multiple traumatic events and child's behavioral problems; child's exposure to multiple traumatic events was associated with lower levels of maternal perceived social support. In turn, lower levels of perceived social support were associated with higher levels of behavioral problems. In conclusion, in accordance with the "social stress framework," social support has a mediation role in the association between exposure to traumatic events and child's behavioral problems. Thus, enhancing social support to mothers to young children in the context of multiple traumatic events is essential for children resiliency.
Calomiris, J J; Armstrong, J L; Seidler, R J
1984-06-01
Bacterial isolates from the drinking water system of an Oregon coastal community were examined to assess the association of metal tolerance with multiple antibiotic resistance. Positive correlations between tolerance to high levels of Cu2+, Pb2+, and Zn2+ and multiple antibiotic resistance were noted among bacteria from distribution waters but not among bacteria from raw waters. Tolerances to higher levels of Al3+ and Sn2+ were demonstrated more often by raw water isolates which were not typically multiple antibiotic resistant. A similar incidence of tolerance to Cd2+ was demonstrated by isolates of both water types and was not associated with multiple antibiotic resistance. These results suggest that simultaneous selection phenomena occurred in distribution water for bacteria which exhibited unique patterns of tolerance to Cu2+, Pb2+, and Zn2+ and antibiotic resistance.
Genetic studies of plasma analytes identify novel potential biomarkers for several complex traits
Deming, Yuetiva; Xia, Jian; Cai, Yefei; Lord, Jenny; Del-Aguila, Jorge L.; Fernandez, Maria Victoria; Carrell, David; Black, Kathleen; Budde, John; Ma, ShengMei; Saef, Benjamin; Howells, Bill; Bertelsen, Sarah; Bailey, Matthew; Ridge, Perry G.; Hefti, Franz; Fillit, Howard; Zimmerman, Earl A.; Celmins, Dzintra; Brown, Alice D.; Carrillo, Maria; Fleisher, Adam; Reeder, Stephanie; Trncic, Nadira; Burke, Anna; Tariot, Pierre; Reiman, Eric M.; Chen, Kewei; Sabbagh, Marwan N.; Beiden, Christine M.; Jacobson, Sandra A.; Sirrel, Sherye A.; Doody, Rachelle S.; Villanueva-Meyer, Javier; Chowdhury, Munir; Rountree, Susan; Dang, Mimi; Kowall, Neil; Killiany, Ronald; Budson, Andrew E.; Norbash, Alexander; Johnson, Patricia Lynn; Green, Robert C.; Marshall, Gad; Johnson, Keith A.; Sperling, Reisa A.; Snyder, Peter; Salloway, Stephen; Malloy, Paul; Correia, Stephen; Bernick, Charles; Munic, Donna; Stern, Yaakov; Honig, Lawrence S.; Bell, Karen L.; Relkin, Norman; Chaing, Gloria; Ravdin, Lisa; Paul, Steven; Flashman, Laura A.; Seltzer, Marc; Hynes, Mary L.; Santulli, Robert B.; Bates, Vernice; Capote, Horacio; Rainka, Michelle; Friedl, Karl; Murali Doraiswamy, P.; Petrella, Jeffrey R.; Borges-Neto, Salvador; James, Olga; Wong, Terence; Coleman, Edward; Schwartz, Adam; Cellar, Janet S.; Levey, Allan L.; Lah, James J.; Behan, Kelly; Scott Turner, Raymond; Johnson, Kathleen; Reynolds, Brigid; Pearlson, Godfrey D.; Blank, Karen; Anderson, Karen; Obisesan, Thomas O.; Wolday, Saba; Allard, Joanne; Lerner, Alan; Ogrocki, Paula; Tatsuoka, Curtis; Fatica, Parianne; Farlow, Martin R.; Saykin, Andrew J.; Foroud, Tatiana M.; Shen, Li; Faber, Kelly; Kim, Sungeun; Nho, Kwangsik; Marie Hake, Ann; Matthews, Brandy R.; Brosch, Jared R.; Herring, Scott; Hunt, Cynthia; Albert, Marilyn; Onyike, Chiadi; D’Agostino, Daniel; Kielb, Stephanie; Graff-Radford, Neill R; Parfitt, Francine; Kendall, Tracy; Johnson, Heather; Petersen, Ronald; Jack, Clifford R.; Bernstein, Matthew; Borowski, Bret; Gunter, Jeff; Senjem, Matt; Vemuri, Prashanthi; Jones, David; Kantarci, Kejal; Ward, Chad; Mason, Sara S.; Albers, Colleen S.; Knopman, David; Johnson, Kris; Chertkow, Howard; Hosein, Chris; Mintzer, Jacob; Spicer, Kenneth; Bachman, David; Grossman, Hillel; Mitsis, Effie; Pomara, Nunzio; Hernando, Raymundo; Sarrael, Antero; Potter, William; Buckholtz, Neil; Hsiao, John; Kittur, Smita; Galvin, James E.; Cerbone, Brittany; Michel, Christina A.; Pogorelec, Dana M.; Rusinek, Henry; de Leon, Mony J; Glodzik, Lidia; De Santi, Susan; Johnson, Nancy; Chuang-Kuo; Kerwin, Diana; Bonakdarpour, Borna; Weintraub, Sandra; Grafman, Jordan; Lipowski, Kristine; Mesulam, Marek-Marsel; Scharre, Douglas W.; Kataki, Maria; Adeli, Anahita; Kaye, Jeffrey; Quinn, Joseph; Silbert, Lisa; Lind, Betty; Carter, Raina; Dolen, Sara; Borrie, Michael; Lee, T-Y; Bartha, Rob; Martinez, Walter; Villena, Teresa; Sadowsky, Carl; Khachaturian, Zaven; Ott, Brian R.; Querfurth, Henry; Tremont, Geoffrey; Frank, Richard; Fleischman, Debra; Arfanakis, Konstantinos; Shah, Raj C.; deToledo-Morrell, Leyla; Sorensen, Greg; Finger, Elizabeth; Pasternack, Stephen; Rachinsky, Irina; Drost, Dick; Rogers, John; Kertesz, Andrew; Furst, Ansgar J.; Chad, Stevan; Yesavage, Jerome; Taylor, Joy L.; Lane, Barton; Rosen, Allyson; Tinklenberg, Jared; Black, Sandra; Stefanovic, Bojana; Caldwell, Curtis; Robin Hsiung, Ging-Yuek; Mudge, Benita; Assaly, Michele; Fox, Nick; Schultz, Susan K.; Boles Ponto, Laura L.; Shim, Hyungsub; Ekstam Smith, Karen; Burns, Jeffrey M.; Swerdlow, Russell H.; Brooks, William M.; Marson, Daniel; Griffith, Randall; Clark, David; Geldmacher, David; Brockington, John; Roberson, Erik; Natelson Love, Marissa; DeCarli, Charles; Carmichael, Owen; Olichney, John; Maillard, Pauline; Fletcher, Evan; Nguyen, Dana; Preda, Andrian; Potkin, Steven; Mulnard, Ruth A.; Thai, Gaby; McAdams-Ortiz, Catherine; Landau, Susan; Jagust, William; Apostolova, Liana; Tingus, Kathleen; Woo, Ellen; Silverman, Daniel H.S.; Lu, Po H.; Bartzokis, George; Thompson, Paul; Donohue, Michael; Thomas, Ronald G.; Walter, Sarah; Gessert, Devon; Brewer, James; Vanderswag, Helen; Sather, Tamie; Jiminez, Gus; Balasubramanian, Archana B.; Mason, Jennifer; Sim, Iris; Aisen, Paul; Davis, Melissa; Morrison, Rosemary; Harvey, Danielle; Thal, Lean; Beckett, Laurel; Neylan, Thomas; Finley, Shannon; Weiner, Michael W.; Hayes, Jacqueline; Rosen, Howard J.; Miller, Bruce L.; Perry, David; Massoglia, Dino; Brawman-Mentzer, Olga; Schuff, Norbert; Smith, Charles D.; Hardy, Peter; Sinha, Partha; Oates, Elizabeth; Conrad, Gary; Koeppe, Robert A.; Lord, Joanne L.; Heidebrink, Judith L.; Arnold, Steven E.; Karlawish, Jason H.; Wolk, David; Clark, Christopher M.; Trojanowki, John Q.; Shaw, Leslie M.; Lee, Virginia; Korecka, Magdalena; Figurski, Michal; Toga, Arthur W.; Crawford, Karen; Neu, Scott; Schneider, Lon S.; Pawluczyk, Sonia; Beccera, Mauricio; Teodoro, Liberty; Spann, Bryan M.; Womack, Kyle; Mathews, Dana; Quiceno, Mary; Foster, Norm; Montine, Tom; Fruehling, J. Jay; Harding, Sandra; Johnson, Sterling; Asthana, Sanjay; Carlsson, Cynthia M.; Petrie, Eric C.; Peskind, Elaine; Li, Gail; Porsteinsson, Anton P.; Goldstein, Bonnie S.; Martin, Kim; Makino, Kelly M.; Ismail, M. Saleem; Brand, Connie; Smith, Amanda; Ashok Raj, Balebail; Fargher, Kristin; Kuller, Lew; Mathis, Chet; Ann Oakley, Mary; Lopez, Oscar L.; Simpson, Donna M.; Sink, Kaycee M.; Gordineer, Leslie; Williamson, Jeff D.; Garg, Pradeep; Watkins, Franklin; Cairns, Nigel J.; Raichle, Marc; Morris, John C.; Householder, Erin; Taylor-Reinwald, Lisa; Holtzman, David; Ances, Beau; Carroll, Maria; Creech, Mary L.; Franklin, Erin; Mintun, Mark A.; Schneider, Stacy; Oliver, Angela; Duara, Ranjan; Varon, Daniel; Greig, Maria T.; Roberts, Peggy; Varma, Pradeep; MacAvoy, Martha G.; Carson, Richard E.; van Dyck, Christopher H.; Davies, Peter; Holtzman, David; Morris, John C.; Bales, Kelly; Pickering, Eve H.; Lee, Jin-Moo; Heitsch, Laura; Kauwe, John; Goate, Alison; Piccio, Laura; Cruchaga, Carlos
2016-01-01
Genome-wide association studies of 146 plasma protein levels in 818 individuals revealed 56 genome-wide significant associations (28 novel) with 47 analytes. Loci associated with plasma levels of 39 proteins tested have been previously associated with various complex traits such as heart disease, inflammatory bowel disease, Type 2 diabetes, and multiple sclerosis. These data suggest that these plasma protein levels may constitute informative endophenotypes for these complex traits. We found three potential pleiotropic genes: ABO for plasma SELE and ACE levels, FUT2 for CA19-9 and CEA plasma levels, and APOE for ApoE and CRP levels. We also found multiple independent signals in loci associated with plasma levels of ApoH, CA19-9, FetuinA, IL6r, and LPa. Our study highlights the power of biological traits for genetic studies to identify genetic variants influencing clinically relevant traits, potential pleiotropic effects, and complex disease associations in the same locus.
Calomiris, J J; Armstrong, J L; Seidler, R J
1984-01-01
Bacterial isolates from the drinking water system of an Oregon coastal community were examined to assess the association of metal tolerance with multiple antibiotic resistance. Positive correlations between tolerance to high levels of Cu2+, Pb2+, and Zn2+ and multiple antibiotic resistance were noted among bacteria from distribution waters but not among bacteria from raw waters. Tolerances to higher levels of Al3+ and Sn2+ were demonstrated more often by raw water isolates which were not typically multiple antibiotic resistant. A similar incidence of tolerance to Cd2+ was demonstrated by isolates of both water types and was not associated with multiple antibiotic resistance. These results suggest that simultaneous selection phenomena occurred in distribution water for bacteria which exhibited unique patterns of tolerance to Cu2+, Pb2+, and Zn2+ and antibiotic resistance. PMID:6742841
Unstable and Multiple Child Care Arrangements and Young Children’s Behavior
Pilarz, Alejandra Ros; Hill, Heather D.
2015-01-01
Growing evidence suggests that child care instability is associated with child behavior problems, but existing studies confound different types of instability; use small, convenience samples; and/or control insufficiently for selection into child care arrangements. This study uses survey and calendar data from the Fragile Families and Child Well-Being Study to estimate the associations between three different types of child care instability—long-term instability, multiplicity, and the use of back-up arrangements—and children’s internalizing, externalizing, and prosocial behaviors at age 3, controlling for a large number of child and family background characteristics. Long-term instability between birth and age 3, as measured in both the survey and calendar data, is associated with higher levels of externalizing behavior problems. Current multiplicity at age 3 (as measured by survey data) is associated with higher levels of both externalizing and internalizing behavior problems, but stable multiplicity over time (as measured using calendar data) is not. Finally, the use of back-up arrangements at age 3 is associated with higher levels of internalizing behaviors. We find no consistent differences in these results by the timing of instability, child gender, family income, or type of care. PMID:25635158
Yu, Cai-Xia; Zhang, Xiu-Zhen; Zhang, Keqin; Tang, Zihui
2015-12-09
The main aim of this study was to evaluate the association between education level and osteoporosis (OP) in general Chinese Men. We conducted a large-scale, community-based, cross-sectional study to investigate the association by using self-report questionnaire to assess education levels. The data of 1092 men were available for analysis in this study. Multiple regression models controlling for confounding factors to include education level were performed to explore the relationship between education level and OP. Positive correlations between education level and T-score of quantitative bone ultrasound (QUS-T score) were reported (β = 0.108, P value < 0.001). Multiple regression analysis indicated that the education level was independently and significantly associated with OP (P < 0.1 for all models). The men with lower education level had a higher prevalence of OP. The education level was independently and significantly associated with OP. The prevalence of OP was more frequent in Chinese men with lower education level. ClinicalTrials.gov Identifier: NCT02451397 ; date of registration: 05/28/2015).
The effects of competition on assisted reproductive technology outcomes.
Henne, Melinda B; Bundorf, M Kate
2010-04-01
To evaluate the relationship between competition among fertility clinics and assisted reproductive technology (ART) treatment outcomes, particularly multiple births. Using clinic-level data from 1995 to 2001, we examined the relationship between competition and clinic-level ART outcomes and practice patterns. National database registry. Clinics performing ART. The number of clinics within a 20-mile (32.19-km) radius of a given clinic. Clinic-level births, singleton births, and multiple births per ART cycle; multiple births per ART birth; average number of embryos transferred per cycle; and the proportion of cycles for women under age 35 years. The number of competing clinics is not strongly associated with ART birth and multiple birth rates. Relative to clinics with no competitors, the rate of multiple births per cycle is lower (-0.03 percentage points) only for clinics with more than 15 competitors. Embryo transfer practices are not statistically significantly associated with the number of competitors. Clinic-level competition is strongly associated with patient mix. The proportion of cycles for patients under 35 years old is 6.4 percentage points lower for clinics with more than 15 competitors than for those with no competitors. Competition among fertility clinics does not appear to increase rates of multiple births from ART by promoting more aggressive embryo transfer decisions. Copyright 2010 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.Published by Elsevier Inc.
Gardner, Margo; Martin, Anne; Brooks-Gunn, Jeanne
2011-01-01
In a sample of urban youth (N = 1,070), we examined the links between primary caregiver affect (i.e., warmth and hostility) and two measures of sexual behavior in adolescence – early sexual initiation and sex with multiple partners. We also examined the extent to which neighborhood disadvantage moderated associations between caregiver affect and adolescent sexual behavior. We found that caregiver hostility was positively associated with early sex and sex with multiple partners in neighborhoods characterized by high levels of disadvantage, but inversely associated with both sex outcomes in neighborhoods characterized by low levels of disadvantage. Caregiver warmth, on the other hand, was inversely associated with early sexual initiation and sex with multiple partners in all neighborhoods regardless of neighborhood disadvantage. PMID:22408364
Axonal loss in the multiple sclerosis spinal cord revisited.
Petrova, Natalia; Carassiti, Daniele; Altmann, Daniel R; Baker, David; Schmierer, Klaus
2018-05-01
Preventing chronic disease deterioration is an unmet need in people with multiple sclerosis, where axonal loss is considered a key substrate of disability. Clinically, chronic multiple sclerosis often presents as progressive myelopathy. Spinal cord cross-sectional area (CSA) assessed using MRI predicts increasing disability and has, by inference, been proposed as an indirect index of axonal degeneration. However, the association between CSA and axonal loss, and their correlation with demyelination, have never been systematically investigated using human post mortem tissue. We extensively sampled spinal cords of seven women and six men with multiple sclerosis (mean disease duration= 29 years) and five healthy controls to quantify axonal density and its association with demyelination and CSA. 396 tissue blocks were embedded in paraffin and immuno-stained for myelin basic protein and phosphorylated neurofilaments. Measurements included total CSA, areas of (i) lateral cortico-spinal tracts, (ii) gray matter, (iii) white matter, (iv) demyelination, and the number of axons within the lateral cortico-spinal tracts. Linear mixed models were used to analyze relationships. In multiple sclerosis CSA reduction at cervical, thoracic and lumbar levels ranged between 19 and 24% with white (19-24%) and gray (17-21%) matter atrophy contributing equally across levels. Axonal density in multiple sclerosis was lower by 57-62% across all levels and affected all fibers regardless of diameter. Demyelination affected 24-48% of the gray matter, most extensively at the thoracic level, and 11-13% of the white matter, with no significant differences across levels. Disease duration was associated with reduced axonal density, however not with any area index. Significant association was detected between focal demyelination and decreased axonal density. In conclusion, over nearly 30 years multiple sclerosis reduces axonal density by 60% throughout the spinal cord. Spinal cord cross sectional area, reduced by about 20%, appears to be a poor predictor of axonal density. © 2017 The Authors. Brain Pathology published by John Wiley & Sons Ltd on behalf of International Society of Neuropathology.
Manda, Prashanti; McCarthy, Fiona; Bridges, Susan M
2013-10-01
The Gene Ontology (GO), a set of three sub-ontologies, is one of the most popular bio-ontologies used for describing gene product characteristics. GO annotation data containing terms from multiple sub-ontologies and at different levels in the ontologies is an important source of implicit relationships between terms from the three sub-ontologies. Data mining techniques such as association rule mining that are tailored to mine from multiple ontologies at multiple levels of abstraction are required for effective knowledge discovery from GO annotation data. We present a data mining approach, Multi-ontology data mining at All Levels (MOAL) that uses the structure and relationships of the GO to mine multi-ontology multi-level association rules. We introduce two interestingness measures: Multi-ontology Support (MOSupport) and Multi-ontology Confidence (MOConfidence) customized to evaluate multi-ontology multi-level association rules. We also describe a variety of post-processing strategies for pruning uninteresting rules. We use publicly available GO annotation data to demonstrate our methods with respect to two applications (1) the discovery of co-annotation suggestions and (2) the discovery of new cross-ontology relationships. Copyright © 2013 The Authors. Published by Elsevier Inc. All rights reserved.
Matute-Blanch, Clara; Villar, Luisa M; Álvarez-Cermeño, José C; Rejdak, Konrad; Evdoshenko, Evgeniy; Makshakov, Gleb; Nazarov, Vladimir; Lapin, Sergey; Midaglia, Luciana; Vidal-Jordana, Angela; Drulovic, Jelena; García-Merino, Antonio; Sánchez-López, Antonio J; Havrdova, Eva; Saiz, Albert; Llufriu, Sara; Alvarez-Lafuente, Roberto; Schroeder, Ina; Zettl, Uwe K; Galimberti, Daniela; Ramió-Torrentà, Lluís; Robles, René; Quintana, Ester; Hegen, Harald; Deisenhammer, Florian; Río, Jordi; Tintoré, Mar; Sánchez, Alex; Montalban, Xavier; Comabella, Manuel
2018-04-01
The prognostic role of cerebrospinal fluid molecular biomarkers determined in early pathogenic stages of multiple sclerosis has yet to be defined. In the present study, we aimed to investigate the prognostic value of chitinase 3 like 1 (CHI3L1), neurofilament light chain, and oligoclonal bands for conversion to clinically isolated syndrome and to multiple sclerosis in 75 patients with radiologically isolated syndrome. Cerebrospinal fluid levels of CHI3L1 and neurofilament light chain were measured by enzyme-linked immunosorbent assay. Uni- and multivariable Cox regression models including as covariates age at diagnosis of radiologically isolated syndrome, number of brain lesions, sex and treatment were used to investigate associations between cerebrospinal fluid CHI3L1 and neurofilament light chain levels and time to conversion to clinically isolated syndrome and multiple sclerosis. Neurofilament light chain levels and oligoclonal bands were independent risk factors for the development of clinically isolated syndrome (hazard ratio = 1.02, P = 0.019, and hazard ratio = 14.7, P = 0.012, respectively) and multiple sclerosis (hazard ratio = 1.03, P = 0.003, and hazard ratio = 8.9, P = 0.046, respectively). The best cut-off to classify cerebrospinal fluid neurofilament light chain levels into high and low was 619 ng/l, and high neurofilament light chain levels were associated with a trend to shorter time to clinically isolated syndrome (P = 0.079) and significant shorter time to multiple sclerosis (P = 0.017). Similarly, patients with radiologically isolated syndrome presenting positive oligoclonal bands converted faster to clinically isolated syndrome and multiple sclerosis (P = 0.005 and P = 0.008, respectively). The effects of high neurofilament light chain levels shortening time to clinically isolated syndrome and multiple sclerosis were more pronounced in radiologically isolated syndrome patients with ≥37 years compared to younger patients. Cerebrospinal fluid CHI3L1 levels did not influence conversion to clinically isolated syndrome and multiple sclerosis in radiologically isolated syndrome patients. Overall, these findings suggest that cerebrospinal neurofilament light chain levels and oligoclonal bands are independent predictors of clinical conversion in patients with radiologically isolated syndrome. The association with a faster development of multiple sclerosis reinforces the importance of cerebrospinal fluid analysis in patients with radiologically isolated syndrome.
Effect of Air Pollution on Exacerbations of Bronchiectasis in Badalona, Spain, 2008-2016.
Garcia-Olivé, Ignasi; Stojanovic, Zoran; Radua, Joaquim; Rodriguez-Pons, Laura; Martinez-Rivera, Carlos; Ruiz Manzano, Juan
2018-05-17
Air pollution has been widely associated with respiratory diseases. Nevertheless, the association between air pollution and exacerbations of bronchiectasis has been less studied. To analyze the effect of air pollution on exacerbations of bronchiectasis. This was a retrospective observational study conducted in Badalona. The number of daily hospital admissions and emergency room visits related to exacerbation of bronchiectasis (ICD-9 code 494.1) between 2008 and 2016 was obtained. We used simple Poisson regressions to test the effects of daily mean temperature, SO2, NO2, CO, and PM10 levels on bronchiectasis-related emergencies and hospitalizations on the same day and 1-4 days after. All p values were corrected for multiple comparisons. SO2 was significantly associated with an increase in the number of hospitalizations (lags 0, 1, 2, and 3). None of these associations remained significant after correcting for multiple comparisons. The number of emergency room visits was associated with higher levels of SO2 (lags 0-4). After correcting for multiple comparisons, the association between emergency room visits and SO2 levels was statistically significant for lag 0 (p = 0.043), lag 1 (p = 0.018), and lag 3 (p = 0.050). The number of emergency room visits for exacerbation of bronchiectasis is associated with higher levels of SO2. © 2018 S. Karger AG, Basel.
Methods for meta-analysis of multiple traits using GWAS summary statistics.
Ray, Debashree; Boehnke, Michael
2018-03-01
Genome-wide association studies (GWAS) for complex diseases have focused primarily on single-trait analyses for disease status and disease-related quantitative traits. For example, GWAS on risk factors for coronary artery disease analyze genetic associations of plasma lipids such as total cholesterol, LDL-cholesterol, HDL-cholesterol, and triglycerides (TGs) separately. However, traits are often correlated and a joint analysis may yield increased statistical power for association over multiple univariate analyses. Recently several multivariate methods have been proposed that require individual-level data. Here, we develop metaUSAT (where USAT is unified score-based association test), a novel unified association test of a single genetic variant with multiple traits that uses only summary statistics from existing GWAS. Although the existing methods either perform well when most correlated traits are affected by the genetic variant in the same direction or are powerful when only a few of the correlated traits are associated, metaUSAT is designed to be robust to the association structure of correlated traits. metaUSAT does not require individual-level data and can test genetic associations of categorical and/or continuous traits. One can also use metaUSAT to analyze a single trait over multiple studies, appropriately accounting for overlapping samples, if any. metaUSAT provides an approximate asymptotic P-value for association and is computationally efficient for implementation at a genome-wide level. Simulation experiments show that metaUSAT maintains proper type-I error at low error levels. It has similar and sometimes greater power to detect association across a wide array of scenarios compared to existing methods, which are usually powerful for some specific association scenarios only. When applied to plasma lipids summary data from the METSIM and the T2D-GENES studies, metaUSAT detected genome-wide significant loci beyond the ones identified by univariate analyses. Evidence from larger studies suggest that the variants additionally detected by our test are, indeed, associated with lipid levels in humans. In summary, metaUSAT can provide novel insights into the genetic architecture of a common disease or traits. © 2017 WILEY PERIODICALS, INC.
Văcăraş, Vitalie; Major, Zoltán Zsigmond; Buzoianu, Anca Dana
Our main purpose was to investigate if the chronic treatment with the disease-modifying drug natalizumab shows quantifiable effect on BDNF levels in multiple sclerosis patients. BDNF plasma concentration was evaluated using enzyme-linked immunosorbent assay in healthy individuals, not treated multiple sclerosis patients and patients treated with natalizumab. Multiple sclerosis patients have a significantly lower amount of peripheral BDNF than healthy individuals. Patients treated with natalizumab have significantly higher BDNF levels than not treated patients. Chronic natalizumab treatment is associated with significantly increased plasma BDNF concentration in multiple sclerosis. Copyright © 2017 Polish Neurological Society. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.
High level of CA 125 due to large endometrioma.
Phupong, Vorapong; Chen, Orawan; Ultchaswadi, Pornthip
2004-09-01
CA 125 is a tumor-associated antigen. Its high levels are usually associated with ovarian malignancies, whereas smaller increases in the levels were associated with benign gynecologic conditions. The authors report a high level of CA 125 in a case of large ovarian endometrioma. A 45-year-old nulliparous Thai woman, presented with an increase of her abdominal girth for 7 months. Transabdominal ultrasonogram demonstrated a large ovarian cyst and multiple small leiomyoma uteri, and serum CA 125 level was 1,006 U/ml. The preoperative diagnosis was ovarian cancer with leiomyoma uteri. Exploratory laparotomy was performed. There were a large right ovarian endometrioma, small left ovarian endometrioma and multiple small leiomyoma. Total abdominal hysterectomy and bilateral salpingo-oophorectomy was performed and histopathology confirmed the diagnosis of endometrioma and leiomyoma. The serum CA 125 level declined to non-detectable at the 4th week. She was well at discharge and throughout her 4th week follow-up period Although a very high level of CA 125 is associated with a malignant process, it can also be found in benign conditions such as a large endometrioma. The case emphasizes the association of high levels of CA 125 with benign gynecologic conditions.
A Matter of Timing: Developmental Theories of Romantic Involvement and Psychosocial Adjustment
Furman, Wyndol; Collibee, Charlene
2014-01-01
The present study compared two theories of the association between romantic involvement and adjustment—a social timetable theory and a developmental task theory. We examined seven waves of longitudinal data on a community based sample of 200 participants (M age Wave 1 = 15 years, 10 months). In each wave, multiple measures of substance use, externalizing symptoms, and internalizing symptoms were gathered, typically from multiple reporters. Multilevel modeling revealed that greater levels of romantic involvement in adolescence were associated with higher levels of substance use and externalizing symptoms, but became associated with lower levels in adulthood. Similarly, having a romantic partner was associated with greater levels of substance use, externalizing symptoms, and internalizing symptoms in adolescence, but was associated with lower levels in young adulthood. The findings were not consistent with a social timetable theory, which predicts that nonnormative involvement is associated with poor adjustment. Instead, the findings are consistent with a developmental task theory which predicts that precocious romantic involvement undermines development and adaptation, but when romantic involvement becomes a salient developmental task in adulthood, it is associated with positive adjustment. Discussion focuses on the processes that may underlie the changing nature of the association between romantic involvement and adjustment. PMID:24703413
Gene- and pathway-based association tests for multiple traits with GWAS summary statistics.
Kwak, Il-Youp; Pan, Wei
2017-01-01
To identify novel genetic variants associated with complex traits and to shed new insights on underlying biology, in addition to the most popular single SNP-single trait association analysis, it would be useful to explore multiple correlated (intermediate) traits at the gene- or pathway-level by mining existing single GWAS or meta-analyzed GWAS data. For this purpose, we present an adaptive gene-based test and a pathway-based test for association analysis of multiple traits with GWAS summary statistics. The proposed tests are adaptive at both the SNP- and trait-levels; that is, they account for possibly varying association patterns (e.g. signal sparsity levels) across SNPs and traits, thus maintaining high power across a wide range of situations. Furthermore, the proposed methods are general: they can be applied to mixed types of traits, and to Z-statistics or P-values as summary statistics obtained from either a single GWAS or a meta-analysis of multiple GWAS. Our numerical studies with simulated and real data demonstrated the promising performance of the proposed methods. The methods are implemented in R package aSPU, freely and publicly available at: https://cran.r-project.org/web/packages/aSPU/ CONTACT: weip@biostat.umn.eduSupplementary information: Supplementary data are available at Bioinformatics online. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.
Metzger, Aude; Le Bars, Emmanuelle; Deverdun, Jeremy; Molino, François; Maréchal, Bénédicte; Picot, Marie-Christine; Ayrignac, Xavier; Carra, Clarisse; Bauchet, Luc; Krainik, Alexandre; Labauge, Pierre; Menjot de Champfleur, Nicolas
2018-03-01
The link between cerebral vasoreactivity and cognitive status in multiple sclerosis remains unclear. The aim of the present study was to investigate a potential decrease of cerebral vasoreactivity in multiple sclerosis patients and correlate it with cognitive status. Thirty-three patients with multiple sclerosis (nine progressive and 24 remitting forms, median age: 39 years, 12 males) and 22 controls underwent MRI with a hypercapnic challenge to assess cerebral vasoreactivity and a neuropsychological assessment. Cerebral vasoreactivity, measured as the cerebral blood flow percent increase normalised by end-tidal carbon dioxide variation, was assessed globally and by regions of interest using the blood oxygen level-dependent technique. Non-parametric statistics tests were used to assess differences between groups, and associations were estimated using linear models. Cerebral vasoreactivity was lower in patients with cognitive impairment than in cognitively normal patients (p=0.004) and was associated with education level in patients (R 2 = 0.35; p = 0.047). There was no decrease in cerebral vasoreactivity between patients and controls. Cognitive impairment in multiple sclerosis may be mediated through decreased cerebral vasoreactivity. Cerebral vasoreactivity could therefore be considered as a marker of cognitive decline in multiple sclerosis. • Cerebral vasoreactivity does not differ between multiple sclerosis patients and controls. • Cerebral vasoreactivity measure is linked to cognitive impairment in multiple sclerosis. • Cerebral vasoreactivity is linked to level of education in multiple sclerosis.
Genetic variants are major determinants of CSF antibody levels in multiple sclerosis
Pauwels, Ine; Gustavsen, Marte W.; van Son, Brechtje; Hilven, Kelly; Bos, Steffan D.; Celius, Elisabeth Gulowsen; Berg-Hansen, Pål; Aarseth, Jan; Myhr, Kjell-Morten; D’Alfonso, Sandra; Barizzone, Nadia; Leone, Maurizio A.; Martinelli Boneschi, Filippo; Sorosina, Melissa; Liberatore, Giuseppe; Kockum, Ingrid; Olsson, Tomas; Hillert, Jan; Alfredsson, Lars; Bedri, Sahl Khalid; Hemmer, Bernhard; Buck, Dorothea; Berthele, Achim; Knier, Benjamin; Biberacher, Viola; van Pesch, Vincent; Sindic, Christian; Bang Oturai, Annette; Søndergaard, Helle Bach; Sellebjerg, Finn; Jensen, Poul Erik H.; Comabella, Manuel; Montalban, Xavier; Pérez-Boza, Jennifer; Malhotra, Sunny; Lechner-Scott, Jeannette; Broadley, Simon; Slee, Mark; Taylor, Bruce; Kermode, Allan G.; Gourraud, Pierre-Antoine; Sawcer, Stephen J.; Andreassen, Bettina Kullle; Dubois, Bénédicte; Harbo, Hanne F.
2015-01-01
Immunological hallmarks of multiple sclerosis include the production of antibodies in the central nervous system, expressed as presence of oligoclonal bands and/or an increased immunoglobulin G index—the level of immunoglobulin G in the cerebrospinal fluid compared to serum. However, the underlying differences between oligoclonal band-positive and -negative patients with multiple sclerosis and reasons for variability in immunoglobulin G index are not known. To identify genetic factors influencing the variation in the antibody levels in the cerebrospinal fluid in multiple sclerosis, we have performed a genome-wide association screen in patients collected from nine countries for two traits, presence or absence of oligoclonal bands (n = 3026) and immunoglobulin G index levels (n = 938), followed by a replication in 3891 additional patients. We replicate previously suggested association signals for oligoclonal band status in the major histocompatibility complex region for the rs9271640*A-rs6457617*G haplotype, correlated with HLA-DRB1*1501, and rs34083746*G, correlated with HLA-DQA1*0301 (P comparing two haplotypes = 8.88 × 10−16). Furthermore, we identify a novel association signal of rs9807334, near the ELAC1/SMAD4 genes, for oligoclonal band status (P = 8.45 × 10−7). The previously reported association of the immunoglobulin heavy chain locus with immunoglobulin G index reaches strong evidence for association in this data set (P = 3.79 × 10−37). We identify two novel associations in the major histocompatibility complex region with immunoglobulin G index: the rs9271640*A-rs6457617*G haplotype (P = 1.59 × 10−22), shared with oligoclonal band status, and an additional independent effect of rs6457617*G (P = 3.68 × 10−6). Variants identified in this study account for up to 2-fold differences in the odds of being oligoclonal band positive and 7.75% of the variation in immunoglobulin G index. Both traits are associated with clinical features of disease such as female gender, age at onset and severity. This is the largest study population so far investigated for the genetic influence on antibody levels in the cerebrospinal fluid in multiple sclerosis, including 6950 patients. We confirm that genetic factors underlie these antibody levels and identify both the major histocompatibility complex and immunoglobulin heavy chain region as major determinants. PMID:25616667
Barton, Allen W; Kogan, Steven M; Cho, Junhan; Brown, Geoffrey L
2015-12-01
This study was designed to examine the associations of biological father and social father involvement during childhood with African American young men's development and engagement in risk behaviors. With a sample of 505 young men living in the rural South of the United States, a dual mediation model was tested in which retrospective reports of involvement from biological fathers and social fathers were linked to young men's substance misuse and multiple sexual partnerships through men's relational schemas and future expectations. Results from structural equation modeling indicated that levels of involvement from biological fathers and social fathers predicted young men's relational schemas; only biological fathers' involvement predicted future expectations. In turn, future expectations predicted levels of substance misuse, and negative relational schemas predicted multiple sexual partnerships. Biological fathers' involvement evinced significant indirect associations with young men's substance misuse and multiple sexual partnerships through both schemas and expectations; social fathers' involvement exhibited an indirect association with multiple sexual partnerships through relational schemas. Findings highlight the unique influences of biological fathers and social fathers on multiple domains of African American young men's psychosocial development that subsequently render young men more or less likely to engage in risk behaviors.
Active Learning in the Middle Grades Classroom: Overcoming the Barriers to Implementation
ERIC Educational Resources Information Center
Edwards, Susan
2015-01-01
The Association for Middle Level Education advocates for instruction that incorporates active learning and multiple learning approaches in middle grades classrooms. The aim of this qualitative study was to examine middle level teachers who are able to implement active learning and multiple learning approaches within the standardized testing and…
Wu, Lin-Lin; Gong, Wei; Shen, Si-Peng; Wang, Zhong-He; Yao, Jia-Xi; Wang, Jun; Yu, Jing; Gao, Rong; Wu, Gang
2017-09-01
Excessive metal exposure has been recognized as one of the detrimental factors for brain damage. However, the potential adverse effects induced by heavy metals on monoamine neurotransmitter pathways remains poorly understood. Our study aimed to investigate the possible association between metal exposure and neurotransmitter metabolism. By a cross-sectional investigation, 224 electroplating workers and 213 non-electroplating exposure workers were recruited in the exposure and control groups. Metal exposure levels were analyzed using inductively-coupled plasma mass spectrometry and monoamine neurotransmitter pathway metabolites were measured by ultra-performance liquid chromatography tandem mass spectrometry in human urine samples. Multivariate linear regression model was used to assess the dose-response relationships of urinary metals and neurotransmitter pathway metabolites. Significant dose-dependent trends of urinary vanadium quartiles with all metabolites were observed, and the trends demonstrated significance after multiple testing correction. It also showed that urinary chromium levels were significantly associated with decreased serotonin level and cadmium was positively associated with norepinephrine and epinephrine. In addition, arsenic was positively associated with tryptophan, serotonin, dopamine and norepinephrine. Iron was positively associated with increased homovanillic acid (HVA) and epinephrine while nickel was negatively associated with increased epinephrine levels. Zinc was positively related to tryptophan, kynurenin (KYN), 5-hydroxyindole acetic acid (5-HIAA), dopamine, HVA and norepinephrine. There was no significant association between urinary copper with any other metabolites after adjusting of multiple metal models. Metal exposure may be associated with neurotransmitter metabolism disturbances. The present work is expected to provide some support in the prevention and management of metal-associated neurological diseases. Copyright © 2017. Published by Elsevier Ltd.
A population-based study on the association between rheumatoid arthritis and voice problems.
Hah, J Hun; An, Soo-Youn; Sim, Songyong; Kim, So Young; Oh, Dong Jun; Park, Bumjung; Kim, Sung-Gyun; Choi, Hyo Geun
2016-07-01
The objective of this study was to investigate whether rheumatoid arthritis increases the frequency of organic laryngeal lesions and the subjective voice complaint rate in those with no organic laryngeal lesion. We performed a cross-sectional study using the data from 19,368 participants (418 rheumatoid arthritis patients and 18,950 controls) of the 2008-2011 Korea National Health and Nutrition Examination Survey. The associations between rheumatoid arthritis and organic laryngeal lesions/subjective voice complaints were analyzed using simple/multiple logistic regression analysis with complex sample adjusting for confounding factors, including age, sex, smoking status, stress level, and body mass index, which could provoke voice problems. Vocal nodules, vocal polyp, and vocal palsy were not associated with rheumatoid arthritis in a multiple regression analysis, and only laryngitis showed a positive association (adjusted odds ratio, 1.59; 95 % confidence interval, 1.01-2.52; P = 0.047). Rheumatoid arthritis was associated with subjective voice discomfort in a simple regression analysis, but not in a multiple regression analysis. Participants with rheumatoid arthritis were older, more often female, and had higher stress levels than those without rheumatoid arthritis. These factors were associated with subjective voice complaints in both simple and multiple regression analyses. Rheumatoid arthritis was not associated with organic laryngeal diseases except laryngitis. Rheumatoid arthritis did not increase the odds ratio for subjective voice complaints. Voice problems in participants with rheumatoid arthritis originated from the characteristics of the rheumatoid arthritis group (higher mean age, female sex, and stress level) rather than rheumatoid arthritis itself.
Cheng, Hui G; Alshaarawy, Omayma; Cantave, Marven D; Anthony, James C
2016-10-01
Exposures to antioxidants (AO) are associated with levels of C-reactive protein (CRP), but the pattern of evidence is mixed, due in part to studying each potential AO, one at a time, when multiple AO exposures might affect CRP levels. By studying multiple AO via a composite indicator approach, we estimate the degree to which serum CRP level is associated with serum AO level. Standardised field survey protocols for the US National Health and Nutrition Examination Survey (NHANES) 2003-2006 yielded nationally representative cross-sectional samples of adults aged 20 years and older (n 8841). NHANES latex-enhanced nephelometry quantified serum CRP levels. Liquid chromatography quantified serum concentrations of vitamins A, E and C and carotenoids. Using structural equations, we regressed CRP level on AO levels, and derived a summary estimate for a composite of these potential antioxidants (CPA), with covariates held constant. The association linking CPA with CRP was inverse, stronger for slightly elevated CRP (1·8≤CRP<10 mg/l; slope= -1·08; 95 % CI -1·39, -0·77) and weaker for highly elevated CRP (≥10 mg/l; slope= -0·52; 95 % CI -0·68, -0·35), with little change when covariates were added. Vitamins A and C, as well as lutein+zeaxanthin, were prominent contributors to the composite. In these cross-sectional data studied via a composite indicator approach, the CPA level and the CRP level were inversely related. The stage is set for more confirmatory longitudinal or intervention research on multiple vitamins. The composite indicator approach might be most useful in epidemiology when several exposure constructs are too weakly inter-correlated to be studied via formal measurement models for underlying latent dimensions.
Harley, Amy E; Sapp, Amy L; Li, Yi; Marino, Miguel; Quintiliani, Lisa M; Sorensen, Glorian
2013-03-01
Multiple modifiable health behaviors contribute to the chronic diseases that are the leading causes of death in the USA. Disparities for meeting recommended health behavior guidelines exist across occupational classes and socioeconomic levels. The purpose of this paper was to investigate sociodemographic and social contextual predictors of multiple health behavior change in a worksite intervention. We analyzed data on four diet and exercise variables from an intervention trial with worksite-level randomization. Eight hundred forty-one employees had complete data from baseline (response rate = 84 %) and follow-up surveys (response rate = 77 %). Multilevel logistic regression estimated associations between least absolute shrinkage and selection operator-selected sociodemographic and social contextual predictor variables and the multiple health behavior change outcome (changing 2+ versus 0 behaviors). Gender, being married/partnered, and perceived discrimination were significantly associated with multiple health behavior change. Sociodemographic and social contextual factors predict multiple health behavior change and could inform the design and delivery of worksite interventions targeting multiple health behaviors.
Jo, Young Goun; Choi, Hyun Jung; Kim, Jung Chul; Cho, Young Nan; Kang, Jeong Hwa; Jin, Hye Mi; Kee, Seung Jung; Park, Yong Wook
2017-05-01
Mucosal-associated invariant T (MAIT) cells and natural killer T (NKT) cells are known to play important roles in autoimmunity, infectious diseases and cancers. However, little is known about the roles of these invariant T cells in multiple trauma. The purposes of this study were to examine MAIT and NKT cell levels in patients with multiple trauma and to investigate potential relationships between these cell levels and clinical parameters. The study cohort was composed of 14 patients with multiple trauma and 22 non-injured healthy controls (HCs). Circulating MAIT and NKT cell levels in the peripheral blood were measured by flow cytometry. The severity of injury was categorised according to the scoring systems, such as Acute Physiology and Chronic Health Evaluation (APACHE) II score, Simplified Acute Physiology Score (SAPS) II, and Injury Severity Score (ISS). Circulating MAIT and NKT cell numbers were significantly lower in multiple trauma patients than in HCs. Linear regression analysis showed that circulating MAIT cell numbers were significantly correlated with age, APACHE II, SAPS II, ISS category, hemoglobin, and platelet count. NKT cell numbers in the peripheral blood were found to be significantly correlated with APACHE II, SAPS II, and ISS category. This study shows numerical deficiencies of circulating MAIT cells and NKT cells in multiple trauma. In addition, these invariant T cell deficiencies were found to be associated with disease severity. These findings provide important information for predicting the prognosis of multiple trauma. © 2017 The Korean Academy of Medical Sciences.
Bjørnevik, Kjetil; Riise, Trond; Cortese, Marianna; Holmøy, Trygve; Kampman, Margitta T; Magalhaes, Sandra; Myhr, Kjell-Morten; Wolfson, Christina; Pugliatti, Maura
2016-01-01
Several recent studies have found a higher risk of multiple sclerosis (MS) among people with a low level of education. This has been suggested to reflect an effect of smoking and lower vitamin D status in the social class associated with lower levels of education. The objective of this paper is to investigate the association between level of education and MS risk adjusting for the known risk factors smoking, infectious mononucleosis, indicators of vitamin D levels and body size. Within the case-control study on Environmental Factors In MS (EnvIMS), 953 MS patients and 1717 healthy controls from Norway reported educational level and history of exposure to putative environmental risk factors. Higher level of education were associated with decreased MS risk (p trend = 0.001) with an OR of 0.53 (95% CI 0.41-0.68) when comparing those with the highest and lowest level of education. This association was only moderately reduced after adjusting for known risk factors (OR 0.61, 95% CI 0.44-0.83). The estimates remained similar when cases with disease onset before age 28 were excluded. These findings suggest that factors related to lower socioeconomic status other than established risk factors are associated with MS risk. © The Author(s), 2015.
Bjørnevik, Kjetil; Riise, Trond; Cortese, Marianna; Holmøy, Trygve; Kampman, Margitta T; Magalhaes, Sandra; Myhr, Kjell-Morten; Wolfson, Christina; Pugliatti, Maura
2016-01-01
Background: Several recent studies have found a higher risk of multiple sclerosis (MS) among people with a low level of education. This has been suggested to reflect an effect of smoking and lower vitamin D status in the social class associated with lower levels of education. Objective: The objective of this paper is to investigate the association between level of education and MS risk adjusting for the known risk factors smoking, infectious mononucleosis, indicators of vitamin D levels and body size. Methods: Within the case-control study on Environmental Factors In MS (EnvIMS), 953 MS patients and 1717 healthy controls from Norway reported educational level and history of exposure to putative environmental risk factors. Results: Higher level of education were associated with decreased MS risk (p trend = 0.001) with an OR of 0.53 (95% CI 0.41–0.68) when comparing those with the highest and lowest level of education. This association was only moderately reduced after adjusting for known risk factors (OR 0.61, 95% CI 0.44–0.83). The estimates remained similar when cases with disease onset before age 28 were excluded. Conclusion: These findings suggest that factors related to lower socioeconomic status other than established risk factors are associated with MS risk. PMID:26014605
ERIC Educational Resources Information Center
Beyranevand, Matthew L.
2010-01-01
Although it is difficult to find any current literature that does not encourage use of multiple representations in mathematics classrooms, there has been very limited research that compared such practice to student achievement level on standardized tests. This study examined the associations between students' achievement levels and their (a)…
Multiple-Choice Exams: An Obstacle for Higher-Level Thinking in Introductory Science Classes
ERIC Educational Resources Information Center
Stanger-Hall, Kathrin F.
2012-01-01
Learning science requires higher-level (critical) thinking skills that need to be practiced in science classes. This study tested the effect of exam format on critical-thinking skills. Multiple-choice (MC) testing is common in introductory science courses, and students in these classes tend to associate memorization with MC questions and may not…
Versican and its associated molecules: potential diagnostic markers for multiple myeloma.
Gupta, Nidhi; Khan, Rehan; Kumar, Raman; Kumar, Lalit; Sharma, Alpana
2015-03-10
Multiple myeloma (MM) represents a malignancy of B-cells characterized by proliferation of malignant plasma cells in the bone marrow (BM). Versican (VCAN), an extracellular matrix (ECM) protein, appears to be involved in multiple processes in several cancers. Identifying optimum diagnostic markers and delineating its association with disease severity might be important for controlling MM. Expression of VCAN and its associated molecules (β-catenin, β1 integrin and FAK) were investigated in 60 subjects to evaluate their usefulness as diagnostic marker. Circulatory and molecular levels of above molecules were analyzed in their BM and Blood using ELISA, Q-PCR and western blotting along with their ROC curve analysis. Circulatory levels of VCAN, β-catenin and FAK were significantly higher in patients with varying significance in each stage. β-Catenin and FAK intracellular levels were significantly elevated in patients. mRNA levels of all molecules were significantly higher in BMMNCs while VCAN and β-catenin also showed increase in PBMCs. Upregulation of these molecules was also observed at protein level. ROC curve analysis for VCAN showed absolute combination of sensitivity and specificity for diagnosis in serum. Significant elevation of VCAN and its associated molecules imply their role in MM. Optimal sensitivity and specificity of VCAN might utilize its importance as potential marker for active disease. Copyright © 2015 Elsevier B.V. All rights reserved.
Endotoxemia Following Multiple Trauma: Risk Factors and Prognostic Implications.
Charbonney, Emmanuel; Tsang, Jennifer Y; Li, Yangmei; Klein, David; Duque, Patricia; Romaschin, Alexander; Marshall, John C
2016-02-01
To evaluate the prevalence and time course of systemic endotoxemia following severe multiple trauma, to define its risk factors, and to explore the correlation between post-trauma endotoxemia and organ dysfunction. Prospective single-center cohort study. Emergency department and ICU of adult tertiary care level I trauma center. Forty-eight severely injured (Injury Severity Score ≥ 16) patients, admitted to ICU within 24 hours of injury. None. Endotoxemia was not evident on initial presentation, but developed subsequently in 75% of patients, even in the absence of Gram-negative infection. Nonsurviving patients had higher endotoxin levels than survivors on day 1 (endotoxemia, 0.48 vs 0.28; p = 0.048). Shock at admission, or surgery within the first 48 hours after trauma, was associated with higher endotoxin levels and predicted subsequent maximal endotoxemia, after adjusting for other significant covariates. Maximal endotoxemia levels were higher in patients who developed organ dysfunction, reflected in a cumulative Multiple Organ Dysfunction Score greater than 25, and patients with an intermediate endotoxemia level (≥ 0.4) had more cardiovascular dysfunction. It is the first study to detect increasing levels of endotoxemia following multiple trauma. Shock and early surgery predict the development of endotoxemia; endotoxemia is particularly associated with cardiovascular dysfunction. However, Gram-negative infections are uncommon in these patients, suggesting that the gastrointestinal tract is the dominant reservoir of endotoxin. Endotoxin may be an appropriate therapeutic target in patients who have sustained severe multiple trauma.
Joint Identification of Genetic Variants for Physical Activity in Korean Population
Kim, Jayoun; Kim, Jaehee; Min, Haesook; Oh, Sohee; Kim, Yeonjung; Lee, Andy H.; Park, Taesung
2014-01-01
There has been limited research on genome-wide association with physical activity (PA). This study ascertained genetic associations between PA and 344,893 single nucleotide polymorphism (SNP) markers in 8842 Korean samples. PA data were obtained from a validated questionnaire that included information on PA intensity and duration. Metabolic equivalent of tasks were calculated to estimate the total daily PA level for each individual. In addition to single- and multiple-SNP association tests, a pathway enrichment analysis was performed to identify the biological significance of SNP markers. Although no significant SNP was found at genome-wide significance level via single-SNP association tests, 59 genetic variants mapped to 76 genes were identified via a multiple SNP approach using a bootstrap selection stability measure. Pathway analysis for these 59 variants showed that maturity onset diabetes of the young (MODY) was enriched. Joint identification of SNPs could enable the identification of multiple SNPs with good predictive power for PA and a pathway enriched for PA. PMID:25026172
Keshari, Pankaj K; Harbo, Hanne F; Myhr, Kjell-Morten; Aarseth, Jan H; Bos, Steffan D; Berge, Tone
2016-04-14
Multiple sclerosis is a chronic inflammatory, demyelinating disease of the central nervous system. Recent genome-wide studies have revealed more than 110 single nucleotide polymorphisms as associated with susceptibility to multiple sclerosis, but their functional contribution to disease development is mostly unknown. Consistent allelic imbalance was observed for rs907091 in IKZF3 and rs11609 in IQGAP1, which are in strong linkage disequilibrium with the multiple sclerosis associated single nucleotide polymorphisms rs12946510 and rs8042861, respectively. Using multiple sclerosis patients and healthy controls heterozygous for rs907091 and rs11609, we showed that the multiple sclerosis risk alleles at IKZF3 and IQGAP1 are expressed at higher levels as compared to the protective allele. Furthermore, individuals homozygous for the multiple sclerosis risk allele at IQGAP1 had a significantly higher total expression of IQGAP1 compared to individuals homozygous for the protective allele. Our data indicate a possible regulatory role for the multiple sclerosis-associated IKZF3 and IQGAP1 variants. We suggest that such cis-acting mechanisms may contribute to the multiple sclerosis association of single nucleotide polymorphisms at IKZF3 and IQGAP1.
Mora-Bautista, Víctor M; Mendoza-Rojas, Víctor; Contreras-García, Gustavo A
2017-06-01
Cornelia de Lange syndrome is a genetic disease characterized by distinctive facial features, failure to thrive, microcephaly and several malformations associated. Its main endocrinological features are anomalies of the genitalia. We present a 13-year-old boy, who suffered from complicated aspiration pneumonia and showed Cornelia de Lange syndrome phenotype, with global developmental delay, suction-swallowing abnormalities, short stature and abnormal genitalia associated. His bone age was delayed, so he underwent full endocrinological panel. Central hypothyroidism, growth hormone deficiency and low luteinizing hormone-follicle-stimulating hormone levels were observed and multiple pituitary hormone deficiencies diagnosis was made. Basal cortisol, adrenocorticotropic hormone and prolactin levels were normal. He received thyroid hormonal substitution. Multiple pituitary hormone deficiencies are an unusual feature of De Lange syndrome. We suggest evaluating all different endocrine axes in these patients. Sociedad Argentina de Pediatría.
Multiple metals predict prolactin and thyrotropin (TSH) levels in men
DOE Office of Scientific and Technical Information (OSTI.GOV)
Meeker, John D., E-mail: meekerj@umich.edu; Rossano, Mary G.; Protas, Bridget
2009-10-15
Exposure to a number of metals can affect neuroendocrine and thyroid signaling, which can result in adverse effects on development, behavior, metabolism, reproduction, and other functions. The present study assessed the relationship between metal concentrations in blood and serum prolactin (PRL) and thyrotropin (TSH) levels, markers of dopaminergic, and thyroid function, respectively, among men participating in a study of environmental influences on male reproductive health. Blood samples from 219 men were analyzed for concentrations of 11 metals and serum levels of PRL and TSH. In multiple linear regression models adjusted for age, BMI and smoking, PRL was inversely associated withmore » arsenic, cadmium, copper, lead, manganese, molybdenum, and zinc, but positively associated with chromium. Several of these associations (Cd, Pb, Mo) are consistent with limited studies in humans or animals, and a number of the relationships (Cr, Cu, Pb, Mo) remained when additionally considering multiple metals in the model. Lead and copper were associated with non-monotonic decrease in TSH, while arsenic was associated with a dose-dependent increase in TSH. For arsenic these findings were consistent with recent experimental studies where arsenic inhibited enzymes involved in thyroid hormone synthesis and signaling. More research is needed for a better understanding of the role of metals in neuroendocrine and thyroid function and related health implications.« less
Boonvisut, Supichaya; Nakayama, Kazuhiro; Makishima, Saho; Watanabe, Kazuhisa; Miyashita, Hiroshi; Lkhagvasuren, Munkhtulga; Kagawa, Yasuo; Iwamoto, Sadahiko
2016-01-13
The Neurocan-cartilage intermediate layer protein 2 (NCAN-CILP2) region forms a tight linkage disequilibrium (LD) block and is associated with plasma lipid levels and non-alcoholic fatty liver disease (NAFLD) in individuals of European descent but not in the Malay and Japanese ethnic groups. Recent genome-wide resequence studies identified a missense single-nucleotide polymorphism (SNP) (rs58542926) of the transmembrane 6 superfamily member 2 (TM6SF2) gene in the NCAN-CILP2 region related to hepatic triglyceride content. This study aims to analyze the influences of SNPs in this region on NAFLD and plasma lipid levels in the Asian and Pacific ethnic groups and to reveal the reasons behind positive and negative genetic associations dependent on ethnicity. Samples and characteristic data were collected from 3,013 Japanese, 119 Palauan, 947 Mongolian, 212 Thai and 401 Chinese people. Hepatic sonography data was obtained from the Japanese individuals. Genotyping data of five SNPs, rs58542926, rs735273, rs1009136, rs1858999, and rs16996148, were used to verify the effect on serum lipid levels by multiple linear regression, and the association with NAFLD in the Japanese population was examined by logistic regression analysis. rs58542926 showed significant association with the plasma triglyceride (TG) level in Japanese (P = 0.0009, effect size = 9.5 (± 3.25) mg/dl/allele) and Thai (P = 0.0008, effect size = 31.6 (± 11.7) mg/dl/allele) study subjects. In Mongolian individuals, there was a significant association of rs58542926 with total cholesterol level (P = 0.0003, 11.7 (± 3.2) mg/dl/allele) but not with TG level. In multiple comparisons in Chinese individuals, rs58542926 was weakly (P = 0.022) associated with TG levels, although the threshold for statistical significance was not reached. In Palauan individuals, there was no significant association with the studied SNPs. rs58542926 also showed significant association with Japanese NAFLD. The minor allele (t) increased NAFLD risk (OR 1.682, 95 % CI 1.289-2.196, p value 0.00013). This study confirmed the genetic association of missense SNP of TM6SF2, rs58542926, with plasma lipid levels in multiple East Asian ethnic groups and with NAFLD in Japanese individuals.
Handbook of aircraft noise metrics
NASA Technical Reports Server (NTRS)
Bennett, R. L.; Pearsons, K. S.
1981-01-01
Information is presented on 22 noise metrics that are associated with the measurement and prediction of the effects of aircraft noise. Some of the instantaneous frequency weighted sound level measures, such as A-weighted sound level, are used to provide multiple assessment of the aircraft noise level. Other multiple event metrics, such as day-night average sound level, were designed to relate sound levels measured over a period of time to subjective responses in an effort to determine compatible land uses and aid in community planning. The various measures are divided into: (1) instantaneous sound level metrics; (2) duration corrected single event metrics; (3) multiple event metrics; and (4) speech communication metrics. The scope of each measure is examined in terms of its: definition, purpose, background, relationship to other measures, calculation method, example, equipment, references, and standards.
Handbook of aircraft noise metrics
NASA Astrophysics Data System (ADS)
Bennett, R. L.; Pearsons, K. S.
1981-03-01
Information is presented on 22 noise metrics that are associated with the measurement and prediction of the effects of aircraft noise. Some of the instantaneous frequency weighted sound level measures, such as A-weighted sound level, are used to provide multiple assessment of the aircraft noise level. Other multiple event metrics, such as day-night average sound level, were designed to relate sound levels measured over a period of time to subjective responses in an effort to determine compatible land uses and aid in community planning. The various measures are divided into: (1) instantaneous sound level metrics; (2) duration corrected single event metrics; (3) multiple event metrics; and (4) speech communication metrics. The scope of each measure is examined in terms of its: definition, purpose, background, relationship to other measures, calculation method, example, equipment, references, and standards.
Langer-Gould, Annette; Lucas, Robyn; Xiang, Anny H; Chen, Lie H; Wu, Jun; Gonzalez, Edlin; Haraszti, Samantha; Smith, Jessica B; Quach, Hong; Barcellos, Lisa F
2018-02-27
Multiple sclerosis (MS) incidence and serum 25-hydroxyvitamin D (25OHD) levels vary by race/ethnicity. We examined the consistency of beneficial effects of 25OHD and/or sun exposure for MS risk across multiple racial/ethnic groups. We recruited incident MS cases and controls (blacks 116 cases/131 controls; Hispanics 183/197; whites 247/267) from the membership of Kaiser Permanente Southern California into the MS Sunshine Study to simultaneously examine sun exposure and 25OHD, accounting for genetic ancestry and other factors. Higher lifetime ultraviolet radiation exposure (a rigorous measure of sun exposure) was associated with a lower risk of MS independent of serum 25OHD levels in blacks (adjusted OR = 0.53, 95% CI = 0.31-0.83; p = 0.007) and whites (OR = 0.68, 95% CI = 0.48-0.94; p = 0.020) with a similar magnitude of effect that did not reach statistical significance in Hispanics (OR = 0.66, 95% CI = 0.42-1.04; p = 0.071). Higher serum 25OHD levels were associated with a lower risk of MS only in whites. No association was found in Hispanics or blacks regardless of how 25OHD was modeled. Lifetime sun exposure appears to reduce the risk of MS regardless of race/ethnicity. In contrast, serum 25OHD levels are not associated with MS risk in blacks or Hispanics. Our findings challenge the biological plausibility of vitamin D deficiency as causal for MS and call into question the targeting of specific serum 25OHD levels to achieve health benefits, particularly in blacks and Hispanics.
Chem I Supplement. Chemistry Related to Isolation of High-Level Nuclear Waste.
ERIC Educational Resources Information Center
Hoffman, Darleane C.; Choppin, Gregory R.
1986-01-01
Discusses some of the problems associated with the safe disposal of high-level nuclear wastes. Describes several waste disposal plans developed by various nations. Outlines the multiple-barrier concept of isolation in deep geological questions associated with the implementation of such a method. (TW)
Kwon, Jin-Woo; Choi, Jin A; La, Tae Yoon
2016-11-01
The aim of this article was to assess the associations of serum 25-hydroxyvitamin D [25(OH)D] and daily sun exposure time with myopia in Korean adults.This study is based on the Korea National Health and Nutrition Examination Survey (KNHANES) of Korean adults in 2010-2012; multiple logistic regression analyses were performed to examine the associations of serum 25(OH)D levels and daily sun exposure time with myopia, defined as spherical equivalent ≤-0.5D, after adjustment for age, sex, household income, body mass index (BMI), exercise, intraocular pressure (IOP), and education level. Also, multiple linear regression analyses were performed to examine the relationship between serum 25(OH)D levels with spherical equivalent after adjustment for daily sun exposure time in addition to the confounding factors above.Between the nonmyopic and myopic groups, spherical equivalent, age, IOP, BMI, waist circumference, education level, household income, and area of residence differed significantly (all P < 0.05). Compared with subjects with daily sun exposure time <2 hour, subjects with sun exposure time ≥2 to <5 hour, and those with sun exposure time ≥5 hour had significantly less myopia (P < 0.001). In addition, compared with subjects were categorized into quartiles of serum 25(OH)D, the higher quartiles had gradually lower prevalences of myopia after adjustment for confounding factors (P < 0.001). In multiple linear regression analyses, spherical equivalent was significantly associated with serum 25(OH)D concentration after adjustment for confounding factors (P = 0.002).Low serum 25(OH)D levels and shorter daily sun exposure time may be independently associated with a high prevalence of myopia in Korean adults. These data suggest a direct role for vitamin D in the development of myopia.
An Adaptive Association Test for Multiple Phenotypes with GWAS Summary Statistics.
Kim, Junghi; Bai, Yun; Pan, Wei
2015-12-01
We study the problem of testing for single marker-multiple phenotype associations based on genome-wide association study (GWAS) summary statistics without access to individual-level genotype and phenotype data. For most published GWASs, because obtaining summary data is substantially easier than accessing individual-level phenotype and genotype data, while often multiple correlated traits have been collected, the problem studied here has become increasingly important. We propose a powerful adaptive test and compare its performance with some existing tests. We illustrate its applications to analyses of a meta-analyzed GWAS dataset with three blood lipid traits and another with sex-stratified anthropometric traits, and further demonstrate its potential power gain over some existing methods through realistic simulation studies. We start from the situation with only one set of (possibly meta-analyzed) genome-wide summary statistics, then extend the method to meta-analysis of multiple sets of genome-wide summary statistics, each from one GWAS. We expect the proposed test to be useful in practice as more powerful than or complementary to existing methods. © 2015 WILEY PERIODICALS, INC.
Yaron, Y; Cherry, M; Kramer, R L; O'Brien, J E; Hallak, M; Johnson, M P; Evans, M I
1999-10-01
We evaluated the value of all 3 common biochemical serum markers, maternal serum alpha-fetoprotein, beta-human chorionic gonadotropin, and unconjugated estriol, and combinations thereof as predictors of pregnancy outcome. A total of 60,040 patients underwent maternal serum screening. All patients had maternal serum alpha-fetoprotein measurements; beta-human chorionic gonadotropin was measured in 45,565 patients, and 24,504 patients had determination of all 3 markers, including unconjugated estriol. The incidences of various pregnancy outcomes were evaluated according to the serum marker levels by using clinically applied cutoff points. In confirmation of previous observations, increased maternal serum alpha-fetoprotein levels (>2.5 multiples of the median) were found to be significantly associated with pregnancy-induced hypertension, miscarriage, preterm delivery, intrauterine growth restriction, intrauterine fetal death, oligohydramnios, and abruptio placentae. Increased beta-human chorionic gonadotropin levels (>2.5 multiples of the median [MoM]) were significantly associated with pregnancy-induced hypertension, miscarriage, preterm delivery, and intrauterine fetal death. Finally, decreased unconjugated estriol levels (<0.5 MoM) were found to be significantly associated with pregnancy-induced hypertension, miscarriage, intrauterine growth restriction, and intrauterine fetal death. As with increased second-trimester maternal serum alpha-fetoprotein levels, increased serum beta-human chorionic gonadotropin and low unconjugated estriol levels are significantly associated with adverse pregnancy outcomes. These are most likely attributed to placental dysfunction. Multiple-marker screening can be used not only for the detection of fetal anomalies and aneu-ploidy but also for detection of high-risk pregnancies.
Genetic variation influences glutamate concentrations in brains of patients with multiple sclerosis.
Baranzini, Sergio E; Srinivasan, Radhika; Khankhanian, Pouya; Okuda, Darin T; Nelson, Sarah J; Matthews, Paul M; Hauser, Stephen L; Oksenberg, Jorge R; Pelletier, Daniel
2010-09-01
Glutamate is the main excitatory neurotransmitter in the mammalian brain. Appropriate transmission of nerve impulses through glutamatergic synapses is required throughout the brain and forms the basis of many processes including learning and memory. However, abnormally high levels of extracellular brain glutamate can lead to neuroaxonal cell death. We have previously reported elevated glutamate levels in the brains of patients suffering from multiple sclerosis. Here two complementary analyses to assess the extent of genomic control over glutamate levels were used. First, a genome-wide association analysis in 382 patients with multiple sclerosis using brain glutamate concentration as a quantitative trait was conducted. In a second approach, a protein interaction network was used to find associated genes within the same pathway. The top associated marker was rs794185 (P < 6.44 x 10(-7)), a non-coding single nucleotide polymorphism within the gene sulphatase modifying factor 1. Our pathway approach identified a module composed of 70 genes with high relevance to glutamate biology. Individuals carrying a higher number of associated alleles from genes in this module showed the highest levels of glutamate. These individuals also showed greater decreases in N-acetylaspartate and in brain volume over 1 year of follow-up. Patients were then stratified by the amount of annual brain volume loss and the same approach was performed in the 'high' (n = 250) and 'low' (n = 132) neurodegeneration groups. The association with rs794185 was highly significant in the group with high neurodegeneration. Further, results from the network-based pathway analysis remained largely unchanged even after stratification. Results from these analyses indicated that variance in the activity of neurochemical pathways implicated in neurodegeneration is explained, at least in part, by the inheritance of common genetic polymorphisms. Spectroscopy-based imaging provides a novel quantitative endophenotype for genetic association studies directed towards identifying new factors that contribute to the heterogeneity of clinical expression of multiple sclerosis.
Qu, Qinglan; Zhao, Dongmei; Zhang, Fengrong; Bao, Hongchu; Yang, Qiuhua
2017-02-01
Objective Betatrophin is a newly identified circulating protein that is significantly associated with type 2 diabetes mellitus (T2DM), adiposity, and metabolic syndrome. The aim of this study was to investigate whether betatrophin levels and polycystic ovary syndrome (PCOS) were associated. Methods Circulating betatrophin levels were measured in 162 patients with PCOS and 156 matched control females using specific enzyme-linked immunosorbent assay kits. Correlations between betatrophin levels and PCOS incidence as well as multiple key endocrine PCOS parameters were analyzed using multiple statistical methods. Results Betatrophin levels were significantly increased in patients with PCOS (685.3 ± 27.7 vs. 772.6 ± 42.5 pg/ml). When sub-grouping all investigated subjects according to the presence of insulin resistance, women with PCOS and insulin resistance exhibited markedly higher betatrophin concentrations. Furthermore, betatrophin levels were significantly correlated with fasting insulin levels and homeostatic model assessment of insulin resistance only in females with PCOS ( r = 0.531 and r = 0.628, respectively). Conclusion We provide the first report that betatrophin is strongly associated with PCOS. This study suggests that betatrophin may potentially serve as an independent predictor for the development of PCOS in at-risk women, especially those with insulin resistance.
Misiewicz-Krzeminska, Irena; Corchete, Luis Antonio; Rojas, Elizabeta A.; Martínez-López, Joaquín; García-Sanz, Ramón; Oriol, Albert; Bladé, Joan; Lahuerta, Juan-José; Miguel, Jesús San; Mateos, María-Victoria; Gutiérrez, Norma C.
2018-01-01
Protein analysis in bone marrow samples from patients with multiple myeloma has been limited by the low concentration of proteins obtained after CD138+ cell selection. A novel approach based on capillary nano-immunoassay could make it possible to quantify dozens of proteins from each myeloma sample in an automated manner. Here we present a method for the accurate and robust quantification of the expression of multiple proteins extracted from CD138-purified multiple myeloma samples frozen in RLT Plus buffer, which is commonly used for nucleic acid preservation and isolation. Additionally, the biological and clinical value of this analysis for a panel of 12 proteins essential to the pathogenesis of multiple myeloma was evaluated in 63 patients with newly diagnosed multiple myeloma. The analysis of the prognostic impact of CRBN/Cereblon and IKZF1/Ikaros mRNA/protein showed that only the protein levels were able to predict progression-free survival of patients; mRNA levels were not associated with prognosis. Interestingly, high levels of Cereblon and Ikaros proteins were associated with longer progression-free survival only in patients who received immunomodulatory drugs and not in those treated with other drugs. In conclusion, the capillary nano-immunoassay platform provides a novel opportunity for automated quantification of the expression of more than 20 proteins in CD138+ primary multiple myeloma samples. PMID:29545347
Misiewicz-Krzeminska, Irena; Corchete, Luis Antonio; Rojas, Elizabeta A; Martínez-López, Joaquín; García-Sanz, Ramón; Oriol, Albert; Bladé, Joan; Lahuerta, Juan-José; Miguel, Jesús San; Mateos, María-Victoria; Gutiérrez, Norma C
2018-05-01
Protein analysis in bone marrow samples from patients with multiple myeloma has been limited by the low concentration of proteins obtained after CD138 + cell selection. A novel approach based on capillary nano-immunoassay could make it possible to quantify dozens of proteins from each myeloma sample in an automated manner. Here we present a method for the accurate and robust quantification of the expression of multiple proteins extracted from CD138-purified multiple myeloma samples frozen in RLT Plus buffer, which is commonly used for nucleic acid preservation and isolation. Additionally, the biological and clinical value of this analysis for a panel of 12 proteins essential to the pathogenesis of multiple myeloma was evaluated in 63 patients with newly diagnosed multiple myeloma. The analysis of the prognostic impact of CRBN /Cereblon and IKZF1 /Ikaros mRNA/protein showed that only the protein levels were able to predict progression-free survival of patients; mRNA levels were not associated with prognosis. Interestingly, high levels of Cereblon and Ikaros proteins were associated with longer progression-free survival only in patients who received immunomodulatory drugs and not in those treated with other drugs. In conclusion, the capillary nano-immunoassay platform provides a novel opportunity for automated quantification of the expression of more than 20 proteins in CD138 + primary multiple myeloma samples. Copyright © 2018 Ferrata Storti Foundation.
Sadeghi Bahmani, Dena; Calabrese, Pasquale; Merkt, Helene; Naegelin, Yvonne; Gerber, Markus; Pühse, Uwe; Holsboer-Trachsler, Edith; Brand, Serge
2017-10-01
This study investigated the interrelatedness of physical disability, physical activity, and depression among patients with multiple sclerosis (MS). We hypothesized that self-reported physical activity would mediate the effect of disability on depressive symptoms. Twenty-seven patients with MS (mean age: 49 years; 44.5% females) completed self-rating scales covering sociodemographic variables, intake of antidepressants, physical activity, and symptoms of depression; disability was measured by the Expanded Disability Status Scale. We found a higher level of disability to be significantly associated with more symptoms of depression. While higher reported physical activity was descriptively associated with lower depression scores and unrelated to Expanded Disability Status Scale, physical activity levels did not mediate the effect of disability on depressive symptoms.
Longitudinal plasma metabolic profiles, infant feeding, and islet autoimmunity in the MIDIA study.
Jørgenrud, Benedicte; Stene, Lars C; Tapia, German; Bøås, Håkon; Pepaj, Milaim; Berg, Jens P; Thorsby, Per M; Orešič, Matej; Hyötyläinen, Tuulia; Rønningen, Kjersti S
2017-03-01
The aim of this study was to investigate the longitudinal plasma metabolic profiles in healthy infants and the potential association with breastfeeding duration and islet autoantibodies predictive of type 1 diabetes. Up to four longitudinal plasma samples from age 3 months from case children who developed islet autoimmunity (n = 29) and autoantibody-negative control children (n = 29) with the HLA DR4-DQ8/DR3-DQ2 genotype were analyzed using two-dimensional gas chromatography coupled to a time-of-flight mass spectrometer for detection of small polar metabolites. Plasma metabolite levels were found to depend strongly on age, with fold changes varying up to 50% from age 3 to 24 months (p < 0.001 after correction for multiple testing). Tyrosine levels tended to be lower in case children, but this was not significant after correction for multiple testing. Ornithine levels were lower in case children compared with the controls at the time of seroconversion, but the difference was not statistically significant after correcting for multiple testing. Breastfeeding for at least 3 months as compared with shorter duration was associated with higher plasma levels of isoleucine, and lower levels of methionine and 3,4-dihydroxybutyric acid at 3 months of age. Plasma levels of several small, polar metabolites changed with age during early childhood, independent of later islet autoimmunity status and sex. Breastfeeding was associated with higher levels of branched-chain amino acids, and lower levels of methionine and 3,4-dihydroxybutyric acid. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
Multiple Levels of Family Factors and Oppositional Defiant Disorder Symptoms Among Chinese Children.
Lin, Xiuyun; Li, Longfeng; Heath, Melissa A; Chi, Peilian; Xu, Shousen; Fang, Xiaoyi
2018-03-01
Family factors are closely associated with child developmental outcomes. This study examined the relationship of oppositional defiant disorder (ODD) symptoms and factors at whole family, dyadic, and individual levels in Chinese children. Participants, who were recruited from 14 primary schools in north, east, and south-west China, included 80 father-child dyads and 169 mother-child dyads. Children in the participating dyads were previously diagnosed with ODD. Results revealed that family cohesion/adaptability was indirectly associated with ODD symptoms via parent-child relationship and child emotion regulation. Parent-child relationship affected ODD symptoms directly and indirectly through child emotion regulation. In addition, the effects of family cohesion/adaptability on parent emotion regulation and child emotion regulation were mediated by the parent-child relationship. The tested model provides a comprehensive framework of how family factors at multiple levels are related to child ODD symptoms and highlights the importance of understanding child emotional and behavioral problems within the family context, more specifically within the multiple levels of family relationships. © 2016 Family Process Institute.
Komatsu, Masayo; Nezu, Satoko; Tomioka, Kimiko; Hazaki, Kan; Harano, Akihiro; Morikawa, Masayuki; Takagi, Masahiro; Yamada, Masahiro; Matsumoto, Yoshitaka; Iwamoto, Junko; Ishizuka, Rika; Saeki, Keigo; Okamoto, Nozomi; Kurumatani, Norio
2013-01-01
To investigate factors associated with activities of daily living in independently living elderly persons in a community. The potential subjects were 4,472 individuals aged 65 years and older who voluntarily participated in a large cohort study, the Fujiwara-kyo study. We used self-administered questionnaires consisting of an activities of daily living (ADL) questionnaire with the Physical Fitness Test established by the Ministry of Education, Culture, Sports, Science and Technology (12 ADL items) to determine the index of higher-level physical independence, demographics, Geriatric Depression Scale, and so on. Mini-mental state examination, measurement of physical fitness, and blood tests were also carried out. A lower ADL level was defined as having a total score of the 12 ADL items (range, 12-36 points) that was below the first quartile of a total score for all the subjects. Factors associated with a low ADL level were examined by multiple logistic regression. A total of 4,198 remained as subjects for analysis. The male, female and 5-year-old groups showed significant differences in the median score of 12 ADL items between any two groups. The highest odds ratio among factors associated with lower ADL level by multiple logistic regression with mutually adjusted independent variables was 4.49 (95%CI: 2.82-7.17) in the groups of "very sharp pain" or "strong pain" during the last month. Low physical ability, self-awareness of limb weakness, a BMI of over 25, low physical activity, cerebrovascular disorder, depression, low cognitive function, unable "to see normally", unable "to hear someone", "muscle, bone and joint pain" were independently associated with lower ADL level. Multiple factors are associated with lower ADL level assessed on the basis of the 12 ADL items.
Increased serum bicarbonate in critically ill patients: a retrospective analysis.
Libório, Alexandre Braga; Noritomi, Danilo Teixeira; Leite, Tacyano Tavares; de Melo Bezerra, Candice Torres; de Faria, Evandro Rodrigues; Kellum, John A
2015-03-01
Although metabolic alkalosis is a common occurrence, no study has evaluated its prevalence, associated factors or outcomes in critically ill patients. This is a retrospective study from the Multiparameter Intelligent Monitoring in Intensive Care II database. From 23,529 adult patient records, 18,982 patients met the inclusion criteria. Serum bicarbonate levels demonstrated a U-shaped association with mortality with knots at 25 and 30 mEq/l. Of the total included patients, 5,565 (29.3 %) had at least one serum bicarbonate level measurement >30 mEq/l. The majority were exposed to multiple factors that are classically associated with metabolic alkalosis (mainly diuretic use, hypernatremia, hypokalemia and high gastric output). Patients with increased serum bicarbonate exhibited increased ICU LOS, more days on mechanical ventilation and higher hospital mortality. After multivariate adjustment, each 5-mEq/l increment in the serum bicarbonate level above 30 mEq/l was associated with an odds ratio of 1.21 for hospital mortality. The association between increased serum bicarbonate levels and mortality occurs independently of its possible etiologies. An increased serum bicarbonate level is common in critically ill patients; this can be attributed to multiple factors in the majority of cases, and its presence and duration negatively influence patient outcomes.
Novakova, Lenka; Axelsson, Markus; Malmeström, Clas; Imberg, Henrik; Elias, Olle; Zetterberg, Henrik; Nerman, Olle; Lycke, Jan
2018-01-01
Neurodegeneration occurs during the early stages of multiple sclerosis. It is an essential, devastating part of the pathophysiology. Tools for measuring the degree of neurodegeneration could improve diagnostics and patient characterization. This study aimed to determine the diagnostic value of biomarkers of degeneration in patients with recent clinical onset of suspected multiple sclerosis, and to evaluate these biomarkers for characterizing disease course. This cross-sectional study included 271 patients with clinical features of suspected multiple sclerosis onset and was the baseline of a prospective study. After diagnostic investigations, the patients were classified into the following disease groups: patients with clinically isolated syndrome (n = 4) or early relapsing remitting multiple sclerosis (early RRMS; n = 93); patients with relapsing remitting multiple sclerosis with disease durations ≥2 years (established RRMS; n = 39); patients without multiple sclerosis, but showing symptoms (symptomatic controls; n = 89); and patients diagnosed with other diseases (n = 46). In addition, we included healthy controls (n = 51) and patients with progressive multiple sclerosis (n = 23). We analyzed six biomarkers of neurodegeneration: cerebrospinal fluid neurofilament light chain levels; cerebral spinal fluid glial fibrillary acidic protein; cerebral spinal fluid tau; retinal nerve fiber layer thickness; macula volume; and the brain parenchymal fraction. Except for increased cerebral spinal fluid neurofilament light chain levels, median 670 ng/L (IQR 400-2110), we could not find signs of early degeneration in the early disease group with recent clinical onset. However, the intrathecal immunoglobin G production and cerebral spinal fluid neurofilament light chain levels showed diagnostic value. Moreover, elevated levels of cerebral spinal fluid glial fibrillary acidic protein, thin retinal nerve fiber layers, and low brain parenchymal fractions were associated with progressive disease, but not with the other phenotypes. Thin retinal nerve fiber layers and low brain parenchymal fractions, which indicated neurodegeneration, were associated with longer disease duration. In clinically suspected multiple sclerosis, intrathecal immunoglobin G production and neurofilament light chain levels had diagnostic value. Therefore, these biomarkers could be included in diagnostic work-ups for multiple sclerosis. We found that the thickness of the retinal nerve fiber layer and the brain parenchymal fraction were not different between individuals that were healthy, symptomatic, or newly diagnosed with multiple sclerosis. This finding suggested that neurodegeneration had not reached a significant magnitude in patients with a recent clinical onset of multiple sclerosis.
Okello, J; Nakimuli-Mpungu, E; Klasen, F; Voss, C; Musisi, S; Broekaert, E; Derluyn, I
2015-07-15
We have previously shown that depression symptoms are associated with multiple risk behaviors and that parental attachments are protective against depression symptoms in post-war adolescents. Accumulating literature indicates that low levels of attachment may sensitize individuals to increased multiple risk behaviors when depression symptoms exist. This investigation examined the interactive effects of attachment and depression symptoms on multiple risk behavior. We conducted hierarchical logistic regression analyses to examine the impact of attachment and depression symptoms on multiple risk behavior in our post-war sample of 551 adolescents in Gulu district. Analyses revealed interactive effects for only maternal attachment-by-depression interaction. Interestingly, high levels of maternal attachment exacerbated the relationship between depression symptoms and multiple risk behaviors while low levels of maternal attachment attenuated this relationship. It is possible that this analysis could be biased by a common underlying factor that influences self-reporting and therefore is correlated with each of self-reported attachment security, depressive symptoms, and multiple risk behaviors. These findings suggest that maternal attachment serves as a protective factor at low levels while serving as an additional risk factor at high levels. Findings support and expand current knowledge about the roles that attachment and depression symptoms play in the development of multiple risk behaviors and suggest a more complex etiology for post-war adolescents. Copyright © 2015 Elsevier B.V. All rights reserved.
Neuroactive steroid levels in plasma and cerebrospinal fluid of male multiple sclerosis patients.
Caruso, Donatella; Melis, Marta; Fenu, Giuseppe; Giatti, Silvia; Romano, Simone; Grimoldi, Maria; Crippa, Donatella; Marrosu, Maria Giovanna; Cavaletti, Guido; Melcangi, Roberto Cosimo
2014-08-01
Neuroactive steroid family includes molecules synthesized in peripheral glands (i.e., hormonal steroids) and directly in the nervous system (i.e., neurosteroids) which are key regulators of the nervous function. As already reported in clinical and experimental studies, neurodegenerative diseases affect the levels of neuroactive steroids. However, a careful analysis comparing the levels of these molecules in cerebrospinal fluid (CSF) and in plasma of multiple sclerosis (MS) patients is still missing. To this aim, the levels of neuroactive steroids were evaluated by liquid chromatography-tandem mass spectrometry in CSF and plasma of male adults affected by Relapsing-Remitting MS and compared with those collected in control patients. An increase in pregnenolone and isopregnanolone levels associated with a decrease in progesterone metabolites, dihydroprogesterone, and tetrahydroprogesterone was observed in CSF of MS patients. Moreover, an increase of 5α-androstane-3α,17β-diol and of 17β-estradiol levels associated with a decrease of dihydrotestosterone also occurred. In plasma, an increase in pregnenolone, progesterone, and dihydrotestosterone and a decrease in dihydroprogesterone and tetrahydroprogesterone levels were reported. This study shows for the first time that the levels of several neuroactive steroids, and particularly those of progesterone and testosterone metabolites, are deeply affected in CSF of relapsing-remitting MS male patients. We here demonstrated that, the cerebrospinal fluid and plasma levels of several neuroactive steroids are modified in relapsing remitting multiple sclerosis male patients. Interestingly, we reported for the first time that, the levels of progesterone and testosterone metabolites are deeply affected in cerebrospinal fluid. These findings may have an important relevance in therapeutic and/or diagnostic field of multiple sclerosis. © 2014 International Society for Neurochemistry.
ERIC Educational Resources Information Center
Kliewer, Wendy; Reid-Quinones, Kathryn; Shields, Brian J.; Foutz, Lauren
2009-01-01
Associations between multiple risks, emotion regulation skill, and basal cortisol levels were examined in a community sample of 69 African American youth (mean age = 11.30 years; 49% male) living in an urban setting. Multiple risks were assessed at Time 1 and consisted of 10 demographic and psychosocial risk factors including parent, child, and…
[Breast feeding and systemic blood pressure in infants].
Hernández-González, Martha A; Díaz-De-León, Luz V; Guízar-Mendoza, Juan M; Amador-Licona, Norma; Cipriano-González, Marisol; Díaz-Pérez, Raúl; Murillo-Ortiz, Blanca O; De-la-Roca-Chiapas, José María; Solorio-Meza, Sergio Eduardo
2012-01-01
Blood pressure levels in childhood influence these levels in adulthood, and breastfeeding has been considered such as a cardioprotective. We evaluated the association between blood pressure levels and feeding type in a group of infants. We conducted a comparative cross-sectional study in term infants with appropriate weight at birth, to compare blood pressure levels in those children with exclusively breastfeeding, mixed-feeding and formula feeding. The comparison of groups was performed using ANOVA and multiple regression analysis was used to identify variables associated with mean arterial blood pressure levels. A p value < 0.05 was considered significant. We included 20 men and 24 women per group. Infant Formula Feeding had higher current weight and weight gain compared with the other two groups (p < 0.05). Systolic, diastolic and mean blood pressure levels, as well as respiratory and heart rate were higher in the groups of exclusively formula feeding and mixed-feeding than in those with exclusively breastfeeding (p < 0.05). Multiple regression analysis identified that variables associated with mean blood pressure levels were current body mass index, weight gain and formula feeding. Infants in breastfeeding show lower blood pressure, BMI and weight gain.
Depressive symptoms in adolescence: the association with multiple health risk behaviors.
Katon, Wayne; Richardson, Laura; Russo, Joan; McCarty, Carolyn A; Rockhill, Carol; McCauley, Elizabeth; Richards, Julie; Grossman, David C
2010-01-01
Although multiple studies of adolescents have examined the association of depression with individual health risk behaviors such as obesity or smoking, this is one of the few studies that examined the association between depression and multiple risk behaviors. A brief mail questionnaire, which screened for age, gender, weight, height, sedentary behaviors, physical activity, perception of general health, functional impairment and depressive symptoms, was completed by a sample of 2291 youth (60.7% response rate) aged 13-17 enrolled in a health care plan. A subset of youth who screened positive on the two-item depression screen and a random sample of those screening negative were approached to participate in a telephone interview with more in-depth information obtained on smoking and at-risk behaviors associated with drug and alcohol use. Youth screening positive for high levels of depressive symptoms compared to those with few or no depressive symptoms were significantly more likely to meet criteria for obesity, had a poorer perception of health, spent more time on the computer, got along less well with parents and friends, had more problems completing school work and were more likely to have experimented with smoking and a wide array of behaviors associated with drug and alcohol use. Because many adverse health behaviors that develop in adolescence continue into adulthood, the association of depressive symptoms with multiple risk behaviors and poor functioning suggest that early interventions are needed at an individual, school, community and primary care level. Copyright 2010 Elsevier Inc. All rights reserved.
Katić, Mašenjka; Pirsl, Filip; Steinberg, Seth M.; Dobbin, Marnie; Curtis, Lauren M.; Pulanić, Dražen; Desnica, Lana; Titarenko, Irina; Pavletic, Steven Z.
2016-01-01
Aim To identify the factors associated with vitamin D status in patients with chronic graft-vs-host disease (cGVHD) and evaluate the association between serum vitamin D (25(OH)D) levels and cGVHD characteristics and clinical outcomes defined by the National Institutes of Health (NIH) criteria. Methods 310 cGVHD patients enrolled in the NIH cGVHD natural history study (clinicaltrials.gov: NCT00092235) were analyzed. Univariate analysis and multiple logistic regression were used to determine the associations between various parameters and 25(OH)D levels, dichotomized into categorical variables: ≤20 and >20 ng/mL, and as a continuous parameter. Multiple logistic regression was used to develop a predictive model for low vitamin D. Survival analysis and association between cGVHD outcomes and 25(OH)D as a continuous as well as categorical variable: ≤20 and >20 ng/mL; <50 and ≥50 ng/mL, and among three ordered categories: ≤20, 20-50, and ≥50 ng/mL, was performed. PMID:27374829
Intimate relationship quality, self-concept and illness acceptance in those with multiple sclerosis.
Wright, Thomas M; Kiropoulos, Litza A
2017-02-01
Lower levels of Intimate Relationship Quality (IRQ) have been found in those with Multiple Sclerosis (MS) compared to the general population. This study examined an MS sample to see whether IRQ was positively associated with self-concept, whether IRQ was positively associated with MS illness acceptance and whether IRQ was predicted by self-concept and illness acceptance. In this cross-sectional study, 115 participants with MS who were in an intimate relationship completed an online survey advertised on MS related websites. The survey assessed demographic variables, MS illness variables and levels of IRQ, self-concept and illness acceptance. Results revealed that IRQ was significantly positively associated with self-concept and with illness acceptance. Multiple hierarchical linear regression analysis revealed that, after controlling for illness duration and level of disability, self-concept significantly predicted IRQ but illness acceptance did not significantly predict IRQ. This study addressed several gaps and methodological flaws in the literature and was the first known to assess predictors of IRQ in those with MS. The results suggest that self-concept could be a potential target for individual and couple psychological interventions to improve IRQ and contribute to improved outcomes for those with MS.
Zheng, Jie; Rodriguez, Santiago; Laurin, Charles; Baird, Denis; Trela-Larsen, Lea; Erzurumluoglu, Mesut A; Zheng, Yi; White, Jon; Giambartolomei, Claudia; Zabaneh, Delilah; Morris, Richard; Kumari, Meena; Casas, Juan P; Hingorani, Aroon D; Evans, David M; Gaunt, Tom R; Day, Ian N M
2017-01-01
Fine mapping is a widely used approach for identifying the causal variant(s) at disease-associated loci. Standard methods (e.g. multiple regression) require individual level genotypes. Recent fine mapping methods using summary-level data require the pairwise correlation coefficients ([Formula: see text]) of the variants. However, haplotypes rather than pairwise [Formula: see text], are the true biological representation of linkage disequilibrium (LD) among multiple loci. In this article, we present an empirical iterative method, HAPlotype Regional Association analysis Program (HAPRAP), that enables fine mapping using summary statistics and haplotype information from an individual-level reference panel. Simulations with individual-level genotypes show that the results of HAPRAP and multiple regression are highly consistent. In simulation with summary-level data, we demonstrate that HAPRAP is less sensitive to poor LD estimates. In a parametric simulation using Genetic Investigation of ANthropometric Traits height data, HAPRAP performs well with a small training sample size (N < 2000) while other methods become suboptimal. Moreover, HAPRAP's performance is not affected substantially by single nucleotide polymorphisms (SNPs) with low minor allele frequencies. We applied the method to existing quantitative trait and binary outcome meta-analyses (human height, QTc interval and gallbladder disease); all previous reported association signals were replicated and two additional variants were independently associated with human height. Due to the growing availability of summary level data, the value of HAPRAP is likely to increase markedly for future analyses (e.g. functional prediction and identification of instruments for Mendelian randomization). The HAPRAP package and documentation are available at http://apps.biocompute.org.uk/haprap/ CONTACT: : jie.zheng@bristol.ac.uk or tom.gaunt@bristol.ac.ukSupplementary information: Supplementary data are available at Bioinformatics online. © The Author 2016. Published by Oxford University Press.
Davis-Yadley, Ashley H; Lipka, Seth; Shen, Huafeng; Devanney, Valerie; Swarup, Supreeya; Barnowsky, Alex; Silpe, Jeff; Mosdale, Josh; Pan, Qinshi; Fridlyand, Svetlana; Sreeharshan, Suhas; Abraham, Albin; Viswanathan, Prakash; Krishnamachari, Bhuma
2015-03-01
Although data exists showing that uncontrolled lipid levels in white and black patients is associated with colorectal adenomas, there are currently no studies looking only at the Hispanic population. With the rapid increase in the Hispanic population, we aimed to look at their risk of colorectal adenomas in association with lipid levels. We retrospectively analyzed 1473 patients undergoing colonoscopy from 2009 to 2011 at a community hospital. Statistical analysis was performed using Chi-squared for categorical variables and t test for continuous variables with age-, gender-, and race-adjusted odds ratios. Unconditional logistic regression model was used to estimate 95 % confidence intervals (CI). SAS 9.3 software was used to perform all statistical analysis. In our general population, there was an association with elevated triglyceride levels greater than 150 and presence of multiple colorectal adenomas with odds ratio (OR) 1.60 (1.03, 2.48). There was an association with proximal colon adenomas and cholesterol levels between 200 and 239 with OR 1.57 (1.07, 2.30), and low-density lipoprotein (LDL) levels of greater than 130 with OR 1.54 (1.04, 2.30). There was no association between high-density lipoproteins (HDL) levels and colorectal adenomas. The Hispanic population showed no statistical correlation between elevated triglycerides, cholesterol, or LDL with the presence, size, location, or multiplicity of colorectal adenomas. We found a significant correlation between elevated lipid levels and colorectal adenomas in white and black patients; however, there was no such association in the Hispanic population. This finding can possibly be due to environmental factors such as dietary, colonic flora, or genetic susceptibility, which fosters further investigation and research.
Feng, Wei; Cui, Xiuqing; Liu, Bing; Liu, Chuanyao; Xiao, Yang; Lu, Wei; Guo, Huan; He, Meian; Zhang, Xiaomin; Yuan, Jing; Chen, Weihong; Wu, Tangchun
2015-01-01
Elevated heavy metals and fasting plasma glucose (FPG) levels were both associated with increased risk of cardiovascular diseases. However, studies on the associations of heavy metals and essential elements with altered FPG and diabetes risk were limited or conflicting. The objective of this study was to evaluate the potential associations of heavy metals and essential trace elements with FPG and diabetes risk among general Chinese population. We conducted a cross-sectional study to investigate the associations of urinary concentrations of 23 metals with FPG, impaired fasting glucose (IFG) and diabetes among 2242 community-based Chinese adults in Wuhan. We used the false discovery rate (FDR) method to correct for multiple hypothesis tests. After adjusting for potential confounders, urinary aluminum, titanium, cobalt, nickel, copper, zinc, selenium, rubidium, strontium, molybdenum, cadmium, antimony, barium, tungsten and lead were associated with altered FPG, IFG or diabetes risk (all P< 0.05); arsenic was only dose-dependently related to diabetes (P< 0.05). After additional adjustment for multiple testing, titanium, copper, zinc, selenium, rubidium, tungsten and lead were still significantly associated with one or more outcomes (all FDR-adjusted P< 0.05). Our results suggest that multiple metals in urine are associated with FPG, IFG or diabetes risk. Because the cross-sectional design precludes inferences about causality, further prospective studies are warranted to validate our findings.
Jiang, Rong; French, John E.; Stober, Vandy P.; Kang-Sickel, Juei-Chuan C.; Zou, Fei
2012-01-01
Background: Individual genetic variation that results in differences in systemic response to xenobiotic exposure is not accounted for as a predictor of outcome in current exposure assessment models. Objective: We developed a strategy to investigate individual differences in single-nucleotide polymorphisms (SNPs) as genetic markers associated with naphthyl–keratin adduct (NKA) levels measured in the skin of workers exposed to naphthalene. Methods: The SNP-association analysis was conducted in PLINK using candidate-gene analysis and genome-wide analysis. We identified significant SNP–NKA associations and investigated the potential impact of these SNPs along with personal and workplace factors on NKA levels using a multiple linear regression model and the Pratt index. Results: In candidate-gene analysis, a SNP (rs4852279) located near the CYP26B1 gene contributed to the 2-naphthyl–keratin adduct (2NKA) level. In the multiple linear regression model, the SNP rs4852279, dermal exposure, exposure time, task replacing foam, age, and ethnicity all were significant predictors of 2NKA level. In genome-wide analysis, no single SNP reached genome-wide significance for NKA levels (all p ≥ 1.05 × 10–5). Pathway and network analyses of SNPs associated with NKA levels were predicted to be involved in the regulation of cellular processes and homeostasis. Conclusions: These results provide evidence that a quantitative biomarker can be used as an intermediate phenotype when investigating the association between genetic markers and exposure–dose relationship in a small, well-characterized exposed worker population. PMID:22391508
Serum osteocalcin is significantly related to indices of obesity and lipid profile in Malaysian men.
Chin, Kok-Yong; Ima-Nirwana, Soelaiman; Mohamed, Isa Naina; Ahmad, Fairus; Ramli, Elvy Suhana Mohd; Aminuddin, Amilia; Ngah, Wan Zurinah Wan
2014-01-01
Recent studies revealed a possible reciprocal relationship between the skeletal system and obesity and lipid metabolism, mediated by osteocalcin, an osteoblast-specific protein. This study aimed to validate the relationship between serum osteocalcin and indices of obesity and lipid parameters in a group of Malaysian men. A total of 373 men from the Malaysian Aging Male Study were included in the analysis. Data on subjects' demography, body mass index (BMI), body fat (BF) mass, waist circumference (WC), serum osteocalcin and fasting lipid levels were collected. Bioelectrical impendence (BIA) method was used to estimate BF. Multiple linear and binary logistic regression analyses were performed to analyze the association between serum osteocalcin and the aforementioned variables, with adjustment for age, ethnicity and BMI. Multiple regression results indicated that weight, BMI, BF mass, BF %, WC were significantly and negatively associated with serum osteocalcin (p < 0.001). There was a significant positive association between serum osteocalcin and high density lipoprotein (HDL) cholesterol (p = 0.032). Binary logistic results indicated that subjects with low serum osteocalcin level were more likely to be associated with high BMI (obese and overweight), high BF%, high WC and low HDL cholesterol (p < 0.05). Subjects with high osteocalcin level also demonstrated high total cholesterol level (p < 0.05) but this association was probably driven by high HDL level. These variables were not associated with serum C-terminal of telopeptide crosslinks in the subjects (p > 0.05). Serum osteocalcin is associated with indices of obesity and HDL level in men. These relationships should be validated by a longitudinal study, with comprehensive hormone profile testing.
Hulland, Erin N; Brown, Jennifer L; Swartzendruber, Andrea L; Sales, Jessica M; Rose, Eve S; DiClemente, Ralph J
2015-01-01
Heightened psychosocial stress coupled with maladaptive coping may be associated with greater sexual risk engagement. This study examined the association between stress levels and coping strategy use as predictors of sexual risk behavior engagement over 24 months among African-American adolescent females (N = 701; M = 17.6 years) enrolled in an STI/HIV risk-reduction intervention program. Participants completed audio computer assisted self-interview (ACASI) measures of global stress, interpersonal stress, coping strategy use, and sexual behaviors prior to intervention participation. Follow-up ACASI assessments were conducted at 6, 12, 18, and 24 months post-intervention. Generalized estimated equation models examined associations between baseline stress levels and coping strategy use as predictors of condom use (past 90 days, last sex) and multiple partners during follow-up. Global stress and individual coping strategy usage were not associated with differences in condom use. Higher interpersonal stress was associated with lower proportion condom use (p = .018), inconsistent condom use (p = .011), and not using a condom at last sex (p = .002). There were no significant associations between stress levels, coping strategy use, and multiple partners. Future research should explore mechanisms that may underlie the association between elevated interpersonal stress and decreased condom use among this population.
Hulland, Erin N.; Brown, Jennifer L.; Swartzendruber, Andrea L.; Sales, Jessica M.; Rose, Eve S.; DiClemente, Ralph J.
2014-01-01
Heightened psychosocial stress coupled with maladaptive coping may be associated with greater sexual risk engagement. This study examined the association between stress levels and coping strategy use as predictors of sexual risk behavior engagement over 24 months among African American adolescent females (N = 701; M = 17.6 years) enrolled in an STI/HIV risk-reduction intervention program. Participants completed audio computer assisted self-interview (ACASI) measures of global stress, interpersonal stress, coping strategy use, and sexual behaviors prior to intervention participation. Follow-up ACASI assessments were conducted at 6-, 12-, 18-, and 24-months post-intervention. Generalized estimated equation models examined associations between baseline stress levels and coping strategy use as predictors of condom use (past 90 days, last sex) and multiple partners during follow-up. Global stress and individual coping strategy usage were not associated with differences in condom use. Higher interpersonal stress was associated with lower proportion condom use (p=0.018), inconsistent condom use (p=0.011), and not using a condom at last sex (p=0.002). There were no significant associations between stress levels, coping strategy use, and multiple partners. Future research should explore mechanisms that may underlie the association between elevated interpersonal stress and decreased condom use among this population. PMID:25159332
Conrad, Selby M; Swenson, Rebecca R; Hancock, Evan; Brown, Larry K
2014-01-01
Adolescents with abuse histories have been shown to be at increased risk to acquire human immunodeficiency virus and sexually transmitted infections. In addition, teens with lower levels of self-restraint or higher levels of distress, such as those with psychiatric concerns, have also demonstrated increased sexual risk behaviors. This study explored sex differences in sexual risk behaviors among a sample of adolescents in a therapeutic/alternative high school setting. Moderated regression analysis showed that a lower level of self-restraint was associated with sexual risk behaviors in boys but not in girls. Rather, the interaction of self-restraint and multiple types of abuse was associated with greater sex risk within girls in this sample. Results suggest that girls and boys with abuse histories and low levels of self-restraint may have different intervention needs related to sexual risk behaviors.
Overexpression of the Cytokine BAFF and Autoimmunity Risk.
Steri, Maristella; Orrù, Valeria; Idda, M Laura; Pitzalis, Maristella; Pala, Mauro; Zara, Ilenia; Sidore, Carlo; Faà, Valeria; Floris, Matteo; Deiana, Manila; Asunis, Isadora; Porcu, Eleonora; Mulas, Antonella; Piras, Maria G; Lobina, Monia; Lai, Sandra; Marongiu, Mara; Serra, Valentina; Marongiu, Michele; Sole, Gabriella; Busonero, Fabio; Maschio, Andrea; Cusano, Roberto; Cuccuru, Gianmauro; Deidda, Francesca; Poddie, Fausto; Farina, Gabriele; Dei, Mariano; Virdis, Francesca; Olla, Stefania; Satta, Maria A; Pani, Mario; Delitala, Alessandro; Cocco, Eleonora; Frau, Jessica; Coghe, Giancarlo; Lorefice, Lorena; Fenu, Giuseppe; Ferrigno, Paola; Ban, Maria; Barizzone, Nadia; Leone, Maurizio; Guerini, Franca R; Piga, Matteo; Firinu, Davide; Kockum, Ingrid; Lima Bomfim, Izaura; Olsson, Tomas; Alfredsson, Lars; Suarez, Ana; Carreira, Patricia E; Castillo-Palma, Maria J; Marcus, Joseph H; Congia, Mauro; Angius, Andrea; Melis, Maurizio; Gonzalez, Antonio; Alarcón Riquelme, Marta E; da Silva, Berta M; Marchini, Maurizio; Danieli, Maria G; Del Giacco, Stefano; Mathieu, Alessandro; Pani, Antonello; Montgomery, Stephen B; Rosati, Giulio; Hillert, Jan; Sawcer, Stephen; D'Alfonso, Sandra; Todd, John A; Novembre, John; Abecasis, Gonçalo R; Whalen, Michael B; Marrosu, Maria G; Meloni, Alessandra; Sanna, Serena; Gorospe, Myriam; Schlessinger, David; Fiorillo, Edoardo; Zoledziewska, Magdalena; Cucca, Francesco
2017-04-27
Genomewide association studies of autoimmune diseases have mapped hundreds of susceptibility regions in the genome. However, only for a few association signals has the causal gene been identified, and for even fewer have the causal variant and underlying mechanism been defined. Coincident associations of DNA variants affecting both the risk of autoimmune disease and quantitative immune variables provide an informative route to explore disease mechanisms and drug-targetable pathways. Using case-control samples from Sardinia, Italy, we performed a genomewide association study in multiple sclerosis followed by TNFSF13B locus-specific association testing in systemic lupus erythematosus (SLE). Extensive phenotyping of quantitative immune variables, sequence-based fine mapping, cross-population and cross-phenotype analyses, and gene-expression studies were used to identify the causal variant and elucidate its mechanism of action. Signatures of positive selection were also investigated. A variant in TNFSF13B, encoding the cytokine and drug target B-cell activating factor (BAFF), was associated with multiple sclerosis as well as SLE. The disease-risk allele was also associated with up-regulated humoral immunity through increased levels of soluble BAFF, B lymphocytes, and immunoglobulins. The causal variant was identified: an insertion-deletion variant, GCTGT→A (in which A is the risk allele), yielded a shorter transcript that escaped microRNA inhibition and increased production of soluble BAFF, which in turn up-regulated humoral immunity. Population genetic signatures indicated that this autoimmunity variant has been evolutionarily advantageous, most likely by augmenting resistance to malaria. A TNFSF13B variant was associated with multiple sclerosis and SLE, and its effects were clarified at the population, cellular, and molecular levels. (Funded by the Italian Foundation for Multiple Sclerosis and others.).
Multiple Phenotype Association Tests Using Summary Statistics in Genome-Wide Association Studies
Liu, Zhonghua; Lin, Xihong
2017-01-01
Summary We study in this paper jointly testing the associations of a genetic variant with correlated multiple phenotypes using the summary statistics of individual phenotype analysis from Genome-Wide Association Studies (GWASs). We estimated the between-phenotype correlation matrix using the summary statistics of individual phenotype GWAS analyses, and developed genetic association tests for multiple phenotypes by accounting for between-phenotype correlation without the need to access individual-level data. Since genetic variants often affect multiple phenotypes differently across the genome and the between-phenotype correlation can be arbitrary, we proposed robust and powerful multiple phenotype testing procedures by jointly testing a common mean and a variance component in linear mixed models for summary statistics. We computed the p-values of the proposed tests analytically. This computational advantage makes our methods practically appealing in large-scale GWASs. We performed simulation studies to show that the proposed tests maintained correct type I error rates, and to compare their powers in various settings with the existing methods. We applied the proposed tests to a GWAS Global Lipids Genetics Consortium summary statistics data set and identified additional genetic variants that were missed by the original single-trait analysis. PMID:28653391
Multiple phenotype association tests using summary statistics in genome-wide association studies.
Liu, Zhonghua; Lin, Xihong
2018-03-01
We study in this article jointly testing the associations of a genetic variant with correlated multiple phenotypes using the summary statistics of individual phenotype analysis from Genome-Wide Association Studies (GWASs). We estimated the between-phenotype correlation matrix using the summary statistics of individual phenotype GWAS analyses, and developed genetic association tests for multiple phenotypes by accounting for between-phenotype correlation without the need to access individual-level data. Since genetic variants often affect multiple phenotypes differently across the genome and the between-phenotype correlation can be arbitrary, we proposed robust and powerful multiple phenotype testing procedures by jointly testing a common mean and a variance component in linear mixed models for summary statistics. We computed the p-values of the proposed tests analytically. This computational advantage makes our methods practically appealing in large-scale GWASs. We performed simulation studies to show that the proposed tests maintained correct type I error rates, and to compare their powers in various settings with the existing methods. We applied the proposed tests to a GWAS Global Lipids Genetics Consortium summary statistics data set and identified additional genetic variants that were missed by the original single-trait analysis. © 2017, The International Biometric Society.
Geng, Biao; Liang, Man-Man; Ye, Xiao-Bing; Zhao, Wen-Ying
2015-01-01
The objective of this study was to investigate the association of serum cancer antigen 15-3 (CA 15-3) and carcinoembryonic antigen (CEA) levels with clinicopathological parameters in patients diagnosed with metastatic breast cancer (MBC). We retrospectively evaluated the medical records of 284 patients diagnosed with MBC between January, 2007 and December, 2012 who fulfilled the specified criteria and the association between the levels of the two tumor marker and clinicopathological parameters was analyzed. Of the 284 patients, elevated CA 15-3 and CEA levels at initial diagnosis of recurrence were identified in 163 (57.4%) and 97 (34.2%) patients, respectively. Elevated CA 15-3 and CEA levels were significantly associated with breast cancer molecular subtypes (P<0.001 and P=0.032, respectively). Cases with luminal subtypes exhibited a higher percentage of elevated CA 15-3 and CEA levels compared to non-luminal subtypes. Elevated CA 15-3 level was correlated with bone metastasis (P=0.017). However, elevation of CEA was observed regardless of the site of metastasis. Elevation of CA 15-3 was significantly more common in MBC with multiple metastatic sites compared to MBC with a single metastasis (P=0.001). However, the incidence of elevated CEA levels did not differ between patients with a single and those with multiple metastatic sites. In conclusion, elevated CA 15-3 and CEA levels at initial diagnosis of recurrence were found to be associated with breast cancer molecular subtypes, whereas an elevated CA 15-3 level was significantly correlated with bone metastasis and an elevated CEA level was observed regardless of metastatic site. The proportion of MBC cases with elevated CA 15-3 levels differed according to the number of metastatic sites.
Association between lifestyle factors and plasma adiponectin levels in Japanese men.
Tsukinoki, Rumi; Morimoto, Kanehisa; Nakayama, Kunio
2005-11-02
Adiponectin is an adipocyte-specific protein that plays a role in obesity, insulin resistant, lipid metabolism, and anti-inflammation. Hypoadiponectinemia may be associated with a higher risk for type 2 diabetes and cardiovascular disease. Some studies suggest that adiponectin levels are modulated by lifestyle factors, but little is known about the associations between lifestyle factors and plasma adiponectin levels in Japanese people. We therefore investigated the associations between lifestyle factors and plasma adiponectin levels in general Japanese men. The subjects were 202 Japanese male workers who participated in an annual health check. They provided details about anthropometrical data, blood collection, their use of prescribed medication, and the clinical history of their families. They also completed a self-administered questionnaire about their lifestyles. Subjects with plasma adiponectin levels below 4.0 microg/ml had significantly lower levels of HDL cholesterol and higher levels of BMI, SBP, DBP, total cholesterol, FBG, and platelets than did subjects with higher adiponectin levels. In multiple logistic regression after multiple adjustment, a plasma adiponectin level below 4.0 microg/ml was significantly associated with smoking (odds ratio [OR] = 2.08, 95% confidence interval [CI] = 1.01-4.30), a daily diet rich in deep-yellow vegetables (OR = 0.25, 95% CI= 0.07-0.91), frequent eating out (OR = 2.45, 95% CI = 1.19-5.08), and physical exercise two or more times a week (OR = 0.21, 95% CI = 0.06-0.74). Our findings show that adiponectin levels in general Japanese men are independently related to smoking, dietary factors, and physical exercise. We think that lifestyle habits might independently modulate adiponectin levels and that adiponectin might be the useful biomarker helping people to avoid developing type 2 diabetes and cardiovascular disease by modifying their lifestyles.
2012-01-01
Visualization and analysis of molecular networks are both central to systems biology. However, there still exists a large technological gap between them, especially when assessing multiple network levels or hierarchies. Here we present RedeR, an R/Bioconductor package combined with a Java core engine for representing modular networks. The functionality of RedeR is demonstrated in two different scenarios: hierarchical and modular organization in gene co-expression networks and nested structures in time-course gene expression subnetworks. Our results demonstrate RedeR as a new framework to deal with the multiple network levels that are inherent to complex biological systems. RedeR is available from http://bioconductor.org/packages/release/bioc/html/RedeR.html. PMID:22531049
Serum ferritin levels are associated with arterial stiffness in healthy Korean adults.
Ha, Ji Yoon; Kim, Min Kyung; Kang, Shinae; Nam, Ji Sun; Ahn, Chul Woo; Kim, Kyung Rae; Park, Jong Suk
2016-08-01
Although an association between serum ferritin and atherosclerosis has been suggested, limited epidemiologic data are available regarding the association between ferritin and arterial stiffness in healthy adults. A total of 2932 healthy subjects were enrolled in this study. Anthropometric and biochemical profiles including ferritin were measured. The arterial stiffness was measured using brachial-ankle pulse wave velocity (baPWV). Serum ferritin levels were classified into quartiles and baPWV values gradually increased with each ferritin quartile. Multiple regression analysis showed that ferritin levels were independently correlated with baPWV. After adjusting for multiple risk factors, as compared with the lowest quartile, the odds ratios for high baPWV (>75(th) percentile) were 1.15 (0.84-1.56), 1.37 (0.97-1.73), and 1.46 (1.29-2.17) among men (p for trend < 0.05) and 1.24 (0.87-1.79), 1.53 (1.09-2.16), and 1.80 (1.25-2.82) among women (p for trend < 0.05), for the second, third, and fourth quartiles of ferritin, respectively. In conclusion, serum ferritin levels are independently associated with arterial stiffness in healthy Korean adults. © The Author(s) 2016.
Martínez, Fernando; Alegret, Núria; Carol, Federico; Laso, M Jesús; Zancajo, Juanjo; García, Esteban; Ros, Vanesa
2018-01-01
The main objective of this study was to identify demographic, clinical, analytical factors or injuries associated with 30-day mortality in patients with pelvic fractures. Prospective observational study of patients with multiple injuries including pelvic fractures between January 2009 and January 2017. We recorded demographic, clinical, and laboratory data on arrival at the emergency department; type of pelvic fracture; treatments; associated lesions; and 30-day mortality. Univariable and multivariable models were used to analyze the data. A total of 2061 multiple-injury patients were attended; 118 had pelvic fractures. Fifteen of the patients with pelvic fractures (12.7%) died within 30 days. Arterial blood pressure on admission was less than 90 mm Hg in 23.7%, heart rate was over 100 beats per minute in 41.52%, lactic acid level was 20 mg/dL or higher in 67.6%, and base excess of -6 or less was recorded for 26.3%. The mean Injury Severity Score was 20 points. Angiographic embolization was required in 80.6% and preperitoneal packing in 3.4%. The main associated lesions were rib fractures (35.6%), hemo-pneumothorax (31.3%), spinal injuries (35.6%), and head injuries (30%). The 6 independent variables associated with risk of death in multiple-injury patients with pelvic fractures are age, female sex, complex fractures (Tile type C), lactic acid level of 20 mg/dL or more, base excess of -6 or less, and bowel perforation.
Bush, Steffani; Gappmaier, Eduard
2016-01-01
Background: Fatigue is a common symptom in people with multiple sclerosis (MS), but its associations with disability, functional mobility, depression, and quality of life (QOL) remain unclear. We aimed to determine the associations between different levels of fatigue and disability, functional mobility, depression, and physical and mental QOL in people with MS. Methods: Eighty-nine individuals with MS (mean [SD] disease duration = 13.6 [9.8] years, mean [SD] Expanded Disability Status Scale [EDSS] score = 5.3 [1.5]) and no concurrent relapses were retrospectively analyzed. Participants were divided into two groups based on five-item Modified Fatigue Impact Scale (MFIS-5) scores: group LF (n = 32, MFIS-5 score ≤10 [low levels of fatigue]) and group HF (n = 57, MFIS-5 score >10 [high levels of fatigue]). Results: Sixty-four percent of the sample reported high levels of fatigue. Compared with group LF, group HF demonstrated significantly (P < .05) greater impairments in the Timed Up and Go test, Activities-specific Balance Confidence scale, and 12-item Multiple Sclerosis Walking Scale scores; depression; and QOL but not in the EDSS scores, which were not significantly different between groups. Conclusions: Fatigue was found to be a predominant symptom in the study participants. Individuals reporting higher levels of fatigue concomitantly exhibited greater impairments in functional mobility, depression, and physical and mental QOL. Disability was not found to be related to level of fatigue. These findings can be important for appropriate assessment and management of individuals with MS with fatigue. PMID:27134580
Consumption of non-cow's milk beverages and serum vitamin D levels in early childhood.
Lee, Grace J; Birken, Catherine S; Parkin, Patricia C; Lebovic, Gerald; Chen, Yang; L'Abbé, Mary R; Maguire, Jonathon L
2014-11-18
Vitamin D fortification of non-cow's milk beverages is voluntary in North America. The effect of consuming non-cow's milk beverages on serum 25-hydroxyvitamin D levels in children is unclear. We studied the association between non-cow's milk consumption and 25-hydroxyvitamin D levels in healthy preschool-aged children. We also explored whether cow's milk consumption modified this association and analyzed the association between daily non-cow's milk and cow's milk consumption. In this cross-sectional study, we recruited children 1-6 years of age attending routinely scheduled well-child visits. Survey responses, and anthropometric and laboratory measurements were collected. The association between non-cow's milk consumption and 25-hydroxyvitamin D levels was tested using multiple linear regression and logistic regression. Cow's milk consumption was explored as an effect modifier using an interaction term. The association between daily intake of non-cow's milk and cow's milk was explored using multiple linear regression. A total of 2831 children were included. The interaction between non-cow's milk and cow's milk consumption was statistically significant (p = 0.03). Drinking non-cow's milk beverages was associated with a 4.2-nmol/L decrease in 25-hydroxyvitamin D level per 250-mL cup consumed among children who also drank cow's milk (p = 0.008). Children who drank only non-cow's milk were at higher risk of having a 25-hydroxyvitamin D level below 50 nmol/L than children who drank only cow's milk (odds ratio 2.7, 95% confidence interval 1.6 to 4.7). Consumption of non-cow's milk beverages was associated with decreased serum 25-hydroxyvitamin D levels in early childhood. This association was modified by cow's milk consumption, which suggests a trade-off between consumption of cow's milk fortified with higher levels of vitamin D and non-cow's milk with lower vitamin D content. © 2014 Canadian Medical Association or its licensors.
System and method for inventorying multiple remote objects
Carrender, Curtis L.; Gilbert, Ronald W.
2007-10-23
A system and method of inventorying multiple objects utilizing a multi-level or a chained radio frequency identification system. The system includes a master tag and a plurality of upper level tags and lower level tags associated with respective objects. The upper and lower level tags communicate with each other and the master tag so that reading of the master tag reveals the presence and absence of upper and lower level tags. In the chained RF system, the upper and lower level tags communicate locally with each other in a manner so that more remote tags that are out of range of some of the upper and lower level tags have their information relayed through adjacent tags to the master tag and thence to a controller.
System and method for inventorying multiple remote objects
Carrender, Curtis L [Morgan Hill, CA; Gilbert, Ronald W [Morgan Hill, CA
2009-12-29
A system and method of inventorying multiple objects utilizing a multi-level or a chained radio frequency identification system. The system includes a master tag and a plurality of upper level tags and lower level tags associated with respective objects. The upper and lower level tags communicate with each other and the master tag so that reading of the master tag reveals the presence and absence of upper and lower level tags. In the chained RF system, the upper and lower level tags communicate locally with each other in a manner so that more remote tags that are out of range of some of the upper and lower level tags have their information relayed through adjacent tags to the master tag and thence to a controller.
An efficient Bayesian meta-analysis approach for studying cross-phenotype genetic associations
Majumdar, Arunabha; Haldar, Tanushree; Bhattacharya, Sourabh; Witte, John S.
2018-01-01
Simultaneous analysis of genetic associations with multiple phenotypes may reveal shared genetic susceptibility across traits (pleiotropy). For a locus exhibiting overall pleiotropy, it is important to identify which specific traits underlie this association. We propose a Bayesian meta-analysis approach (termed CPBayes) that uses summary-level data across multiple phenotypes to simultaneously measure the evidence of aggregate-level pleiotropic association and estimate an optimal subset of traits associated with the risk locus. This method uses a unified Bayesian statistical framework based on a spike and slab prior. CPBayes performs a fully Bayesian analysis by employing the Markov Chain Monte Carlo (MCMC) technique Gibbs sampling. It takes into account heterogeneity in the size and direction of the genetic effects across traits. It can be applied to both cohort data and separate studies of multiple traits having overlapping or non-overlapping subjects. Simulations show that CPBayes can produce higher accuracy in the selection of associated traits underlying a pleiotropic signal than the subset-based meta-analysis ASSET. We used CPBayes to undertake a genome-wide pleiotropic association study of 22 traits in the large Kaiser GERA cohort and detected six independent pleiotropic loci associated with at least two phenotypes. This includes a locus at chromosomal region 1q24.2 which exhibits an association simultaneously with the risk of five different diseases: Dermatophytosis, Hemorrhoids, Iron Deficiency, Osteoporosis and Peripheral Vascular Disease. We provide an R-package ‘CPBayes’ implementing the proposed method. PMID:29432419
González-Garza, Blanca Idalia; Stow, Adam; Sánchez-Teyer, Lorenzo Felipe; Zapata-Pérez, Omar
2015-12-01
The Yucatán Peninsula in Mexico contains some of the largest breeding groups of the globally distributed and critically endangered hawksbill turtle (Eretmochelys imbricata). An improved understanding of the breeding system of this species and how its genetic variation is structured among nesting areas is required before the threats to its survival can be properly evaluated. Here, we genotype 1195 hatchlings and 41 nesting females at 12 microsatellite loci to assess levels of multiple paternity, genetic variation and whether individual levels of homozygosity are associated with reproductive success. Of the 50 clutches analyzed, only 6% have multiple paternity. The distribution of pairwise relatedness among nesting localities (rookeries) was not random with elevated within-rookery relatedness, and declining relatedness with geographic distance indicating some natal philopatry. Although there was no strong evidence that particular rookeries had lost allelic variation via drift, younger turtles had significantly lower levels of genetic variation than older turtles, suggesting some loss of genetic variation. At present there is no indication that levels of genetic variation are associated with measures of reproductive success such as clutch size, hatching success, and frequency of infertile eggs.
Hensler, Thorsten; Sauerland, Stefan; Bouillon, Bertil; Raum, Marcus; Rixen, Dieter; Helling, Hanns-J; Andermahr, Jonas; Neugebauer, Edmund A M
2002-05-01
Our knowledge about the bidirectional interactions between brain and whole organism after trauma is still limited. It was the purpose of this prospective clinical study to determine the influence of severe head trauma (SHT) as well as trauma in different anatomic injury regions on posttraumatic inflammatory mediator levels from patients with multiple injuries. Thirty-five healthy controls, 33 patients with an isolated SHT, 47 patients with multiple injuries without SHT, and 45 patients with both SHT and multiple injuries were studied. The posttraumatic plasma levels of soluble tumor necrosis factor receptors p55 and p75, interleukin (IL)-6, IL-10, and polymorphonuclear neutrophil (PMN) elastase were monitored using enzyme-linked immunosorbent assay technique. The influence of head injuries as well as thorax, abdomen, and extremity injuries on the mediator release from patients with multiple injuries was investigated by multivariate linear regression models. The soluble tumor necrosis factor receptor p55/p75 ratio was significantly elevated within 3 hours of trauma in all three injury groups and returned to reference ratios after 12 hours. The lowest increase was found in patients suffering from an isolated SHT. Lowest mediator levels in this patient population were also found for IL-6, IL-10, and PMN elastase during the first 36 hours after trauma. Additional injuries to the head, thorax, abdomen, and extremity modulated mediator levels to a different degree. No specific effect was found for SHT when compared with other injury groups. Thorax injuries caused the quickest rise in mediator levels, whereas abdominal injuries significantly increased PMN elastase levels 12 to 24 hours after trauma. Traumatic injuries cause the liberation of various mediators, without any specific association between anatomic injury pattern and the pattern of mediator release.
Software engineering the mixed model for genome-wide association studies on large samples
USDA-ARS?s Scientific Manuscript database
Mixed models improve the ability to detect phenotype-genotype associations in the presence of population stratification and multiple levels of relatedness in genome-wide association studies (GWAS), but for large data sets the resource consumption becomes impractical. At the same time, the sample siz...
Jan, Aftab; Dawkins, Ian; Murphy, Niamh; Collier, Patrick; Baugh, John; Ledwidge, Mark; McDonald, Kenneth; Watson, Chris J
2013-01-01
Persistently elevated natriuretic peptide (NP) levels in heart failure (HF) patients are associated with impaired prognosis. Recent work suggests that NP-guided therapy can improve outcome, but the mechanisms behind an elevated BNP remain unclear. Among the potential stimuli for NP in clinically stable patients are persistent occult fluid overload, wall stress, inflammation, fibrosis, and ischemia. The purpose of this study was to identify associates of B-type natriuretic peptide (BNP) in a stable HF population. In a prospective observational study of 179 stable HF patients, the association between BNP and markers of collagen metabolism, inflammation, and Doppler-echocardiographic parameters including left ventricular ejection fraction (LVEF), left atrial volume index (LAVI), and E/e prime (E/e') was measured. Univariable associates of elevated BNP were age, LVEF, LAVI, E/e', creatinine, and markers of collagen turnover. In a multiple linear regression model, age, creatinine, and LVEF remained significant associates of BNP. E/e' and markers of collagen turnover had a persistent impact on BNP independent of these covariates. Multiple variables are associated with persistently elevated BNP levels in stable HF patients. Clarification of the relative importance of NP stimuli may help refine NP-guided therapy, potentially improving outcome for this at-risk population.
Trauma-Related Dissociation Is Linked With Maladaptive Personality Functioning
Granieri, Antonella; Guglielmucci, Fanny; Costanzo, Antonino; Caretti, Vincenzo; Schimmenti, Adriano
2018-01-01
Background: Extensive research has demonstrated the positive associations among the exposure to traumatic experiences, the levels of dissociation, and the severity of psychiatric symptoms in adults. However, it has been hypothesized in clinical literature that an excessive activation of the dissociative processes following multiple traumatic experiences may jeopardize the psychological and behavioral functioning of the individuals, fostering higher levels of maladaptive personality functioning. Methods: The study involved 322 adult volunteers from Italy. Participants completed measures on traumatic experiences, dissociation, and maladaptive personality traits. Results: The number of traumatic experiences reported by participants were positively associated with dissociation scores and maladaptive personality scores. Mediation analyses showed that dissociation acted as a partial mediator in the relationship between traumatic experiences and overall maladaptive personality functioning. Regression curve analyses showed that the positive association between maladaptive personality functioning and dissociation was stronger among participants with higher exposure to traumatic experiences. Conclusion: Exposure to multiple traumatic experiences may increase the risk for an excessive activation of the dissociative processes, which in turn may generate severe impairments in multiple domains of personality functioning. PMID:29887807
Krischer, Jeffrey P.
2016-01-01
OBJECTIVE To define prognostic classification factors associated with the progression from single to multiple autoantibodies, multiple autoantibodies to dysglycemia, and dysglycemia to type 1 diabetes onset in relatives of individuals with type 1 diabetes. RESEARCH DESIGN AND METHODS Three distinct cohorts of subjects from the Type 1 Diabetes TrialNet Pathway to Prevention Study were investigated separately. A recursive partitioning analysis (RPA) was used to determine the risk classes. Clinical characteristics, including genotype, antibody titers, and metabolic markers were analyzed. RESULTS Age and GAD65 autoantibody (GAD65Ab) titers defined three risk classes for progression from single to multiple autoantibodies. The 5-year risk was 11% for those subjects >16 years of age with low GAD65Ab titers, 29% for those ≤16 years of age with low GAD65Ab titers, and 45% for those subjects with high GAD65Ab titers regardless of age. Progression to dysglycemia was associated with islet antigen 2 Ab titers, and 2-h glucose and fasting C-peptide levels. The 5-year risk is 28%, 39%, and 51% for respective risk classes defined by the three predictors. Progression to type 1 diabetes was associated with the number of positive autoantibodies, peak C-peptide level, HbA1c level, and age. Four risk classes defined by RPA had a 5-year risk of 9%, 33%, 62%, and 80%, respectively. CONCLUSIONS The use of RPA offered a new classification approach that could predict the timing of transitions from one preclinical stage to the next in the development of type 1 diabetes. Using these RPA classes, new prevention techniques can be tailored based on the individual prognostic risk characteristics at different preclinical stages. PMID:27208341
ERIC Educational Resources Information Center
Han, Sehee; Kim, Heaseung; Lee, Hee-Sun
2013-01-01
The purpose of this study is to examine the association between social capital and subjective well-being (life satisfaction) by using multilevel analysis considering both individual and area-level social capital while adjusting for various control variables at multiple-levels in Seoul, South Korea. The data was from the 2010 (Wave 2) Seoul Welfare…
Serum Albumin and Disease Severity of Non-Cystic Fibrosis Bronchiectasis.
Lee, Seung Jun; Kim, Hyo-Jung; Kim, Ju-Young; Ju, Sunmi; Lim, Sujin; Yoo, Jung Wan; Nam, Sung-Jin; Lee, Gi Dong; Cho, Hyun Seop; Kim, Rock Bum; Cho, Yu Ji; Jeong, Yi Yeong; Kim, Ho Cheol; Lee, Jong Deog
2017-08-01
A clinical classification system has been developed to define the severity and predict the prognosis of subjects with non-cystic fibrosis (CF) bronchiectasis. We aimed to identify laboratory parameters that are correlated with the bronchiectasis severity index (BSI) and FACED score. The medical records of 107 subjects with non-CF bronchiectasis for whom BSI and FACED scores could be calculated were retrospectively reviewed. The correlations between the laboratory parameters and BSI or FACED score were assessed, and multiple-linear regression analysis was performed to identify variables independently associated with BSI and FACED score. An additional subgroup analysis was performed according to sex. Among all of the enrolled subjects, 49 (45.8%) were male and 58 (54.2%) were female. The mean BSI and FACED scores were 9.43 ± 3.81 and 1.92 ± 1.59, respectively. The serum albumin level (r = -0.49), bilirubin level (r = -0.31), C-reactive protein level (r = 0.22), hemoglobin level (r = -0.2), and platelet/lymphocyte ratio (r = 0.31) were significantly correlated with BSI. Meanwhile, serum albumin (r = -0.37) and bilirubin level (r = -0.25) showed a significant correlation with the FACED score. Multiple-linear regression analysis showed that the serum bilirubin level was independently associated with BSI, and the serum albumin level was independently associated with both scoring systems. Subgroup analysis revealed that the level of uric acid was also a significant variable independently associated with the BSI in male bronchiectasis subjects. Several laboratory variables were identified as possible prognostic factors for non-CF bronchiectasis. Among them, the serum albumin level exhibited the strongest correlation and was identified as an independent variable associated with the BSI and FACED scores. Copyright © 2017 by Daedalus Enterprises.
Özkurt, Zübeyde Nur; Sucak, Gülsan Türköz; Akı, Şahika Zeynep; Yağcı, Münci; Haznedar, Rauf
2017-03-16
We hypothesized the levels of free light chains obtained before and after autologous stem cell transplantation can be useful in predicting transplantation outcome. We analyzed 70 multiple myeloma patients. Abnormal free light chain ratios before stem cell transplantation were found to be associated early progression, although without any impact on overall survival. At day +30, the normalization of levels of involved free light chain related with early progression. According to these results almost one-third reduction of free light chain levels can predict favorable prognosis after autologous stem cell transplantation.
Emeville, Elise; Giton, Frank; Giusti, Arnaud; Oliva, Alejandro; Fiet, Jean; Thomé, Jean-Pierre; Blanchet, Pascal; Multigner, Luc
2013-01-01
Background Studies relating long-term exposure to persistent organochlorine pollutants (POPs) with endocrine activities (endocrine disrupting chemicals) on circulating levels of steroid hormones have been limited to a small number of hormones and reported conflicting results. Objective We examined the relationship between serum concentrations of dehydroepiandrosterone, dehydroepiandrosterone sulphate, androstenedione, androstenediol, testosterone, free and bioavailable testosterone, dihydrotestosterone, estrone, estrone sulphate, estradiol, sex-hormone binding globulin, follicle-stimulating hormone, and luteinizing hormone as a function of level of exposure to three POPs known to interfere with hormone-regulated processes in different way: dichlorodiphenyl dichloroethene (DDE), polychlorinated biphenyl (PCB) congener 153, and chlordecone. Methods We collected fasting, morning serum samples from 277 healthy, non obese, middle-aged men from the French West Indies. Steroid hormones were determined by gas chromatography-mass spectrometry, except for dehydroepiandrosterone sulphate, which was determined by immunological assay, as were the concentrations of sex-hormone binding globulin, follicle-stimulating hormone and luteinizing hormone. Associations were assessed by multiple linear regression analysis, controlling for confounding factors, in a backward elimination procedure, in multiple bootstrap samples. Results DDE exposure was negatively associated to dihydrotestosterone level and positively associated to luteinizing hormone level. PCB 153 was positively associated to androstenedione and estrone levels. No association was found for chlordecone. Conclusions These results suggested that the endocrine response pattern, estimated by determining blood levels of steroid hormones, varies depending on the POPs studied, possibly reflecting differences in the modes of action generally attributed to these compounds. It remains to be investigated whether this response pattern is predictive of the subsequent occurrence of disease. PMID:23785499
Canver, Matthew C; Lessard, Samuel; Pinello, Luca; Wu, Yuxuan; Ilboudo, Yann; Stern, Emily N; Needleman, Austen J; Galactéros, Frédéric; Brugnara, Carlo; Kutlar, Abdullah; McKenzie, Colin; Reid, Marvin; Chen, Diane D; Das, Partha Pratim; A Cole, Mitchel; Zeng, Jing; Kurita, Ryo; Nakamura, Yukio; Yuan, Guo-Cheng; Lettre, Guillaume; Bauer, Daniel E; Orkin, Stuart H
2017-04-01
Cas9-mediated, high-throughput, saturating in situ mutagenesis permits fine-mapping of function across genomic segments. Disease- and trait-associated variants identified in genome-wide association studies largely cluster at regulatory loci. Here we demonstrate the use of multiple designer nucleases and variant-aware library design to interrogate trait-associated regulatory DNA at high resolution. We developed a computational tool for the creation of saturating-mutagenesis libraries with single or multiple nucleases with incorporation of variants. We applied this methodology to the HBS1L-MYB intergenic region, which is associated with red-blood-cell traits, including fetal hemoglobin levels. This approach identified putative regulatory elements that control MYB expression. Analysis of genomic copy number highlighted potential false-positive regions, thus emphasizing the importance of off-target analysis in the design of saturating-mutagenesis experiments. Together, these data establish a widely applicable high-throughput and high-resolution methodology to identify minimal functional sequences within large disease- and trait-associated regions.
Measuring and partitioning the high-order linkage disequilibrium by multiple order Markov chains.
Kim, Yunjung; Feng, Sheng; Zeng, Zhao-Bang
2008-05-01
A map of the background levels of disequilibrium between nearby markers can be useful for association mapping studies. In order to assess the background levels of linkage disequilibrium (LD), multilocus LD measures are more advantageous than pairwise LD measures because the combined analysis of pairwise LD measures is not adequate to detect simultaneous allele associations among multiple markers. Various multilocus LD measures based on haplotypes have been proposed. However, most of these measures provide a single index of association among multiple markers and does not reveal the complex patterns and different levels of LD structure. In this paper, we employ non-homogeneous, multiple order Markov Chain models as a statistical framework to measure and partition the LD among multiple markers into components due to different orders of marker associations. Using a sliding window of multiple markers on phased haplotype data, we compute corresponding likelihoods for different Markov Chain (MC) orders in each window. The log-likelihood difference between the lowest MC order model (MC0) and the highest MC order model in each window is used as a measure of the total LD or the overall deviation from the gametic equilibrium for the window. Then, we partition the total LD into lower order disequilibria and estimate the effects from two-, three-, and higher order disequilibria. The relationship between different orders of LD and the log-likelihood difference involving two different orders of MC models are explored. By applying our method to the phased haplotype data in the ENCODE regions of the HapMap project, we are able to identify high/low multilocus LD regions. Our results reveal that the most LD in the HapMap data is attributed to the LD between adjacent pairs of markers across the whole region. LD between adjacent pairs of markers appears to be more significant in high multilocus LD regions than in low multilocus LD regions. We also find that as the multilocus total LD increases, the effects of high-order LD tends to get weaker due to the lack of observed multilocus haplotypes. The overall estimates of first, second, third, and fourth order LD across the ENCODE regions are 64, 23, 9, and 3%.
Kim, So Young; Sim, Songyong; Choi, Hyo Geun
2017-01-01
Although an association between energy drinks and suicide has been suggested, few prior studies have considered the role of emotional factors including stress, sleep, and school performance in adolescents. This study aimed to evaluate the association of energy drinks with suicide, independent of possible confounders including stress, sleep, and school performance. In total, 121,106 adolescents with 13-18 years olds from the 2014 and 2015 Korea Youth Risk Behavior Web-based Survey were surveyed for age, sex, region of residence, economic level, paternal and maternal education level, sleep time, stress level, school performance, frequency of energy drink intake, and suicide attempts. Subjective stress levels were classified into severe, moderate, mild, a little, and no stress. Sleep time was divided into 6 groups: < 6 h; 6 ≤ h < 7; 7 ≤ h < 8; 8 ≤ h < 9; and ≥ 9 h. School performance was classified into 5 levels: A (highest), B (middle, high), C (middle), D (middle, low), and E (lowest). Frequency of energy drink consumption was divided into 3 groups: ≥ 3, 1-2, and 0 times a week. The associations of sleep time, stress level, and school performance with suicide attempts and the frequency of energy drink intake were analyzed using multiple and ordinal logistic regression analysis, respectively, with complex sampling. The relationship between frequency of energy drink intake and suicide attempts was analyzed using multiple logistic regression analysis with complex sampling. Higher stress levels, lack of sleep, and low school performance were significantly associated with suicide attempts (each P < 0.001). These variables of high stress level, abnormal sleep time, and low school performance were also proportionally related with higher energy drink intake (P < 0.001). Frequent energy drink intake was significantly associated with suicide attempts in multiple logistic regression analyses (AOR for frequency of energy intake ≥ 3 times a week = 3.03, 95% CI = 2.64-3.49, P < 0.001). Severe stress, inadequate sleep, and low school performance were related with more energy drink intake and suicide attempts in Korean adolescents. Frequent energy drink intake was positively related with suicide attempts, even after adjusting for stress, sleep time, and school performance.
Kim, So Young; Sim, Songyong
2017-01-01
Objective Although an association between energy drinks and suicide has been suggested, few prior studies have considered the role of emotional factors including stress, sleep, and school performance in adolescents. This study aimed to evaluate the association of energy drinks with suicide, independent of possible confounders including stress, sleep, and school performance. Methods In total, 121,106 adolescents with 13–18 years olds from the 2014 and 2015 Korea Youth Risk Behavior Web-based Survey were surveyed for age, sex, region of residence, economic level, paternal and maternal education level, sleep time, stress level, school performance, frequency of energy drink intake, and suicide attempts. Subjective stress levels were classified into severe, moderate, mild, a little, and no stress. Sleep time was divided into 6 groups: < 6 h; 6 ≤ h < 7; 7 ≤ h < 8; 8 ≤ h < 9; and ≥ 9 h. School performance was classified into 5 levels: A (highest), B (middle, high), C (middle), D (middle, low), and E (lowest). Frequency of energy drink consumption was divided into 3 groups: ≥ 3, 1–2, and 0 times a week. The associations of sleep time, stress level, and school performance with suicide attempts and the frequency of energy drink intake were analyzed using multiple and ordinal logistic regression analysis, respectively, with complex sampling. The relationship between frequency of energy drink intake and suicide attempts was analyzed using multiple logistic regression analysis with complex sampling. Results Higher stress levels, lack of sleep, and low school performance were significantly associated with suicide attempts (each P < 0.001). These variables of high stress level, abnormal sleep time, and low school performance were also proportionally related with higher energy drink intake (P < 0.001). Frequent energy drink intake was significantly associated with suicide attempts in multiple logistic regression analyses (AOR for frequency of energy intake ≥ 3 times a week = 3.03, 95% CI = 2.64–3.49, P < 0.001). Conclusion Severe stress, inadequate sleep, and low school performance were related with more energy drink intake and suicide attempts in Korean adolescents. Frequent energy drink intake was positively related with suicide attempts, even after adjusting for stress, sleep time, and school performance. PMID:29135989
Yi, Ming; Mudunuri, Uma; Che, Anney; Stephens, Robert M
2009-06-29
One of the challenges in the analysis of microarray data is to integrate and compare the selected (e.g., differential) gene lists from multiple experiments for common or unique underlying biological themes. A common way to approach this problem is to extract common genes from these gene lists and then subject these genes to enrichment analysis to reveal the underlying biology. However, the capacity of this approach is largely restricted by the limited number of common genes shared by datasets from multiple experiments, which could be caused by the complexity of the biological system itself. We now introduce a new Pathway Pattern Extraction Pipeline (PPEP), which extends the existing WPS application by providing a new pathway-level comparative analysis scheme. To facilitate comparing and correlating results from different studies and sources, PPEP contains new interfaces that allow evaluation of the pathway-level enrichment patterns across multiple gene lists. As an exploratory tool, this analysis pipeline may help reveal the underlying biological themes at both the pathway and gene levels. The analysis scheme provided by PPEP begins with multiple gene lists, which may be derived from different studies in terms of the biological contexts, applied technologies, or methodologies. These lists are then subjected to pathway-level comparative analysis for extraction of pathway-level patterns. This analysis pipeline helps to explore the commonality or uniqueness of these lists at the level of pathways or biological processes from different but relevant biological systems using a combination of statistical enrichment measurements, pathway-level pattern extraction, and graphical display of the relationships of genes and their associated pathways as Gene-Term Association Networks (GTANs) within the WPS platform. As a proof of concept, we have used the new method to analyze many datasets from our collaborators as well as some public microarray datasets. This tool provides a new pathway-level analysis scheme for integrative and comparative analysis of data derived from different but relevant systems. The tool is freely available as a Pathway Pattern Extraction Pipeline implemented in our existing software package WPS, which can be obtained at http://www.abcc.ncifcrf.gov/wps/wps_index.php.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Kim, Yangho; Lee, Byung-Kook, E-mail: bklee@sch.ac.kr
Introduction: The objective of this study was to evaluate associations between blood lead, cadmium, and mercury levels with estimated glomerular filtration rate in a general population of South Korean adults. Methods: This was a cross-sectional study based on data obtained in the Korean National Health and Nutrition Examination Survey (KNHANES) (2008-2010). The final analytical sample consisted of 5924 participants. Estimated glomerular filtration rate (eGFR) was calculated using the MDRD Study equation as an indicator of glomerular function. Results: In multiple linear regression analysis of log2-transformed blood lead as a continuous variable on eGFR, after adjusting for covariates including cadmium andmore » mercury, the difference in eGFR levels associated with doubling of blood lead were -2.624 mL/min per 1.73 m Superscript-Two (95% CI: -3.803 to -1.445). In multiple linear regression analysis using quartiles of blood lead as the independent variable, the difference in eGFR levels comparing participants in the highest versus the lowest quartiles of blood lead was -3.835 mL/min per 1.73 m Superscript-Two (95% CI: -5.730 to -1.939). In a multiple linear regression analysis using blood cadmium and mercury, as continuous or categorical variables, as independent variables, neither metal was a significant predictor of eGFR. Odds ratios (ORs) and 95% CI values for reduced eGFR calculated for log2-transformed blood metals and quartiles of the three metals showed similar trends after adjustment for covariates. Discussion: In this large, representative sample of South Korean adults, elevated blood lead level was consistently associated with lower eGFR levels and with the prevalence of reduced eGFR even in blood lead levels below 10 {mu}g/dL. In conclusion, elevated blood lead level was associated with lower eGFR in a Korean general population, supporting the role of lead as a risk factor for chronic kidney disease.« less
Torniainen-Holm, Minna; Suvisaari, Jaana; Lindgren, Maija; Härkänen, Tommi; Dickerson, Faith; Yolken, Robert H
2018-03-01
Earlier studies have documented an association between cytomegalovirus and cognitive impairment, but results have been inconsistent. Few studies have investigated the association of cytomegalovirus and Epstein-Barr virus with cognitive decline longitudinally. Our aim was to examine whether cytomegalovirus and Epstein-Barr virus are associated with cognitive decline in adults. The study sample is from the Finnish Health 2000 Survey (BRIF8901, n = 7112), which is representative of the Finnish adult population. The sample was followed up after 11 years in the Health 2011 Survey. In addition, persons with dementia were identified from healthcare registers. In the Finnish population aged 30 and over, the seroprevalence of cytomegalovirus was estimated to be 84% and the seroprevalence of Epstein-Barr virus 98%. Seropositivity of the viruses and antibody levels were mostly not associated with cognitive performance. In the middle-aged adult group, cytomegalovirus serointensity was associated with impaired performance in verbal learning. However, the association disappeared when corrected for multiple testing. No interactions between infection and time or between the two infections were significant when corrected for multiple testing. Seropositivity did not predict dementia diagnosis. The results suggest that adult levels of antibodies to cytomegalovirus and Epstein-Barr virus may not be associated with a significant decline in cognitive function or with dementia at population level. Copyright © 2018. Published by Elsevier Inc.
Ondeck, Nathaniel T; Fu, Michael C; Skrip, Laura A; McLynn, Ryan P; Cui, Jonathan J; Basques, Bryce A; Albert, Todd J; Grauer, Jonathan N
2018-04-09
The presence of missing data is a limitation of large datasets, including the National Surgical Quality Improvement Program (NSQIP). In addressing this issue, most studies use complete case analysis, which excludes cases with missing data, thus potentially introducing selection bias. Multiple imputation, a statistically rigorous approach that approximates missing data and preserves sample size, may be an improvement over complete case analysis. The present study aims to evaluate the impact of using multiple imputation in comparison with complete case analysis for assessing the associations between preoperative laboratory values and adverse outcomes following anterior cervical discectomy and fusion (ACDF) procedures. This is a retrospective review of prospectively collected data. Patients undergoing one-level ACDF were identified in NSQIP 2012-2015. Perioperative adverse outcome variables assessed included the occurrence of any adverse event, severe adverse events, and hospital readmission. Missing preoperative albumin and hematocrit values were handled using complete case analysis and multiple imputation. These preoperative laboratory levels were then tested for associations with 30-day postoperative outcomes using logistic regression. A total of 11,999 patients were included. Of this cohort, 63.5% of patients had missing preoperative albumin and 9.9% had missing preoperative hematocrit. When using complete case analysis, only 4,311 patients were studied. The removed patients were significantly younger, healthier, of a common body mass index, and male. Logistic regression analysis failed to identify either preoperative hypoalbuminemia or preoperative anemia as significantly associated with adverse outcomes. When employing multiple imputation, all 11,999 patients were included. Preoperative hypoalbuminemia was significantly associated with the occurrence of any adverse event and severe adverse events. Preoperative anemia was significantly associated with the occurrence of any adverse event, severe adverse events, and hospital readmission. Multiple imputation is a rigorous statistical procedure that is being increasingly used to address missing values in large datasets. Using this technique for ACDF avoided the loss of cases that may have affected the representativeness and power of the study and led to different results than complete case analysis. Multiple imputation should be considered for future spine studies. Copyright © 2018 Elsevier Inc. All rights reserved.
Bani-Ahmad, M A; Khabour, O F; Gharibeh, M Y; Alshlool, K N
2017-11-01
The reduction in blood viscosity and iron store were proposed to be connected to the reduction in the risk of cardiovascular disease (CVD) among multiple blood donors. Herein, we evaluated the modulation of serum lipids levels in accordance with donation events. Furthermore, atherogenic impacts on the risk of CVD were investigated. A total of 100 voluntarily male donors were included in the study. Fifty donors were multiple time donors (MTD) and 50 were single time donors (STD). Levels of serum lipids were determined and atherogenic indices including TG/HDL and CHO/HDL ratios were calculated. QRISK2 parameters were determined to evaluate the 10-years risk of developing CVD. Among MTD, there were significantly higher serum levels of triglycerides (TG) and very low-density lipoproteins (VLDL) combined with significantly lower HDL level. These modulations were significantly correlated to the extent of donation. Both CHO/HDL and TG/HDL ratios were also significantly higher among MTD. However, only TG/HDL ratio was strongly correlated to the donation extent even when controlled for age, BMI and smoking status. Despite the significant difference in QRISK2 parameters between study groups, none of these parameters was correlated to the extent of donation when controlling for age, BMI and smoking status. We demonstrate that multiple blood donation is associated with an unfavorable modulation of serum levels of lipids that is influenced by donation extent. This modulation is not associated with an increased risk of CVD but may weakly contribute in a higher risk for coronary heart disease (CHD). Copyright © 2017 Elsevier Masson SAS. All rights reserved.
Bossola, Maurizio; Vulpio, Carlo; Colacicco, Luigi; Scribano, Donata; Zuppi, Cecilia; Tazza, Luigi
2012-02-11
The aim of our study was to measure reactive oxygen metabolites (ROMs) in chronic hemodialysis (HD) patients and evaluate the possible association with cardiovascular disease (CVD) and mortality. We measured ROMs in 76 HD patients and correlated with CVD, cardiovascular (CV) events in the follow-up and all-cause and CVD-related mortality. The levels of ROMs presented a median value of 270 (238.2-303.2) CARR U (interquartile range). We created a ROC curve (ROMs levels vs. CVD) and we identified a cut-off point of 273 CARR U. Patients with ROMs levels ≥273 CARR U were significantly older, had higher C-reactive protein levels and lower creatinine concentrations. The prevalence of CVD was higher in patients with ROMs levels ≥273 (87.1%) than in those with ROMs levels <273 CARR U (17.7%; p<0.0001). ROMs levels were significantly higher in patients with CVD (317±63.8) than in those without (242.7±49.1; p<0.0001). At multiple regression analysis, age, creatinine and C-reactive protein were independent factors associated with ROMs. At multiple logistic regression analysis the association between ROMs and CVD was independent (OR: 1.02, 95% CI: 1.00-1.05; p=0.03). Twenty six patients developed cardiovascular (CV) events during the follow-up. Of these, seven were in the group with ROMs levels <273 CARR U and 19 in the group with ROMs levels ≥273 CARR U. The logistic regression analysis showed that both age (OR: 1.06, 95% CI: 1.01-1.12; p=0.013) and ROMs levels (OR: 1.10, 95% CI: 1.00-1.02; p=0.045) were independently associated with CV events in the follow-up. ROMs are independently associated with CVD and predict CV events in chronic HD patients.
Trigo, Fernanda M B; Luizon, Marcelo R; Dutra, Hélio S; Maiolino, Angelo; Nucci, Márcio; Simões, Belinda P
2014-01-01
Stem cell transplantation affects patient׳s vulnerability to infections due to immunological changes related to chemotherapy. Multiple myeloma is characterized by susceptibility to infections, and IL-6 and TNF-α increased levels affect immune response (IR). Polymorphisms in promoter region of cytokine genes may alter expression levels and affect IR. We performed interaction analysis of IL-6 (-174G/C) and TNF-α (-308G/A) polymorphisms with infection susceptibility in 148 patients classified accordingly to infection status and found an interaction when compared groups with and without bacteremia (p=0.0380). The interaction may be more important than single effects for the IR associated with the infection susceptibility in ASCT.
Weinger, Jason G.; Omari, Kakuri M.; Marsden, Kurt; Raine, Cedric S.; Shafit-Zagardo, Bridget
2009-01-01
Multiple sclerosis is a disease that is characterized by inflammation, demyelination, and axonal damage; it ultimately forms gliotic scars and lesions that severely compromise the function of the central nervous system. Evidence has shown previously that altered growth factor receptor signaling contributes to lesion formation, impedes recovery, and plays a role in disease progression. Growth arrest-specific protein 6 (Gas6), the ligand for the TAM receptor tyrosine kinase family, consisting of Tyro3, Axl, and Mer, is important for cell growth, survival, and clearance of debris. In this study, we show that levels of membrane-bound Mer (205 kd), soluble Mer (∼150 kd), and soluble Axl (80 kd) were all significantly elevated in homogenates from established multiple sclerosis lesions comprised of both chronic active and chronic silent lesions. Whereas in normal tissue Gas6 positively correlated with soluble Axl and Mer, there was a negative correlation between Gas6 and soluble Axl and Mer in established multiple sclerosis lesions. In addition, increased levels of soluble Axl and Mer were associated with increased levels of mature ADAM17, mature ADAM10, and Furin, proteins that are associated with Axl and Mer solubilization. Soluble Axl and Mer are both known to act as decoy receptors and block Gas6 binding to membrane-bound receptors. These data suggest that in multiple sclerosis lesions, dysregulation of protective Gas6 receptor signaling may prolong lesion activity. PMID:19541935
Multiple imputation methods for bivariate outcomes in cluster randomised trials.
DiazOrdaz, K; Kenward, M G; Gomes, M; Grieve, R
2016-09-10
Missing observations are common in cluster randomised trials. The problem is exacerbated when modelling bivariate outcomes jointly, as the proportion of complete cases is often considerably smaller than the proportion having either of the outcomes fully observed. Approaches taken to handling such missing data include the following: complete case analysis, single-level multiple imputation that ignores the clustering, multiple imputation with a fixed effect for each cluster and multilevel multiple imputation. We contrasted the alternative approaches to handling missing data in a cost-effectiveness analysis that uses data from a cluster randomised trial to evaluate an exercise intervention for care home residents. We then conducted a simulation study to assess the performance of these approaches on bivariate continuous outcomes, in terms of confidence interval coverage and empirical bias in the estimated treatment effects. Missing-at-random clustered data scenarios were simulated following a full-factorial design. Across all the missing data mechanisms considered, the multiple imputation methods provided estimators with negligible bias, while complete case analysis resulted in biased treatment effect estimates in scenarios where the randomised treatment arm was associated with missingness. Confidence interval coverage was generally in excess of nominal levels (up to 99.8%) following fixed-effects multiple imputation and too low following single-level multiple imputation. Multilevel multiple imputation led to coverage levels of approximately 95% throughout. © 2016 The Authors. Statistics in Medicine Published by John Wiley & Sons Ltd. © 2016 The Authors. Statistics in Medicine Published by John Wiley & Sons Ltd.
Coker, Eric; Gunier, Robert; Bradman, Asa; Harley, Kim; Kogut, Katherine; Molitor, John; Eskenazi, Brenda
2017-05-09
We previously showed that potential prenatal exposure to agricultural pesticides was associated with adverse neurodevelopmental outcomes in children, yet the effects of joint exposure to multiple pesticides is poorly understood. In this paper, we investigate associations between the joint distribution of agricultural use patterns of multiple pesticides (denoted as "pesticide profiles") applied near maternal residences during pregnancy and Full-Scale Intelligence Quotient (FSIQ) at 7 years of age. Among a cohort of children residing in California's Salinas Valley, we used Pesticide Use Report (PUR) data to characterize potential exposure from use within 1 km of maternal residences during pregnancy for 15 potentially neurotoxic pesticides from five different chemical classes. We used Bayesian profile regression (BPR) to examine associations between clustered pesticide profiles and deficits in childhood FSIQ. BPR identified eight distinct clusters of prenatal pesticide profiles. Two of the pesticide profile clusters exhibited some of the highest cumulative pesticide use levels and were associated with deficits in adjusted FSIQ of -6.9 (95% credible interval: -11.3, -2.2) and -6.4 (95% credible interval: -13.1, 0.49), respectively, when compared with the pesticide profile cluster that showed the lowest level of pesticides use. Although maternal residence during pregnancy near high agricultural use of multiple neurotoxic pesticides was associated with FSIQ deficit, the magnitude of the associations showed potential for sub-additive effects. Epidemiologic analysis of pesticides and their potential health effects can benefit from a multi-pollutant approach to analysis.
Rackham, Matthew D; Cundy, Thomas P; Antoniou, Georgia; Freeman, Brian J C; Sutherland, Leanne M; Cundy, Peter J
2010-04-20
Prospective cohort study. To determine the predictors of serum chromium levels after stainless steel posterior spinal instrumentation for adolescent idiopathic scoliosis. Abnormally elevated serum chromium levels have been detected in patients with adolescent idiopathic scoliosis after stainless steel instrumentation. To date, the relationship among serum chromium levels, time of implantation, and implant characteristics (including surface area, rod length, numbers of hooks, screws, and cross connectors) has not been studied. Thirty patients with adolescent idiopathic scoliosis undergoing posterior instrumented spinal arthrodesis using stainless steel implants between 1998 and 2002 were prospectively studied. Serum chromium levels were measured between October 2006 and June 2007. Postoperative radiographs were used to measure rod lengths, number of hooks, screws, cross-connectors, and cables. The surface area of each component and the total surface area for each patient were calculated. Possible associations between serum chromium levels, time of implantation, and implant characteristics were investigated. Implant exposure, whether expressed in the form of total metal implant surface area, rod length, or number of metal interfaces, was found to be positively associated with serum chromium levels. Specifically, chromium levels increased by a multiplicative factor of 1.0060 for every additional square centimeter of total metal implant surface area (P = 0.02). In addition, the chromium level was found to decrease by a multiplicative factor of 0.7766 for every additional year since surgery (P = 0.02). After adjusting for the number of years since surgery, metal implant exposure is positively associated with elevated serum chromium levels in adolescent idiopathic scoliosis patients with stainless steel posterior spinal implants. This is the first study to identify statistically significant positive associations between specific spinal implant characteristics (other than corrosion identified by radiographs) and serum chromium levels.
Missing Data and Multiple Imputation: An Unbiased Approach
NASA Technical Reports Server (NTRS)
Foy, M.; VanBaalen, M.; Wear, M.; Mendez, C.; Mason, S.; Meyers, V.; Alexander, D.; Law, J.
2014-01-01
The default method of dealing with missing data in statistical analyses is to only use the complete observations (complete case analysis), which can lead to unexpected bias when data do not meet the assumption of missing completely at random (MCAR). For the assumption of MCAR to be met, missingness cannot be related to either the observed or unobserved variables. A less stringent assumption, missing at random (MAR), requires that missingness not be associated with the value of the missing variable itself, but can be associated with the other observed variables. When data are truly MAR as opposed to MCAR, the default complete case analysis method can lead to biased results. There are statistical options available to adjust for data that are MAR, including multiple imputation (MI) which is consistent and efficient at estimating effects. Multiple imputation uses informing variables to determine statistical distributions for each piece of missing data. Then multiple datasets are created by randomly drawing on the distributions for each piece of missing data. Since MI is efficient, only a limited number, usually less than 20, of imputed datasets are required to get stable estimates. Each imputed dataset is analyzed using standard statistical techniques, and then results are combined to get overall estimates of effect. A simulation study will be demonstrated to show the results of using the default complete case analysis, and MI in a linear regression of MCAR and MAR simulated data. Further, MI was successfully applied to the association study of CO2 levels and headaches when initial analysis showed there may be an underlying association between missing CO2 levels and reported headaches. Through MI, we were able to show that there is a strong association between average CO2 levels and the risk of headaches. Each unit increase in CO2 (mmHg) resulted in a doubling in the odds of reported headaches.
Xu, Ping; Krischer, Jeffrey P
2016-06-01
To define prognostic classification factors associated with the progression from single to multiple autoantibodies, multiple autoantibodies to dysglycemia, and dysglycemia to type 1 diabetes onset in relatives of individuals with type 1 diabetes. Three distinct cohorts of subjects from the Type 1 Diabetes TrialNet Pathway to Prevention Study were investigated separately. A recursive partitioning analysis (RPA) was used to determine the risk classes. Clinical characteristics, including genotype, antibody titers, and metabolic markers were analyzed. Age and GAD65 autoantibody (GAD65Ab) titers defined three risk classes for progression from single to multiple autoantibodies. The 5-year risk was 11% for those subjects >16 years of age with low GAD65Ab titers, 29% for those ≤16 years of age with low GAD65Ab titers, and 45% for those subjects with high GAD65Ab titers regardless of age. Progression to dysglycemia was associated with islet antigen 2 Ab titers, and 2-h glucose and fasting C-peptide levels. The 5-year risk is 28%, 39%, and 51% for respective risk classes defined by the three predictors. Progression to type 1 diabetes was associated with the number of positive autoantibodies, peak C-peptide level, HbA1c level, and age. Four risk classes defined by RPA had a 5-year risk of 9%, 33%, 62%, and 80%, respectively. The use of RPA offered a new classification approach that could predict the timing of transitions from one preclinical stage to the next in the development of type 1 diabetes. Using these RPA classes, new prevention techniques can be tailored based on the individual prognostic risk characteristics at different preclinical stages. © 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.
Yang, Shuna; Yuan, Junliang; Zhang, Xiaoyu; Fan, Huimin; Li, Yue; Yin, Jiangmei; Hu, Wenli
2017-09-01
Enlarged perivascular spaces (EPVS) have been identified as a marker of cerebral small vessel diseases (CSVD). Ambulatory blood pressure (ABP) is the strongest predictor of hypertension-related brain damage. However, the relationship between ABP levels and EPVS is unclear. This study aimed to investigate the association between ABP levels and EPVS by 24-hour ambulatory blood pressure monitoring (ABPM). We prospectively recruited inpatients for physical examinations in our hospital from May 2013 to Jun 2016. 24-hour ABPM data and cranial magnetic resonance imaging information were collected. EPVS in basal ganglia (BG) and centrum semiovale (CSO) were identified and classified into three categories by the severity. White matter hyperintensities were scored by Fazekas scale. Spearman correlation analysis and multiple logistic regression analysis were used to determine the relationship between ABP levels and EPVS. A total of 573 subjects were enrolled in this study. 24-hour, day and night systolic blood pressure (SBP) levels were positively related to higher numbers of EPVS in BG (24-hour SBP: r = 0.23, p < 0.01; day SBP: r = 0.25, p < 0.01; night SBP: r = 0.30, p < 0.01). The association was unchanged after controlling for confounders by multiple logistic regression analysis. 24-hour and day diastolic blood pressure (DBP) levels increased with an increasing degree of EPVS in CSO (p = 0.04 and 0.049, respectively). But the association disappeared after adjusting for confounders. Spearman correlation analysis indicated that ABP levels were not associated with higher numbers of EPVS in CSO (p > 0.05). DBP levels were not independently associated with the severity of EPVS in BG and CSO. Higher SBP levels were independently associated with EPVS in BG, but not in CSO, which supported EPVS in BG to be a marker of CSVD. Pathogenesis of EPVS in BG and CSO might be different.
Zhu, Xiang; Stephens, Matthew
2017-01-01
Bayesian methods for large-scale multiple regression provide attractive approaches to the analysis of genome-wide association studies (GWAS). For example, they can estimate heritability of complex traits, allowing for both polygenic and sparse models; and by incorporating external genomic data into the priors, they can increase power and yield new biological insights. However, these methods require access to individual genotypes and phenotypes, which are often not easily available. Here we provide a framework for performing these analyses without individual-level data. Specifically, we introduce a “Regression with Summary Statistics” (RSS) likelihood, which relates the multiple regression coefficients to univariate regression results that are often easily available. The RSS likelihood requires estimates of correlations among covariates (SNPs), which also can be obtained from public databases. We perform Bayesian multiple regression analysis by combining the RSS likelihood with previously proposed prior distributions, sampling posteriors by Markov chain Monte Carlo. In a wide range of simulations RSS performs similarly to analyses using the individual data, both for estimating heritability and detecting associations. We apply RSS to a GWAS of human height that contains 253,288 individuals typed at 1.06 million SNPs, for which analyses of individual-level data are practically impossible. Estimates of heritability (52%) are consistent with, but more precise, than previous results using subsets of these data. We also identify many previously unreported loci that show evidence for association with height in our analyses. Software is available at https://github.com/stephenslab/rss. PMID:29399241
Hall, Molly A; Verma, Anurag; Brown-Gentry, Kristin D; Goodloe, Robert; Boston, Jonathan; Wilson, Sarah; McClellan, Bob; Sutcliffe, Cara; Dilks, Holly H; Gillani, Nila B; Jin, Hailing; Mayo, Ping; Allen, Melissa; Schnetz-Boutaud, Nathalie; Crawford, Dana C; Ritchie, Marylyn D; Pendergrass, Sarah A
2014-12-01
We performed a Phenome-wide association study (PheWAS) utilizing diverse genotypic and phenotypic data existing across multiple populations in the National Health and Nutrition Examination Surveys (NHANES), conducted by the Centers for Disease Control and Prevention (CDC), and accessed by the Epidemiological Architecture for Genes Linked to Environment (EAGLE) study. We calculated comprehensive tests of association in Genetic NHANES using 80 SNPs and 1,008 phenotypes (grouped into 184 phenotype classes), stratified by race-ethnicity. Genetic NHANES includes three surveys (NHANES III, 1999-2000, and 2001-2002) and three race-ethnicities: non-Hispanic whites (n = 6,634), non-Hispanic blacks (n = 3,458), and Mexican Americans (n = 3,950). We identified 69 PheWAS associations replicating across surveys for the same SNP, phenotype-class, direction of effect, and race-ethnicity at p<0.01, allele frequency >0.01, and sample size >200. Of these 69 PheWAS associations, 39 replicated previously reported SNP-phenotype associations, 9 were related to previously reported associations, and 21 were novel associations. Fourteen results had the same direction of effect across more than one race-ethnicity: one result was novel, 11 replicated previously reported associations, and two were related to previously reported results. Thirteen SNPs showed evidence of pleiotropy. We further explored results with gene-based biological networks, contrasting the direction of effect for pleiotropic associations across phenotypes. One PheWAS result was ABCG2 missense SNP rs2231142, associated with uric acid levels in both non-Hispanic whites and Mexican Americans, protoporphyrin levels in non-Hispanic whites and Mexican Americans, and blood pressure levels in Mexican Americans. Another example was SNP rs1800588 near LIPC, significantly associated with the novel phenotypes of folate levels (Mexican Americans), vitamin E levels (non-Hispanic whites) and triglyceride levels (non-Hispanic whites), and replication for cholesterol levels. The results of this PheWAS show the utility of this approach for exposing more of the complex genetic architecture underlying multiple traits, through generating novel hypotheses for future research.
Nuclear microscopy in Parkinson's disease
NASA Astrophysics Data System (ADS)
Watt, F.; Lee, T.; Thong, P. S. P.; Tang, S. M.
1995-09-01
Rats have been subjected to unilateral lesioning with the selective neurotoxin 6-OHDA in order to induce Parkinsonism. Analysis using the NUS Nuclear Microscope facility have shown that iron levels are raised by an average of 26% in the lesioned subtantia nigra region of the brain compared with the non-lesioned side. In addition the background tissue level of iron is also elevated by 31% in the lesioned side, indicating that there is a general increase in iron levels as a result of the lesioning. This result is consistent with the other observations that other diseases of the brain are frequently associated with altered iron levels (eg. progressive nuclear palsy, multiple system atrophy, Alzheimers disease, multiple sclerosis).
Human health is affected by simultaneous exposure to stressors and amenities, but research typically considers single exposures. In order to account for multiple ambient environmental conditions, we constructed an Environmental Quality Index (EQI) using principle components analy...
Wang, Yu; Shumansky, Karey; Sin, Don D; Man, SF Paul; Akhabir, Loubna; Connett, John E; Anthonisen, Nicholas R; Paré, Peter D; Sandford, Andrew J; He, Jian-Qing
2015-01-01
Objective: We reported association of haplotypes formed by IL-1b (IL1B)-511C/T (rs16944) and a variable number of tandem repeats (rs2234663) in intron 3 of IL-1 receptor antagonist (IL1RN) with rate of lung function decline in smoking-induced COPD. The aim of current study was to further investigate this association. Methods: We genotyped an additional 19 polymorphisms in IL1 cluster (including IL1A, IL1B and IL1RN) in non-Hispanic whites who had the fastest (n = 268) and the slowest (n = 292) decline of FEV1% predicted in the same study. We also analyzed the association of all 21 polymorphisms with serum CRP levels. Results: None of 21 polymorphisms showed significant association with rate of decline of lung function or CRP levels after adjusting for multiple comparisons. Before adjusting for multiple comparisons, only IL1RN_19327 (rs315949) showed significant association with lung function decline (P = 0.03, additive model). The frequencies of genotypes containing the IL1RN_19327A allele were 71.9% and 62.2%, respectively in the fast and slow decline groups (P = 0.02, odds ratio = 1.6, 95% confidence interval = 1.1-2.3); the IL1B_5200 (rs1143633) and rs2234663 in IL1RN were associated with serum CRP levels (P=0.04 and 0.03, respectively). Conclusions: No single marker was significantly associated with either rate of lung function decline or serum CRP levels. PMID:26722511
Cardarelli, Roberto; Singh, Meharvan; Meyer, Jason; Balyakina, Elizabeth; Perez, Oscar; King, Michael
2014-07-01
Hypogonadism is highly prevalent in men older than 45 years and is associated with an increased risk of chronic diseases, including obesity, metabolic syndrome, diabetes, and cardiovascular disease. The objective of this study was to determine whether lifestyle factors such as smoking, diet, and exercise are associated with reduced testosterone levels. In this cross-sectional study, 147 men older than 44 years were recruited from a collaborative network of primary care clinics in the Dallas/Fort Worth, Texas, metropolitan area. Free testosterone levels were measured in plasma samples via an enzyme-linked immunosorbent assay-based method, and analyzed by simple and multiple linear regression in relationship to age, race/ethnicity, smoking, diet, exercise, obesity, diabetes, hypertension, and dyslipidemia. The participants had a mean free testosterone level of 3.1 ng/mL (standard deviation [SD] = 1.5) and mean age of 56.8 years (SD = 7.9). In simple regression analysis, free testosterone levels were associated with increased age (β = -0.04; P = .02), diet (β = -0.49; P = .05), diabetes (β = -0.9; P = .003), and hypertension (β = -0.55; P = .03) but not with race/ethnicity, smoking, exercise, obesity, or dyslipidemia. In multiple regression analysis, free testosterone values were significantly associated only with age (β = -0.05; P = .01) and diet (β = -0.72; P = .01). This study implicates diet, in addition to advanced age as a possible risk factor in the development of reduced testosterone levels. © The Author(s) 2014.
Preliminary evidence that self-efficacy predicts physical activity in multiple sclerosis.
Motl, Robert W; McAuley, Edward; Doerksen, Shawna; Hu, Liang; Morris, Katherine S
2009-09-01
Individuals with multiple sclerosis (MS) are less physically active than non diseased people. One method for increasing physical activity levels involves the identification of factors that correlate with physical activity and that are modifiable by a well designed intervention. This study examined two types of self-efficacy as cross-sectional and prospective correlates of objectively measured physical activity in 16 individuals with a diagnosis of MS. The participants completed two measures of self-efficacy and then wore an accelerometer for a 5-day period at baseline and then at 3 months follow-up. Self-efficacy for continued physical activity was associated with baseline and follow-up levels of physical activity. Self-efficacy for overcoming barriers was associated with follow-up levels of physical activity and change in physical activity across a 3-month period. Researchers should consider self-efficacy as a possible component of an intervention that is designed to increase physical activity levels in those with MS. International Journal of Rehabilitation Research
Mansur, Rodrigo B.; Cunha, Graccielle R.; Asevedo, Elson; Zugman, André; Zeni-Graiff, Maiara; Rios, Adiel C.; Sethi, Sumit; Maurya, Pawan K.; Levandowski, Mateus L.; Gadelha, Ary; Pan, Pedro M.; Stertz, Laura; Belangero, Síntia I.; Kauer-Sant' Anna, Márcia; Teixeira, Antônio L.; Mari, Jair J.; Rohde, Luis A.; Miguel, Euripedes C.; McIntyre, Roger S.; Grassi-Oliveira, Rodrigo; Bressan, Rodrigo A.; Brietzke, Elisa
2016-01-01
Background Socioeconomic disadvantage (SED) has been consistently associated with early life mental health problems. SED has been shown to impact multiple biological systems, including the regulation of neurotrophic proteins, immune-inflammatory and oxidative stress markers, which, conversely, have been reported to be relevant to physiological and pathological neurodevelopment This study investigated the relationship between SED, different domains of psychopathology, serum levels of interleukin-6 (IL6), thiobarbituric acid-reactive substance (TBARS) and brain-derived neurotrophic factor (BDNF). We hypothesized that a composite of socioeconomic risk would be associated with psychopathology and altered levels of peripheral biomarkers. In addition, we hypothesized that SED would moderate the associations between mental health problems, IL6, TBARS and BDNF. Methods and Findings Using a cross-sectional design, we measured the serum levels of IL6, TBARS and BDNF in 495 children aged 6 to 12. We also investigated socio-demographic characteristics and mental health problems using the Child Behaviour Checklist (CBCL) DSM-oriented scales. SED was evaluated using a cumulative risk model. Generalized linear models were used to assess associations between SED, biomarkers levels and psychopathology. SED was significantly associated with serum levels of IL6 (RR = 1.026, 95% CI 1.004; 1.049, p = 0.020) and TBARS (RR = 1.077, 95% CI 1.028; 1.127, p = 0.002). The association between SED and BDNF was not statistically significant (RR = 1.031, 95% CI 0.997; 1.066, p = 0.077). SED was also significantly associated with all CBCL DSM-oriented scales (all p < 0.05), whereas serum biomarkers (i.e. IL6, TBARS, BDNF) were associated with specific subscales. Moreover, the associations between serum biomarkers and domains of psychopathology were moderated by SED, with stronger correlations between mental health problems, IL6, TBARS, and BDNF being observed in children with high SED. Conclusions In children, SED is highly associated with mental health problems. Our findings suggest that this association may be moderated via effects on multiple interacting neurobiological systems. PMID:27489945
Mokhtarzade, Motahare; Ranjbar, Rouholah; Majdinasab, Nastaran; Patel, Darpan; Molanouri Shamsi, Mehdieh
2017-08-01
Multiple sclerosis is associated with immune system dysfunction and chronic inflammation; however, possible relations between immunologic and metabolic factors and some psychological indexes such as fatigue and quality of life, especially in relation to exercise training, have not yet been investigated. The present study was designed to investigate the effect of aerobic interval training on interleukin-10/tumor necrosis factor ratio and adipokine (leptin and adiponectin) concentrations in women with multiple sclerosis. Furthermore, the relationship between these factors with fatigue and quality of life were assessed. Forty women with multiple sclerosis (Expanded Disability Status Scale ≤3) were randomized into either a non-exercising control or training group. The training group performed 8-weeks of upper and lower limb aerobic interval training. Serum concentrations of tumor necrosis factorα, interleukin-10, leptin, and adiponectin were measured before and after the 8-week intervention. Moreover, antropometric measures and measures for fatigue and quality of life were determined at the onset of and after exercise training. The results revealed that leptin and tumor necrosis factorα levels significantly decreased subsequent to the aerobic interval training. Although blood adiponectin levels considerably increased in the training group, interleukin-10 and interleukin-10/tumor necrosis factorα ratio underwent no substantial change after the exercise training. In addition, the aerobic interval training was associated with improvement in fatigue, quality of life, and maximal oxygen consumption. Our findings suggested that aerobic interval training can be an effective strategy for managing the immune system at least by its significant impact on inflammatory cytokines and adipokines levels in women with multiple sclerosis. Additionally, this positive impact improved fatigue and adipose tissue indicators.
Macotela, Yazmin; Emanuelli, Brice; Bång, Anneli M.; Espinoza, Daniel O.; Boucher, Jeremie; Beebe, Kirk; Gall, Walter; Kahn, C. Ronald
2011-01-01
Environmental factors, such as the macronutrient composition of the diet, can have a profound impact on risk of diabetes and metabolic syndrome. In the present study we demonstrate how a single, simple dietary factor—leucine—can modify insulin resistance by acting on multiple tissues and at multiple levels of metabolism. Mice were placed on a normal or high fat diet (HFD). Dietary leucine was doubled by addition to the drinking water. mRNA, protein and complete metabolomic profiles were assessed in the major insulin sensitive tissues and serum, and correlated with changes in glucose homeostasis and insulin signaling. After 8 weeks on HFD, mice developed obesity, fatty liver, inflammatory changes in adipose tissue and insulin resistance at the level of IRS-1 phosphorylation, as well as alterations in metabolomic profile of amino acid metabolites, TCA cycle intermediates, glucose and cholesterol metabolites, and fatty acids in liver, muscle, fat and serum. Doubling dietary leucine reversed many of the metabolite abnormalities and caused a marked improvement in glucose tolerance and insulin signaling without altering food intake or weight gain. Increased dietary leucine was also associated with a decrease in hepatic steatosis and a decrease in inflammation in adipose tissue. These changes occurred despite an increase in insulin-stimulated phosphorylation of p70S6 kinase indicating enhanced activation of mTOR, a phenomenon normally associated with insulin resistance. These data indicate that modest changes in a single environmental/nutrient factor can modify multiple metabolic and signaling pathways and modify HFD induced metabolic syndrome by acting at a systemic level on multiple tissues. These data also suggest that increasing dietary leucine may provide an adjunct in the management of obesity-related insulin resistance. PMID:21731668
Baines, Cornelia Johanna; McKeown-Eyssen, Gail Elizabeth; Riley, Nicole; Cole, David Edward C; Marshall, Lynn; Loescher, Barry; Jazmaji, Vartouhi
2004-09-01
Multiple chemical sensitivity (MCS), although poorly understood, is associated with considerable morbidity. To investigate potential biological mechanisms underlying MCS in a case-control study. Two hundred and twenty-three MCS cases and 194 controls (urban females, aged 30-64 years) fulfilled reproducible eligibility criteria with discriminant validity. Routine laboratory results and serum levels of volatile organic compounds (VOCs) were compared. Dose-response relationships, a criterion for causality, were examined linking exposures to likelihood of case status. Routine laboratory investigations revealed clinically unimportant case-control differences in means. Confounder-adjusted odds ratios (OR) showed MCS was negatively associated with lymphocyte count and total plasma homocysteine, positively associated with mean cell haemoglobin concentration, alanine aminotransferase and serum vitamin B6, and not associated with thyroid stimulating hormone, folate or serum vitamin B12. More cases than controls had detectable serum chloroform (P = 0.001) with the OR for detectability 2.78 (95% confidence interval = 1.73-4.48, P < 0.001). Chloroform levels were higher in cases. However, cases had significantly lower means of detectable serum levels of ethylbenzene, m&p-xylene, 3-methylpentane and hexane, and means of all serum levels of 1,3,5- and 1,2,3-trimethylbenzene, 2- and 3-methylpentane, and m&p-xylene. Our findings are inconsistent with proposals that MCS is associated with vitamin deficiency or thyroid dysfunction, but the association of lower lymphocyte counts with an increased likelihood of MCS is consistent with theories of immune dysfunction in MCS. Whether avoidance of exposures or different metabolic pathways in cases explain the observed lower VOC levels or the higher chloroform levels should be investigated.
Shin, Jung Eun; Choi, Chi-Hoon; Lee, Jong Min; Kwon, Jun Soo; Lee, So Hee; Kim, Hyun-Chung; Han, Na Young; Choi, Soo-Hee; Yoo, So Young
2017-01-01
Individuals with posttraumatic stress disorder (PTSD) had experiences of enormous psychological stress that can result in neurocognitive and neurochemical changes. To date, the causal relationship between them remains unclear. The present study is to investigate the association between neurocognitive characteristics and neural metabolite concentrations in North Korean refugees with PTSD. A total of 53 North Korean refugees with or without PTSD underwent neurocognitive function tests. For neural metabolite scanning, magnetic resonance spectroscopy of the hippocampus and anterior cingulate cortex (ACC) has been conducted. We assessed between-group differences in neurocognitive test scores and metabolite levels. Additionally, a multiple regression analysis was carried out to evaluate the association between neurocognitive function and metabolite levels in patients with PTSD. Memory function, but not other neurocognitive functions, was significantly lower in the PTSD group compared with the non-PTSD group. Hippocampal N-acetylaspartate (NAA) levels were not different between groups; however, NAA levels were significantly lower in the ACC of the PTSD group than the non-PTSD group (t = 2.424, p = 0.019). The multiple regression analysis showed a negative association between hippocampal NAA levels and delayed recall score on the auditory verbal learning test (β = -1.744, p = 0.011) in the non-PTSD group, but not in the PTSD group. We identified specific memory impairment and the role of NAA levels in PTSD. Our findings suggest that hippocampal NAA has a protective role in memory impairment and development of PTSD after exposure to traumatic events.
Climbing Bloom's taxonomy pyramid: Lessons from a graduate histology course.
Zaidi, Nikki B; Hwang, Charles; Scott, Sara; Stallard, Stefanie; Purkiss, Joel; Hortsch, Michael
2017-09-01
Bloom's taxonomy was adopted to create a subject-specific scoring tool for histology multiple-choice questions (MCQs). This Bloom's Taxonomy Histology Tool (BTHT) was used to analyze teacher- and student-generated quiz and examination questions from a graduate level histology course. Multiple-choice questions using histological images were generally assigned a higher BTHT level than simple text questions. The type of microscopy technique (light or electron microscopy) used for these image-based questions did not result in any significant differences in their Bloom's taxonomy scores. The BTHT levels for teacher-generated MCQs correlated positively with higher discrimination indices and inversely with the percent of students answering these questions correctly (difficulty index), suggesting that higher-level Bloom's taxonomy questions differentiate well between higher- and lower-performing students. When examining BTHT scores for MCQs that were written by students in a Multiple-Choice Item Development Assignment (MCIDA) there was no significant correlation between these scores and the students' ability to answer teacher-generated MCQs. This suggests that the ability to answer histology MCQs relies on a different skill set than the aptitude to construct higher-level Bloom's taxonomy questions. However, students significantly improved their average BTHT scores from the midterm to the final MCIDA task, which indicates that practice, experience and feedback increased their MCQ writing proficiency. Anat Sci Educ 10: 456-464. © 2017 American Association of Anatomists. © 2017 American Association of Anatomists.
Austin, Peter C; Mamdani, Muhammad M; Juurlink, David N; Hux, Janet E
2006-09-01
To illustrate how multiple hypotheses testing can produce associations with no clinical plausibility. We conducted a study of all 10,674,945 residents of Ontario aged between 18 and 100 years in 2000. Residents were randomly assigned to equally sized derivation and validation cohorts and classified according to their astrological sign. Using the derivation cohort, we searched through 223 of the most common diagnoses for hospitalization until we identified two for which subjects born under one astrological sign had a significantly higher probability of hospitalization compared to subjects born under the remaining signs combined (P<0.05). We tested these 24 associations in the independent validation cohort. Residents born under Leo had a higher probability of gastrointestinal hemorrhage (P=0.0447), while Sagittarians had a higher probability of humerus fracture (P=0.0123) compared to all other signs combined. After adjusting the significance level to account for multiple comparisons, none of the identified associations remained significant in either the derivation or validation cohort. Our analyses illustrate how the testing of multiple, non-prespecified hypotheses increases the likelihood of detecting implausible associations. Our findings have important implications for the analysis and interpretation of clinical studies.
SYNTHETIC BIOLOGY. Emergent genetic oscillations in a synthetic microbial consortium.
Chen, Ye; Kim, Jae Kyoung; Hirning, Andrew J; Josić, Krešimir; Bennett, Matthew R
2015-08-28
A challenge of synthetic biology is the creation of cooperative microbial systems that exhibit population-level behaviors. Such systems use cellular signaling mechanisms to regulate gene expression across multiple cell types. We describe the construction of a synthetic microbial consortium consisting of two distinct cell types—an "activator" strain and a "repressor" strain. These strains produced two orthogonal cell-signaling molecules that regulate gene expression within a synthetic circuit spanning both strains. The two strains generated emergent, population-level oscillations only when cultured together. Certain network topologies of the two-strain circuit were better at maintaining robust oscillations than others. The ability to program population-level dynamics through the genetic engineering of multiple cooperative strains points the way toward engineering complex synthetic tissues and organs with multiple cell types. Copyright © 2015, American Association for the Advancement of Science.
Single-unit muscle sympathetic nervous activity and its relation to cardiac noradrenaline spillover
Lambert, Elisabeth A; Schlaich, Markus P; Dawood, Tye; Sari, Carolina; Chopra, Reena; Barton, David A; Kaye, David M; Elam, Mikael; Esler, Murray D; Lambert, Gavin W
2011-01-01
Abstract Recent work using single-unit sympathetic nerve recording techniques has demonstrated aberrations in the firing pattern of sympathetic nerves in a variety of patient groups. We sought to examine whether nerve firing pattern is associated with increased noradrenaline release. Using single-unit muscle sympathetic nerve recording techniques coupled with direct cardiac catheterisation and noradrenaline isotope dilution methodology we examined the relationship between single-unit firing patterns and cardiac and whole body noradrenaline spillover to plasma. Participants comprised patients with hypertension (n = 6), depression (n = 7) and panic disorder (n = 9) who were drawn from our ongoing studies. The patient groups examined did not differ in their single-unit muscle sympathetic nerve firing characteristics nor in the rate of spillover of noradrenaline to plasma from the heart. The median incidence of multiple spikes per beat was 9%. Patients were stratified according to the firing pattern: low level of incidence (less than 9% incidence of multiple spikes per beat) and high level of incidence (greater than 9% incidence of multiple spikes per beat). High incidence of multiple spikes within a cardiac cycle was associated with higher firing rates (P < 0.0001) and increased probability of firing (P < 0.0001). Whole body noradrenaline spillover to plasma and (multi-unit) muscle sympathetic nerve activity in subjects with low incidence of multiple spikes was not different to that of those with high incidence of multiple spikes. In those with high incidence of multiple spikes there occurred a parallel activation of the sympathetic outflow to the heart, with cardiac noradrenaline spillover to plasma being two times that of subjects with low nerve firing rates (11.0 ± 1.5 vs. 22.0 ± 4.5 ng min−1, P < 0.05). This study indicates that multiple within-burst firing and increased single-unit firing rates of the sympathetic outflow to the skeletal muscle vasculature is associated with high cardiac noradrenaline spillover. PMID:21486790
ERIC Educational Resources Information Center
Toomey, Russell B.; Card, Noel A.; Casper, Deborah M.
2014-01-01
The current study used reports from 318 early adolescents to examine the associations of peer-reported gender nonconformity with peer- and self-reported overt and relational victimization and aggression, and possible sex differences in these associations. Multiple-group structural equation modeling revealed that higher levels of peer-reported…
Fu, Junling; Li, Ge; Li, Lujiao; Yin, Jinhua; Cheng, Hong; Han, Lanwen; Zhang, Qian; Li, Naishi; Xiao, Xinhua; Grant, Struan F.A.; Li, Mingyao; Gao, Shan; Mi, Jie; Li, Ming
2017-01-01
Genome-wide association studies have identified multiple variants associated with adult obesity, mostly in European-ancestry populations. We aimed to systematically assess the contribution of key loci, which had been previously shown to be associated in East Asian adults, to childhood obesity, related adipokine profiles and metabolic traits in a Chinese pediatric population. Twelve single-nucleotide polymorphisms (SNPs) plus metabolic profiles and levels of five adipokines (leptin, adiponectin, resistin, fibroblast growth factor 21 and retinol binding protein 4) were evaluated in 3,506 Chinese children and adolescents aged 6-18. After correction for multiple comparisons, six of these SNPs were robustly associated with childhood obesity: FTO-rs1558902 (P=5.6×10−5), MC4R-rs2331841 (P=4.4×10−4), GNPDA2-rs16858082 (P = 3.4×10−4), PCSK1-rs261967 (P = 0.001), SEC16B-rs516636 (P = 0.004) and MAP2K5-rs4776970 (P = 0.004), with odds ratios ranging from 1.211 to 1.421; while ITIH4-rs2535633 and BDNF-rs2030323 yielded nominal association with the same trait (P < 0.05). Moreover, the risk alleles of six SNPs displayed significant (P < 0.004) or nominal (P < 0.05) association with leptin levels, namely at in/near PCSK1, MC4R, FTO, MAP2K5, GNPDA2 and BDNF plus their cumulative genetic score yielded stronger association with increased leptin levels (P = 6.2×10−11). Our results reveal that key obesity-associated loci previously reported in Europeans, but also associated with East Asian adults, are also associated with obesity and/or metabolic quantitative traits in Chinese children. These associations coincide with six brain-expressed loci that correlate with leptin levels, thus may point to an important neuronal influence on body weight regulation in the pediatric setting. PMID:29212175
Fu, Junling; Li, Ge; Li, Lujiao; Yin, Jinhua; Cheng, Hong; Han, Lanwen; Zhang, Qian; Li, Naishi; Xiao, Xinhua; Grant, Struan F A; Li, Mingyao; Gao, Shan; Mi, Jie; Li, Ming
2017-11-07
Genome-wide association studies have identified multiple variants associated with adult obesity, mostly in European-ancestry populations. We aimed to systematically assess the contribution of key loci, which had been previously shown to be associated in East Asian adults, to childhood obesity, related adipokine profiles and metabolic traits in a Chinese pediatric population. Twelve single-nucleotide polymorphisms (SNPs) plus metabolic profiles and levels of five adipokines (leptin, adiponectin, resistin, fibroblast growth factor 21 and retinol binding protein 4) were evaluated in 3,506 Chinese children and adolescents aged 6-18. After correction for multiple comparisons, six of these SNPs were robustly associated with childhood obesity: FTO -rs1558902 ( P =5.6×10 -5 ), MC4R -rs2331841 ( P =4.4×10 -4 ), GNPDA2 -rs16858082 ( P = 3.4×10 -4 ), PCSK1 -rs261967 ( P = 0.001), SEC16B -rs516636 ( P = 0.004) and MAP2K5 -rs4776970 ( P = 0.004), with odds ratios ranging from 1.211 to 1.421; while ITIH4 -rs2535633 and BDNF -rs2030323 yielded nominal association with the same trait ( P < 0.05). Moreover, the risk alleles of six SNPs displayed significant ( P < 0.004) or nominal ( P < 0.05) association with leptin levels, namely at in/near PCSK1, MC4R, FTO, MAP2K5, GNPDA2 and BDNF plus their cumulative genetic score yielded stronger association with increased leptin levels ( P = 6.2×10 -11 ). Our results reveal that key obesity-associated loci previously reported in Europeans, but also associated with East Asian adults, are also associated with obesity and/or metabolic quantitative traits in Chinese children. These associations coincide with six brain-expressed loci that correlate with leptin levels, thus may point to an important neuronal influence on body weight regulation in the pediatric setting.
Kamei, Nozomu; Yamane, Kiminori; Nakanishi, Shuhei; Ishida, Kazufumi; Ohtaki, Megu; Okubo, Masamichi; Kohno, Nobuoki
2005-06-01
The effects of the prolonged elevation of nonesterified fatty acid (NEFA) levels on insulin secretion have been controversial and thought to be sex-specific. To investigate the association between a westernized lifestyle and the effects of NEFA on insulin secretion in Japanese men, we examined 67 nondiabetic Japanese-American men and 220 nondiabetic native Japanese men who underwent a 75-g oral glucose tolerance test (OGTT). Most Japanese Americans we surveyed are genetically identical to Japanese living in Japan, but their lifestyle is more westernized. Sets of multiple regression analyses were performed to evaluate the relationship between the sum of the immunoreactive insulin (IRI) levels during the OGTT ((Sigma)IRI) and clinical parameters. Japanese Americans had higher levels of fasting IRI, (Sigma)IRI, and a higher insulin resistance index (homeostasis model assessment for insulin resistance [HOMA-IR]) than native Japanese, whereas there were no significant differences in fasting NEFA and triglyceride levels. A multiple regression analysis adjusted for age, fasting triglycerides, and body mass index (BMI) demonstrated that the fasting NEFA level was an independent determinant of the (Sigma)IRI only in Japanese-American men ( P = .001), but not in native Japanese men ( P = .054). Even when HOMA-IR was included in models instead of BMI, the NEFA level was a significant variable of (Sigma)IRI only in Japanese Americans ( P < .001), and not in native Japanese ( P = .098). In addition, a multiple regression analysis adjusted for age, fasting triglycerides, and BMI demonstrated that the fasting NEFA level was the only independent determinant of (Sigma)C-peptide in Japanese-American men ( P = .041). In conclusion, NEFA seems to be associated with insulin secretion independent of obesity or HOMA-IR. A westernized lifestyle may increase the effects of serum fasting NEFA levels on total insulin secretion after a glucose load in Japanese men.
Large-scale gene-centric meta-analysis across 32 studies identifies multiple lipid loci
USDA-ARS?s Scientific Manuscript database
Genome-wide association studies (GWASs) have identified many SNPs underlying variations in plasma-lipid levels. We explore whether additional loci associated with plasma-lipid phenotypes, such as high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), total cholest...
Level of education and multiple sclerosis risk over a 50-year period: Registry-based sibling study.
Bjørnevik, Kjetil; Riise, Trond; Benjaminsen, Espen; Celius, Elisabeth G; Dahl, Ole P; Kampman, Margitta T; Løken-Amsrud, Kristin I; Midgard, Rune; Myhr, Kjell-Morten; Torkildsen, Øivind; Vatne, Anita; Grytten, Nina
2017-02-01
The conflicting results from studies on socioeconomic status (SES) and multiple sclerosis (MS) risk might be due to a change in the distribution of environmental exposures over time or to methodological limitations in previous research. To examine the association between SES and MS risk during 50 years. We included patients registered in Norwegian MS registries and prevalence studies born between 1930 and 1979, and identified their siblings and parents using the Norwegian Population Registry. Information on education was retrieved from the National Education Registry, categorized into four levels (primary, secondary, undergraduate and graduate) and compared in patients and siblings using conditional logistic regression. A total of 4494 MS patients and 9193 of their siblings were included in the analyses. Level of education was inversely associated with MS risk ( p trend < 0.001) with an odds ratio (OR) of 0.73 (95% confidence interval (CI): 0.59-0.90) when comparing the highest and lowest levels. The effect estimates did not vary markedly between participants born before or after the median year of birth (1958), but we observed a significant effect modification by parental education ( p = 0.047). Level of education was inversely associated with MS risk, and the estimates were similar in the earliest and latest birth cohorts.
Air quality and acute deaths in California, 2000-2012.
Young, S Stanley; Smith, Richard L; Lopiano, Keneth K
2017-08-01
Many studies have shown an association between air quality and acute deaths, and such associations are widely interpreted as causal. Several factors call causation and even association into question, for example multiple testing and multiple modeling, publication bias and confirmation bias. Many published studies are difficult or impossible to reproduce because of lack of access to confidential data sources. Here we make publically available a dataset containing daily air quality levels, PM 2.5 and ozone, daily temperature levels, minimum and maximum and daily maximum relative humidity levels for the eight most populous California air basins, thirteen years, >2M deaths, over 37,000 exposure days. The data are analyzed using standard time series analysis, and a sensitivity analysis is computed varying model parameters, locations and years. Our analysis finds little evidence for association between air quality and acute deaths. These results are consistent with those for the widely cited NMMAPS dataset when the latter are restricted to California. The daily death variability was mostly explained by time of year or weather variables; Neither PM 2.5 nor ozone added appreciably to the prediction of daily deaths. These results call into question the widespread belief that association between air quality and acute deaths is causal/near-universal. Copyright © 2017 Elsevier Inc. All rights reserved.
Lyon, Debra E.; Cohen, Ronald; Chen, Huaihou; Kelly, Debra L.; McCain, Nancy L.; Starkweather, Angela; Sturgill, Jamie; Jackson-Cook, Colleen K.
2016-01-01
Cancer and its treatment are frequently associated with cancer-related cognitive impairment (CRCI). While CRCI has been linked to chemotherapy, there is increasing evidence that the condition may start prior to treatment and for some, remain unresolved after active treatment and into survivorship. Although the pathophysiology of the condition is complex, alterations in systemic cytokines, signaling molecules activated in response to infection or injury that trigger inflammation, are a possible mechanism linked to cognitive dysfunction in breast cancer and other conditions. Given the conflicting results in the literature, the lack of focus on domain-specific cognitive testing, and the need for a longer time period given the multiple modalities of standard treatments for early-stage breast cancer, this longitudinal study was conducted to address these gaps. Methods We assessed 75 women with early-stage breast cancer at five points over two years, starting prior to the initial chemotherapy through 24 months after chemotherapy initiation. Measures included a validated computerized evaluation of domain-specific cognitive functioning and a 17-plex panel of plasma cytokines. Linear mixed-effects models were applied to test the relationships of clinical variables and cytokine concentrations to each cognitive domain. Results: Levels and patterns of cytokine concentrations varied over time: six of the 17 cytokines (IL-6, IL-12, IL-17, G-CSF, MIPS-1β, and MCP-1) had the most variability. Some cytokine levels (e.g., IL-6) increased during chemotherapy but then decreased subsequently, while others (e.g., IL-17) consistently declined from baseline over time. There were multiple relationships among cytokines and cognition, which varied over time. At baseline, elevated concentrations of G-CSF and reduced concentrations of IL-17 were associated with faster psychomotor speed. At the second time-point (prior to the mid-chemotherapy), multiple cytokines had significant associations with psychomotor speed, complex attention, executive function, verbal memory, cognitive flexibility, composite memory and visual memory. Six months after chemotherapy initiation and at the one-year point, there were multiple, significant relationships among cytokines and multiple cognitive. At two years, fewer significant relationships were noted; however, lower concentrations of IL-7, a hematopoietic cytokine, were associated with better psychomotor speed, complex attention, and memory (composite, verbal and visual). MCP-1 was inversely associated with psychomotor speed and complex attention and higher levels of MIP-1β were related to better complex attention. Conclusion Levels and patterns of cytokines changed over time and demonstrated associations with domain-specific cognitive functioning that varied over time. The observed associations between cytokines and cognitive performance provides evidence that not only prototypical cytokines (i.e. IL-6, TNF-α, and IL1-β) but also cytokines from multiple classes may contribute to the inflammatory environment that is associated with cognitive dysfunction. Future studies to better delineate the cytokine changes, both individually and in networks, are needed to precisely assess a mechanistic link between cytokines and cognitive function in women receiving treatments for breast cancer. PMID:27890459
Kahnert, Kathrin; Alter, Peter; Welte, Tobias; Huber, Rudolf M; Behr, Jürgen; Biertz, Frank; Watz, Henrik; Bals, Robert; Vogelmeier, Claus F; Jörres, Rudolf A
2018-06-04
Recent investigations showed single associations between uric acid levels, functional parameters, exacerbations and mortality in COPD patients. The aim of this study was to describe the role of uric acid within the network of multiple relationships between function, exacerbation and comorbidities. We used baseline data from the German COPD cohort COSYCONET which were evaluated by standard multiple regression analyses as well as path analysis to quantify the network of relations between parameters, particularly uric acid. Data from 1966 patients were analyzed. Uric acid was significantly associated with reduced FEV 1 , reduced 6-MWD, higher burden of exacerbations (GOLD criteria) and cardiovascular comorbidities, in addition to risk factors such as BMI and packyears. These associations remained significant after taking into account their multiple interdependences. Compared to uric acid levels the diagnosis of hyperuricemia and its medication played a minor role. Within the limits of a cross-sectional approach, our results strongly suggest that uric acid is a biomarker of high impact in COPD and plays a genuine role for relevant outcomes such as physical capacity and exacerbations. These findings suggest that more attention should be paid to uric acid in the evaluation of COPD disease status.
A case control study of multiple myeloma at four nuclear facilities.
Wing, S; Richardson, D; Wolf, S; Mihlan, G; Crawford-Brown, D; Wood, J
2000-04-01
Reported elevations of multiple myeloma among nuclear workers exposed to external penetrating ionizing radiation, based on small numbers of cases, prompted this multi-facility study of workers at US Department of Energy facilities. Ninety-eight multiple myeloma deaths and 391 age-matched controls were selected from the combined roster of 115,143 workers hired before 1979 at Hanford, Los Alamos National Laboratory, Oak Ridge National Laboratory, and the Savannah River site. These workers were followed for vital status through 1990 (1986 for Hanford). Demographic, work history, and occupational exposure data were derived from personnel, occupational medicine, industrial hygiene, and health physics records. Exposure-disease associations were evaluated using conditional logistic regression. Cases were disproportionately African American, male, and hired prior to 1948. Lifetime cumulative whole body ionizing radiation dose was not associated with multiple myeloma, however, there was a significant effect of age at exposure, with positive associations between multiple myeloma and doses received at older ages. Dose response associations increased in magnitude with exposure age (from 40 to 50) and lag assumption (from 5 to 15 years), while a likelihood ratio goodness of fit test reached the highest value for cumulative doses received at ages above 45 with a 5-year lag (X2=5.43,1 df; relative risk = 6.9% per 10 mSv). Dose response associations persisted with adjustment for potential confounders. Multiple myeloma was associated with low level whole body penetrating ionizing radiation doses at older ages. The exposure age effect is at odds with interpretations of A-bomb survivor studies but in agreement with several studies of cancer among nuclear workers.
Yang, Yong
2017-11-01
Most health studies focus on one health outcome and examine the influence of one or multiple risk factors. However, in reality, various pathways, interactions, and associations exist not only between risk factors and health outcomes but also among the risk factors and among health outcomes. The advance of system science methods, Big Data, and accumulated knowledge allows us to examine how multiple risk factors influence multiple health outcomes at multiple levels (termed a 3M study). Using the study of neighborhood environment and health as an example, I elaborate on the significance of 3M studies. 3M studies may lead to a significantly deeper understanding of the dynamic interactions among risk factors and outcomes and could help us design better interventions that may be of particular relevance for upstream interventions. Agent-based modeling (ABM) is a promising method in the 3M study, although its potentials are far from being fully explored. Future challenges include the gap of epidemiologic knowledge and evidence, lack of empirical data sources, and the technical challenges of ABM. © 2017 New York Academy of Sciences.
Li, Ying; Meng, Lu; Li, Yue; Sato, Yasuto
2014-03-01
Although the association between depression and body composition has been widely discussed, the effects of depression on lean body mass (LBM) are unclear. The present study aimed to investigate the association of depression with LBM. The study included 2406 participants aged 18-69 years. The sex and body mass index (BMI) stratified analysis of covariance was performed to compare total LBM and percentage LBM (%LBM) in subjects with different depression score levels. Multiple linear regression analysis was conducted to estimate the association between depression score and serum albumin level. An analysis of covariance stratified by sex showed that participants with moderate-to-severe depression had significantly decreased total LBM and total and regional %LBM in men, except for total LBM and percentage gynoid LBM, which was observed in women. In the BMI stratified analysis of covariance, depression was significantly associated with decreased total and regional %LBM and with increased total and regional percentage fat body mass. In people with BMI≥25kg/m(2), the associations between depression or depressive syndrome and LBM, and total and regional %LBM are stronger compared to those with BMI<25kg/m(2). Multiple linear regression analysis showed that depression score was significantly negatively associated with serum albumin level. This is a cross-sectional study based on a general population, some information about clinical diagnosis and medication use is not available. Depression had a significant negative association with LBM and serum albumin level. Copyright © 2014 Elsevier B.V. All rights reserved.
Physical Activity and Its Correlates in Youth with Multiple Sclerosis.
Grover, Stephanie A; Sawicki, Carolyn P; Kinnett-Hopkins, Dominique; Finlayson, Marcia; Schneiderman, Jane E; Banwell, Brenda; Till, Christine; Motl, Robert W; Yeh, E Ann
2016-12-01
To investigate physical activity levels in youth with multiple sclerosis and monophasic acquired demyelinating syndromes ([mono-ADS], ie, children without relapsing disease) compared with healthy controls and to determine factors that contribute to engagement in physical activity. We hypothesized that greater physical activity goal setting and physical activity self-efficacy would be associated with greater levels of vigorous physical activity in youth with multiple sclerosis. A total of 68 consecutive patients (27 multiple sclerosis, 41 mono-ADS) and 37 healthy controls completed fatigue, depression, Physical Activity Self-Efficacy Scale, perceived disability, Exercise Goal-Setting scale, and physical activity questionnaires, and wore an accelerometer for 7 days. All patients had no ambulatory limitations (Expanded Disability Status Scale, scores all <4). Youth with multiple sclerosis engaged in fewer minutes per day of vigorous (P = .009) and moderate and vigorous physical activity (P = .048) than did patients with mono-ADS and healthy controls. A lower proportion of the group with multiple sclerosis (63%) reported participating in any strenuous physical activity than the mono-ADS (85%) and healthy control (89%) groups (P = .020). When we adjusted for age and sex, the Physical Activity Self-Efficacy Scale and Exercise Goal-Setting scale were associated positively with vigorous physical activity in the group with multiple sclerosis. Fatigue and depression did not predict physical activity or accelerometry metrics. Youth with multiple sclerosis participate in less physical activity than their counterparts with mono-ADS and healthy controls. Physical activity self-efficacy and exercise goal setting serve as potentially modifiable correlates of physical activity, and are measures suited to future interventions aimed to increase physical activity in youth with multiple sclerosis. Copyright © 2016 Elsevier Inc. All rights reserved.
Barro, Christian; Benkert, Pascal; Disanto, Giulio; Tsagkas, Charidimos; Amann, Michael; Naegelin, Yvonne; Leppert, David; Gobbi, Claudio; Granziera, Cristina; Yaldizli, Özgür; Michalak, Zuzanna; Wuerfel, Jens; Kappos, Ludwig; Parmar, Katrin; Kuhle, Jens
2018-05-30
Neuro-axonal injury is a key factor in the development of permanent disability in multiple sclerosis. Neurofilament light chain in peripheral blood has recently emerged as a biofluid marker reflecting neuro-axonal damage in this disease. We aimed at comparing serum neurofilament light chain levels in multiple sclerosis and healthy controls, to determine their association with measures of disease activity and their ability to predict future clinical worsening as well as brain and spinal cord volume loss. Neurofilament light chain was measured by single molecule array assay in 2183 serum samples collected as part of an ongoing cohort study from 259 patients with multiple sclerosis (189 relapsing and 70 progressive) and 259 healthy control subjects. Clinical assessment, serum sampling and MRI were done annually; median follow-up time was 6.5 years. Brain volumes were quantified by structural image evaluation using normalization of atrophy, and structural image evaluation using normalization of atrophy, cross-sectional, cervical spinal cord volumes using spinal cord image analyser (cordial). Results were analysed using ordinary linear regression models and generalized estimating equation modelling. Serum neurofilament light chain was higher in patients with a clinically isolated syndrome or relapsing remitting multiple sclerosis as well as in patients with secondary or primary progressive multiple sclerosis than in healthy controls (age adjusted P < 0.001 for both). Serum neurofilament light chain above the 90th percentile of healthy controls values was an independent predictor of Expanded Disability Status Scale worsening in the subsequent year (P < 0.001). The probability of Expanded Disability Status Scale worsening gradually increased by higher serum neurofilament light chain percentile category. Contrast enhancing and new/enlarging lesions were independently associated with increased serum neurofilament light chain (17.8% and 4.9% increase per lesion respectively; P < 0.001). The higher the serum neurofilament light chain percentile level, the more pronounced was future brain and cervical spinal volume loss: serum neurofilament light chain above the 97.5th percentile was associated with an additional average loss in brain volume of 1.5% (P < 0.001) and spinal cord volume of 2.5% over 5 years (P = 0.009). Serum neurofilament light chain correlated with concurrent and future clinical and MRI measures of disease activity and severity. High serum neurofilament light chain levels were associated with both brain and spinal cord volume loss. Neurofilament light chain levels are a real-time, easy to measure marker of neuro-axonal injury that is conceptually more comprehensive than brain MRI.
Ziaei, Shirin; Frith, Amy Lynn; Ekström, Eva-Charlotte; Naved, Ruchira Tabassum
2016-01-01
Experience of domestic violence has negative mental health consequences for women. The association of cumulative and specific forms of domestic violence, particularly emotional violence and controlling behavior, with common mental disorders and stress has rarely been studied in pregnant women. The aim of this study is to evaluate associations of specific and multiple forms of lifetime domestic violence and controlling behavior with distress and cortisol level during pregnancy in rural Bangladeshi women. In this observational sub-study of larger MINIMat trial, 3504 pregnant women were interviewed using a shortened Conflict Tactic Scale about their lifetime experience of domestic violence including physical, sexual, emotional domestic violence and controlling behavior. Women's levels of emotional distress were assessed using the self-reported questionnaire (SRQ-20) developed by WHO, and levels of morning salivary cortisol were measured in a subsample (n = 1300) of women during week 28-32 of pregnancy. Regression analyses were used to estimate the associations of lifetime physical, sexual, emotional domestic violence and controlling behavior with levels of distress and cortisol during pregnancy. The prevalence of lifetime domestic violence was 57% and emotional distress was 35% in these pregnant women. All forms of domestic violence were associated with higher levels of emotional distress. Women who experienced either emotional violence or controlling behavior had the highest levels of emotional distress. There was a dose-response relationship between cumulative number of the different forms of domestic violence and women's levels of emotional distress. There was no association between women's experience of domestic violence and level of morning salivary cortisol. Including emotional violence and controlling behavior as major types of violence in future research and health interventions is warranted. Furthermore, the extent of the negative impacts of domestic violence on pregnant women, multiple forms of violence and their cumulative effects need to be investigated.
Frith, Amy Lynn; Ekström, Eva-Charlotte; Naved, Ruchira Tabassum
2016-01-01
Background Experience of domestic violence has negative mental health consequences for women. The association of cumulative and specific forms of domestic violence, particularly emotional violence and controlling behavior, with common mental disorders and stress has rarely been studied in pregnant women. The aim of this study is to evaluate associations of specific and multiple forms of lifetime domestic violence and controlling behavior with distress and cortisol level during pregnancy in rural Bangladeshi women. Methods and findings In this observational sub-study of larger MINIMat trial, 3504 pregnant women were interviewed using a shortened Conflict Tactic Scale about their lifetime experience of domestic violence including physical, sexual, emotional domestic violence and controlling behavior. Women’s levels of emotional distress were assessed using the self-reported questionnaire (SRQ-20) developed by WHO, and levels of morning salivary cortisol were measured in a subsample (n = 1300) of women during week 28–32 of pregnancy. Regression analyses were used to estimate the associations of lifetime physical, sexual, emotional domestic violence and controlling behavior with levels of distress and cortisol during pregnancy. The prevalence of lifetime domestic violence was 57% and emotional distress was 35% in these pregnant women. All forms of domestic violence were associated with higher levels of emotional distress. Women who experienced either emotional violence or controlling behavior had the highest levels of emotional distress. There was a dose-response relationship between cumulative number of the different forms of domestic violence and women’s levels of emotional distress. There was no association between women’s experience of domestic violence and level of morning salivary cortisol. Conclusion Including emotional violence and controlling behavior as major types of violence in future research and health interventions is warranted. Furthermore, the extent of the negative impacts of domestic violence on pregnant women, multiple forms of violence and their cumulative effects need to be investigated. PMID:27992478
ERIC Educational Resources Information Center
Gadea, Marien; Martinez-Bisbal, M. Carmen; Marti-Bonmati, Luis; Espert, Raul; Casanova, Bonaventura; Coret, Francisco; Celda, Bernardo
2004-01-01
Lower levels of N-acetylaspartate (NAA), a marker of axonal damage, have been found in the normal-appearing white matter (NAWM) of relapsing-remitting multiple sclerosis (RRMS) patients with low physical disability. However, its relation to the clinical status of these patients remains unclear. We explored the association between NAA levels…
ERIC Educational Resources Information Center
Goksel Karatepe, Altlnay; Kaya, Taciser; Gunaydn, Rezzan; Demirhan, Aylin; Ce, Plnar; Gedizlioglu, Muhtesem
2011-01-01
Aim: The aim of this study was to assess the quality of life (QoL) in patients with multiple sclerosis (MS), and to evaluate its association with disability and psychosocial factors especially depression and fatigue. Methods: Demographic characteristics, education level, disease severity, and disease duration were documented for each patient. QoL,…
Learning with Multiple Representations: An Example of a Revision Lesson in Mathematics
ERIC Educational Resources Information Center
Wong, Darren; Poo, Sng Peng; Hock, Ng Eng; Kang, Wee Loo
2011-01-01
We describe an example of learning with multiple representations in an A-level revision lesson on mechanics. The context of the problem involved the motion of a ball thrown vertically upwards in air and studying how the associated physical quantities changed during its flight. Different groups of students were assigned to look at the ball's motion…
Stam, L. F.; Laurie, C. C.
1996-01-01
A molecular mapping experiment shows that a major gene effect on a quantitative trait, the level of alcohol dehydrogenase expression in Drosophila melanogaster, is due to multiple polymorphisms within the Adh gene. These polymorphisms are located in an intron, the coding sequence, and the 3' untranslated region. Because of nonrandom associations among polymorphisms at different sites, the individual effects combine (in some cases epistatically) to produce ``superalleles'' with large effect. These results have implications for the interpretation of major gene effects detected by quantitative trait locus mapping methods. They show that large effects due to a single locus may be due to multiple associated polymorphisms (or sequential fixations in isolated populations) rather than individual mutations of large effect. PMID:8978044
Unique Associations Between Big Five Personality Aspects and Multiple Dimensions of Well-Being.
Sun, Jessie; Kaufman, Scott Barry; Smillie, Luke D
2018-04-01
Personality traits are associated with well-being, but the precise correlates vary across well-being dimensions and within each Big Five domain. This study is the first to examine the unique associations between the Big Five aspects (rather than facets) and multiple well-being dimensions. Two samples of U.S. participants (total N = 706; M age = 36.17; 54% female) recruited via Amazon's Mechanical Turk completed measures of the Big Five aspects and subjective, psychological, and PERMA well-being. One aspect within each domain was more strongly associated with well-being variables. Enthusiasm and Withdrawal were strongly associated with a broad range of well-being variables, but other aspects of personality also had idiosyncratic associations with distinct forms of positive functioning (e.g., Compassion with positive relationships, Industriousness with accomplishment, and Intellect with personal growth). An aspect-level analysis provides an optimal (i.e., parsimonious yet sufficiently comprehensive) framework for describing the relation between personality traits and multiple ways of thriving in life. © 2016 Wiley Periodicals, Inc.
Genetic Variants Associated with Lipid Profiles in Chinese Patients with Type 2 Diabetes
Xing, Xiaoyan; Zhang, Bo; Zhang, Xuelian; Hong, Jing; Yang, Wenying
2015-01-01
Dyslipidemia is a strong risk factor for cardiovascular disease among patients with type 2 diabetes (T2D). The aim of this study was to identify lipid-related genetic variants in T2D patients of Han Chinese ancestry. Among 4,908 Chinese T2D patients who were not taking lipid-lowering medications, single nucleotide polymorphisms (SNPs) in seven genes previously found to be associated with lipid traits in genome-wide association studies conducted in populations of European ancestry (ABCA1, GCKR, BAZ1B, TOMM40, DOCK7, HNF1A, and HNF4A) were genotyped. After adjusting for multiple covariates, SNPs in ABCA1, GCKR, BAZ1B, TOMM40, and HNF1A were identified as significantly associated with triglyceride levels in T2D patients (P < 0.05). The associations between the SNPs in ABCA1 (rs3890182), GCKR (rs780094), and BAZ1B (rs2240466) remained significant even after correction for multiple testing (P = 8.85×10−3, 7.88×10−7, and 2.03×10−6, respectively). BAZ1B (rs2240466) also was associated with the total cholesterol level (P = 4.75×10−2). In addition, SNP rs157580 in TOMM40 was associated with the low-density lipoprotein cholesterol level (P = 6.94×10−3). Our findings confirm that lipid-related genetic loci are associated with lipid profiles in Chinese patients with type 2 diabetes. PMID:26252223
Agent Orange exposure and prevalence of self-reported diseases in Korean Vietnam veterans.
Yi, Sang-Wook; Ohrr, Heechoul; Hong, Jae-Seok; Yi, Jee-Jeon
2013-09-01
The aim of this study was to evaluate the association between Agent Orange exposure and self-reported diseases in Korean Vietnam veterans. A postal survey of 114 562 Vietnam veterans was conducted. The perceived exposure to Agent Orange was assessed by a 6-item questionnaire. Two proximity-based Agent Orange exposure indices were constructed using division/brigade-level and battalion/company-level unit information. Adjusted odds ratios (ORs) for age and other confounders were calculated using a logistic regression model. The prevalence of all self-reported diseases showed monotonically increasing trends as the levels of perceived self-reported exposure increased. The ORs for colon cancer (OR, 1.13), leukemia (OR, 1.56), hypertension (OR, 1.03), peripheral vasculopathy (OR, 1.07), enterocolitis (OR, 1.07), peripheral neuropathy (OR, 1.07), multiple nerve palsy (OR, 1.14), multiple sclerosis (OR, 1.24), skin diseases (OR, 1.05), psychotic diseases (OR, 1.07) and lipidemia (OR, 1.05) were significantly elevated for the high exposure group in the division/brigade-level proximity-based exposure analysis, compared to the low exposure group. The ORs for cerebral infarction (OR, 1.08), chronic bronchitis (OR, 1.05), multiple nerve palsy (OR, 1.07), multiple sclerosis (OR, 1.16), skin diseases (OR, 1.05), and lipidemia (OR, 1.05) were significantly elevated for the high exposure group in the battalion/company-level analysis. Korean Vietnam veterans with high exposure to Agent Orange experienced a higher prevalence of several self-reported chronic diseases compared to those with low exposure by proximity-based exposure assessment. The strong positive associations between perceived self-reported exposure and all self-reported diseases should be evaluated with discretion because the likelihood of reporting diseases was directly related to the perceived intensity of Agent Orange exposure.
Human health is affected by exposures operating from multiple domains across level of urbanicity. To accommodate this, we constructed an environmental quality index(EQI) using data from five domains (air, water, land, built, sociodemographic) for each United States (U.S.) county;...
Kordas, Katarzyna; Ardoino, Graciela; Coffman, Donna L.; Queirolo, Elena I.; Ciccariello, Daniela; Mañay, Nelly; Ettinger, Adrienne S.
2015-01-01
While it is known that toxic metals contribute individually to child cognitive and behavioral deficits, we still know little about the effects of exposure to multiple metals, particularly when exposures are low. We studied the association between children's blood lead and hair arsenic, cadmium, and manganese and their performance on the Bayley Scales of Infant Development III. Ninety-two preschool children (age 13–42 months) from Montevideo, Uruguay, provided a hair sample and 78 had a blood lead level (BLL) measurement. Using latent class analysis (LCA), we identified four groups of exposure based on metal concentrations: (1) low metals, (2) low-to-moderate metals, (3) high lead and cadmium, and (4) high metals. Using the four-group exposure variable as the main predictor, and fitting raw scores on the cognitive, receptive vocabulary, and expressive vocabulary scales as dependent variables, both complete-case and multiple imputation (MI) analyses were conducted. We found no association between multiple-metal exposures and neurodevelopment in covariate-adjusted models. This study demonstrates the use of LCA together with MI to determine patterns of exposure to multiple toxic metals and relate these to child neurodevelopment. However, because the overall study population was small, other studies with larger sample sizes are needed to investigate these associations. PMID:25694786
Controlled Release of Multiple Therapeutics from Silicone Hydrogel Contact Lenses.
White, Charles James; DiPasquale, Stephen Anthony; Byrne, Mark Edward
2016-04-01
The majority of contact lens wearers experience a significant level of ocular discomfort associated with lens wear, often within hours of wear, related to dry lenses, inflammation, protein adhesion to the lens surface, etc. Application of controlled drug release techniques has focused on the incorporation and/or release of a single comfort molecule from a lens including high molecular weight comfort agents or pharmaceutical agents. Previous studies have sought to mitigate the occurrence of only single propagators of discomfort. Clinical studies with eye drop solutions have shown that a mixture of diverse comfort agents selected to address multiple propagators of discomfort provide the greatest and longest lasting sensations of comfort for the patient. In this paper, multiple propagators of discomfort are addressed through the simultaneous release of four molecules from a novel contact lens to ensure high level of lens wear comfort. Silicone hydrogel contact lenses were engineered via molecular imprinting strategies to simultaneously release up to four template molecules including hydropropyl methylcellulose (HPMC), trehalose, ibuprofen, and prednisolone. By adjusting the ratio of functional monomer to comfort molecule, a high level of control was demonstrated over the release rate. HPMC, trehalose, ibuprofen, and prednisolone were released at therapeutically relevant concentrations with varying rates from a single lens. The results indicate use as daily disposable lenses for single day release or extended-wear lenses with multiple day release. Imprinted lenses are expected to lead to higher efficacy for patients compared to topical eye drops by improving compliance and mitigating concentration peaks and valleys associated with multiple drops.
Controlled Release of Multiple Therapeutics from Silicone Hydrogel Contact Lenses
White, Charles J.; DiPasquale, Stephen A.; Byrne, Mark E.
2016-01-01
Purpose The majority of contact lens wearers experience a significant level of ocular discomfort associated with lens wear, often within hours of wear, related to dry lenses, inflammation, protein adhesion to the lens surface, etc. Application of controlled drug release techniques has focused on the incorporation and/or release of a single comfort molecule from a lens including high molecular weight comfort agents or pharmaceutical agents. Previous studies have sought to mitigate the occurrence of only single propagators of discomfort. Clinical studies with eye drop solutions have shown that a mixture of diverse comfort agents selected to address multiple propagators of discomfort provide the greatest and longest lasting sensations of comfort for the patient. In this paper, multiple propagators of discomfort are addressed through the simultaneous release of four molecules from a novel contact lens to ensure high level of lens wear comfort. Methods Silicone hydrogel contact lenses were engineered via molecular imprinting strategies to simultaneously release up to four template molecules including hydropropyl methylcellulose (HPMC), trehalose, ibuprofen, and prednisolone. Results By adjusting the ratio of functional monomer to comfort molecule, a high level of control was demonstrated over the release rate. HPMC, trehalose, ibuprofen, and prednisolone were released at therapeutically relevant concentrations with varying rates from a single lens. Conclusions The results indicate use as daily disposable lenses for single day release or extended-wear lenses with multiple day release. Imprinted lenses are expected to lead to higher efficacy for patients compared to topical eye drops by improving compliance and mitigating concentration peaks and valleys associated with multiple drops. PMID:26945177
Intrinsic brain connectivity in fibromyalgia is associated with chronic pain intensity.
Napadow, Vitaly; LaCount, Lauren; Park, Kyungmo; As-Sanie, Sawsan; Clauw, Daniel J; Harris, Richard E
2010-08-01
Fibromyalgia (FM) is considered to be the prototypical central chronic pain syndrome and is associated with widespread pain that fluctuates spontaneously. Multiple studies have demonstrated altered brain activity in these patients. The objective of this study was to investigate the degree of connectivity between multiple brain networks in patients with FM, as well as how activity in these networks correlates with the level of spontaneous pain. Resting-state functional magnetic resonance imaging (FMRI) data from 18 patients with FM and 18 age-matched healthy control subjects were analyzed using dual-regression independent components analysis, which is a data-driven approach for the identification of independent brain networks. Intrinsic, or resting-state, connectivity was evaluated in multiple brain networks: the default mode network (DMN), the executive attention network (EAN), and the medial visual network (MVN), with the MVN serving as a negative control. Spontaneous pain levels were also analyzed for covariance with intrinsic connectivity. Patients with FM had greater connectivity within the DMN and right EAN (corrected P [P(corr)] < 0.05 versus controls), and greater connectivity between the DMN and the insular cortex, which is a brain region known to process evoked pain. Furthermore, greater intensity of spontaneous pain at the time of the FMRI scan correlated with greater intrinsic connectivity between the insula and both the DMN and right EAN (P(corr) < 0.05). These findings indicate that resting brain activity within multiple networks is associated with spontaneous clinical pain in patients with FM. These findings may also have broader implications for how subjective experiences such as pain arise from a complex interplay among multiple brain networks.
Coker, Eric; Gunier, Robert; Bradman, Asa; Harley, Kim; Kogut, Katherine; Molitor, John; Eskenazi, Brenda
2017-01-01
We previously showed that potential prenatal exposure to agricultural pesticides was associated with adverse neurodevelopmental outcomes in children, yet the effects of joint exposure to multiple pesticides is poorly understood. In this paper, we investigate associations between the joint distribution of agricultural use patterns of multiple pesticides (denoted as “pesticide profiles”) applied near maternal residences during pregnancy and Full-Scale Intelligence Quotient (FSIQ) at 7 years of age. Among a cohort of children residing in California’s Salinas Valley, we used Pesticide Use Report (PUR) data to characterize potential exposure from use within 1 km of maternal residences during pregnancy for 15 potentially neurotoxic pesticides from five different chemical classes. We used Bayesian profile regression (BPR) to examine associations between clustered pesticide profiles and deficits in childhood FSIQ. BPR identified eight distinct clusters of prenatal pesticide profiles. Two of the pesticide profile clusters exhibited some of the highest cumulative pesticide use levels and were associated with deficits in adjusted FSIQ of −6.9 (95% credible interval: −11.3, −2.2) and −6.4 (95% credible interval: −13.1, 0.49), respectively, when compared with the pesticide profile cluster that showed the lowest level of pesticides use. Although maternal residence during pregnancy near high agricultural use of multiple neurotoxic pesticides was associated with FSIQ deficit, the magnitude of the associations showed potential for sub-additive effects. Epidemiologic analysis of pesticides and their potential health effects can benefit from a multi-pollutant approach to analysis. PMID:28486423
Choi, Ted; Eskin, Eleazar
2013-01-01
Gene expression data, in conjunction with information on genetic variants, have enabled studies to identify expression quantitative trait loci (eQTLs) or polymorphic locations in the genome that are associated with expression levels. Moreover, recent technological developments and cost decreases have further enabled studies to collect expression data in multiple tissues. One advantage of multiple tissue datasets is that studies can combine results from different tissues to identify eQTLs more accurately than examining each tissue separately. The idea of aggregating results of multiple tissues is closely related to the idea of meta-analysis which aggregates results of multiple genome-wide association studies to improve the power to detect associations. In principle, meta-analysis methods can be used to combine results from multiple tissues. However, eQTLs may have effects in only a single tissue, in all tissues, or in a subset of tissues with possibly different effect sizes. This heterogeneity in terms of effects across multiple tissues presents a key challenge to detect eQTLs. In this paper, we develop a framework that leverages two popular meta-analysis methods that address effect size heterogeneity to detect eQTLs across multiple tissues. We show by using simulations and multiple tissue data from mouse that our approach detects many eQTLs undetected by traditional eQTL methods. Additionally, our method provides an interpretation framework that accurately predicts whether an eQTL has an effect in a particular tissue. PMID:23785294
Castañeda-Moreno, V A; De la Cruz-Mosso, U; Torres-Carrillo, N; Macías-Islas, M A; Padilla-De la Torre, O; Mireles-Ramírez, M A; González-Pérez, O; Ruiz-Sandoval, J L; Huerta, M; Trujillo, X; Ortuño-Sahagún, D; Muñoz-Valle, J F
2018-07-15
Macrophage migration inhibitory factor (MIF) is a cytokine associated with tissue damage in multiple autoimmune diseases such as systemic lupus erythematosus, rheumatoid arthritis and psoriatic arthritis. The role of MIF in multiple sclerosis (MS) and the contribution of its polymorphisms are unknown in our population. Therefore, we decided to investigate the genetic association of -794 CATT 5-8 (rs5844572) and -173 G>C (rs755622) MIF polymorphisms with MS, clinical variables and MIF serum levels in the population of western Mexico. 230 MS patients diagnosed according to McDonald criteria and 248 control subjects (CS) were recruited for this study, both polymorphisms were genotyped by PCR and PCR-RFLP and MIF serum levels were measured by ELISA kit. Severity and progression of MS were evaluated by EDSS and MSSS scores, respectively. Genotypes carrying the 5 repeats alleles of -794 CATT 5-8 MIF polymorphism present higher MIF serum levels in comparison with no carriers, and the presence of 5,7 heterozygous genotype contribute to the increase of disease severity and damage progression in MS patients. Notably when we stratified by sex, an effect of risk alleles (7 repeats and -173*C) of both MIF polymorphisms on EDSS and MSSS scores on males was found (p < 0.01). This study suggests that polymorphic alleles of MIF polymorphisms could act as sex-specific disease modifiers that increase the severity and progression of MS in male Mexican-Mestizo western population. Copyright © 2018 Elsevier B.V. All rights reserved.
Tutterrow, Yeung L.; Avril, Marion; Singh, Kavita; Long, Carole A.; Leke, Robert J.; Sama, Grace; Salanti, Ali; Smith, Joseph D.; Leke, Rose G. F.
2012-01-01
Placental malaria, caused by sequestration of Plasmodium falciparum-infected erythrocytes in the placenta, is associated with increased risk of maternal morbidity and poor birth outcomes. The parasite antigen VAR2CSA (variant surface antigen 2-chondroitin sulfate A) is expressed on infected erythrocytes and mediates binding to chondroitin sulfate A, initiating inflammation and disrupting homeostasis at the maternal-fetal interface. Although antibodies can prevent sequestration, it is unclear whether parasite clearance is due to antibodies to a single Duffy binding-like (DBL) domain or to an extensive repertoire of antibodies to multiple DBL domains and allelic variants. Accordingly, plasma samples collected longitudinally from pregnant women were screened for naturally acquired antibodies against an extensive panel of VAR2CSA proteins, including 2 to 3 allelic variants for each of 5 different DBL domains. Analyses were performed on plasma samples collected from 3 to 9 months of pregnancy from women living in areas in Cameroon with high and low malaria transmission. The results demonstrate that high antibody levels to multiple VAR2CSA domains, rather than a single domain, were associated with the absence of placental malaria when antibodies were present from early in the second trimester until term. Absence of placental malaria was associated with increasing antibody breadth to different DBL domains and allelic variants in multigravid women. Furthermore, the antibody responses of women in the lower-transmission site had both lower magnitude and lesser breadth than those in the high-transmission site. These data suggest that immunity to placental malaria results from high antibody levels to multiple VAR2CSA domains and allelic variants and that antibody breadth is influenced by malaria transmission intensity. PMID:22331427
Amano, Hoichi; Fukuda, Yoshiharu; Yokoo, Takashi; Yamaoka, Kazue
2018-03-27
Shift workers have a high risk of cardiovascular disease (CVD). Systemic inflammation measured has been associated with the risk of CVD onset, in addition to classical risk factors. However, the association between work schedule and inflammatory cytokine levels remains unclear. The purpose of this study was to examine the association between work schedule and interleukin-6 (IL-6)/high-sensitivity C-reactive protein (hs-CRP) levels among Japanese workers. The present cross-sectional study was a part of the Japanese Study of Health, Occupation and Psychosocial Factors Related Equity (J-HOPE). A total of 5259 persons who measured inflammatory cytokine were analyzed in this study. One-way analysis of variance was used to test log-transformed IL-6/hs-CRP differences by work schedule. Multiple regression analysis was used to examine the difference adjusted for other possible CVD risk factors. There were 3660 participants who had a regular work schedule; the remaining schedules were shift work without night work for 181 participants, shift work with night work for 1276 participants, and only night work for 142 participants. The unadjusted model showed that only night workers were significantly related to high levels of IL-6 compared with regular workers. Even in the multiple regression analysis, the higher level of IL-6 among only night workers remained significant (β=0.058, P=0.01). On the contrary, hs-CRP was not. The present study revealed that only night shift work is significantly associated with high levels of IL-6 in Japanese workers. These observations help us understand the mechanism for the association between work schedule and CVD onset.
Gonzalez, Andrea; Boyle, Michael H; Georgiades, Katholiki; Duncan, Laura; Atkinson, Leslie R; MacMillan, Harriet L
2012-09-09
Overweight and obesity are steadily increasing worldwide with the greatest prevalence occurring in high-income countries. Many factors influence body mass index (BMI); however multiple influences assessed in families and individuals are rarely studied together in a prospective design. Our objective was to model the impact of multiple influences at the child (low birth weight, history of maltreatment, a history of childhood mental and physical conditions, and school difficulties) and family level (parental income and education, parental mental and physical health, and family functioning) on BMI in early adulthood. We used data from the Ontario Child Health Study, a prospective, population-based study of 3,294 children (ages 4-16 years) enrolled in 1983 and followed up in 2001 (N = 1,928; ages 21-35 years). Using multilevel models, we tested the association between family and child-level variables and adult BMI after controlling for sociodemographic variables and health status in early adulthood. At the child level, presence of psychiatric disorder and school difficulties were related to higher BMI in early adulthood. At the family level, receipt of social assistance was associated with higher BMI, whereas family functioning, having immigrant parents and higher levels of parental education were associated with lower BMI. We found that gender moderated the effect of two risk factors on BMI: receipt of social assistance and presence of a medical condition in childhood. In females, but not in males, the presence of these risk factors was associated with higher BMI in early adulthood. Overall, these findings indicate that childhood risk factors associated with higher BMI in early adulthood are multi-faceted and long-lasting. These findings highlight the need for preventive interventions to be implemented at the family level in childhood.
Factors associated with subjective well-being in cancer workers in Queensland.
Poulsen, Michael G; Poulsen, Anne A; Khan, Asaduzzaman; Poulsen, Emma E; Khan, Shanchita R
2012-06-01
This study aims to describe factors associated with subjective well-being (SWB) in cancer workers in Queensland and compares results to normative data for the Australian population. This study was based on a cross-sectional survey of 544 cancer workers in Queensland with a response rate of 54%. SWB was measured using the Personal Wellbeing Index for Adults. Multiple regression analyses were performed to identify explanatory variables, which were independently associated with SWB. Results were compared with normative Australian data. The overall mean SWB for study participants was 74.63, which was comparable to the mean of 75.02 for the Australian population (P = 0.47). Female cancer workers had significantly lower levels of SWB compared to the normative data of female Australians (74.44 compared to 75.7, P = 0.03). Multiple regression analyses showed that higher levels of SWB were associated with having 11-30 h of direct patient care hours per week, being married, no child or elder care commitments, good physical health, low levels of both psychological distress and burnout, and high levels of work engagement. Cancer workers' overall levels of SWB were similar to the national mean scores. Amount of time in direct patient care was linked with SWB, with an optimal time between 11 and 30 h per week associated with high SWB. The majority of the factors significantly associated with SWB were of a personal nature such as marital status and physical and mental health. These data provide a valuable baseline for future research in this area, especially in the area of interventions to promote SWB of workers. © 2012 The Authors. Journal of Medical Imaging and Radiation Oncology © 2012 The Royal Australian and New Zealand College of Radiologists.
Young, J; Mucsi, I; Rollet-Kurhajec, K C; Klein, M B
2016-05-01
Fibroblast growth factor 23 (FGF23) has been associated with cardiovascular mortality. We estimate associations between the level of plasma FGF23 and exposure to abacavir (ABC) and to other components of antiretroviral therapy in patients co-infected with HIV and hepatitis C. Both intact and c-terminal FGF23 were measured in plasma using commercial assays for a sub-cohort of 295 patients selected at random from the 1150 patients enrolled in the Canadian Co-infection Cohort. The multiplicative effects of antiretroviral drug exposures and covariates on median FGF23 were then estimated using a hierarchical Bayesian model. The median level of intact FGF23 was independent of either past or recent exposure to abacavir, with multiplicative ratios of 1.00 and 1.07, 95% credible intervals 0.90-1.12 and 0.94-1.23, respectively. Median intact FGF23 tended to increase with past use of both nonnucleoside reverse-transcriptase inhibitors and protease inhibitors, but tended to decrease with recent use of either tenofovir, efavirenz or lopinavir. There were no obvious associations between the median level of c-terminal FGF23 and individual drugs or drug classes. Age, female gender, smoking and the aspartate aminotransferase to platelet ratio index were all associated with a higher median c-terminal FGF23 but not with a higher median intact FGF23. The level of FGF23 in plasma was independent of exposure to ABC. Lower levels of intact FGF23 with recent use of tenofovir, efavirenz or lopinavir may reflect their adverse effects on bone and vitamin D metabolism relative to other drugs in their respective drug classes. © 2015 British HIV Association.
Baker, Lindsey A.; Silverstein, Merril
2009-01-01
Using the Health and Retirement Study, this research examines well-being among grandparents raising grandchildren during middle to late life, specifically looking at how other roles in which a grandparent is participating (such as worker, volunteer, parent or caregiver) may influence depressive symptoms among grandparent caregivers. Results indicate that grandparents who have recently begun raising a grandchild experience lower levels of well-being when compared to grandparents who are not raising a grandchild regardless of the grandparent's level of participation in roles beyond that of grandparent caregiver, while grandparents who have been raising a grandchild for longer periods of time seem to benefit from their participation in multiple roles. However, a higher level of participation in outside roles is associated with a decline in well-being among grandparents who stopped raising a grandchild, suggesting that, for these grandparents, participation in multiple roles acted mainly as a stressor, rather than as a resource. PMID:19890447
Eom, Jinhee; Choi, Jaeyeon; Kim, Jiye; Kim, Yunje
2014-01-01
Following few decades of commercial use, perfluorooctanoate (PFOA) and perfluorooctane sulfonate (PFOS) have been found in human blood and serum. We determined the amounts of PFOA and PFOS in human plasma (n = 183) and the effects of multiple uses of food-contact materials and smoking habits and alcohol consumption using liquid chromatography time-of-flight mass spectrometry (LC/TOF-MS). For the paper cups, the PFOA level in the plasma of the heavy user group was 1.37 times higher than that of the light user group. However, no association between the effects of multiple uses of food-contact materials and the plasma levels of PFOA and PFOS was found, except for paper cups. Active smokers had lower plasma levels of PFOA and PFOS than non-smokers. We show that multiple uses of food-contact materials do not appear to be a significant source of PFOA and PFOS. PMID:25032739
Burnout, stress and satisfaction among Australian and New Zealand radiation oncology trainees.
Leung, John; Rioseco, Pilar
2017-02-01
To evaluate the incidence of burnout among radiation oncology trainees in Australia and New Zealand and the stress and satisfaction factors related to burnout. A survey of trainees was conducted in mid-2015. There were 42 Likert scale questions on stress, 14 Likert scale questions on satisfaction and the Maslach Burnout Inventory-Human Services Survey assessed burnout. A principal component analysis identified specific stress and satisfaction areas. Categorical variables for the stress and satisfaction factors were computed. Associations between respondent's characteristics and stress and satisfaction subscales were examined by independent sample t-tests and analysis of variance. Effect sizes were calculated using Cohens's d when significant mean differences were observed. This was also done for respondent characteristics and the three burnout subscales. Multiple regression analyses were performed. The response rate was 81.5%. The principal component analysis for stress identified five areas: demands on time, professional development/training, delivery demands, interpersonal demands and administration/organizational issues. There were no significant differences by demographic group or area of interest after P-values were adjusted for the multiple tests conducted. The principal component analysis revealed two satisfaction areas: resources/professional activities and value/delivery of services. There were no significant differences by demographic characteristics or area of interest in the level of satisfaction after P-values were adjusted for the multiple tests conducted. The burnout results revealed 49.5% of respondents scored highly in emotional exhaustion and/or depersonalization and 13.1% had burnout in all three measures. Multiple regression analysis revealed the stress subscales 'demands on time' and 'interpersonal demands' were associated with emotional exhaustion. 'Interpersonal demands' was also associated with depersonalization and correlated negatively with personal accomplishment. The satisfaction of value/delivery of services subscale was associated with higher levels of personal accomplishment. There is a significant level of burnout among radiation oncology trainees in Australia and New Zealand. Further work addressing intervention would be appropriate to reduce levels of burnout. © 2016 The Authors. Journal of Medical Imaging and Radiation Oncology published by John Wiley & Sons Australia, Ltd on behalf of The Royal Australian and New Zealand College of Radiologists.
Fan, Liping; Fu, Danhui; Zhang, Jinping; Wang, Qingqing; Ye, Yamei; Xie, Qianling
2017-01-01
The aim of this study was to evaluate whether blood transfusions affect overall survival (OS) and progression-free survival (PFS) in newly diagnosed multiple myeloma (MM) patients without hematopoietic stem cell transplantation. A total of 181 patients were enrolled and divided into two groups: 68 patients in the transfused group and 113 patients in the nontransfused group. Statistical analyses showed that there were significant differences in ECOG scoring, Ig isotype, platelet (Plt) counts, hemoglobin (Hb) level, serum creatinine (Scr) level, and β2-microglobulin (β2-MG) level between the two groups. Univariate analyses showed that higher International Staging System staging, Plt counts < 100 × 109/L, Scr level ≥ 177 μmol/L, serum β2-MG ≥ 5.5 μmol/L, serum calcium (Ca) ≥ 2.75 mmol/L, and thalidomide use were associated with both OS and PFS in MM patients. Age ≥ 60 was associated with OS and Ig isotype was associated with PFS in MM patients. Moreover, blood transfusion was associated with PFS but not OS in MM patients. Multivariate analyses showed that blood transfusion was not an independent factor for PFS in MM patients. Our preliminary results suggested that newly diagnosed MM patients may benefit from a liberal blood transfusion strategy, since blood transfusion is not an independent impact factor for survival. PMID:28567420
Liu, Jie; Wei Zuo, Shang; Li, Yue; Jia, Xin; Jia, Sen Hao; Zhang, Tao; Xiang Song, Yu; Qi Wei, Ying; Xiong, Jiang; Hua Hu, Yong; Guo, Wei
2016-01-01
The associations between hyperhomocysteinaemia (HHcy), methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism, and abdominal aortic aneurysm (AAA) remain controversial, with only few studies focused on these associations within the Chinese population. We performed subgroup and interaction analyses in a Chinese Han population to investigate these associations. In all, 155 AAA patients and 310 control subjects were evaluated for serum total homocysteine levels and MTHFR C677T polymorphisms. Multiple logistic regression models were used to evaluate the aforementioned associations. Interaction and stratified analyses were conducted according to age, sex, smoking status, drinking status, and chronic disease histories. The multiple logistic analyses showed a significant association between HHcy and AAA but no significant association between MTHFR C677T polymorphism and AAA. The interaction analysis showed that age and peripheral arterial disease played an interactive role in the association between HHcy and AAA, while drinking status played an interactive role in the association between MTHFR C677T polymorphism and AAA. In conclusion, HHcy is an independent risk factor of AAA in a Chinese Han population, especially in the elderly and peripheral arterial disease subgroups. Longitudinal studies and clinical trials aimed to reduce homocysteine levels are warranted to assess the causal nature of these relationships PMID:26865327
Schneider, Julie M; Fujii, Mary L; Lamp, Catherine L; Lönnerdal, Bo; Zidenberg-Cherr, Sheri
2007-11-01
Iron and zinc share common food sources, and children at risk of iron deficiency may also develop zinc deficiency. We determined the prevalence of zinc and copper deficiency and examined factors associated with serum zinc and copper in young children from low-income families at risk of iron deficiency. A cross-sectional study design was used to assess serum zinc and copper, along with an interview-assisted survey to assess factors associated with serum zinc and copper in a convenience sample. Participants were 435 children aged 12 to 36 months recruited from select clinics of the Special Supplemental Nutrition Program for Women, Infants, and Children in Contra Costa and Tulare Counties, California. Frequencies were used to report prevalence. Multiple linear regressions were conducted to examine factors associated with serum zinc and copper, controlling for age, sex, and ethnicity. The prevalence of low serum zinc level (<70 microg/dL [<10.7 micromol/L]) was 42.8%, and low serum copper level (<90 microg/dL [<14.2 micromol/L]) was <1%. Mean+/-standard deviation of serum copper was 150+/-22 microg/dL (23.6+/-3.5 micromol/L) and 140+/-24 microg/dL (22.1+/-3.8 micromol/L) for anemic and non-anemic children, respectively (t test, P=0.026). In multiple linear regression consumption of sweetened beverages was negatively associated with serum zinc level, and consumption of >15 g/day meat was positively associated with serum zinc level, whereas current consumption of breast milk and >15 g/day beans were positively associated with serum copper level. The prevalence of low serum zinc concentration in the sample was high, and warrants further investigation amongst vulnerable populations.
Jönsson, Anna K.; Lesén, Eva; Mårdby, Ann-Charlotte; Sundell, Karolina Andersson
2016-01-01
Objective Generic substitution has contributed to economic savings but switching products may affect patient adherence, particularly among those using multiple medications. The aim was to analyse if use of multiple medications influenced the association between switching products and refill adherence to angiotensin-converting-enzyme (ACE) inhibitors in Sweden. Study Design and Setting New users of ACE-inhibitors, starting between 1 July 2006 and 30 June 2007, were identified in the Swedish Prescribed Drug Register. Refill adherence was assessed using the continuous measure of medication acquisition (CMA) and analysed with linear regression and analysis of covariance. Results The study population included 42735 individuals whereof 51.2% were exposed to switching ACE-inhibitor and 39.6% used multiple medications. Refill adherence was higher among those exposed to switching products than those not, but did not vary depending on the use of multiple medications or among those not. Refill adherence varied with age, educational level, household income, country of birth, previous hospitalisation and previous cardiovascular diagnosis. Conclusion The results indicate a positive association between refill adherence and switching products, mainly due to generic substitution, among new users of ACE-inhibitors in Sweden. This association was independent of use of multiple medications. PMID:27192203
Saunders, Edward J; Dadaev, Tokhir; Leongamornlert, Daniel A; Al Olama, Ali Amin; Benlloch, Sara; Giles, Graham G; Wiklund, Fredrik; Gronberg, Henrik; Haiman, Christopher A; Schleutker, Johanna; Nordestgaard, Borge G; Travis, Ruth C; Neal, David; Pasayan, Nora; Khaw, Kay-Tee; Stanford, Janet L; Blot, William J; Thibodeau, Stephen N; Maier, Christiane; Kibel, Adam S; Cybulski, Cezary; Cannon-Albright, Lisa; Brenner, Hermann; Park, Jong Y; Kaneva, Radka; Batra, Jyotsna; Teixeira, Manuel R; Pandha, Hardev; Govindasami, Koveela; Muir, Ken; Easton, Douglas F; Eeles, Rosalind A; Kote-Jarai, Zsofia
2016-04-12
Germline mutations within DNA-repair genes are implicated in susceptibility to multiple forms of cancer. For prostate cancer (PrCa), rare mutations in BRCA2 and BRCA1 give rise to moderately elevated risk, whereas two of B100 common, low-penetrance PrCa susceptibility variants identified so far by genome-wide association studies implicate RAD51B and RAD23B. Genotype data from the iCOGS array were imputed to the 1000 genomes phase 3 reference panel for 21 780 PrCa cases and 21 727 controls from the Prostate Cancer Association Group to Investigate Cancer Associated Alterations in the Genome (PRACTICAL) consortium. We subsequently performed single variant, gene and pathway-level analyses using 81 303 SNPs within 20 Kb of a panel of 179 DNA-repair genes. Single SNP analyses identified only the previously reported association with RAD51B. Gene-level analyses using the SKAT-C test from the SNP-set (Sequence) Kernel Association Test (SKAT) identified a significant association with PrCa for MSH5. Pathway-level analyses suggested a possible role for the translesion synthesis pathway in PrCa risk and Homologous recombination/Fanconi Anaemia pathway for PrCa aggressiveness, even though after adjustment for multiple testing these did not remain significant. MSH5 is a novel candidate gene warranting additional follow-up as a prospective PrCa-risk locus. MSH5 has previously been reported as a pleiotropic susceptibility locus for lung, colorectal and serous ovarian cancers.
do Prado, Mara Rúbia Maciel Cardoso; Oliveira, Fabiana de Cássia Carvalho; Assis, Karine Franklin; Ribeiro, Sarah Aparecida Vieira; do Prado, Pedro Paulo; Sant'Ana, Luciana Ferreira da Rocha; Priore, Silvia Eloiza; Franceschini, Sylvia do Carmo Castro
2015-01-01
Abstract Objective: To assess the prevalence of vitamin D deficiency and its associated factors in women and their newborns in the postpartum period. Methods: This cross-sectional study evaluated vitamin D deficiency/insufficiency in 226 women and their newborns in Viçosa (Minas Gerais, BR) between December 2011 and November 2012. Cord blood and venous maternal blood were collected to evaluate the following biochemical parameters: vitamin D, alkaline phosphatase, calcium, phosphorus and parathyroid hormone. Poisson regression analysis, with a confidence interval of 95%, was applied to assess vitamin D deficiency and its associated factors. Multiple linear regression analysis was performed to identify factors associated with 25(OH)D deficiency in the newborns and women from the study. The criteria for variable inclusion in the multiple linear regression model was the association with the dependent variable in the simple linear regression analysis, considering p<0.20. Significance level was α <5%. Results: From 226 women included, 200 (88.5%) were 20-44 years old; the median age was 28 years. Deficient/insufficient levels of vitamin D were found in 192 (85%) women and in 182 (80.5%) neonates. The maternal 25(OH)D and alkaline phosphatase levels were independently associated with vitamin D deficiency in infants. Conclusions: This study identified a high prevalence of vitamin D deficiency and insufficiency in women and newborns and the association between maternal nutritional status of vitamin D and their infants' vitamin D status. PMID:26100593
Mostafa, Aliehossadat; Jalilvand, Somayeh; Shoja, Zabihollah; Nejati, Ahmad; Shahmahmoodi, Shohreh; Sahraian, Mohammad Ali; Marashi, Sayed Mahdi
2017-07-01
The relationship between infections and autoimmune diseases is complex and there are several reports highlighting the role of human endogenous retroviruses (HERVs) in these patients. The levels of multiple sclerosis-associated retrovirus (MSRV)-type DNA of Env gene was measured in peripheral blood mononuclear cells from 52 patients with relapsing-remitting multiple sclerosis (RRMS) and 40 healthy controls using specific quantitative PCR (qPCR) analysis. Furthermore, we analyzed the status of HERV-W/MSRV in these patients with regards to both EBV (DNA load and anti-EBNA1 IgG antibody) and vitamin D concentration. MSRV DNA copy number were significantly higher in RRMS patients than healthy controls (P < 0.0001). Interestingly, an inverse correlation was found between MSRV DNA copy number and serum vitamin D concentration (P < 0.01), but not for EBV load or anti-EBNA-1 IgG antibody. © 2017 Wiley Periodicals, Inc.
Chrabot, Beverly S.; Kariuki, Silvia N.; Zervou, Maria I.; Feng, Xuan; Arrington, Jasmine; Jolly, Meenakshi; Boumpas, Dimitrios T.; Reder, Anthony T.; Goulielmos, George N.; Niewold, Timothy B.
2013-01-01
Alleles of IRF8 are associated with susceptibility to both systemic lupus erythematosus (SLE) and multiple sclerosis (MS). While high type I interferon (IFN) is thought to be causal in SLE, type I IFN is used as a therapy in MS. We investigated whether IRF8 alleles were associated with type I IFN levels or serologic profiles in SLE and MS. Alleles which have been previously associated with SLE or MS were genotyped in SLE and MS patients. The MS-associated rs17445836G allele was associated with anti-dsDNA autoantibodies in SLE patients (meta-analysis OR=1.92). The same allele was associated with decreased serum IFN activity in SLE patients with anti-dsDNA antibodies, and with decreased type I IFN-induced gene expression in PBMC from anti-dsDNA negative SLE patients. In secondary progressive MS patients, rs17445836G was associated with decreased serum type I IFN. Rs17445836G was associated with increased IRF8 expression in SLE patient B cells. In summary, IRF8 rs17445836G is associated with human autoimmune disease characterized by low type I IFN levels, and this may have pharmacogenetic relevance as type I IFN is modulated in SLE and MS. The association with autoantibodies and increased IRF8 expression in B cells supports a role for rs17445836G in humoral tolerance. PMID:23965942
Incidence of leukemia, lymphoma, and multiple myeloma in Czech uranium miners: a case-cohort study.
Rericha, Vladimír; Kulich, Michal; Rericha, Robert; Shore, David L; Sandler, Dale P
2006-06-01
Uranium miners are chronically exposed to low levels of radon and its progeny. We investigated whether radon exposure is associated with increased incidence of leukemia, lymphoma, or multiple myeloma in this population. We conducted a retrospective case-cohort study in 23,043 uranium miners and identified a total of 177 incident cases of leukemia, lymphoma, and myeloma. Detailed information on occupational radon exposure was obtained for the cases and a randomly selected subcohort of 2,393 subjects. We used the proportional hazards model with power relative risk (RR) function to estimate and test the effects of cumulative radon exposures on incidence rates. Incidence of all leukemia combined and chronic lymphocytic leukemia (CLL) alone was positively associated with cumulative radon exposure. The RR comparing high radon exposure [110 working level months (WLM) ; 80th percentile] to low radon exposure (3 WLM ; 20th percentile) was 1.75 [95% confidence interval (CI) , 1.10-2.78 ; p = 0.014] for all leukemia combined and 1.98 (95% CI, 1.10-3.59 ; p = 0.016) for CLL. Myeloid leukemia and Hodgkin lymphoma were also associated with radon, but RRs were not statistically significant. There was no apparent association of radon with either non-Hodgkin lymphoma or multiple myeloma. Exposure to radon and its progeny was associated with an increased risk of developing leukemia in underground uranium miners. CLL, not previously believed to be radiogenic, was linked to radon exposure.
Incidence of Leukemia, Lymphoma, and Multiple Myeloma in Czech Uranium Miners: A Case–Cohort Study
Řeřicha, Vladimír; Kulich, Michal; Řeřicha, Robert; Shore, David L.; Sandler, Dale P.
2006-01-01
Objective Uranium miners are chronically exposed to low levels of radon and its progeny. We investigated whether radon exposure is associated with increased incidence of leukemia, lymphoma, or multiple myeloma in this population. Design We conducted a retrospective case–cohort study in 23,043 uranium miners and identified a total of 177 incident cases of leukemia, lymphoma, and myeloma. Detailed information on occupational radon exposure was obtained for the cases and a randomly selected subcohort of 2,393 subjects. We used the proportional hazards model with power relative risk (RR) function to estimate and test the effects of cumulative radon exposures on incidence rates. Results Incidence of all leukemia combined and chronic lymphocytic leukemia (CLL) alone was positively associated with cumulative radon exposure. The RR comparing high radon exposure [110 working level months (WLM); 80th percentile] to low radon exposure (3 WLM; 20th percentile) was 1.75 [95% confidence interval (CI), 1.10–2.78; p = 0.014] for all leukemia combined and 1.98 (95% CI, 1.10–3.59; p = 0.016) for CLL. Myeloid leukemia and Hodgkin lymphoma were also associated with radon, but RRs were not statistically significant. There was no apparent association of radon with either non-Hodgkin lymphoma or multiple myeloma. Exposure to radon and its progeny was associated with an increased risk of developing leukemia in underground uranium miners. CLL, not previously believed to be radiogenic, was linked to radon exposure. PMID:16759978
ERIC Educational Resources Information Center
Nelson, David A.
1991-01-01
Forward-masked psychophysical tuning curves were obtained at multiple probe levels from 26 normal-hearing listeners and 24 ears of 21 hearing-impaired listeners with cochlear hearing loss. Results indicated that some cochlear hearing losses influence the sharp tuning capabilities usually associated with outer hair cell function. (Author/JDD)
ERIC Educational Resources Information Center
Whitehouse, Andrew J. O.; Mattes, Eugen; Maybery, Murray T.; Sawyer, Michael G.; Jacoby, Peter; Keelan, Jeffrey A.; Hickey, Martha
2012-01-01
Background: Preliminary evidence suggests that prenatal testosterone exposure may be associated with language delay. However, no study has examined a large sample of children at multiple time-points. Methods: Umbilical cord blood samples were obtained at 861 births and analysed for bioavailable testosterone (BioT) concentrations. When…
Sociodemographic factors associated with pregnant women's level of knowledge about oral health
Barbieri, Wander; Peres, Stela Verzinhasse; Pereira, Carla de Britto; Peres, João; de Sousa, Maria da Luz Rosário; Cortellazzi, Karine Laura
2018-01-01
ABSTRACT Objective To evaluate knowledge on oral health and associated sociodemographic factors in pregnant women. Methods A cross-sectional study with a sample of 195 pregnant women seen at the Primary Care Unit Paraisópolis I, in São Paulo (SP), Brazil. For statistical analysis, χ2 or Fisher's exact test and multiple logistic regression were used. A significance level of 5% was used in all analyses. Results Schooling level equal to or greater than 8 years and having one or two children were associated with an adequate knowledge about oral health. Conclusion Oral health promotion strategies during prenatal care should take into account sociodemographic aspects. PMID:29694612
Gnanapavan, Sharmilee; Yousaf, Nasim; Heywood, Wendy; Grant, Donna; Mills, Kevin; Chernajovsky, Yuti; Keir, Geoff; Giovannoni, Gavin
2014-11-15
GAP-43 has been studied in the rodent and mammalian brain and shown to be present specifically in areas undergoing axonal elongation and synapse formation. GAP-43 was cloned using the baculovirus expression system and purified. A sandwich ELISA was developed using the recombinant GAP-43 as standard and validated. CSF GAP-43 levels were analysed in benign intracranial hypertension, movement disorders, multiple sclerosis, neuropathy, CNS infections, motor neuron disease, and headache (neurological controls). GAP-43 levels were low in all disorders analysed (in particular motor neuron disease; p=0.001, and movement disorders and multiple sclerosis; p<0.0001) compared to controls, aside from CNS infections. GAP-43 is preferentially reduced in the CSF of neurological disorders associated with neurodegeneration. Copyright © 2014. Published by Elsevier B.V.
On the interrelation of multiplication and division in secondary school children.
Huber, Stefan; Fischer, Ursula; Moeller, Korbinian; Nuerk, Hans-Christoph
2013-01-01
Each division problem can be transformed into as a multiplication problem and vice versa. Recent research has indicated strong developmental parallels between multiplication and division in primary school children. In this study, we were interested in (i) whether these developmental parallels persist into secondary school, (ii) whether similar developmental parallels can be observed for simple and complex problems, (iii) whether skill level modulates this relationship, and (iv) whether the correlations are specific and not driven by general cognitive or arithmetic abilities. Therefore, we assessed performance of 5th and 6th graders attending two secondary school types of the German educational system in simple and complex multiplication as well as division while controlling for non-verbal intelligence, short-term memory, and other arithmetic abilities. Accordingly, we collected data from students differing in skills levels due to either age (5th < 6th grade) or school type (general < intermediate secondary school). We observed moderate to strong bivariate and partial correlations between multiplication and division with correlations being higher for simple tasks but nevertheless reliable for complex tasks. Moreover, the association between simple multiplication and division depended on students' skill levels as reflected by school types, but not by age. Partial correlations were higher for intermediate than for general secondary school children. In sum, these findings emphasize the importance of the inverse relationship between multiplication and division which persists into later developmental stages. However, evidence for skill-related differences in the relationship between multiplication and division was restricted to the differences for school types.
Reider, Nadia; Salter, Amber R; Cutter, Gary R; Tyry, Tuula; Marrie, Ruth Ann
2017-04-01
Physical activity levels among persons with multiple sclerosis (MS) are worryingly low. We aimed to identify the factors associated with physical activity for people with MS, with an emphasis on factors that have not been studied previously (bladder and hand dysfunction) and are potentially modifiable. This study was a secondary analysis of data collected in the spring of 2012 during the North American Research Committee on Multiple Sclerosis (NARCOMS) Registry. NARCOMS participants were surveyed regarding smoking using questions from the Behavioral Risk Factor Surveillance Survey; disability using the Patient Determined Disease Steps; fatigue, cognition, spasticity, sensory, bladder, vision and hand function using self-reported Performance Scales; health literacy using the Medical Term Recognition Test; and physical activity using questions from the Health Information National Trends Survey. We used a forward binary logistic regression to develop a predictive model in which physical activity was the outcome variable. Of 8,755 respondents, 1,707 (19.5%) were classified as active and 7,068 (80.5%) as inactive. In logistic regression, being a current smoker, moderate or severe level of disability, depression, fatigue, hand, or bladder dysfunction and minimal to mild spasticity were associated with lower odds of meeting physical activity guidelines. MS type was not linked to activity level. Several modifiable clinical and lifestyle factors influenced physical activity in MS. Prospective studies are needed to evaluate whether modification of these factors can increase physical activity participation in persons with MS. © 2016 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.
Candidate gene analysis for Alzheimer's disease in adults with Down syndrome.
Lee, Joseph H; Lee, Annie J; Dang, Lam-Ha; Pang, Deborah; Kisselev, Sergey; Krinsky-McHale, Sharon J; Zigman, Warren B; Luchsinger, José A; Silverman, Wayne; Tycko, Benjamin; Clark, Lorraine N; Schupf, Nicole
2017-08-01
Individuals with Down syndrome (DS) overexpress many genes on chromosome 21 due to trisomy and have high risk of dementia due to the Alzheimer's disease (AD) neuropathology. However, there is a wide range of phenotypic differences (e.g., age at onset of AD, amyloid β levels) among adults with DS, suggesting the importance of factors that modify risk within this particularly vulnerable population, including genotypic variability. Previous genetic studies in the general population have identified multiple genes that are associated with AD. This study examined the contribution of polymorphisms in these genes to the risk of AD in adults with DS ranging from 30 to 78 years of age at study entry (N = 320). We used multiple logistic regressions to estimate the likelihood of AD using single-nucleotide polymorphisms (SNPs) in candidate genes, adjusting for age, sex, race/ethnicity, level of intellectual disability and APOE genotype. This study identified multiple SNPs in APP and CST3 that were associated with AD at a gene-wise level empirical p-value of 0.05, with odds ratios in the range of 1.5-2. SNPs in MARK4 were marginally associated with AD. CST3 and MARK4 may contribute to our understanding of potential mechanisms where CST3 may contribute to the amyloid pathway by inhibiting plaque formation, and MARK4 may contribute to the regulation of the transition between stable and dynamic microtubules. Copyright © 2017 Elsevier Inc. All rights reserved.
Yang, Qin; He, Yijian; Kabahuma, Mercy; Chaya, Timothy; Kelly, Amy; Borrego, Eli; Bian, Yang; El Kasmi, Farid; Yang, Li; Teixeira, Paulo; Kolkman, Judith; Nelson, Rebecca; Kolomiets, Michael; L Dangl, Jeffery; Wisser, Randall; Caplan, Jeffrey; Li, Xu; Lauter, Nick; Balint-Kurti, Peter
2017-09-01
Alleles that confer multiple disease resistance (MDR) are valuable in crop improvement, although the molecular mechanisms underlying their functions remain largely unknown. A quantitative trait locus, qMdr 9.02 , associated with resistance to three important foliar maize diseases-southern leaf blight, gray leaf spot and northern leaf blight-has been identified on maize chromosome 9. Through fine-mapping, association analysis, expression analysis, insertional mutagenesis and transgenic validation, we demonstrate that ZmCCoAOMT2, which encodes a caffeoyl-CoA O-methyltransferase associated with the phenylpropanoid pathway and lignin production, is the gene within qMdr 9.02 conferring quantitative resistance to both southern leaf blight and gray leaf spot. We suggest that resistance might be caused by allelic variation at the level of both gene expression and amino acid sequence, thus resulting in differences in levels of lignin and other metabolites of the phenylpropanoid pathway and regulation of programmed cell death.
O'Lenick, Cassandra R; Winquist, Andrea; Mulholland, James A; Friberg, Mariel D; Chang, Howard H; Kramer, Michael R; Darrow, Lyndsey A; Sarnat, Stefanie Ebelt
2017-02-01
A broad literature base provides evidence of association between air pollution and paediatric asthma. Socioeconomic status (SES) may modify these associations; however, previous studies have found inconsistent evidence regarding the role of SES. Effect modification of air pollution-paediatric asthma morbidity by multiple indicators of neighbourhood SES was examined in Atlanta, Georgia. Emergency department (ED) visit data were obtained for 5-18 years old with a diagnosis of asthma in 20-county Atlanta during 2002-2008. Daily ZIP Code Tabulation Area (ZCTA)-level concentrations of ozone, nitrogen dioxide, fine particulate matter and elemental carbon were estimated using ambient monitoring data and emissions-based chemical transport model simulations. Pollutant-asthma associations were estimated using a case-crossover approach, controlling for temporal trends and meteorology. Effect modification by ZCTA-level (neighbourhood) SES was examined via stratification. We observed stronger air pollution-paediatric asthma associations in 'deprivation areas' (eg, ≥20% of the ZCTA population living in poverty) compared with 'non-deprivation areas'. When stratifying analyses by quartiles of neighbourhood SES, ORs indicated stronger associations in the highest and lowest SES quartiles and weaker associations among the middle quartiles. Our results suggest that neighbourhood-level SES is a factor contributing vulnerability to air pollution-related paediatric asthma morbidity in Atlanta. Children living in low SES environments appear to be especially vulnerable given positive ORs and high underlying asthma ED rates. Inconsistent findings of effect modification among previous studies may be partially explained by choice of SES stratification criteria, and the use of multiplicative models combined with differing baseline risk across SES populations. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.
Røsjø, Egil; Myhr, Kjell-Morten; Løken-Amsrud, Kristin Ingeleiv; Bakke, Søren Jacob; Beiske, Antonie G; Bjerve, Kristian S; Hovdal, Harald; Lilleås, Finn; Midgard, Rune; Pedersen, Tom; Benth, Jūratė Saltytė; Torkildsen, Øivind; Wergeland, Stig; Michelsen, Annika E; Aukrust, Pål; Ueland, Thor; Holmøy, Trygve
2014-06-15
To explore the relationships between vitamin A, D and E and inflammation in relapsing remitting multiple sclerosis, we assessed their associations with 11 inflammation markers in 9 serial serum samples from 85 patients, before and during interferon-β1a treatment. A negative association was found between vitamin A and pentraxin 3 independent of interferon-β1a use, whereas positive associations between vitamin D and interleukin-1 receptor antagonist and secreted frizzled-related protein 3 were seen before, and between vitamin E and chemokine (C-X-C motif) ligand 16 during interferon-β1a treatment. These findings suggest associations with diverse inflammatory pathways, which may be differentially influenced by interferon-β1a treatment. Copyright © 2014 Elsevier B.V. All rights reserved.
Kim, Lee Kyung; Roh, Eun; Kim, Min Joo; Kim, Min Kyeong; Park, Kyeong Seon; Kwak, Soo Heon; Cho, Young Min; Park, Kyong Soo; Jang, Hak Chul; Jung, Hye Seung
2016-11-01
Glycemic variability is known to induce oxidative stress. We investigated the relationships between glycemic variability and serum bilirubin levels, an endogenous anti-oxidant, in patients with diabetes. A cross-sectional study was carried out with 77 patients with type 2 diabetes who had been recruited to two clinical studies from 2008 to 2014. There were no participants with diseases of the pancreas, liver, biliary tract and chronic renal insufficiency. Glycemic variation was calculated by a continuous glucose monitoring system, and correlation analyses were carried out to evaluate their association with bilirubin levels. Multiple linear regression was carried out to identify independent factors influencing bilirubin levels and glycemic variation. Among the participants, 42.3% were men. The mean (standard deviation) age was 61.5 years (10.4 years), body mass index was 24.2 kg/m 2 (2.8 kg/m 2 ), diabetes duration was 17.7 years (9.5 years), hemoglobin A 1c was 60.7 mmol/mol (7.1 mmol/mol; 7.7 [0.7]%) and bilirubin was 11.8 μmol/L (4.10 μmol/L). Serum bilirubin levels were not different according to age, body mass index and hemoglobin A 1c . However, the mean amplitude of glucose excursion was positively associated with bilirubin levels in women (r = 0.588, P < 0.001). After adjustment with duration of diabetes, serum albumin, liver enzymes, and mean glucose, the correlation between bilirubin and mean amplitude of glucose excursion remained significant (r = 0.566, P < 0.001). Multiple linear regression analyses showed that bilirubin was an independent determinant for the mean amplitude of glucose excursion in women. 1,5-Anhydroglucitol was also associated with bilirubin levels in women. Bilirubin level within the physiological range might be an independent predictor for glycemic variability in women with type 2 diabetes. © 2016 The Authors. Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd.
Auditing the multiply-related concepts within the UMLS
Mougin, Fleur; Grabar, Natalia
2014-01-01
Objective This work focuses on multiply-related Unified Medical Language System (UMLS) concepts, that is, concepts associated through multiple relations. The relations involved in such situations are audited to determine whether they are provided by source vocabularies or result from the integration of these vocabularies within the UMLS. Methods We study the compatibility of the multiple relations which associate the concepts under investigation and try to explain the reason why they co-occur. Towards this end, we analyze the relations both at the concept and term levels. In addition, we randomly select 288 concepts associated through contradictory relations and manually analyze them. Results At the UMLS scale, only 0.7% of combinations of relations are contradictory, while homogeneous combinations are observed in one-third of situations. At the scale of source vocabularies, one-third do not contain more than one relation between the concepts under investigation. Among the remaining source vocabularies, seven of them mainly present multiple non-homogeneous relations between terms. Analysis at the term level also shows that only in a quarter of cases are the source vocabularies responsible for the presence of multiply-related concepts in the UMLS. These results are available at: http://www.isped.u-bordeaux2.fr/ArticleJAMIA/results_multiply_related_concepts.aspx. Discussion Manual analysis was useful to explain the conceptualization difference in relations between terms across source vocabularies. The exploitation of source relations was helpful for understanding why some source vocabularies describe multiple relations between a given pair of terms. PMID:24464853
2013-01-01
Background In statistical modeling, finding the most favorable coding for an exploratory quantitative variable involves many tests. This process involves multiple testing problems and requires the correction of the significance level. Methods For each coding, a test on the nullity of the coefficient associated with the new coded variable is computed. The selected coding corresponds to that associated with the largest statistical test (or equivalently the smallest pvalue). In the context of the Generalized Linear Model, Liquet and Commenges (Stat Probability Lett,71:33–38,2005) proposed an asymptotic correction of the significance level. This procedure, based on the score test, has been developed for dichotomous and Box-Cox transformations. In this paper, we suggest the use of resampling methods to estimate the significance level for categorical transformations with more than two levels and, by definition those that involve more than one parameter in the model. The categorical transformation is a more flexible way to explore the unknown shape of the effect between an explanatory and a dependent variable. Results The simulations we ran in this study showed good performances of the proposed methods. These methods were illustrated using the data from a study of the relationship between cholesterol and dementia. Conclusion The algorithms were implemented using R, and the associated CPMCGLM R package is available on the CRAN. PMID:23758852
Mohammadi, Nabiallah; Adib, Minoo; Alsahebfosoul, Fereshteh; Kazemi, Mohammad; Etemadifar, Masoud
2016-01-15
Human Leukocyte Antigen G (HLA-G) gene polymorphism and expression rate have recently been suggested to have a potential role in susceptibility to Multiple Sclerosis (MS), a chronic inflammatory demyelinating and neurodegenerative disease of the central nervous system with unknown etiology. The aim of this study was to investigate the association of the frequency of HLA-G gene 14 bp insertion/deletion polymorphism and its plasma level with MS susceptibility. In this study, the HLA-G gene from 212 patients and 210 healthy individuals was amplified using real time PCR and screened for the 14 bp insertion/deletion polymorphism. In addition, HLA-G plasma levels of the patients were measured and compared to normal controls by ELISA method. Our results revealed that 14 bp insertion in HLA-G could result in lower plasma HLA-G level of the subjects, regardless of their health status and vice versa. Additionally, significant correlation of HLA-G genotype and its plasma level with MS susceptibility was observed. In conclusion, not only HLA-G 14 bp insertion/deletion polymorphism could be associated with expression rate of the HLA-G gene and its plasma level, but also could be considered as a risk factor for susceptibility to MS in our study population. Copyright © 2015 Elsevier B.V. All rights reserved.
Hofmann, Jonathan N.; Moore, Steven C.; Lim, Unhee; Park, Yikyung; Baris, Dalsu; Hollenbeck, Albert R.; Matthews, Charles E.; Gibson, Todd M.; Hartge, Patricia; Purdue, Mark P.
2013-01-01
Several studies have reported an increased risk of multiple myeloma associated with excess body weight. We investigated the risk of multiple myeloma in relation to separate measures of adiposity and energy balance at different ages in the National Institutes of Health-AARP Diet and Health Study, a large prospective cohort study in the United States. Participants completed a baseline questionnaire (1995–1996; n = 485,049), and a subset of participants completed a second questionnaire (1996–1997; n = 305,618) in which we solicited more detailed exposure information. Hazard ratios and 95% confidence intervals were estimated for the risk of multiple myeloma (overall, n = 813; subset, n = 489) in relation to several measures of obesity and leisure time physical activity. Multiple myeloma risk was associated with increasing body mass index (BMI) at cohort entry (per 5-kg/m2 increase, hazard ratio (HR) = 1.10, 95% confidence interval (CI): 1.00, 1.22); similar associations were observed for BMI at age 50 years (HR = 1.14, 95% CI: 1.02, 1.28), age 35 years (HR = 1.20, 95% CI: 1.05, 1.36), and age 18 years (HR = 1.13, 95% CI: 0.98, 1.32) without adjustment for baseline BMI. Risk of multiple myeloma was not associated with physical activity level at any age. These findings support the hypothesis that excess body weight, both in early adulthood and later in life, is a risk factor for multiple myeloma and suggest that maintaining a healthy body weight throughout life may reduce multiple myeloma risk. PMID:23543160
Pelletier Brochu, Jade; Meilleur, Dominique; DiMeglio, Giuseppina; Taddeo, Danielle; Lavoie, Eric; Erdstein, Julius; Pauzé, Robert; Pesant, Caroline; Thibault, Isabelle; Frappier, Jean-Yves
2018-04-23
Few studies have examined how the perceived quality of multiple interpersonal relationships is related to eating disorder (ED) symptom severity in adolescents and how psychological variables might influence these associations. The aim of this study is to determine whether the perceived level of trust, communication, and alienation in the relationship with one's mother, father, and peers are predictive of ED severity in adolescent females and to test the mediating effects of low self-esteem and negative mood on these associations. Adolescent females aged 12 to 18 (N = 186) with a diagnosis of Anorexia Nervosa (Restrictive; AN-R or Binge/Purge; AN-B/P) completed self-report measures evaluating the perceived quality of interpersonal relationships, ED symptom severity, low self-esteem, and negative mood. Multiple regressions revealed that the level of perceived alienation in the relationship with one's mother and peers was positively associated with ED symptom severity. Low self-esteem and negative mood acted as mediators of these associations. Considering that a high level of perceived alienation in the relationship with one's mother and peers appears to be associated with more severe ED symptoms through its impact on self-esteem and mood, improvements in the quality of these interactions are likely to be an effective target of intervention among adolescents.
Stress in multiple sclerosis: review of new developments and future directions.
Lovera, Jesus; Reza, Tara
2013-11-01
In the experimental autoimmune encephalitis model of multiple sclerosis, the effects of stress on disease severity depend on multiple factors, including the animal's genetics and the type of stressor. The studies in humans relating stress to the risk of developing multiple sclerosis have found discordant results. The studies looking at the association of stress with relapses show a fairly consistent association, where higher stress is associated with a higher risk of relapse. Higher stress levels also appear to increase the risk of development of gadolinium-enhancing lesions. A recent randomized trial shows that reducing stress using stress management therapy (SMT), a cognitive-behavioral therapy approach, results in a statistically significant reduction in new magnetic resonance imaging lesions. The magnitude of this effect is large and comparable to the effects of existent disease-modifying therapies, but no data exist yet proving that SMT reduces relapses or clinical progression; the effect of SMT appears to be short-lived. Additional work is needed to improve the duration of this effect and make this therapy more widely accessible.
Takabatake, Daisuke; Oishi, Kazuyuki
2016-01-01
Microangiopathic hemolytic anemia (MAHA) is a mechanical hemolytic anemia characterized by the emergence of fragmented red cells in peripheral blood. Here, we report a case of breast cancer associated with cancer-related (CR)-MAHA along with a literature review. The patient was a 54-year-old woman who made an emergency visit to our hospital because of low back pain, shoulder pain, visual impairment, and anemia. She was diagnosed with stage IV, ER-positive, PgR-positive, HER2-negative left breast cancer (invasive lobular carcinoma), with left axillary adenopathy, metastasis to the soft tissue of the orbital region, multiple bone metastases, pleural dissemination, and metastasis to the stomach and para-aortic lymph nodes. Chemotherapy was initiated successfully; tumor marker levels normalized and the visceral metastases almost disappeared. Hormone therapy was administered for maintenance. Two and a half years later, rapid elevation in tumor marker levels and severe anemia were noted, and fragmented red cells and poikilocytes emerged in the peripheral blood. Positron emission tomography-computed tomography and bone scintigraphy revealed multiple bone metastases, but no evidence of visceral metastasis. CR-MAHA associated with multiple bone metastases was diagnosed, and Paclitaxel chemotherapy was initiated with frequent blood transfusions. Her anemia gradually improved, with a decrease in tumor marker levels and the number of blood transfusions. Three months later, tumor marker levels increased again. Because the anemia was also exacerbated, chemotherapy was changed to eribulin. Tumor marker levels temporally decreased, and the anemia tended to improve, but 3 months later, the levels were elevated again and the anemia was exacerbated. A switch to another regimen was planned, but best supportive care was chosen instead because of rapid deterioration of liver function. The patient died a month later. CR-MAHA is thought to have a different pathologic mechanism from TTP or HUS. Although CR-MAHA is a clinical condition associated with a very poor prognosis, we consider it controllable for long period by rapid introduction of chemotherapy in many cases. CR-MAHA is a nearly oncologic emergency that medical oncologists need to be able to recognize even though it rarely occurs in breast cancer.
Study of multi-level atomic systems with the application of magnetic field
NASA Astrophysics Data System (ADS)
Hu, Jianping; Roy, Subhankar; Ummal Momeen, M.
2018-04-01
The complexity of multiple energy levels associated with each atomic system determines the various processes related to light- matter interactions. It is necessary to understand the influence of different levels in a given atomic system. In this work we focus on multi- level atomic schemes with the application of magnetic field. We analyze the different EIT windows which appears in the presence of moderately high magnetic field (∼ 10 G) strength.
Xie, Xue-Feng; Huang, Xiao-Hui; Shen, Ai-Zong; Li, Jun; Sun, Ye-Huan
2018-05-01
Leptin, synthesised by adipocytes, has been identified as a hormone that can influence inflammatory activity. Several studies have investigated leptin levels in patients with multiple sclerosis (MS), but the results are not consistent. This study aims to derive a more precise evaluation on the relationship between circulating leptin levels and MS. A comprehensive literature searched up to July 2017 was conducted to evaluate the association of circulating leptin levels and MS. The random-effect model was applied to calculate pooled standardised mean difference (SMD) and its 95% CI. Circulating leptin levels of patients with MS and healthy controls. Of 2155 studies identified, 33 met eligibility criteria and 9 studies with 645 patients with MS and 586 controls were finally included in the meta-analysis. Meta-analysis revealed that, compared with the healthy control group, the MS group had significantly higher plasma/serum leptin levels, with the SMD of 0.70% and 95% CI (0.24 to 1.15). Subgroup analyses suggested that the leptin levels of patients with MS were associated with region, age, study sample size, measurement type, gender and blood sample type. Overall, our study suggests that patients with MS have a significantly higher leptin level than in healthy controls. Further mechanism studies and longitudinal large cohort studies are still needed to further reveal the role of leptin in the pathogenesis of MS. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.
Kim, Seoyoun; Ferraro, Kenneth F.
2014-01-01
Purpose of the Study: The study investigates whether productive activities by older adults reduce bodily inflammation, as indicated by C-reactive protein (CRP), a biomeasure associated with the risk of cardiovascular diseases. Design and Methods: The study uses a representative survey of adults aged 57–85 from the National Social Life, Health, and Aging Project (N = 1,790). Linear regression models were used to analyze the effects of multiple roles (employment, volunteering, attending meetings, and caregiving) and the frequency of activity within each role on log values of CRP concentration (mg/L) drawn from assayed blood samples. Results: Number of roles for productive activities was associated with lower levels of CRP net of chronic conditions, lifestyle factors, and socioeconomic resources. When specific types of activity were examined, volunteering manifested the strongest association with lower levels of inflammation, particularly in the 70+ group. There was no evidence that frequent engagement in volunteer activity was associated with heightened inflammation. Implications: Productive activities—and frequent volunteering in particular—may protect individuals from inflammation that is associated with increased risk of hypertension and cardiovascular disease. PMID:23969258
Palmer, Cameron; Pe’er, Itsik
2016-01-01
Missing data are an unavoidable component of modern statistical genetics. Different array or sequencing technologies cover different single nucleotide polymorphisms (SNPs), leading to a complicated mosaic pattern of missingness where both individual genotypes and entire SNPs are sporadically absent. Such missing data patterns cannot be ignored without introducing bias, yet cannot be inferred exclusively from nonmissing data. In genome-wide association studies, the accepted solution to missingness is to impute missing data using external reference haplotypes. The resulting probabilistic genotypes may be analyzed in the place of genotype calls. A general-purpose paradigm, called Multiple Imputation (MI), is known to model uncertainty in many contexts, yet it is not widely used in association studies. Here, we undertake a systematic evaluation of existing imputed data analysis methods and MI. We characterize biases related to uncertainty in association studies, and find that bias is introduced both at the imputation level, when imputation algorithms generate inconsistent genotype probabilities, and at the association level, when analysis methods inadequately model genotype uncertainty. We find that MI performs at least as well as existing methods or in some cases much better, and provides a straightforward paradigm for adapting existing genotype association methods to uncertain data. PMID:27310603
Pickering, Amy J; Ercumen, Ayse; Arnold, Benjamin F; Kwong, Laura H; Parvez, Sarker Masud; Alam, Mahfuja; Sen, Debashis; Islam, Sharmin; Kullmann, Craig; Chase, Claire; Ahmed, Rokeya; Unicomb, Leanne; Colford, John M; Luby, Stephen P
2018-06-14
Enteric pathogens can be transmitted through multiple environmental pathways, yet little is known about the relative contribution of each pathway to diarrhea risk among children. We aimed to identify fecal transmission pathways in the household environment associated with prospectively measured child diarrhea in rural Bangladesh. We measured the presence and levels of E. coli in tubewells, stored drinking water, pond water, child hand rinses, courtyard soil, flies, and food in 1843 households. Gastrointestinal symptoms among children ages 0-60 months were recorded concurrently at the time of environmental sample collection and again a median of 6 days later. Incident diarrhea (3 or more loose stools in a 24-hr period) was positively associated with the concentration of E. coli on child hands measured on the first visit (incidence rate ratio [IRR]=1.23, 95% CI 1.06, 1.43 for a log10 increase), while other pathways were not associated. In cross-sectional analysis, there were no associations between concurrently measured environmental contamination and diarrhea. Our findings suggest higher levels of E. coli on child hands are strongly associated with subsequent diarrheal illness rates among children in rural Bangladesh.
Hyperparathyroidism Mimicking Metastatic Bone Disease: A Case Report and Review of Literature.
Gupta, Monica; Singhal, Lalita; Kumar, Akshay
2018-06-01
Multiple osteolytic lesions are usually associated with metastatic involvement of the bone; however, metabolic bone diseases should also be included in the differential diagnosis. In this study, we describe a case of primary hyperparathyroidism (PHPT) with multiple osteolytic lesions that was diagnosed initially as having metastatic bone involvement. The laboratory results showed hypercalcemia and raised alkaline phosphatase along with fibrosis in the bone marrow biopsy with no increase in tumor markers and normal serum protein electrophoresis. The parathyroid hormone levels were high, which pointed toward a diagnosis of PHPT. Sestamibi scan revealed uptake at the level of the left inferior pole of the thyroid gland, which was suggestive of parathyroid adenoma. The possibility of hyperparathyroidism should be kept in mind when a patient presents with multiple osteolytic lesions and hypercalcemia.
Morrison, Heather; Roscoe, Eileen M; Atwell, Amy
2011-01-01
We evaluated antecedent exercise for treating the automatically reinforced problem behavior of 4 individuals with autism. We conducted preference assessments to identify leisure and exercise items that were associated with high levels of engagement and low levels of problem behavior. Next, we conducted three 3-component multiple-schedule sequences: an antecedent-exercise test sequence, a noncontingent leisure-item control sequence, and a social-interaction control sequence. Within each sequence, we used a 3-component multiple schedule to evaluate preintervention, intervention, and postintervention effects. Problem behavior decreased during the postintervention component relative to the preintervention component for 3 of the 4 participants during the exercise-item assessment; however, the effects could not be attributed solely to exercise for 1 of these participants. PMID:21941383
Acquired dysfibrinogenemia secondary to multiple myeloma.
Kotlín, Roman; Sobotková, Alzbeta; Riedel, Tomás; Salaj, Peter; Suttnar, Jirí; Reicheltová, Zuzana; Májek, Pavel; Khaznadar, Tarek; Dyr, Jan E
2008-01-01
Abnormal coagulation properties indicative of a dysfibrinogen were found in the plasma of a 72-year-old male with multiple myeloma (IgGkappa, stage IIIA). The patient had high paraprotein concentration (85.75 g/l) and prolonged thrombin time (76.8 s), activated partial thromboplastin time (39.5 s), prothrombin time (23.5 s) and reptilase time (72.0 s). The fibrinogen level was increased. The fibrin polymerization induced by both thrombin and reptilase was impaired. Scanning electron microscopy revealed abnormal clot morphology. After six months of treatment, the paraprotein level decreased (19.48 g/l) and coagulation normalized as well as fibrin polymerization and fibrin clot morphology. It was found that the paraprotein interacts with the gamma-chain of fibrinogen. Acquired dysfibrinogenemia associated with multiple myeloma was diagnosed in the 72-year-old patient.
On the interrelation of multiplication and division in secondary school children
Huber, Stefan; Fischer, Ursula; Moeller, Korbinian; Nuerk, Hans-Christoph
2013-01-01
Multiplication and division are conceptually inversely related: Each division problem can be transformed into as a multiplication problem and vice versa. Recent research has indicated strong developmental parallels between multiplication and division in primary school children. In this study, we were interested in (i) whether these developmental parallels persist into secondary school, (ii) whether similar developmental parallels can be observed for simple and complex problems, (iii) whether skill level modulates this relationship, and (iv) whether the correlations are specific and not driven by general cognitive or arithmetic abilities. Therefore, we assessed performance of 5th and 6th graders attending two secondary school types of the German educational system in simple and complex multiplication as well as division while controlling for non-verbal intelligence, short-term memory, and other arithmetic abilities. Accordingly, we collected data from students differing in skills levels due to either age (5th < 6th grade) or school type (general < intermediate secondary school). We observed moderate to strong bivariate and partial correlations between multiplication and division with correlations being higher for simple tasks but nevertheless reliable for complex tasks. Moreover, the association between simple multiplication and division depended on students' skill levels as reflected by school types, but not by age. Partial correlations were higher for intermediate than for general secondary school children. In sum, these findings emphasize the importance of the inverse relationship between multiplication and division which persists into later developmental stages. However, evidence for skill-related differences in the relationship between multiplication and division was restricted to the differences for school types. PMID:24133476
Smeijers, Danique; Bulten, Erik; Franke, Barbara; Buitelaar, Jan; Verkes, Robbert-Jan
2017-07-01
Previous research showed that the disposition to react with disproportionate aggression in adults is influenced by an interaction between a variant in the X-chromosomal monoamine oxidase A gene (MAOA) and early traumatic events. Such studies have often focused on a single type of trauma, whereas we know that experiencing multiple trauma types is associated with more detrimental consequences. The differential susceptibility hypothesis suggests that individuals who are most susceptible to adversity, are also most likely to benefit from supportive experiences in childhood. Differences in susceptibility are thought to be partly genetically driven. In the present study we explored whether a genotype of MAOA linked to lower expression of the gene (MAOA-L) modified the effect of multiple types of trauma on aggression and/or altered responsiveness to treatment among adults with severe aggression. Forensic psychiatric outpatients (FPOs) (N=150) receiving treatment for aggression regulation problems were recruited. Traumatic events and aggression were measured using self-report. FPOs with multiple trauma types and those with the MAOA-L allele reported more severe levels of aggression. No interaction effects between MAOA genotype and trauma emerged. There were no differences in response to the intervention between FPOs with and without the MAOA-L variant, whereas FPOs with a single type of trauma showed the slowest reduction of aggression. FPOs with multiple types of trauma reported the highest levels of aggression over the course of treatment. Future research is needed to elucidate this association in further detail. The current study emphasized the importance of early recognition of early traumatic events. Copyright © 2017 Elsevier B.V. and ECNP. All rights reserved.
Chilenski, Sarah M
2011-12-01
This study examined how multiple dimensions and levels of the community context associated with early adolescent problem behaviors in rural communities. Four thousand, five hundred and nine eighth-grade students in 28 rural and small town school districts in two states participated in surveys regarding substance use and delinquency in 2005. Locations of alcohol retailers, tobacco retailers, youth-serving organizations, and student residences were geocoded. Associations of the number of proximal alcohol and tobacco retailers, and youth-serving organizations with an early-adolescent problem behavior index were tested in Nonlinear Mixed Models that controlled for multiple district-level and individual characteristics. Multi-level model results demonstrated that the number of alcohol and tobacco retail locations within a one-mile radius of each adolescent's home positively associated with student-reported problem behaviors above and beyond the influence of school district and individual characteristics. Results suggest that the proximal community context added significantly to the district context when understanding the occurrence of early adolescent problem behaviors. Recognizing this variability in geographically determined risk within a community will likely enhance the effectiveness of community prevention activities.
Kuračka, Lubomír; Kalnovičová, Terézia; Kucharská, Jarmila; Turčáni, Peter
2014-01-01
In the pathogenesis of demyelinating diseases including multiple sclerosis (MS) an important role is played by oxidative stress. Increased energy requirements during remyelination of axons and mitochondria failure is one of the causes of axonal degeneration and disability in MS. In this context, we analyzed to what extent the increase in purine catabolism is associated with selected blood lipophilic antioxidants and if there is any association with alterations in serum levels of coenzyme Q10. Blood serum and cerebrospinal fluid (CSF) samples from 42 patients with diagnosed MS and 34 noninflammatory neurologic patients (control group) were analyzed. Compared to control group, MS patients had significantly elevated values of all purine nucleotide metabolites, except adenosine. Serum lipophilic antioxidants γ -tocopherol, β -carotene, and coenzyme Q10 for the vast majority of MS patients were deficient or moved within the border of lower physiological values. Serum levels of TBARS, marker of lipid peroxidation, were increased by 81% in the MS patients. The results indicate that the deficit of lipophilic antioxidants in blood of MS patients may have a negative impact on bioenergetics of reparative remyelinating processes and promote neurodegeneration.
Chilenski, Sarah M.
2013-01-01
This study examined how multiple dimensions and levels of the community context associated with early adolescent problem behaviors in rural communities. Four thousand, five hundred and nine eighth-grade students in 28 rural and small town school districts in two states participated in surveys regarding substance use and delinquency in 2005. Locations of alcohol retailers, tobacco retailers, youth-serving organizations, and student residences were geocoded. Associations of the number of proximal alcohol and tobacco retailers, and youth-serving organizations with an early-adolescent problem behavior index were tested in Nonlinear Mixed Models that controlled for multiple district-level and individual characteristics. Multi-level model results demonstrated that the number of alcohol and tobacco retail locations within a one-mile radius of each adolescent’s home positively associated with student-reported problem behaviors above and beyond the influence of school district and individual characteristics. Results suggest that the proximal community context added significantly to the district context when understanding the occurrence of early adolescent problem behaviors. Recognizing this variability in geographically determined risk within a community will likely enhance the effectiveness of community prevention activities. PMID:21336674
Assessment of item-writing flaws in multiple-choice questions.
Nedeau-Cayo, Rosemarie; Laughlin, Deborah; Rus, Linda; Hall, John
2013-01-01
This study evaluated the quality of multiple-choice questions used in a hospital's e-learning system. Constructing well-written questions is fraught with difficulty, and item-writing flaws are common. Study results revealed that most items contained flaws and were written at the knowledge/comprehension level. Few items had linked objectives, and no association was found between the presence of objectives and flaws. Recommendations include education for writing test questions.
Atteraya, Madhu Sudhan; Ebrahim, Nasser B; Gnawali, Shreejana
2018-02-01
We examined the prevalence of child maltreatment as measured by the level of physical (moderate to severe) and emotional abuse and child labor, and the associated household level determinants of child maltreatment in Nepal. We used a nationally representative data set from the fifth round of the Nepal Multiple Indicator Cluster Survey (the 2014 NMICS). The main independent variables were household level characteristics. Dependent variables included child experience of moderate to severe physical abuse, emotional abuse, and child labor (domestic work and economic activities). Bivariate analyses and logistic regressions were used to examine the associations between independent and dependent variables. The results showed that nearly half of the children (49.8%) had experienced moderate physical abuse, 21.5% experienced severe physical abuse, and 77.3% experienced emotional abuse. About 27% of the children had engaged in domestic work and 46.7% in various economic activities. At bivariate level, educational level of household's head and household wealth status had shown significant statistical association with child maltreatment (p<0.001). Results from multivariate logistic regressions showed that higher education levels and higher household wealth status protected children from moderate to severe physical abuse, emotional abuse and child labor. In general, child maltreatment is a neglected social issue in Nepal and the high rates of child maltreatment calls for mass awareness programs focusing on parents, and involving all stakeholders including governments, local, and international organizations. Copyright © 2017 Elsevier Ltd. All rights reserved.
Association between serum uric acid level and multiple system atrophy: A meta-analysis.
Zhang, Xi; Liu, De-Shan; An, Chun-Yao; Liu, Yu-Zhao; Liu, Xiao-Hong; Zhang, Fang; Ning, Lu-Ning; Li, Chang-Ling; Ma, Chun-Mei; Hu, Rui-Ting
2018-06-01
Lower serum uric acid (UA) levels are considered to be related to the risk to develop many neurodegenerative disorders. However, the association between serum UA level and multiple system atrophy (MSA) remains controversial. The aim of this meta-analysis was to evaluate the relationship between serum UA level and MSA. PubMed, Web of Science, Embase, Cochrane Library and China National Knowledge Infrastructure (CNKI) were searched for eligible studies. Standardized mean difference (SMD) and 95% confidence intervals (95% CI) were calculated in a fixed-effects model or a random-effects model when appropriate. Subgroup analyses were carried out based on gender. A total of 6 eligible studies involving 547 MSA patients and 637 healthy individuals were identified. Meta-analysis results revealed that individuals with MSA had lower sera levels of UA as compared with healthy controls (pooled SMD is -0.51, 95%CI: -0.88 to -0.14; p = 0.006). The subgroup analysis to detect sex differences showed that the pooled SMD was -0.61 (95% CI: -0.82 to -0.40; p < 0.0001) for males and -0.22 (95% CI: -0.55 to 0.10; p = 0.18) for females compared with healthy controls. Our meta-analysis revealed that lower serum level of UA is associated with an increased risk of MSA and the relationship is significant in men but not in women. Copyright © 2018 Elsevier B.V. All rights reserved.
Knowles, Jacky; Kupka, Roland; Dumble, Sam; Garrett, Greg S.; Pandav, Chandrakant S.; Yadav, Kapil; Touré, Ndeye Khady; Foriwa Amoaful, Esi; Gorstein, Jonathan
2018-01-01
Single and multiple variable regression analyses were conducted using data from stratified, cluster sample design, iodine surveys in India, Ghana, and Senegal to identify factors associated with urinary iodine concentration (UIC) among women of reproductive age (WRA) at the national and sub-national level. Subjects were survey household respondents, typically WRA. For all three countries, UIC was significantly different (p < 0.05) by household salt iodine category. Other significant differences were by strata and by household vulnerability to poverty in India and Ghana. In multiple variable regression analysis, UIC was significantly associated with strata and household salt iodine category in India and Ghana (p < 0.001). Estimated UIC was 1.6 (95% confidence intervals (CI) 1.3, 2.0) times higher (India) and 1.4 (95% CI 1.2, 1.6) times higher (Ghana) among WRA from households using adequately iodised salt than among WRA from households using non-iodised salt. Other significant associations with UIC were found in India, with having heard of iodine deficiency (1.2 times higher; CI 1.1, 1.3; p < 0.001) and having improved dietary diversity (1.1 times higher, CI 1.0, 1.2; p = 0.015); and in Ghana, with the level of tomato paste consumption the previous week (p = 0.029) (UIC for highest consumption level was 1.2 times lowest level; CI 1.1, 1.4). No significant associations were found in Senegal. Sub-national data on iodine status are required to assess equity of access to optimal iodine intake and to develop strategic responses as needed. PMID:29690505
Brewer, LaPrincess C; Redmond, Nicole; Slusser, Joshua P; Scott, Christopher G; Chamberlain, Alanna M; Djousse, Luc; Patten, Christi A; Roger, Veronique L; Sims, Mario
2018-06-05
Ideal cardiovascular health metrics (defined by the American Heart Association Life's Simple 7 [LS7]) are suboptimal among blacks, which results in high risk of cardiovascular disease. We examined the association of multiple stressors with LS7 components among blacks. Using a community-based cohort of blacks (N=4383), we examined associations of chronic stress, minor stressors, major life events, and a cumulative stress score with LS7 components (smoking, diet, physical activity, body mass index, blood pressure, total cholesterol, and fasting plasma glucose) and an LS7 composite score. Multivariable logistic regression assessed the odds of achieving intermediate/ideal levels of cardiovascular health adjusted for demographic, socioeconomic, behavioral, and biomedical factors. The LS7 components with the lowest percentages of intermediate/ideal cardiovascular health levels were diet (39%), body mass index (47%), and physical activity (51%). Higher chronic, minor, and cumulative stress scores were associated with decreased odds (odds ratio [OR]) of achieving intermediate/ideal levels for smoking (OR [95% confidence interval], 0.80 [0.73-0.88], 0.84 [0.75-0.94], and 0.81 [0.74-0.90], respectively). Participants with more major life events had decreased odds of achieving intermediate/ideal levels for smoking (OR, 0.84; 95% confidence interval, 0.76-0.92) and fasting plasma glucose (OR, 0.90; 95% confidence interval, 0.82-0.98). Those with higher scores for minor stressors and major life events were less likely to achieve intermediate or ideal LS7 composite scores (OR [95% confidence interval], 0.89 [0.81-0.97] and 0.91 [0.84-0.98], respectively). Blacks with higher levels of multiple stress measures are less likely to achieve intermediate or ideal levels of overall cardiovascular health (LS7 composite score), specific behaviors (smoking), and biological factors (fasting plasma glucose). © 2018 The Authors and Mayo Clinic. Published on behalf of the American Heart Association, Inc., by Wiley.
An, Hongyan; Lim, Chai; Guillemin, Gilles J; Vollmer-Conna, Ute; Rawlinson, William; Bryant, Katherine; Tedla, Nicodemus
2016-01-01
Leukocyte immunoglobulin-like receptor A3 (LILRA3) is a soluble immune regulatory molecule primarily expressed by monocytes and macrophages. A homozygous 6.7kbp LILRA3 gene deletion that removes the first seven of its eight exons is predicted to lead to lack of LILRA3 protein, although this has not been experimentally confirmed. Moreover, there are conflicting results with regards to the link between the LILRA3 homozygous genetic deletion and susceptibility to multiple sclerosis (MS) in different European populations. The aim of this study was to investigate whether LILRA3 gene deletion is associated with MS susceptibility in a North American cohort of European ancestry and assess if serum LILRA3 protein level is a marker of clinical subtype and/or disease severity in MS. A total of 456 patients with MS and 99 unrelated healthy controls were genotyped for the 6.7kbp LILRA3 gene deletion and levels of LILRA3 protein in sera determined by in-house sandwich ELISA. We showed that LILRA3 gene deletion was not associated with MS susceptibility and did not affect the age of disease onset, clinical subtype or disease severity. However, we discovered for the first time that homozygous LILRA3 gene deletion results in lack of production of LILRA3 protein. Importantly, LILRA3 protein level was significantly increased in sera of patients with MS when compared with control subjects, particularly in more severe type primary progressive MS. Multiple regression analysis showed that LILRA3 level in serum was one of the strongest independent markers of disease severity in MS, which potentially can be used as a diagnostic marker.
Witt, Andreas; Münzer, Annika; Ganser, Helene G; Fegert, Jörg M; Goldbeck, Lutz; Plener, Paul L
2016-07-01
Most victims of child abuse have experienced more than one type of maltreatment, yet there is a lack of understanding of the impact of specific combinations of types of maltreatment. This study aimed to identify meaningful classes of maltreatment profiles and to associate them with short-term clinical outcomes. A total of 358 German children and adolescents aged 4-17 with a known history of child maltreatment were included in the study. Through interviews and questionnaires, information was obtained from participants and their primary caregivers on history of maltreatment, sociodemographics, psychopathology, level of psychosocial functioning, and health-related quality of life. Types of abuse were categorized into six major groups: sexual abuse in general, sexual abuse with penetration, physical abuse, emotional abuse, neglect, and exposure to domestic violence. A latent class analysis (LCA) was performed to determine distinct multi-type maltreatment profiles, which were then assessed for their associations with the sociodemographic and clinical outcome variables. The LCA revealed that participants could be categorized into three meaningful classes according to history of maltreatment: (1) experience of multiple types of maltreatment excluding sexual abuse (63.1%), (2) experience of multiple types of maltreatment including sexual abuse (26.5%), and (3) experience of predominantly sexual abuse (10.3%). Members of Class 2 showed significantly worse short-term outcomes on psychopathology, level of functioning, and quality of life compared to the other classes. Three distinct profiles of multiple types of maltreatment were empirically identified in this sample. Exposure to multiple types of abuse was associated with poorer outcomes. Copyright © 2016 Elsevier Ltd. All rights reserved.
Kesisoglou, Filippos; Rossenu, Stefaan; Farrell, Colm; Van Den Heuvel, Michiel; Prohn, Marita; Fitzpatrick, Shaun; De Kam, Pieter-Jan; Vargo, Ryan
2014-11-01
Development of in vitro-in vivo correlations (IVIVCs) for extended-release (ER) products is commonly pursued during pharmaceutical development to increase product understanding, set release specifications, and support biowaivers. This manuscript details the development of Level C and Level A IVIVCs for ER formulations of niacin, a highly variable and extensively metabolized compound. Three ER formulations were screened in a cross-over study against immediate-release niacin. A Multiple Level C IVIVC was established for both niacin and its primary metabolite nicotinuric acid (NUA) as well as total niacin metabolites urinary excretion. For NUA, but not for niacin, Level A IVIVC models with acceptable prediction errors were achievable via a modified IVIVC rather than a traditional deconvolution/convolution approach. Hence, this is in contradiction with current regulatory guidelines that suggest that when a Multiple Level C IVIVC is established, Level A models should also be readily achievable. We demonstrate that for a highly variable, highly metabolized compound such as niacin, development of a Level A IVIVC model fully validated according to agency guidelines may be challenging. However, Multiple Level C models are achievable and could be used to guide release specifications and formulation/manufacturing changes. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association.
Association of ADRB2 polymorphism with triglyceride levels in Tongans.
Naka, Izumi; Ohashi, Jun; Kimura, Ryosuke; Inaoka, Tsukasa; Matsumura, Yasuhiro
2013-07-23
Our previous study demonstrated that the A-allele of the single nucleotide polymorphism (SNP) rs34623097 located in the upstream region of the β2 adrenergic receptor gene (ADRB2) is significantly associated with risk for obesity in Oceanic populations. To investigate whether the ADRB2 polymorphisms explain part of the individual differences in lipid mobilization, energy expenditure and glycogen breakdown, the associations of 10 ADRB2 SNPs with total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol and triglyceride levels were examined in 128 adults in Tonga. A multiple linear regression analysis adjusted for age, sex, and body mass index revealed that rs34623097 was significantly associated with triglyceride levels (P-value = 0.037). A copy of the rs34623097-A allele increased serum triglyceride levels by 70.1 mg/dL (0.791 mmol/L). None of the ADRB2 SNPs showed a significant association with total-cholesterol, high-density lipoprotein cholesterol, or low-density lipoprotein cholesterol. In a Tongan population, a SNP located in the upstream region of ADRB2 is associated with triglyceride levels independent of body mass index.
Bright, Charlotte Lyn; Jun, Hyun-Jin; Stapleton, Laura M.
2015-01-01
Throughout adolescence, alcohol consumption and aggressive behaviors are associated with multiple problematic outcomes. Few studies have examined neighborhood-level predictors and individual and family-level sociodemographic variables to describe longitudinal trajectories of these problem behaviors. Therefore, this study investigated the unique contributions of neighborhood and sociodemographic factors in the shared development of aggressive behaviors and drinking in adolescents. We analyzed alcohol consumption frequency and frequency of aggressive behaviors using parallel process latent growth curve models with demographic indicators and neighborhood constructs as predictors. At all ages, alcohol use and aggression positively covaried. Male gender was associated with both aggressive episodes and alcohol use at age 12. African American ethnicity was associated with higher levels of early aggression. Higher neighborhood income was associated with lower levels of early aggression. Findings lend support to current efforts to curb early initiation of alcohol use and aggression. PMID:26413037
HIROKAWA, Kumi; MIWA, Machiko; TANIGUCHI, Toshiyo; TSUCHIYA, Masao; KAWAKAMI, Norito
2015-01-01
Levels of job stress have been shown to be inversely associated with testosterone levels, but some inconsistent results have been documented. We investigated the moderating effects of testosterone levels on associations between job stress-factors and psychological stress responses in Japanese medical workers. The participants were 63 medical staff (20 males and 43 women; mean age: 30.6 years; SD=7.3) in Okayama, Japan. Their job-stress levels and psychological stress responses were evaluated using self-administered questionnaires, and their salivary testosterone collected. Multiple regression analyses showed that job demand was positively associated with stress responses in men and women. An interaction between testosterone and support from colleagues had a significant effect on depression and anxiety for women. In women with lower testosterone levels, a reducing effect of support from colleagues on depression and anxiety was intensified. In women with higher testosterone levels, depression and anxiety levels were identical regardless of support from colleagues. Testosterone may function as a moderator between perceived work environment and psychological stress responses for female medical workers. PMID:26632120
Microbial genotype-phenotype mapping by class association rule mining.
Tamura, Makio; D'haeseleer, Patrik
2008-07-01
Microbial phenotypes are typically due to the concerted action of multiple gene functions, yet the presence of each gene may have only a weak correlation with the observed phenotype. Hence, it may be more appropriate to examine co-occurrence between sets of genes and a phenotype (multiple-to-one) instead of pairwise relations between a single gene and the phenotype. Here, we propose an efficient class association rule mining algorithm, netCAR, in order to extract sets of COGs (clusters of orthologous groups of proteins) associated with a phenotype from COG phylogenetic profiles and a phenotype profile. netCAR takes into account the phylogenetic co-occurrence graph between COGs to restrict hypothesis space, and uses mutual information to evaluate the biconditional relation. We examined the mining capability of pairwise and multiple-to-one association by using netCAR to extract COGs relevant to six microbial phenotypes (aerobic, anaerobic, facultative, endospore, motility and Gram negative) from 11,969 unique COG profiles across 155 prokaryotic organisms. With the same level of false discovery rate, multiple-to-one association can extract about 10 times more relevant COGs than one-to-one association. We also reveal various topologies of association networks among COGs (modules) from extracted multiple-to-one correlation rules relevant with the six phenotypes; including a well-connected network for motility, a star-shaped network for aerobic and intermediate topologies for the other phenotypes. netCAR outperforms a standard CAR mining algorithm, CARapriori, while requiring several orders of magnitude less computational time for extracting 3-COG sets. Source code of the Java implementation is available as Supplementary Material at the Bioinformatics online website, or upon request to the author. Supplementary data are available at Bioinformatics online.
Anand, Sonia S; Xie, Changchun; Paré, Guillaume; Montpetit, Alexandre; Rangarajan, Sumathy; McQueen, Matthew J; Cordell, Heather J; Keavney, Bernard; Yusuf, Salim; Hudson, Thomas J; Engert, James C
2009-02-01
Myocardial infarction (MI) is a leading cause of death globally, but specific genetic variants that influence MI and MI risk factors have not been assessed on a global basis. We included 8795 individuals of European, South Asian, Arab, Iranian, and Nepalese origin from the INTERHEART case-control study that genotyped 1536 single-nucleotide polymorphisms (SNPs) from 103 genes. One hundred and two SNPs were nominally associated with MI, but the statistical significance did not remain after adjustment for multiple testing. A subset of 940 SNPs from 69 genes were tested against MI risk factors. One hundred and sixty-three SNPs were nominally associated with a MI risk factor and 13 remained significant after adjusting for multiple testing. Of these 13, 11 were associated with apolipoprotein (Apo) B/A1 levels: 8 SNPs from 3 genes were associated with Apo B, and 3 cholesteryl ester transfer protein SNPs were associated with Apo A1. Seven of 8 of the SNPs associated with Apo B levels were nominally associated with MI (P<0.05), whereas none of the 3 cholesteryl ester transfer protein SNPs were associated with MI (P> or =0.17). Of the 3 SNPs most significantly associated with MI, rs7412, which defines the Apo E2 isoform, was associated with both a lower Apo B/A1 ratio (P=1.0x10(-7)) and lower MI risk (P=0.0004). Two low-density lipoprotein receptor variants, 1 intronic (rs6511720) and 1 in the 3' untranslated region (rs1433099) were both associated with a lower Apo B/A1 ratio (P<1.0x10(-5)) and a lower risk of MI (P=0.004 and P=0.003, respectively). Thirteen common SNPs were associated with MI risk factors. Importantly, SNPs associated with Apo B levels were associated with MI, whereas SNPs associated with Apo A1 levels were not. The Apo E isoform, and 2 common low-density lipoprotein receptor variants (rs1433099 and rs6511720) influence MI risk in this multiethnic sample.
Multiple Cerebral Infarcts in a Young Patient Associated With Marijuana Use.
Volpon, Leila Costa; Sousa, Camila Lacerda Muniz de Melo; Moreira, Silvia Keiko Kavaguti; Teixeira, Sara Reis; Carlotti, Ana Paula de Carvalho Panzeri
: Cerebrovascular events associated with marijuana use have been reported previously. This association is plausible, but not well-established yet. A 14-year-old girl, long-term heavy cannabis user, presented with generalized tonic-clonic seizures and decreased level of consciousness a few hours after smoking cannabis. Brain magnetic resonance imaging showed multiple areas of acute, subacute and chronic ischemic lesions in the left frontal lobe, basal ganglia, and corpus callosum. History of other illicit drug use and other known causes of stroke were ruled out. Cannabis might cause stroke through direct effects on the cerebral blood circulation, orthostatic hypotension, vasculitis, vasospasm, and atrial fibrillation. Long-term daily use of marijuana in young people may cause serious damage to the cerebrovascular system.
A simple test of association for contingency tables with multiple column responses.
Decady, Y J; Thomas, D R
2000-09-01
Loughin and Scherer (1998, Biometrics 54, 630-637) investigated tests of association in two-way tables when one of the categorical variables allows for multiple-category responses from individual respondents. Standard chi-squared tests are invalid in this case, and they developed a bootstrap test procedure that provides good control of test levels under the null hypothesis. This procedure and some others that have been proposed are computationally involved and are based on techniques that are relatively unfamiliar to many practitioners. In this paper, the methods introduced by Rao and Scott (1981, Journal of the American Statistical Association 76, 221-230) for analyzing complex survey data are used to develop a simple test based on a corrected chi-squared statistic.
NASA Technical Reports Server (NTRS)
Kosko, Bart
1991-01-01
Mappings between fuzzy cubes are discussed. This level of abstraction provides a surprising and fruitful alternative to the propositional and predicate-calculas reasoning techniques used in expert systems. It allows one to reason with sets instead of propositions. Discussed here are fuzzy and neural function estimators, neural vs. fuzzy representation of structured knowledge, fuzzy vector-matrix multiplication, and fuzzy associative memory (FAM) system architecture.
ERIC Educational Resources Information Center
Berta, Whitney; Virani, Tazim; Bajnok, Irmajean; Edwards, Nancy; Rowan, Margo
2014-01-01
Our study responds to calls for theory-driven approaches to studying innovation diffusion processes in health care. While most research on diffusion in health care is situated at the service delivery level, we study innovations and associated processes that have diffused to the system level, and refer to work on complex adaptive systems and whole…
Stress in childhood, adolescence and early adulthood, and cortisol levels in older age.
Harris, Mathew A; Cox, Simon R; Brett, Caroline E; Deary, Ian J; MacLullich, Alasdair M J
2017-03-01
The glucocorticoid hypothesis suggests that overexposure to stress may cause permanent upregulation of cortisol. Stress in youth may therefore influence cortisol levels even in older age. Using data from the 6-Day Sample, we investigated the effects of high stress in childhood, adolescence and early adulthood - as well as individual variables contributing to these measures; parental loss, social deprivation, school and home moves, illness, divorce and job instability - upon cortisol levels at age 77 years. Waking, waking +45 min (peak) and evening salivary cortisol samples were collected from 159 participants, and the 150 who were not using steroid medications were included in this study. After correcting for multiple comparisons, the only significant association was between early-adulthood job instability and later-life peak cortisol levels. After excluding participants with dementia or possible mild cognitive impairment, early-adulthood high stress showed significant associations with lower evening and mean cortisol levels, suggesting downregulation by stress, but these results did not survive correction for multiple comparisons. Overall, our results do not provide strong evidence of a relationship between stress in youth and later-life cortisol levels, but do suggest that some more long-term stressors, such as job instability, may indeed produce lasting upregulation of cortisol, persisting into the mid-to-late seventies.
Stress in childhood, adolescence and early adulthood, and cortisol levels in older age
Harris, Mathew A.; Cox, Simon R.; Brett, Caroline E.; Deary, Ian J.; MacLullich, Alasdair M. J.
2017-01-01
Abstract The glucocorticoid hypothesis suggests that overexposure to stress may cause permanent upregulation of cortisol. Stress in youth may therefore influence cortisol levels even in older age. Using data from the 6-Day Sample, we investigated the effects of high stress in childhood, adolescence and early adulthood – as well as individual variables contributing to these measures; parental loss, social deprivation, school and home moves, illness, divorce and job instability – upon cortisol levels at age 77 years. Waking, waking +45 min (peak) and evening salivary cortisol samples were collected from 159 participants, and the 150 who were not using steroid medications were included in this study. After correcting for multiple comparisons, the only significant association was between early-adulthood job instability and later-life peak cortisol levels. After excluding participants with dementia or possible mild cognitive impairment, early-adulthood high stress showed significant associations with lower evening and mean cortisol levels, suggesting downregulation by stress, but these results did not survive correction for multiple comparisons. Overall, our results do not provide strong evidence of a relationship between stress in youth and later-life cortisol levels, but do suggest that some more long-term stressors, such as job instability, may indeed produce lasting upregulation of cortisol, persisting into the mid-to-late seventies. PMID:28140738
Weyland, Patricia G; Grant, William B; Howie-Esquivel, Jill
2014-09-02
Serum 25-hydroxyvitamin D (25(OH)D) levels have been found to be inversely associated with both prevalent and incident cardiovascular disease (CVD) risk factors; dyslipidemia, hypertension and diabetes mellitus. This review looks for evidence of a causal association between low 25(OH)D levels and increased CVD risk. We evaluated journal articles in light of Hill's criteria for causality in a biological system. The results of our assessment are as follows. Strength of association: many randomized controlled trials (RCTs), prospective and cross-sectional studies found statistically significant inverse associations between 25(OH)D levels and CVD risk factors. Consistency of observed association: most studies found statistically significant inverse associations between 25(OH)D levels and CVD risk factors in various populations, locations and circumstances. Temporality of association: many RCTs and prospective studies found statistically significant inverse associations between 25(OH)D levels and CVD risk factors. Biological gradient (dose-response curve): most studies assessing 25(OH)D levels and CVD risk found an inverse association exhibiting a linear biological gradient. Plausibility of biology: several plausible cellular-level causative mechanisms and biological pathways may lead from a low 25(OH)D level to increased risk for CVD with mediators, such as dyslipidemia, hypertension and diabetes mellitus. Experimental evidence: some well-designed RCTs found increased CVD risk factors with decreasing 25(OH)D levels. Analogy: the association between serum 25(OH)D levels and CVD risk is analogous to that between 25(OH)D levels and the risk of overall cancer, periodontal disease, multiple sclerosis and breast cancer. all relevant Hill criteria for a causal association in a biological system are satisfied to indicate a low 25(OH)D level as a CVD risk factor.
Panizzon, Matthew S; Hauger, Richard L; Xian, Hong; Jacobson, Kristen; Lyons, Michael J; Franz, Carol E; Kremen, William S
2018-05-01
Animal and human research suggests that testosterone is associated with hippocampal structure and function. Studies examining the association between testosterone and either hippocampal structure or hippocampal-mediated cognitive processes have overwhelmingly focused on the effects of testosterone alone, without considering the interaction of other neuroendocrine factors. The aim of the present study was to examine the interactive effects of testosterone and cortisol in relation to hippocampal volume and episodic memory in a sample of late-middle aged men from the Vietnam Era Twin Study of Aging. The average age of participants was 56.3 years (range 51-60). Salivary hormone samples were collected at multiple time-points on two non-consecutive at-home days, and an in-lab assessment. Area under the curve with respect to ground measures for cortisol and testosterone were utilized. Significant testosterone-by-cortisol interactions were observed for hippocampal volume, and episodic memory. When cortisol levels were elevated (1 SD above the mean), testosterone levels were positively associated with hippocampal volume and memory performance. However, when cortisol levels were low (1 SD below the mean), testosterone levels were inversely related to hippocampal volume and memory performance. These findings suggest that in context of high cortisol levels, testosterone may be neuroprotective. In contrast, low testosterone may also be neuroprotective in the context of low cortisol levels. To our knowledge this is the first demonstration of such an interaction in a structural brain measure and an associated cognitive ability. These results argue in favor of broadening neuroendocrine research to consider the simultaneous and interactive effects of multiple hormones on brain structure and function. Copyright © 2018 Elsevier Ltd. All rights reserved.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Lee, Byung-Kook; Kim, Yangho, E-mail: yanghokm@nuri.net
Introduction: We present data on the association of manganese (Mn) level with hypertension in a representative sample of the adult Korean population who participated in the Korean National Health and Nutrition Examination Survey (KNHANES) 2008. Methods: This study was based on the data obtained by KNHANES 2008, which was conducted for three years (2007-2009) using a rolling sampling design involving a complex, stratified, multistage, probability-cluster survey of a representative sample of the noninstitutionalized civilian population of South Korea. Results: Multiple regression analysis after controlling for covariates, including gender, age, regional area, education level, smoking, drinking status, hemoglobin, and serum creatinine,more » showed that the beta coefficients of log blood Mn were 3.514, 1.878, and 2.517 for diastolic blood pressure, and 3.593, 2.449, and 2.440 for systolic blood pressure in female, male, and all participants, respectively. Multiple regression analysis including three other blood metals, lead, mercury, and cadmium, revealed no significant effects of the three metals on blood pressure and showed no effect on the association between blood Mn and blood pressure. In addition, doubling the blood Mn increased the risk of hypertension 1.828, 1.573, and 1.567 fold in women, men, and all participants, respectively, after adjustment for covariates. The addition of blood lead, mercury, and cadmium as covariates did not affect the association between blood Mn and the prevalence of hypertension. Conclusion: Blood Mn level was associated with an increased risk of hypertension in a representative sample of the Korean adult population. - Highlights: {yields} We showed the association of manganese with hypertension in Korean population. {yields} This study was based on the data obtained by KNHANES 2008. {yields} Blood manganese level was associated with an increased risk of hypertension.« less
Bekris, Lynn M.; Millard, Steven P.; Galloway, Nichole M.; Vuletic, Simona; Albers, John J.; Li, Ge; Galasko, Douglas R.; DeCarli, Charles; Farlow, Martin R.; Clark, Chris M.; Quinn, Joseph F.; Kaye, Jeffrey A.; Schellenberg, Gerard D.; Tsuang, Debby; Peskind, Elaine R.; Yu, Chang-En
2010-01-01
The ε4 allele of the apolipoprotein E gene (APOE) is associated with increased risk and earlier age at onset in late onset Alzheimer’s disease (AD). Other factors, such as expression level of apolipoprotein E protein (apoE), have been postulated to modify the APOE related risk of developing AD. Multiple loci in and outside of APOE are associated with a high risk of AD. The aim of this exploratory hypothesis generating investigation was to determine if some of these loci predict cerebrospinal fluid (CSF) apoE levels in healthy non-demented subjects. CSF apoE levels were measured from healthy non-demented subjects 21–87 years of age (n = 134). Backward regression models were used to evaluate the influence of 21 SNPs, within and surrounding APOE, on CSF apoE levels while taking into account age, gender, APOE ε4 and correlation between SNPs (linkage disequilibrium). APOE ε4 genotype does not predict CSF apoE levels. Three SNPs within the TOMM40 gene, one APOE promoter SNP and two SNPs within distal APOE enhancer elements (ME1 and BCR) predict CSF apoE levels. Further investigation of the genetic influence of these loci on apoE expression levels in the central nervous system is likely to provide new insight into apoE regulation as well as AD pathogenesis. PMID:18430993
do Prado, Mara Rúbia Maciel Cardoso; Oliveira, Fabiana de Cássia Carvalho; Assis, Karine Franklin; Ribeiro, Sarah Aparecida Vieira; do Prado Junior, Pedro Paulo; Sant'Ana, Luciana Ferreira da Rocha; Priore, Silvia Eloiza; Franceschini, Sylvia do Carmo Castro
2015-01-01
To assess the prevalence of vitamin D deficiency and its associated factors in women and their newborns in the postpartum period. This cross-sectional study evaluated vitamin D deficiency/insufficiency in 226 women and their newborns in Viçosa (Minas Gerais, BR) between December 2011 and November 2012. Cord blood and venous maternal blood were collected to evaluate the following biochemical parameters: vitamin D, alkaline phosphatase, calcium, phosphorus and parathyroid hormone. Poisson regression analysis, with a confidence interval of 95% was applied to assess vitamin D deficiency and its associated factors. Multiple linear regression analysis was performed to identify factors associated with 25(OH)D deficiency in the newborns and women from the study. The criteria for variable inclusion in the multiple linear regression model was the association with the dependent variable in the simple linear regression analysis, considering p<0.20. Significance level was α<5%. From 226 women included, 200 (88.5%) were 20 to 44 years old; the median age was 28 years. Deficient/insufficient levels of vitamin D were found in 192 (85%) women and in 182 (80.5%) neonates. The maternal 25(OH)D and alkaline phosphatase levels were independently associated with vitamin D deficiency in infants. This study identified a high prevalence of vitamin D deficiency and insufficiency in women and newborns and the association between maternal nutritional status of vitamin D and their infants' vitamin D status. Copyright © 2015 Sociedade de Pediatria de São Paulo. Publicado por Elsevier Editora Ltda. All rights reserved.
Avasarala, Jagannadha; Zachariah, Phenu
2015-11-15
Maintaining adequate levels of vitamin D may have a protective effect and lower the risk of multiple sclerosis (MS). For patients with MS, maintaining an adequate level of vitamin D level is probably associated with lessening of the frequency and severity of their symptoms. However, what remains unclear is whether if this is true across all racial/ethnic backgrounds. In African-Americans (AAs) this effect is not only absent but curiously enough, low levels of vitamin D do not matter since the bioavailability of this molecule in AA subjects is normal. It is this paradox that led to this brief report and we suggest more research and database construction based on race/ethnicity be done, as a first step to understand the biological mechanisms that confer or negate the effect of vitamin D levels in MS. Copyright © 2015 Elsevier B.V. All rights reserved.
Preterm birth and multiple pregnancy in European countries participating in the PERISTAT project.
Blondel, B; Macfarlane, A; Gissler, M; Breart, G; Zeitlin, J
2006-05-01
To compare rates of preterm birth among multiple births in European countries, to estimate their contribution to overall preterm birth rates and to explore factors which could explain differences between preterm birth rates. Analyses of data from vital statistics, birth registers or national samples of births. Eleven member states of the European Union. All live births or representative samples of births at national or regional level for the year 2000 or most recent year. Description of rates of preterm birth before 37 and 32 weeks, estimation of population attributable risks (PAR), study of associations between preterm birth rates in multiples and singletons and nonspontaneous labour using Spearman's rank correlation coefficient. Preterm birth rates, PAR, proportions of deliveries with nonspontaneous onset (caesarean sections before labour or induction of labour). The proportion of multiple births before 37 weeks varied from 68.4% in Austria to 42.2% in the Republic of Ireland. In half of the countries, over 20% of all preterm births were attributable to multiple births. A strong association was found between the proportions of births before 37 weeks among multiple and singleton births (r= 0.81; P < 0.001). An association was observed between the rates of preterm birth and the proportions of deliveries with nonspontaneous onset among twins. Wide variations in rates of preterm births and deliveries with nonspontaneous onset were found between countries, suggesting marked differences in clinical practice which could have long-term implications for the health of children from multiple births.
... or multiple myeloma Infections, such as hepatitis or mononucleosis Lower than normal T-cell levels may be due to: Acute viral infections Aging Cancer Immune system diseases, such as HIV/AIDS Radiation therapy Steroid treatment Risks Risks associated with having blood ...
Exogenous and endogenous hormones and breast cancer
ChenMD, Wendy Y.
2008-01-01
Exposure to higher levels of both exogenous and endogenous hormone is associated with breast cancer risk. Because of the association between breast cancer and HRT, only the minimal duration of HRT use is recommended for symptom control, and it is not recommended for chronic disease management. Current research issues include the role of progestins, other types of HRT, duration of unopposed estrogen use, and characteristics of cancers that develop on HRT. Circulating sex steroid levels are associated with breast cancer risk, but multiple issues need to be addressed before they are used routinely in clinical practice. Current research issues include measurement of levels for routine clinical practice, integration with standard breast cancer risk models and genetic polymorphism data, and applicability to estrogen-receptor-negative cancers. PMID:18971119
Kim, Oh Yoen; Kwak, So-Young; Kim, Boeun; Kim, Young-Sun; Kim, Hye Young; Shin, Min-Jeong
2017-01-01
Low socioeconomic status (SES) is linked to higher incidence/mortality of cardiovascular disease, but emerging evidence inconsistently reported that education level, a proxy for SES, is related to cardiovascular risk and metabolic syndrome (MetS) in Koreans. Furthermore, limited information is available on whether dietary components would mediate the relationship between education level and cardiovascular risk. We hypothesized that selected food consumption mediates the association between education level and MetS prevalence. Data from the Korea National Health and Nutritional Examination Survey (2008-2011) were included in cross-sectional analyses (n = 11,029, 30-64 years). The possible mediating effect of selected food groups (fruits, raw vegetables, red meat, milk, and soft drinks) on the association between education level and MetS was tested using a multiple mediation model. Education level was negatively associated with MetS prevalence. The association between lower education level and higher MetS prevalence was partially mediated by selected food consumption (lower intakes of fruit, red meat and milk; higher intakes of vegetable and soft drink) after adjusted for covariates. Gender also modified the association between education level and MetS prevalence that was more prominent in women than in men. Selected food consumption substantially contributes to the association between education level and MetS in Korean adults, especially among women. © 2017 S. Karger AG, Basel.
Application of fuzzy set and Dempster-Shafer theory to organic geochemistry interpretation
NASA Technical Reports Server (NTRS)
Kim, C. S.; Isaksen, G. H.
1993-01-01
An application of fuzzy sets and Dempster Shafter Theory (DST) in modeling the interpretational process of organic geochemistry data for predicting the level of maturities of oil and source rock samples is presented. This was accomplished by (1) representing linguistic imprecision and imprecision associated with experience by a fuzzy set theory, (2) capturing the probabilistic nature of imperfect evidences by a DST, and (3) combining multiple evidences by utilizing John Yen's generalized Dempster-Shafter Theory (GDST), which allows DST to deal with fuzzy information. The current prototype provides collective beliefs on the predicted levels of maturity by combining multiple evidences through GDST's rule of combination.
Goodwin, L; Gazard, B; Aschan, L; MacCrimmon, S; Hotopf, M; Hatch, S L
2017-04-09
Inequalities in mental health are well documented using individual social statuses such as socioeconomic status (SES), ethnicity and migration status. However, few studies have taken an intersectional approach to investigate inequalities in mental health using latent class analysis (LCA). This study will examine the association between multiple indicator classes of social identity with common mental disorder (CMD). Data on CMD symptoms were assessed in a diverse inner London sample of 1052 participants in the second wave of the South East London Community Health study. LCA was used to define classes of social identity using multiple indicators of SES, ethnicity and migration status. Adjusted associations between CMD and both individual indicators and multiple indicators of social identity are presented. LCA identified six groups that were differentiated by varying levels of privilege and disadvantage based on multiple SES indicators. This intersectional approach highlighted nuanced differences in odds of CMD, with the economically inactive group with multiple levels of disadvantage most likely to have a CMD. Adding ethnicity and migration status further differentiated between groups. The migrant, economically inactive and White British, economically inactive classes both had increased odds of CMD. This is the first study to examine the intersections of SES, ethnicity and migration status with CMD using LCA. Results showed that both the migrant, economically inactive and the White British, economically inactive classes had a similarly high prevalence of CMD. Findings suggest that LCA is a useful methodology for investigating health inequalities by intersectional identities.
Clonazepam-associated Bradycardia in a Disabled Elderly Woman with Multiple Complications
Maruyoshi, Hidetomo; Maruyoshi, Natsue; Hirosue, Motone; Ikeda, Komei; Shimamoto, Masaaki
2017-01-01
We herein report an 87-year-old woman who was taking clonazepam at 1.5 mg/day. She was hospitalized with an old cerebral infarction complicated with symptomatic epilepsy, dementia, dyslipidemia, and chronic cholecystitis. Electrocardiogram revealed severe bradycardia at 31 beats/min. The bradycardia disappeared on day 3 after clonazepam withdrawal, although the serum clonazepam level had been within normal limits. She was diagnosed with clonazepam-associated bradycardia, which was likely related to the potential calcium channel-blocking properties of clonazepam. Because of age-related pharmacokinetic and pharmacodynamic changes, the adverse effects of clonazepam should be considered, especially in disabled elderly individuals with multiple comorbidities. PMID:28794360
Clonazepam-associated Bradycardia in a Disabled Elderly Woman with Multiple Complications.
Maruyoshi, Hidetomo; Maruyoshi, Natsue; Hirosue, Motone; Ikeda, Komei; Shimamoto, Masaaki
2017-09-01
We herein report an 87-year-old woman who was taking clonazepam at 1.5 mg/day. She was hospitalized with an old cerebral infarction complicated with symptomatic epilepsy, dementia, dyslipidemia, and chronic cholecystitis. Electrocardiogram revealed severe bradycardia at 31 beats/min. The bradycardia disappeared on day 3 after clonazepam withdrawal, although the serum clonazepam level had been within normal limits. She was diagnosed with clonazepam-associated bradycardia, which was likely related to the potential calcium channel-blocking properties of clonazepam. Because of age-related pharmacokinetic and pharmacodynamic changes, the adverse effects of clonazepam should be considered, especially in disabled elderly individuals with multiple comorbidities.
Acoustical Detection Of Leakage In A Combustor
NASA Technical Reports Server (NTRS)
Puster, Richard L.; Petty, Jeffrey L.
1993-01-01
Abnormal combustion excites characteristic standing wave. Acoustical leak-detection system gives early warning of failure, enabling operating personnel to stop combustion process and repair spray bar before leak grows large enough to cause damage. Applicable to engines, gas turbines, furnaces, and other machines in which acoustic emissions at known frequencies signify onset of damage. Bearings in rotating machines monitored for emergence of characteristic frequencies shown in previous tests associated with incipient failure. Also possible to monitor for signs of trouble at multiple frequencies by feeding output of transducer simultaneously to multiple band-pass filters and associated circuitry, including separate trigger circuit set to appropriate level for each frequency.
Miura, Yasuo; Matsui, Yusuke; Kaneko, Hitomi; Watanabe, Mitsumasa; Tsudo, Mitsuru
2010-01-01
Iron chelation therapy (ICT) has been applied for the patients with iron overload-associated liver dysfunction since it is one of the causes of death in patients with intractable hematological diseases requiring multiple red blood cell transfusions. Recently, deferasirox (DSX), a novel, once-daily oral iron chelator, was demonstrated to have similar efficacy to the conventional continuous infusion of deferoxamine on a decrease in serum ferritin (SF) level in heavily transfused patients. We show three cases of transfusion-mediated iron-overloaded patients with an elevated serum alanine aminotransaminase (ALT). All three patients who received the ICT with DSX showed a decrease in ALT level in association with a decrease in SF level. It is suggested that DSX therapy could be considered to expect the improvement of liver damage for iron-overloaded patients with an abnormal ALT level. PMID:20592762
Jiang, Wei; Yu, Weichuan
2017-02-15
In genome-wide association studies (GWASs) of common diseases/traits, we often analyze multiple GWASs with the same phenotype together to discover associated genetic variants with higher power. Since it is difficult to access data with detailed individual measurements, summary-statistics-based meta-analysis methods have become popular to jointly analyze datasets from multiple GWASs. In this paper, we propose a novel summary-statistics-based joint analysis method based on controlling the joint local false discovery rate (Jlfdr). We prove that our method is the most powerful summary-statistics-based joint analysis method when controlling the false discovery rate at a certain level. In particular, the Jlfdr-based method achieves higher power than commonly used meta-analysis methods when analyzing heterogeneous datasets from multiple GWASs. Simulation experiments demonstrate the superior power of our method over meta-analysis methods. Also, our method discovers more associations than meta-analysis methods from empirical datasets of four phenotypes. The R-package is available at: http://bioinformatics.ust.hk/Jlfdr.html . eeyu@ust.hk. Supplementary data are available at Bioinformatics online. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com
Chang, Su-Hsin; Luo, Suhong; O'Brian, Katiuscia K; Thomas, Theodore S; Colditz, Graham A; Carlsson, Nils P; Carson, Kenneth R
2015-01-01
Multiple myeloma is one of the most common haematological malignancies in the USA and is consistently preceded by monoclonal gammopathy of undetermined significance (MGUS). We aimed to assess the association between metformin use and progression of MGUS to multiple myeloma. We did a retrospective cohort study of patients registered in the US Veterans Health Administration database and diagnosed with MGUS between Oct 1, 1999, and Dec 31, 2009. We included patients (aged >18 years) with at least one International Classification of Diseases (9th revision) code for diabetes mellitus and one treatment for their diabetes before MGUS diagnosis. We reviewed patient-level clinical data to verify diagnoses and extract any available data for size of baseline M-protein and type of MGUS. We defined metformin users as patients with diabetes who were given metformin consistently for 4 years after their diabetes diagnosis and before multiple myeloma development, death, or censorship. Our primary outcome was time from MGUS diagnosis to multiple myeloma diagnosis. We used Kaplan-Meier curves and Cox models to analyse the association between metformin use and MGUS progression. We obtained data for 3287 patients, of whom 2003 (61%) were included in the final analytical cohort. Median follow-up was 69 months (IQR 49–96). 463 (23%) participants were metformin users and 1540 (77%) participants were non-users. 13 (3%) metformin users progressed to multiple myeloma compared with 74 (5%) non-users. After adjustment, metformin use was associated with a reduced risk of progression to multiple myeloma (hazard ratio 0·47, 95% CI 0·25–0·87). For patients with diabetes diagnosed with MGUS, metformin use for 4 years or longer was associated with a reduced risk of progression of MGUS to multiple myeloma. Prospective studies are needed to establish whether this association is causal and whether these results can be extrapolated to non-diabetic individuals. Barnes-Jewish Hospital Foundation, National Institutes of Health, Agency for Healthcare Research and Quality, American Cancer Society.
Özkan Tuncay, Fatma; Mollaoğlu, Mukadder
2017-12-01
To determine the effects of cooling suit on fatigue and activities of daily living of individuals with multiple sclerosis. Fatigue is one of the most common symptoms in people with multiple sclerosis and adversely affects their activities of daily living. Studies evaluating fatigue associated with multiple sclerosis have reported that most of the fatigue cases are related to the increase in body temperature and that cooling therapy is effective in coping with fatigue. This study used a two sample, control group design. The study sample comprised 75 individuals who met the inclusion criteria. Data were collected with study forms. After the study data were collected, cooling suit treatment was administered to the experimental group. During home visits paid at the fourth and eighth weeks after the intervention, the aforementioned scales were re-administered to the participants in the experimental and control groups. The analyses performed demonstrated that the severity levels of fatigue experienced by the participants in the experimental group wearing cooling suit decreased. The experimental group also exhibited a significant improvement in the participants' levels of independence in activities of daily living. The cooling suit worn by individuals with multiple sclerosis was determined to significantly improve the participants' levels of fatigue and independence in activities of daily living. The cooling suit therapy was found to be an effective intervention for the debilitating fatigue suffered by many multiple sclerosis patients, thus significantly improving their level of independence in activities of daily living. © 2017 John Wiley & Sons Ltd.
Can we prevent or treat multiple sclerosis by individualised vitamin D supply?
2013-01-01
Apart from its principal role in bone metabolism and calcium homeostasis, vitamin D has been attributed additional effects including an immunomodulatory, anti-inflammatory, and possibly even neuroprotective capacity which implicates a possible role of vitamin D in autoimmune diseases like multiple sclerosis (MS). Indeed, several lines of evidence including epidemiologic, preclinical, and clinical data suggest that reduced vitamin D levels and/or dysregulation of vitamin D homeostasis is a risk factor for the development of multiple sclerosis on the one hand, and that vitamin D serum levels are inversely associated with disease activity and progression on the other hand. However, these data are not undisputable, and many questions regarding the preventive and therapeutic capacity of vitamin D in multiple sclerosis remain to be answered. In particular, available clinical data derived from interventional trials using vitamin D supplementation as a therapeutic approach in MS are inconclusive and partly contradictory. In this review, we summarise and critically evaluate the existing data on the possible link between vitamin D and multiple sclerosis in light of the crucial question whether optimization of vitamin D status may impact the risk and/or the course of multiple sclerosis. PMID:23356351
Marioni, Riccardo E; Deary, Ian J; Murray, Gordon D; Lowe, Gordon D O; Rafnsson, Snorri B; Strachan, Mark W J; Luciano, Michelle; Houlihan, Lorna M; Gow, Alan J; Harris, Sarah E; Stewart, Marlene C; Rumley, Ann; Fowkes, F Gerry R; Price, Jackie F
2010-01-01
It is unknown whether the relationship between raised inflammatory biomarker levels and late-life cognitive ability is causal. We explored this issue by testing the association between genetic regulators of plasma C-reactive protein (CRP) and cognition. Data were analysed from four cohorts based in central Scotland (Total N = 4,782). Associations were tested between variants in the CRP gene and both plasma CRP levels and a battery of neuropsychological tests, including a vocabulary-based estimate of peak prior cognitive ability and a general (summary) cognitive factor score, or 'g'. CRP levels were associated with a number of variants in the CRP gene (SNPs), including rs1205, rs1130864, rs1800947, and rs1417938 (P range 4.2e-06 to 0.041). Higher CRP levels were also associated with vocabulary-adjusted cognitive ability, used here to estimate lifetime cognitive change (P range 1.7e-04 to 0.038). After correction for multiple testing and adjustment for age and sex, no statistically significant associations were found between the SNPs and cognition. CRP is unlikely to be a causal determinant of late-life cognitive ability.
Gray, B.R.; Haro, R.J.; Rogala, J.T.; Sauer, J.S.
2005-01-01
1. Macroinvertebrate count data often exhibit nested or hierarchical structure. Examples include multiple measurements along each of a set of streams, and multiple synoptic measurements from each of a set of ponds. With data exhibiting hierarchical structure, outcomes at both sampling (e.g. Within stream) and aggregated (e.g. Stream) scales are often of interest. Unfortunately, methods for modelling hierarchical count data have received little attention in the ecological literature. 2. We demonstrate the use of hierarchical count models using fingernail clam (Family: Sphaeriidae) count data and habitat predictors derived from sampling and aggregated spatial scales. The sampling scale corresponded to that of a standard Ponar grab (0.052 m(2)) and the aggregated scale to impounded and backwater regions within 38-197 km reaches of the Upper Mississippi River. Impounded and backwater regions were resampled annually for 10 years. Consequently, measurements on clams were nested within years. Counts were treated as negative binomial random variates, and means from each resampling event as random departures from the impounded and backwater region grand means. 3. Clam models were improved by the addition of covariates that varied at both the sampling and regional scales. Substrate composition varied at the sampling scale and was associated with model improvements, and reductions (for a given mean) in variance at the sampling scale. Inorganic suspended solids (ISS) levels, measured in the summer preceding sampling, also yielded model improvements and were associated with reductions in variances at the regional rather than sampling scales. ISS levels were negatively associated with mean clam counts. 4. Hierarchical models allow hierarchically structured data to be modelled without ignoring information specific to levels of the hierarchy. In addition, information at each hierarchical level may be modelled as functions of covariates that themselves vary by and within levels. As a result, hierarchical models provide researchers and resource managers with a method for modelling hierarchical data that explicitly recognises both the sampling design and the information contained in the corresponding data.
Viborg, Njördur; Wångby-Lundh, Margit; Lundh, Lars-Gunnar; Wallin, Ulf; Johnsson, Per
2018-01-01
The developmental study of subtypes of disordered eating (DE) during adolescence may be relevant to understand the development of eating disorders. The purpose of the present study was to identify subgroups with different profiles of DE in a community sample of adolescent girls aged 13-15 years, and to study the stability of these profiles and subgroups over a one-year interval in order to find patterns that may need to be addressed in further research and prevention. Cluster analysis according to the LICUR procedure was performed on five aspects of DE, and the structural and individual stability of these clusters was analysed. The clusters were compared with regard to BMI, body esteem, deliberate self-harm, and other kinds of psychological difficulties. The analysis revealed six clusters (Multiple eating problems including purging, Multiple eating problems without purging, Social eating problems, Weight concerns, Fear of not being able to stop eating, and No eating problems) all of which had structurally stable profiles and five of which showed stability at the individual level. The more pronounced DE clusters (Multiple eating problems including/without purging) were consistently associated with higher levels of psychological difficulties and lower levels of body esteem. Furthermore, girls that reported purging reported engaging in self-harm to a larger extent. Subgroups of 13-15 year old girls show stable patterns of disordered eating that are associated with higher rates of psychological impairment and lower body esteem. The subgroup of girls who engage in purging also engage in more deliberate self-harm.
The impact of multiple low-level BCR-ABL1 mutations on response to ponatinib.
Parker, Wendy T; Yeung, David T O; Yeoman, Alexandra L; Altamura, Haley K; Jamison, Bronte A; Field, Chani R; Hodgson, J Graeme; Lustgarten, Stephanie; Rivera, Victor M; Hughes, Timothy P; Branford, Susan
2016-04-14
The third-generation tyrosine kinase inhibitor (TKI) ponatinib shows activity against all common BCR-ABL1 single mutants, including the highly resistant BCR-ABL1-T315I mutant, improving outcome for patients with refractory chronic myeloid leukemia (CML). However, responses are variable, and causal baseline factors have not been well-studied. The type and number of low-level BCR-ABL1 mutations present after imatinib resistance has prognostic significance for subsequent treatment with nilotinib or dasatinib as second-line therapy. We therefore investigated the impact of low-level mutations detected by sensitive mass-spectrometry before ponatinib initiation (baseline) on treatment response in 363 TKI-resistant patients enrolled in the PONATINIB for Chronic Myeloid Leukemia Evaluation and Ph(+)Acute Lymphoblastic Leukemia trial, including 231 patients in chronic phase (CP-CML). Low-level mutations were detected in 53 patients (15%, including low-level T315I in 14 patients); most, however, did not undergo clonal expansion during ponatinib treatment and, moreover, no specific individual mutations were associated with inferior outcome. We demonstrate however, that the number of mutations detectable by mass spectrometry after TKI resistance is associated with response to ponatinib treatment and could be used to refine the therapeutic approach. Although CP-CML patients with T315I (63/231, 27%) had superior responses overall, those with multiple mutations detectable by mass spectrometry (20, 32%) had substantially inferior responses compared with those with T315I as the sole mutation detected (43, 68%). In contrast, for CP-CML patients without T315I, the inferior responses previously observed with nilotinib/dasatinib therapy for imatinib-resistant patients with multiple mutations were not seen with ponatinib treatment, suggesting that ponatinib may prove to be particularly advantageous for patients with multiple mutations detectable by mass spectrometry after TKI resistance. © 2016 by The American Society of Hematology.
Bacchini, Dario; Licenziati, Maria Rosaria; Affuso, Gaetana; Garrasi, Alessandra; Corciulo, Nicola; Driul, Daniela; Tanas, Rita; Fiumani, Perla Maria; Di Pietro, Elena; Pesce, Sabino; Crinò, Antonino; Maltoni, Giulio; Iughetti, Lorenzo; Sartorio, Alessandro; Deiana, Manuela; Lombardi, Francesca; Valerio, Giuliana
2017-06-01
Research has provided evidence that obesity is associated with peer victimization and low levels of self-concept. No study has examined the relationship between BMI z-score, self-concept in multiple domains, and peer victimization. The aim of the research was to investigate the interplay between BMI z-score, self-concept in multiple domains (physical, athletic, social), and peer victimization, testing direct, mediated, and moderated associations. Eighty hundred fifteen outpatient children and adolescents were consecutively recruited in 14 hospitals distributed over the Italian country. The sample consisted of 419 males and 396 females; mean age 10.91 ± 1.97 years (range 6-14 years) and mean BMI z-score 1.85 ± 0.74 (range -0.97 ± 3.27). Peer victimization and self-concept were assessed with a revised Olweus Bully/Victim Questionnaire and with the Self-Perception Profile for Children. A structural equation model approach was used to determine the associations among variables, testing two competing models. In both models, path analysis revealed that BMI z-score was directly associated with peer victimization and self-concept in multiple domains. In the first model, peer victimization mediated the relationship between BMI-score and self-concept, whereas in the alternative model, self-concept mediated the relationship between BMI z-score and peer victimization. Interaction analyses revealed that social competence moderated the relationship between BMI z-score and peer victimization and that peer victimization moderated the relationship between BMI z-score and physical appearance. Higher levels of BMI z-score are a risk factor for peer victimization and poor self-concept. When high levels of BMI z-score are associated with a negative self-concept, the risk of victimization increases. Preventive and supportive interventions are needed to avoid negative consequences on quality of life in children and adolescents with obesity.
Protective factors associated with fewer multiple problem behaviors among homeless/runaway youth.
Lightfoot, Marguerita; Stein, Judith A; Tevendale, Heather; Preston, Kathleen
2011-01-01
Although homeless youth exhibit numerous problem behaviors, protective factors that can be targeted and modified by prevention programs to decrease the likelihood of involvement in risky behaviors are less apparent. The current study tested a model of protective factors for multiple problem behavior in a sample of 474 homeless youth (42% girls; 83% minority) ages 12 to 24 years. Higher levels of problem solving and planning skills were strongly related to lower levels of multiple problem behaviors in homeless youth, suggesting both the positive impact of preexisting personal assets of these youth and important programmatic targets for further building their resilience and decreasing problem behaviors. Indirect relationships between the background factors of self-esteem and social support and multiple problem behaviors were significantly mediated through protective skills. The model suggests that helping youth enhance their skills in goal setting, decision making, and self-reliant coping could lessen a variety of problem behaviors commonly found among homeless youth.
Protective Factors Associated with Fewer Multiple Problem Behaviors Among Homeless/Runaway Youth
Lightfoot, Marguerita; Stein, Judith A.; Tevendale, Heather; Preston, Kathleen
2015-01-01
Although homeless youth exhibit numerous problem behaviors, protective factors that can be targeted and modified by prevention programs to decrease the likelihood of involvement in risky behaviors are less apparent. The current study tested a model of protective factors for multiple problem behavior in a sample of 474 homeless youth (42% girls; 83% minority) ages 12 to 24 years. Higher levels of problem solving and planning skills were strongly related to lower levels of multiple problem behaviors in homeless youth, suggesting both the positive impact of preexisting personal assets of these youth and important programmatic targets for further building their resilience and decreasing problem behaviors. Indirect relationships between the background factors of self-esteem and social support and multiple problem behaviors were significantly mediated through protective skills. The model suggests that helping youth enhance their skills in goal setting, decision making, and self-reliant coping could lessen a variety of problem behaviors commonly found among homeless youth. PMID:22023279
McD Taylor, David; Pereira, Peter; Seymour, Jamie; Winkel, Kenneth D
2002-06-01
We describe a patient stung by an unknown jellyfish species offshore in Far North Queensland. The sting caused immediate and severe pain, multiple whip-like skin lesions and constitutional symptoms. The jellyfish tentacular nematocysyts were similar to, but distinct from, those of Carukia barnesi, a cause of the 'Irukandji' syndrome. The patients symptoms largely resolved over seven months and were associated with elevated cardiac troponin levels, in the absence of other evidence of cardiac disease. This case highlights the envenomation risks associated with marine recreation, and the need for critical evaluation of cardiac troponin assays and for further research in marine toxicology.
Erkenekli, Kudret; Oztas, Efser; Kuscu, Elif; Keskin, Uğur; Kurt, Yasemin Gulcan; Tas, Ahmet; Yilmaz, Nafiye
2017-01-01
Dyslipidemia is common in women with polycystic ovary syndrome (PCOS) irrespective of age. Our aim was to investigate soluble tumor necrosis factor like weak inducer of apoptosis (sTWEAK), a cardiovascular risk marker in PCOS, and to determine if it is associated with dyslipidemia in youth. A prospective-observational study was carried out including 35 PCOS patients and 35 healthy controls. Serum sTWEAK levels were measured using commercially available kits. Multiple logistic regression analysis was then performed to verify the statistically significant differences in the possible predictors of dyslipidemia. Serum sTWEAK levels and the percentage of women with dyslipidemia were significantly higher in the PCOS group (p = 0.024 and p < 0.001, respectively). Participants were further divided into 2 subgroups based on the presence of dyslipidemia. The percentage of women with PCOS was significantly higher in the dyslipidemic group when compared with controls; 70.7 vs. 20.7%, respectively (p < 0.001). Multiple logistic regression analysis revealed that both the presence of PCOS (OR 7.924, 95% CI 2.117-29.657, p = 0.002) and increased levels of sTWEAK (>693 pg/ml; OR 3.810, 95% CI 1.075-13.501, p = 0.038) were independently associated with dyslipidemia. Increased levels of both sTWEAK and PCOS were found to be independently associated with dyslipidemia in youth. © 2016 S. Karger AG, Basel.
Arnedo, Mireia; Taffé, Patrick; Sahli, Roland; Furrer, Hansjakob; Hirschel, Bernard; Elzi, Luigia; Weber, Rainer; Vernazza, Pietro; Bernasconi, Enos; Darioli, Roger; Bergmann, Sven; Beckmann, Jacques S; Telenti, Amalio; Tarr, Philip E
2007-09-01
HIV-1 infected individuals have an increased cardiovascular risk which is partially mediated by dyslipidemia. Single nucleotide polymorphisms in multiple genes involved in lipid transport and metabolism are presumed to modulate the risk of dyslipidemia in response to antiretroviral therapy. The contribution to dyslipidemia of 20 selected single nucleotide polymorphisms of 13 genes reported in the literature to be associated with plasma lipid levels (ABCA1, ADRB2, APOA5, APOC3, APOE, CETP, LIPC, LIPG, LPL, MDR1, MTP, SCARB1, and TNF) was assessed by longitudinally modeling more than 4400 plasma lipid determinations in 438 antiretroviral therapy-treated participants during a median period of 4.8 years. An exploratory genetic score was tested that takes into account the cumulative contribution of multiple gene variants to plasma lipids. Variants of ABCA1, APOA5, APOC3, APOE, and CETP contributed to plasma triglyceride levels, particularly in the setting of ritonavir-containing antiretroviral therapy. Variants of APOA5 and CETP contributed to high-density lipoprotein-cholesterol levels. Variants of CETP and LIPG contributed to non-high-density lipoprotein-cholesterol levels, a finding not reported previously. Sustained hypertriglyceridemia and low high-density lipoprotein-cholesterol during the study period was significantly associated with the genetic score. Single nucleotide polymorphisms of ABCA1, APOA5, APOC3, APOE, and CETP contribute to plasma triglyceride and high-density lipoprotein-cholesterol levels during antiretroviral therapy exposure. Genetic profiling may contribute to the identification of patients at risk for antiretroviral therapy-related dyslipidemia.
Rosa, Erica Carine Campos Caldas; Dos Santos, Renan Renato Cruz; Fernandes, Luis Fernando Amarante; Neves, Francisco de Assis Rocha; Coelho, Michella Soares; Amato, Angelica Amorim
2018-01-01
We investigated leukocyte relative telomere length (TL) in patients with type 2 diabetes (T2D) diagnosed for no longer than five years and its association with clinical and biochemical variables. Peripheral blood leukocyte relative TL was investigated in 108 patients with T2D (87 women, 21 men) and 125 (37 women, 88 men) age-matched control subjects with normal glucose tolerance, by quantitative polymerase chain reaction. Multiple linear regression analysis was used to examine the association between relative TL and demographic, anthropometric and biochemical indicators of metabolic control among patients with T2D. Patients with T2D had a median time since diagnosis of 1 year and most were on metformin monotherapy, with satisfactory glucose control determined by HbA1c levels. Median relative TL was not different between patients with T2D and control subjects. However, multiple linear regression analyses showed that relative TL was inversely associated with time since T2D diagnosis, fasting plasma glucose levels and HbA1c levels, but not with HbA1c levels assessed in the preceding 5-12 months, after adjustment for age, sex and body mass index. This study suggests that relative TL is not shorter in patients with recently diagnosed T2D, but is inversely correlated with glucose levels, even among patients with overall satisfactory glucose control. Copyright © 2017 Elsevier B.V. All rights reserved.
[''Liva"--population survey of female sexual habits].
Olesen, Tina Bech; Jensen, Kirsten Egebjerg; Munk, Christian; Tolstrup, Janne Schurmann; Kjaer, Susanne Krüger
2010-11-22
Sexual and contraceptive habits, e.g. early age at first intercourse, multiple sexual partners and non-use of condoms, are well-established risk factors for sexually transmitted infections and unwanted pregnancy. The aim was to examine if and how educational level and degree of urbanization are related to age at first intercourse, lifetime number of sexual partners and condom use. We used data from a large population-based questionnaire survey conducted during 2004-2005, including a random sample of 20,478 women (18-45 years) (participation rate: 81.4%). We used multiple logistic regression analysis to estimate odds ratios (OR) of early sexual debut (≤ 15 years old), having had > 5 lifetime sexual partners and never-use of condoms associated with educational level and degree of urbanization. The OR of having had an early sexual debut was almost twofold higher among women with a lower educational level (OR = 1.93; 95% CI: 1.73-2.15) than among women with higher educational level, and the OR of having had > 5 lifetime sexual partners was highest among women in the capital centre (OR = 2.36; 95% CI: 2.16-2.57) compared with women in the small provincial town areas. Furthermore, the OR of never-use of condoms was 2.53 (95% CI: 2.15-2.97) for women with a lower educational level compared with those with a higher educational level (mutually adjusted for age, degree of urbanization and educational level). Low educational level is associated with young age at first sexual intercourse and never-use of condoms, and living in an area of high urbanization is associated with a higher lifetime number of sexual partners. This information may be of importance for prevention in relation to women's reproductive health.
Syrengelas, Dimitrios; Kalampoki, Vassiliki; Kleisiouni, Paraskevi; Konstantinou, Dimitrios; Siahanidou, Tania
2014-07-01
The aims of this study were to investigate gross motor development in Greek infants and establish AIMS percentile curves and to examine possible association of AIMS scores with socioeconomic parameters. Mean AIMS scores of 1068 healthy Greek full-term infants were compared at monthly age level with the respective mean scores of the Canadian normative sample. In a subgroup of 345 study participants, parents provided, via interview, information about family socioeconomic status. Multiple linear regression analysis was performed to evaluate the relationship of infant motor development with socioeconomic parameters. Mean AIMS scores did not differ significantly between Greek and Canadian infants in any of the 19 monthly levels of age. In multiple linear regression analysis, the educational level of the mother and also whether the infant was being raised by grandparents/babysitter were significantly associated with gross motor development (p=0.02 and p<0.001, respectively), whereas there was no significant correlation of mean AIMS scores with gender, birth order, maternal age, paternal educational level and family monthly income. Gross motor development of healthy Greek full-term infants, assessed by AIMS during the first 19months of age, follows a similar course to that of the original Canadian sample. Specific socioeconomic factors are associated with the infants' motor development. Copyright © 2014 Elsevier Ltd. All rights reserved.
Goos, Jeroen D C; Kester, M I; Barkhof, Frederik; Klein, Martin; Blankenstein, Marinus A; Scheltens, Philip; van der Flier, Wiesje M
2009-11-01
Microbleeds (MBs) are commonly observed in Alzheimer disease. A minority of patients has multiple MBs. We aimed to investigate associations of multiple MBs in Alzheimer disease with clinical and MRI characteristics and cerebrospinal fluid biomarkers. Patients with Alzheimer disease with multiple (>or=8) MBs on T2*-weighted MRI were matched for age, sex, and field strength with patients with Alzheimer disease without MBs on a 1:2 basis. We included 21 patients with multiple MBs (73+/-7 years, 33% female) and 42 patients without MBs (72+/-7 years, 38% female). Mini-Mental State Examination was used to assess dementia severity. Cognitive functions were assessed using neuropsychological tests. Medial temporal lobe atrophy (0 to 4), global cortical atrophy (0 to 3), and white matter hyperintensities (0 to 30) were assessed using visual rating scales. In a subset, apolipoprotein E genotype and cerebrospinal fluid amyloid beta 1-42, total tau and tau phosphorylated at threonine 181 were determined. Patients with multiple MBs performed worse on Mini-Mental State Examination (multiple MB: 17+/-7; no MB: 22+/-4, P<0.05) despite similar disease duration. Atrophy was not related to presence of MBs, but patients with multiple MBs had more white matter hyperintensities (multiple MB: 8.8+/-4.8; no MB: 3.2+/-3.6, P<0.05). Adjusted for age, sex, white matter hyperintensities, and medial temporal lobe atrophy, the multiple MB group additionally performed worse on Visual Association Test object naming and animal fluency. Patients with multiple MBs had lower cerebrospinal fluid amyloid beta 1-42 levels (307+/-61) than patients without MBs (505+/-201, P<0.05). Adjusted for the same covariates, total tau, and tau phosphorylated at threonine 181 were higher in the multiple MB group. Microbleeds are associated with the clinical manifestation and biochemical hallmarks of Alzheimer disease, suggesting possible involvement of MBs in the pathogenesis of Alzheimer disease.
ERIC Educational Resources Information Center
McCoy, John L.
Step-wise multiple regression and typological analysis were used to analyze the extent to which selected factors influence vertical mobility and achieved level of living. A sample of 418 male household heads who were 18 to 45 years old in Washington County, Mississippi were interviewed during 1971. A prescreening using census and local housing…
ERIC Educational Resources Information Center
Wetterneck, Chad T.; Woods, Douglas W.
2006-01-01
Exposure and response prevention (ERP) was evaluated as treatment for three repetitive behaviors in an 11-year-old boy using a multiple baseline across behaviors design. The repetitive behaviors and associated self-reported distress were eliminated. At 3-month follow-up, the frequency for two of the three behaviors returned to baseline levels.…
Simpson, Steve; van der Mei, Ingrid; Lucas, Robyn M; Ponsonby, Anne-Louise; Broadley, Simon; Blizzard, Leigh; Taylor, Bruce
2018-01-01
Low vitamin D and/or sun exposure have been associated with increased risk of multiple sclerosis (MS) onset. However, comparatively, few studies have prospectively examined associations between these factors and clinical course. To evaluate the association of sun exposure parameters and vitamin D levels with conversion to MS and relapse risk in a prospectively monitored cohort of 145 participants followed after a first demyelinating event up to 5-year review (AusLong Study). Sun exposure prior to and after onset measured by annual questionnaire; ultraviolet radiation (UVR) "load" estimated by location of residence over the life course and ambient UVR levels. Serum 25-hydroxyvitamin D [25(OH)D] concentrations measured at baseline, 2/3-year, and 5-year review. MS conversion and relapse assessed by neurologist assessment and medical record review. Over two-thirds (69%) of those followed to 5-year review (100/145) converted to MS, with a total of 252 relapses. Higher pre-MS onset sun exposure was associated with reduced risk of MS conversion, with internal consistency between measures and dose-response relationships. Analogous associations were also seen with risk of relapse, albeit less strong. No consistent associations were observed between postonset sun exposure and clinical course, however. Notably, those who increased their sun exposure during follow-up had significantly reduced hazards of MS conversion and relapse. Serum 25(OH)D levels and vitamin D supplementation were not associated with conversion to MS or relapse hazard. We found that preonset sun exposure was protective against subsequent conversion to MS and relapses. While consistent associations between postonset sun exposure or serum 25(OH)D level and clinical course were not evident, possibly masked by behavior change, those participants who markedly increased their sun exposure demonstrated a reduced MS conversion and relapse hazard, suggesting beneficial effects of sun exposure on clinical course.
Synaptic pathology in the cerebellar dentate nucleus in chronic multiple sclerosis.
Albert, Monika; Barrantes-Freer, Alonso; Lohrberg, Melanie; Antel, Jack P; Prineas, John W; Palkovits, Miklós; Wolff, Joachim R; Brück, Wolfgang; Stadelmann, Christine
2017-11-01
In multiple sclerosis, cerebellar symptoms are associated with clinical impairment and an increased likelihood of progressive course. Cortical atrophy and synaptic dysfunction play a prominent role in cerebellar pathology and although the dentate nucleus is a predilection site for lesion development, structural synaptic changes in this region remain largely unexplored. Moreover, the mechanisms leading to synaptic dysfunction have not yet been investigated at an ultrastructural level in multiple sclerosis. Here, we report on synaptic changes of dentate nuclei in post-mortem cerebella of 16 multiple sclerosis patients and eight controls at the histological level as well as an electron microscopy evaluation of afferent synapses of the cerebellar dentate and pontine nuclei of one multiple sclerosis patient and one control. We found a significant reduction of afferent dentate synapses in multiple sclerosis, irrespective of the presence of demyelination, and a close relationship between glial processes and dentate synapses. Ultrastructurally, we show autophagosomes containing degradation products of synaptic vesicles within dendrites, residual bodies within intact-appearing axons and free postsynaptic densities opposed to astrocytic appendages. Our study demonstrates loss of dentate afferent synapses and provides, for the first time, ultrastructural evidence pointing towards neuron-autonomous and neuroglia-mediated mechanisms of synaptic degradation in chronic multiple sclerosis. © 2016 International Society of Neuropathology.
[Plasma IL-18 levels are related to insulin and are modulated by IL-18 gene polymorphisms].
Martinez-Hervas, Sergio; Martínez-Barquero, Vanesa; Nuñez Savall, Ester; Lendínez, Verónica; Olivares, Laura; Benito, Esther; Real, Jose T; Chaves, F Javier; Ascaso, Juan F
2015-01-01
Atherosclerosis is an inflammatory chronic disease influenced by multiple factors. Different prospective studies have shown that plasmatic levels of inflammatory markers were related to atherosclerosis and cardiovascular disease. To evaluate whether plasmatic levels of interleukin 18 (IL-18) are modulated by SNPs (single nucleotide polymorphisms) of the IL 18 gene and its possible association with insulin levels and other cardiovascular risk factors. 746 individuals were studied for a period of two years by opportunistic selection in the metropolitan area of Valencia. Parameters of lipid and glucose metabolism were analyzed by standard methodology. IL-18 was measured by ELISA. Individuals with insulin resistance showed significant higher levels of IL-18. IL 18 was significantly correlated with insulin levels and other cardiovascular risk factors. The CC genotype of the rs1834481 SNP was significantly associated with lower levels of IL-18. However, the GG genotype of the rs7559479 was associated with significant higher levels of IL-18. IL-18 is associated with insulin resistance and other cardiovascular risk factors, being those levels genetically regulated. Copyright © 2015 Sociedad Española de Arteriosclerosis. Published by Elsevier España. All rights reserved.
Association of serum uric acid with high-sensitivity C-reactive protein in postmenopausal women.
Raeisi, A; Ostovar, A; Vahdat, K; Rezaei, P; Darabi, H; Moshtaghi, D; Nabipour, I
2017-02-01
To explore the independent correlation between serum uric acid and low-grade inflammation (measured by high-sensitivity C-reactive protein, hs-CRP) in postmenopausal women. A total of 378 healthy Iranian postmenopausal women were randomly selected in a population-based study. Circulating hs-CRP levels were measured by highly specific enzyme-linked immunosorbent assay method and an enzymatic calorimetric method was used to measure serum levels of uric acid. Pearson correlation coefficient, multiple linear regression and logistic regression models were used to analyze the association between uric acid and hs-CRP levels. A statistically significant correlation was seen between serum levels of uric acid and log-transformed circulating hs-CRP (r = 0.25, p < 0.001). After adjustment for age and cardiovascular risk factors (according to NCEP ATP III criteria), circulating hs-CRP levels were significantly associated with serum uric acid levels (β = 0.20, p < 0.001). After adjustment for age and cardiovascular risk factors, hs-CRP levels ≥3 mg/l were significantly associated with higher uric acid levels (odds ratio =1.52, 95% confidence interval 1.18-1.96). Higher serum uric acid levels were positively and independently associated with circulating hs-CRP in healthy postmenopausal women.
Krönke, J; Kuchenbauer, F; Kull, M; Teleanu, V; Bullinger, L; Bunjes, D; Greiner, A; Kolmus, S; Köpff, S; Schreder, M; Mügge, L-O; Straka, C; Engelhardt, M; Döhner, H; Einsele, H; Bassermann, F; Bargou, R; Knop, S; Langer, C
2017-06-01
Lenalidomide is an immunomodulatory compound with high clinical activity in multiple myeloma. Lenalidomide binding to the Cereblon (CRBN) E3 ubiquitin ligase results in targeted ubiquitination and degradation of the lymphoid transcription factors Ikaros (IKZF1) and Aiolos (IKZF3) leading to growth inhibition of multiple myeloma cells. Recently, Basigin (BSG) was identified as another protein regulated by CRBN that is involved in the activity of lenalidomide. Here, we analyzed the prognostic value of IKZF1, IKZF3, CRBN and BSG mRNA expression levels in pretreatment plasma cells from 60 patients with newly diagnosed multiple myeloma uniformly treated with lenalidomide in combination with intensive chemotherapy within a clinical trial. We found that IKZF1 mRNA expression levels are significantly associated with progression-free survival (PFS). Patients in the lowest quartile (Q1) of IKZF1 expression had a superior PFS compared with patients in the remaining quartiles (Q2-Q4; 3-year PFS of 86 vs 51%, P=0.01). This translated into a significant better overall survival (100 vs 74%, P=0.03). Subgroup analysis revealed a significant impact of IKZF1, IKZF3 and BSG expression levels on PFS in cytogenetically defined standard-risk but not high-risk patients. Our data suggest a prognostic role of IKZF1, IKZF3 and BSG expression levels in lenalidomide-treated multiple myeloma.
Gómez, Luis F; Lucumí, Diego I; Parra, Diana C; Lobelo, Felipe
2008-01-01
Determining the association between the degree of urbanisation and excessive television-viewing and video-game use amongst children aged 5 to 12 years old. Data from the Colombian National Nutritional Survey 2005 was used in the analysis. Television viewing and video-game use was determined through parental reports for 13,090 children and classified as being excessive (e' 2 hours/day) or suitable (<2 hours/day). Five levels of urbanisation were determined using criteria from the National Planning Department and the population size of the rural or urban settings included in the survey. Multiple logistical regression analysis was conducted while taking potential confounders into account. There was a gradual increase in the probability of TV or videogames being used for 2 hours or more as the degree of urbanisation increased. This association was statistically significant for urbanisation level 3 and higher (urbanisation level 2, OR=1,33: 0,89-1,99 95 %CI; urbanisation level 3, 1,35=OR: 1,00-1,80 95 %CI; urbanisation level 4, 1,61=OR: 1,16-2,23 95 %CI and urbanisation level 5, 1,7=OR: 1,17-2,46 95 %CI). Colombian children living in areas of high-to-moderate urbanisation and population density are at a higher risk of excessive exposure to electronic media entertainment. Due to its multiple health implications (in particular obesity and cardio-metabolic health), such sedentary behaviour should be monitored and its determinants in the Colombian paediatric population must be understand for making effective public health interventions.
Oduro, Abraham R.; Fryauff, David J.; Koram, Kwadwo A.; Rogers, William O.; Anto, Francis; Atuguba, Frank; Anyorigiya, Thomas; Adjuik, Martin; Ansah, Patrick; Hodgson, Abraham; Nkrumah, Francis
2010-01-01
Demographics and health practices of 2,232 pregnant women in rural northeastern Ghana and characteristics of their 2,279 newborns were analyzed to determine benefits associated with intermittent preventive treatment (IPTp), antenatal care, and/or bed net use during pregnancy. More than half reported bed net use, 90% reported at least two antenatal care visits, and > 82% took at least one IPTp dose of sulfadoxine-pyrimethamine. Most used a bed net and IPTp (45%) or IPTp alone (38%). Low birth weight (< 2,500 grams) characterized 18.3% of the newborns and was significantly associated with female sex, Nankam ethnicity, first-born status, and multiple births. Among newborns of primigravidae, IPTp was associated with a significantly greater birth weight, significantly fewer low birth weight newborns, improved hemoglobin levels, and less anemia. Babies of multigravidae derived no benefit to birth weight or hemoglobin level from single or multiple doses of sulfadoxine-pyrimethamine during pregnancy. No differences or benefits were seen when a bed net was the only protective factor. PMID:20595482
Gilmour, Sarah J.; Sebolt, Audrey M.; Salazar, Maite P.; Everard, John D.; Thomashow, Michael F.
2000-01-01
We further investigated the role of the Arabidopsis CBF regulatory genes in cold acclimation, the process whereby certain plants increase in freezing tolerance upon exposure to low temperature. The CBF genes, which are rapidly induced in response to low temperature, encode transcriptional activators that control the expression of genes containing the C-repeat/dehydration responsive element DNA regulatory element in their promoters. Constitutive expression of either CBF1 or CBF3 (also known as DREB1b and DREB1a, respectively) in transgenic Arabidopsis plants has been shown to induce the expression of target COR (cold-regulated) genes and to enhance freezing tolerance in nonacclimated plants. Here we demonstrate that overexpression of CBF3 in Arabidopsis also increases the freezing tolerance of cold-acclimated plants. Moreover, we show that it results in multiple biochemical changes associated with cold acclimation: CBF3-expressing plants had elevated levels of proline (Pro) and total soluble sugars, including sucrose, raffinose, glucose, and fructose. Plants overexpressing CBF3 also had elevated P5CS transcript levels suggesting that the increase in Pro levels resulted, at least in part, from increased expression of the key Pro biosynthetic enzyme Δ1-pyrroline-5-carboxylate synthase. These results lead us to propose that CBF3 integrates the activation of multiple components of the cold acclimation response. PMID:11115899
A., Albu; A., Zirnea; O., Georgescu; D., Terzea; D., Jinga; S., Fica
2008-01-01
Malignant insulinomas are rare tumors (10% of insulinomas) that often present as multicentric macro nodules with multiple liver metastases before diagnosis. We report the case of a 55 year old female with a medical history of severe hypoglycemic attacks for two months. Blood tests showed a decreased value of glycemia (30mg/dl) associated with increased insulin level (16μU/ml) and an increased glycemia/insulinemia ratio of 1.87 supporting the diagnosis of insulinoma. Abdominal CT showed a 1.5 cm mass localized in the head of the pancreas with disseminated hepatic tumors, confirmed as neuroendocrine metastases by biopsy (which proved the presence of a malignant insulinoma). Primary hyperparathyroidism was diagnosed based on mild elevation of calcium (10.4 mg/dl) associated with a high level of PTH (71,2 pg/ml). The coexistence of the two endocrinopathies suggested the presence of type 1 multiple endocrine neoplasia (MEN 1). Because of multiple hepatic masses and liver function impairment, surgery and hepatic artery embolization were not performed. Somatostatin analog therapy was started with symptomatic control in the beginning, but rapid loss of beneficial effect. Finally, systemic chemotherapy with doxorubicin was administered, but the disease was progressive and after three months we decided to stop it. The patient died at home after one month, probably in hypoglycemic coma. PMID:20108468
Lossius, Andreas; Riise, Trond; Pugliatti, Maura; Bjørnevik, Kjetil; Casetta, Ilaria; Drulovic, Jelena; Granieri, Enrico; Kampman, Margitta T; Landtblom, Anne-Marie; Lauer, Klaus; Magalhaes, Sandra; Myhr, Kjell-Morten; Pekmezovic, Tatjana; Wesnes, Kristin; Wolfson, Christina; Holmøy, Trygve
2014-05-01
Seasonal fluctuations in solar radiation and vitamin D levels could modulate the immune response against Epstein-Barr virus (EBV) infection and influence the subsequent risk of multiple sclerosis (MS). Altogether 1660 MS patients and 3050 controls from Norway and Italy participating in the multinational case-control study of Environmental Factors In Multiple Sclerosis (EnvIMS) reported season of past infectious mononucleosis (IM). IM was generally reported more frequently in Norway (p=0.002), but was associated with MS to a similar degree in Norway (odds ratio (OR) 2.12, 95% confidence interval (CI) 1.64-2.73) and Italy (OR 1.72, 95% CI 1.17-2.52). For all participants, there was a higher reported frequency of IM during spring compared to fall (p<0.0005). Stratified by season of IM, the ORs for MS were 1.58 in spring (95% CI 1.08-2.31), 2.26 in summer (95% CI 1.46-3.51), 2.86 in fall (95% CI 1.69-4.85) and 2.30 in winter (95% CI 1.45-3.66). IM is associated with MS independently of season, and the association is not stronger for IM during spring, when vitamin D levels reach nadir. The distribution of IM may point towards a correlation with solar radiation or other factors with a similar latitudinal and seasonal variation.
2013-01-01
Background Wolbachia pipientis, a diverse group of α-proteobacteria, can alter arthropod host reproduction and confer a reproductive advantage to Wolbachia-infected females (cytoplasmic incompatibility (CI)). This advantage can alter host population genetics because Wolbachia-infected females produce more offspring with their own mitochondrial DNA (mtDNA) haplotypes than uninfected females. Thus, these host haplotypes become common or fixed (selective sweep). Although simulations suggest that for a CI-mediated sweep to occur, there must be a transient phase with repeated initial infections of multiple individual hosts by different Wolbachia strains, this has not been observed empirically. Wolbachia has been found in the tsetse fly, Glossina fuscipes fuscipes, but it is not limited to a single host haplotype, suggesting that CI did not impact its population structure. However, host population genetic differentiation could have been generated if multiple Wolbachia strains interacted in some populations. Here, we investigated Wolbachia genetic variation in G. f. fuscipes populations of known host genetic composition in Uganda. We tested for the presence of multiple Wolbachia strains using Multi-Locus Sequence Typing (MLST) and for an association between geographic region and host mtDNA haplotype using Wolbachia DNA sequence from a variable locus, groEL (heat shock protein 60). Results MLST demonstrated that some G. f. fuscipes carry Wolbachia strains from two lineages. GroEL revealed high levels of sequence diversity within and between individuals (Haplotype diversity = 0.945). We found Wolbachia associated with 26 host mtDNA haplotypes, an unprecedented result. We observed a geographical association of one Wolbachia lineage with southern host mtDNA haplotypes, but it was non-significant (p = 0.16). Though most Wolbachia-infected host haplotypes were those found in the contact region between host mtDNA groups, this association was non-significant (p = 0.17). Conclusions High Wolbachia sequence diversity and the association of Wolbachia with multiple host haplotypes suggest that different Wolbachia strains infected G. f. fuscipes multiple times independently. We suggest that these observations reflect a transient phase in Wolbachia evolution that is influenced by the long gestation and low reproductive output of tsetse. Although G. f. fuscipes is superinfected with Wolbachia, our data does not support that bidirectional CI has influenced host genetic diversity in Uganda. PMID:23384159
Pothi, Radhika; Hesketh, Andrew; Möller-Levet, Carla; Hodgson, David A; Laing, Emma E; Stewart, Graham R; Smith, Colin P
2018-01-01
Abstract Stress-induced adaptations require multiple levels of regulation in all organisms to repair cellular damage. In the present study we evaluated the genome-wide transcriptional and translational changes following heat stress exposure in the soil-dwelling model actinomycete bacterium, Streptomyces coelicolor. The combined analysis revealed an unprecedented level of translational control of gene expression, deduced through polysome profiling, in addition to transcriptional changes. Our data show little correlation between the transcriptome and ‘translatome’; while an obvious downward trend in genome wide transcription was observed, polysome associated transcripts following heat-shock showed an opposite upward trend. A handful of key protein players, including the major molecular chaperones and proteases were highly induced at both the transcriptional and translational level following heat-shock, a phenomenon known as ‘potentiation’. Many other transcripts encoding cold-shock proteins, ABC-transporter systems, multiple transcription factors were more highly polysome-associated following heat stress; interestingly, these protein families were not induced at the transcriptional level and therefore were not previously identified as part of the stress response. Thus, stress coping mechanisms at the level of gene expression in this bacterium go well beyond the induction of a relatively small number of molecular chaperones and proteases in order to ensure cellular survival at non-physiological temperatures. PMID:29746664
Bucca, Giselda; Pothi, Radhika; Hesketh, Andrew; Möller-Levet, Carla; Hodgson, David A; Laing, Emma E; Stewart, Graham R; Smith, Colin P
2018-05-09
Stress-induced adaptations require multiple levels of regulation in all organisms to repair cellular damage. In the present study we evaluated the genome-wide transcriptional and translational changes following heat stress exposure in the soil-dwelling model actinomycete bacterium, Streptomyces coelicolor. The combined analysis revealed an unprecedented level of translational control of gene expression, deduced through polysome profiling, in addition to transcriptional changes. Our data show little correlation between the transcriptome and 'translatome'; while an obvious downward trend in genome wide transcription was observed, polysome associated transcripts following heat-shock showed an opposite upward trend. A handful of key protein players, including the major molecular chaperones and proteases were highly induced at both the transcriptional and translational level following heat-shock, a phenomenon known as 'potentiation'. Many other transcripts encoding cold-shock proteins, ABC-transporter systems, multiple transcription factors were more highly polysome-associated following heat stress; interestingly, these protein families were not induced at the transcriptional level and therefore were not previously identified as part of the stress response. Thus, stress coping mechanisms at the level of gene expression in this bacterium go well beyond the induction of a relatively small number of molecular chaperones and proteases in order to ensure cellular survival at non-physiological temperatures.
Kim, Seoyoun; Ferraro, Kenneth F
2014-10-01
The study investigates whether productive activities by older adults reduce bodily inflammation, as indicated by C-reactive protein (CRP), a biomeasure associated with the risk of cardiovascular diseases. The study uses a representative survey of adults aged 57-85 from the National Social Life, Health, and Aging Project (N = 1,790). Linear regression models were used to analyze the effects of multiple roles (employment, volunteering, attending meetings, and caregiving) and the frequency of activity within each role on log values of CRP concentration (mg/L) drawn from assayed blood samples. Number of roles for productive activities was associated with lower levels of CRP net of chronic conditions, lifestyle factors, and socioeconomic resources. When specific types of activity were examined, volunteering manifested the strongest association with lower levels of inflammation, particularly in the 70+ group. There was no evidence that frequent engagement in volunteer activity was associated with heightened inflammation. Productive activities-and frequent volunteering in particular-may protect individuals from inflammation that is associated with increased risk of hypertension and cardiovascular disease. © The Author 2013. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.
Factors associated with increased felt stigma among individuals with epilepsy.
Bautista, Ramon Edmundo D; Shapovalov, Denys; Shoraka, Ali Reza
2015-08-01
The aim of the study is to determine whether certain demographic, clinical, and psychosocial traits are associated with higher levels of felt stigma among persons with epilepsy (PWE) patients followed at a level 4 epilepsy center. We performed a direct survey of 182 consenting patients that included the Epilepsy Stigma Scale. On univariate analysis, higher levels of perceived stigma were associated with age, marital status, race, driving, work status, seizure etiology, Quality of Life in Epilepsy-10 (QOLIE-10) scores, and health literacy. Among coping reactions, the use of denial, behavioral disengagement and venting were also associated with higher degrees of felt stigma. Using multiple linear regression, being single, poorer QOLIE-10 scores, difficulties understanding written information, and the use of behavioral disengagement were independently associated with poorer scores on the Epilepsy Stigma Scale. Our study paints a compelling profile of a PWE who has greater perceived stigma. Programs that increase the level of social support, improve health literacy, and enhance quality of life may also help decrease the amount of felt stigma among PWE. Copyright © 2015 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.
Wertz, Jonathon; Doshi, Ankur A; Guyette, Francis X; Callaway, Clifton W; Rittenberger, Jon C
2013-10-01
Following successful resuscitation from cardiac arrest, a prothrombotic state may contribute to end-organ dysfunction. We examined whether the level of serum thrombin-antithrombin (TAT) in patients hospitalized after cardiac arrest was associated with survival or the development of multiple organ failure (MOF). A prospective cohort study of subjects with in-hospital cardiac arrest (IHCA) or out-of-hospital cardiac arrest (OHCA) treated between 1/1/2007 and 5/30/2010 at a single tertiary care referral center. TAT levels were measured at hospital arrival and 24h after cardiac arrest. Logistic regression was used to determine associations between TAT levels and survival and development of MOF. Data were available for 86 subjects. TAT levels decreased over time. Initial TAT levels (OR 0.03; 95%CI 0.001, 0.62) and category of illness severity (OR 0.39; 95% CI 0.21, 0.73) were associated with survival. Male gender (OR 3.86; 95% CI 1.17, 12.75) and category of illness severity (OR 1.86; 95% CI 1.09, 3.20), but not TAT levels were associated with development of MOF. Neither the 24-h TAT level, nor the change in TAT from initial to 24h was associated with survival when adjusted for category of illness severity. Initial serum TAT levels and category of illness severity are associated with survival. TAT levels are not associated with development of MOF. Initial TAT levels may be a useful prognostic adjunct in the post arrest population. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.
Kanai, Takahiro; Shiizaki, Kazuhiro; Betsui, Hiroyuki; Aoyagi, Jun; Yamagata, Takanori
2018-05-16
Autosomal dominant polycystic kidney disease (ADPKD) is the most common hereditary renal disorder. ADPKD is characterized clinically by the presence of multiple bilateral renal cysts that lead to chronic renal failure. The cysts evolve from renal tubular epithelial cells that express the Klotho gene. Notably, Klotho acts as a co-receptor for fibroblast growth factor 23 (FGF23); in this context, it induces phosphaturia and maintains serum phosphate at a normal level. Many reports have shown that decreases in the soluble Klotho level and increases in the FGF23 level are associated with glomerular filtration rate (GFR) decline, but a recent study observed these changes in patient with normal eGFR. It remains unclear whether the decrease in the Klotho level precedes the increase in FGF23. Here, we present an ADPKD patient with enlarged kidneys due to multiple cysts who had a decreased soluble Klotho level but a normal eGFR and a normal FGF23 level. The patient's serum phosphate level was normal, as was the fractional excretion of phosphate (FEP). This appears to be the first reported case to show a decreased soluble Klotho level plus normal eGFR, FGF23, and FEP. These results suggest that Klotho decreases before FGF23 increases and further suggest that Klotho is not required to maintain normal serum phosphate levels in ADPKD if the FEP and serum phosphate levels are normal.
Dynamic regulation of genetic pathways and targets during aging in Caenorhabditis elegans.
He, Kan; Zhou, Tao; Shao, Jiaofang; Ren, Xiaoliang; Zhao, Zhongying; Liu, Dahai
2014-03-01
Numerous genetic targets and some individual pathways associated with aging have been identified using the worm model. However, less is known about the genetic mechanisms of aging in genome wide, particularly at the level of multiple pathways as well as the regulatory networks during aging. Here, we employed the gene expression datasets of three time points during aging in Caenorhabditis elegans (C. elegans) and performed the approach of gene set enrichment analysis (GSEA) on each dataset between adjacent stages. As a result, multiple genetic pathways and targets were identified as significantly down- or up-regulated. Among them, 5 truly aging-dependent signaling pathways including MAPK signaling pathway, mTOR signaling pathway, Wnt signaling pathway, TGF-beta signaling pathway and ErbB signaling pathway as well as 12 significantly associated genes were identified with dynamic expression pattern during aging. On the other hand, the continued declines in the regulation of several metabolic pathways have been demonstrated to display age-related changes. Furthermore, the reconstructed regulatory networks based on three of aging related Chromatin immunoprecipitation experiments followed by sequencing (ChIP-seq) datasets and the expression matrices of 154 involved genes in above signaling pathways provide new insights into aging at the multiple pathways level. The combination of multiple genetic pathways and targets needs to be taken into consideration in future studies of aging, in which the dynamic regulation would be uncovered.
Liu, Fangwei; Shen, Xubo; Wang, Ruifeng; Yu, Na; Shi, Yongjun; Xiong, Shimin; Xiong, Chengliang; Zhou, Yuanzhong
2018-01-01
Background Both sex hormone-binding globulin and central obesity have been found to be associated with metabolic and cardiovascular diseases. However, the direct relation between sex hormone-binding globulin and central obesity has not been demonstrated. Methodology We performed a cross-sectional study of 1166 male participants from Zunyi, Guizhou, western China, in 2013. Each participant completed a questionnaire and had a brief clinical exam with a fasting blood sample taken. All blood samples underwent standard laboratory testing for sex hormone-binding globulin. Level of serum sex hormone-binding globulin was compared by demographic characteristics, and multiple linear regression was used to evaluate the independent association of variables and sex hormone-binding globulin level. Results The mean serum level of sex hormone-binding globulin was increased in old-aged men (older than 40 years; mean 44.68±20.58 nmol/L), low diastolic blood pressure (<90mmHg; 43.76±20.50 nmol/L), waist-to-height ratio <0.5 (48.73±20.59 nmol/L), no education (52.36±22.91 nmol/L), farm occupation (43.58±20.60nmol/L), non-alcohol or former user (44.78±20.94 nmol/L) and long-term medication history (44.79±21.50 nmol/L). Factors independently associated with sex hormone binding globulin level on multiple regression were waist-to-height ratio (β=- 11.84 [95% confidence interval -13.96,-9.72]), age(β=12.40 [9.63,15.17]) and diastolic blood pressure (β=-5.07 [-7.44,-2.71]). Conclusions Central obesity has an independent inverse relation with serum level of sex hormone binding globulin among western Chinese men.
Iskandar, Anita R; Liu, Chun; Smith, Donald E; Hu, Kang-Quan; Choi, Sang-Woon; Ausman, Lynne M; Wang, Xiang-Dong
2013-04-01
Nicotine, a large constituent of cigarette smoke, is associated with an increased risk of lung cancer, but the data supporting this relationship are inconsistent. Here, we found that nicotine treatment not only induced emphysema but also increased both lung tumor multiplicity and volume in 4-nitrosamino-1-(3-pyridyl)-1-butanone (NNK)-initiated lung cancer in A/J mice. This tumor-promoting effect of nicotine was accompanied by significant reductions in survival probability and lung Sirtuin 1 (SIRT1) expression, which has been proposed as a tumor suppressor. The decreased level of SIRT1 was associated with increased levels of AKT phosphorylation and interleukin (il)-6 mRNA but decreased tumor suppressor p53 and retinoic acid receptor (RAR)-β mRNA levels in the lungs. Using this mouse model, we then determined whether β-cryptoxanthin (BCX), a xanthophyll that is strongly associated with a reduced risk of lung cancer in several cohort studies, can inhibit nicotine-induced emphysema and lung tumorigenesis. We found that BCX supplementation at two different doses was associated with reductions of the nicotine-promoted lung tumor multiplicity and volume, as well as emphysema in mice treated with both NNK and nicotine. Moreover, BCX supplementation restored the nicotine-suppressed expression of lung SIRT1, p53, and RAR-β to that of the control group, increased survival probability, and decreased the levels of lung il-6 mRNA and phosphorylation of AKT. The present study indicates that BCX is a preventive agent against emphysema and lung cancer with SIRT1 as a potential target. In addition, our study establishes a relevant animal lung cancer model for studying tumor growth within emphysematous microenvironments.
School league tables: a new population based predictor of dental restorative treatment need.
Crowley, Evelyn; O'Brien, Graham; Marcenes, Wagner
2003-06-01
To test whether dental restorative treatment need was related to the school league tables and level of social deprivation of the school ward. An ecological study using clinical data aggregated at school level, collected in the school dental screening examinations (1996-97), National Census (1991) and the results of the UK school league tables--Key Stage 2 SATs (1996-97). State primary schools in the Greenwich District of SE London, UK (1996-97). 12,854 pupils (6-11 years of age) in 62 schools. The percentage of 6 to 11 year old pupils per school requiring dental restorative treatment. Deprivation as measured by the overall Jarman Under Privileged Area Index (UPA) of the school ward was not associated with dental restorative treatment need (p > 0.05). Only two components of the Jarman Index, level of unemployment and the number of lone parent families in the school ward were found to be significantly associated with dental restorative treatment need (p < 0.05). Results of stepwise multiple linear regression analysis showed that the association with the school league table results in all three subjects, English, Mathematics and Science remained statistically significant after adjusting for levels of unemployment and single parents. Results of multiple linear regression analysis showed that a high level of dental restorative treatment need was significantly associated with poor school league table results in English, Mathematics and Science (p < 0.05) after adjusting for the overall Jarman score of the school ward. A separate analysis for the 11-year-old pupils aggregated by school (n = 46 schools) gave similar results. Aggregate measures of academic achievement may be a potential indicator of dental restorative treatment need.
Ashtari, Fereshte; Esmaeil, Nafiseh; Mansourian, Marjan; Poursafa, Parinaz; Mirmosayyeb, Omid; Barzegar, Mahdi; Pourgheisari, Hajar
2018-06-15
The evidence for an impact of ambient air pollution on the incidence and severity of multiple sclerosis (MS) is still limited. In the present study, we assessed the association between daily air pollution levels and MS prevalence and severity in Isfahan city, Iran. Data related to MS patients has been collected from 2008 to 2016 in a referral university clinic. The air quality index (AQI) data, were collected from 6 monitoring stations of Isfahan department of environment. The distribution map presenting the sites of air pollution monitoring stations as well as the residential address of MS patients was plotted on geographical information system (GIS). An increase in AQI level in four areas of the city (north, west, east and south) was associated with higher expanded disability status scale (EDSS) of MS patients[logistic regression odds ratio = 1.01 (95% CI = 1.008,1.012)]. Moreover, significant inverse association between the complete remission after the first attack with AQI level in total areas [logistic regression odds ratio = 0.987 (95% CI = 0.977, 0.997)] was found in crude model. However, after adjustment for confounding variables through multivariate logistic regression, AQI level was associated with degree of complete remission after first attack 1.005 (95% CI = 1.004, 1.006). The results of our study suggest that air pollution could play a role in the severity and remission of MS disease. However, more detailed studies with considering the complex involvement of different environmental factors including sunlight exposure, diet, depression and vitamin D are needed to determine the outcome of MS. Copyright © 2018 Elsevier B.V. All rights reserved.
Liu, Bin; Geng, Huizhen; Yang, Juan; Zhang, Ying; Deng, Langhui; Chen, Weiqing; Wang, Zilian
2016-03-17
Hyperlipidemia and high fasting plasma glucose levels at the first prenatal visit (First Visit FPG) are both related to gestational diabetes mellitus, maternal obesity/overweight and fetal overgrowth. The purpose of the present study is to investigate the correlation between First Visit FPG and lipid concentrations, and their potential association with offspring size at delivery. Pregnant women that received regular prenatal care and delivered in our center in 2013 were recruited for the study. Fasting plasma glucose levels were tested at the first prenatal visit (First Visit FPG) and prior to delivery (Before Delivery FPG). HbA1c and lipid profiles were examined at the time of OGTT test. Maternal and neonatal clinical data were collected for analysis. Data was analyzed by independent sample t test, Pearson correlation, and Chi-square test, followed by partial correlation and multiple linear regression analyses to confirm association. Statistical significance level was α =0.05. Analyses were based on 1546 mother-baby pairs. First Visit FPG was not correlated with any lipid parameters after adjusting for maternal pregravid BMI, maternal age and gestational age at First Visit FPG. HbA1c was positively correlated with triglyceride and Apolipoprotein B in the whole cohort and in the NGT group after adjusting for maternal age and maternal BMI at OGTT test. Multiple linear regression analyses showed neonatal birth weight, head circumference and shoulder circumference were all associated with First Visit FPG and triglyceride levels. Fasting plasma glucose at first prenatal visit is not associated with lipid concentrations in mid-pregnancy, but may influence fetal growth together with triglyceride concentration.
APPROACHES TO RISK ASSESSMENT FOR MULTIPLE CHEMICAL EXPOSURES
The Environmental Criteria and Assessment Office (ECAO) in Cincinnati has developed health risk assessment methods for chronic exposure to single chemical from a single route of exposure. Risk assessments for carcinogens associated an exposure level with a particular incidence of...
McKenzie, Karen; Murray, Aja; Booth, Tom
2013-09-25
The present study aimed to investigate whether there is an association between type of living environment (urban versus rural) and anxiety, depression and psychosis in the Scottish population. Data were obtained from the Scottish Neighbourhood Statistics database on Scottish Index of Multiple Deprivation and urban-rural classifications for 6505 data zones across Scotland. Multiple regression was used to test the association between prescriptions for psychotropic medication for anxiety, depression and psychosis, and type of living environment according to urban-rural classification, controlling for a range of socio-economic factors. Urban-rural classification significantly predicted poorer mental health both before (β=-.29) and after (β=-.20) controlling for a large number of socio-economic variables, with more urban areas having higher rates of prescription for psychotropic medication for anxiety, depression and psychosis. The current study focussed on macro-level variables and did not include individual level data. As such, the study did not include data on individual diagnoses, but instead used drug prescriptions for anxiety, depression and psychosis as a proxy for level of affective disorders within data zones. More urban living environments in Scotland are associated with higher rates of prescription for psychotropic medication for anxiety, depression and psychosis. © 2013 Elsevier B.V. All rights reserved.
Association of ADRB2 polymorphism with triglyceride levels in Tongans
2013-01-01
Background Our previous study demonstrated that the A-allele of the single nucleotide polymorphism (SNP) rs34623097 located in the upstream region of the β2 adrenergic receptor gene (ADRB2) is significantly associated with risk for obesity in Oceanic populations. Methods To investigate whether the ADRB2 polymorphisms explain part of the individual differences in lipid mobilization, energy expenditure and glycogen breakdown, the associations of 10 ADRB2 SNPs with total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol and triglyceride levels were examined in 128 adults in Tonga. Results A multiple linear regression analysis adjusted for age, sex, and body mass index revealed that rs34623097 was significantly associated with triglyceride levels (P-value = 0.037). A copy of the rs34623097-A allele increased serum triglyceride levels by 70.1 mg/dL (0.791 mmol/L). None of the ADRB2 SNPs showed a significant association with total-cholesterol, high-density lipoprotein cholesterol, or low-density lipoprotein cholesterol. Conclusions In a Tongan population, a SNP located in the upstream region of ADRB2 is associated with triglyceride levels independent of body mass index. PMID:23875540
NASA Astrophysics Data System (ADS)
Brubaker, P. A.
1985-06-01
It has been suggested, mainly through animal studies, that exposure to high noise levels may be associated with lower birth weight, reduced gestational length and other adverse reproductive outcomes. Few studies have been done on humans to show this association. The Air Force employs pregnant women in areas where there is a high potential for exposure to high noise levels. This study proposes a method to determine if there is an association between high frequency noise levels or = 115 dBA and adverse reproductive outcomes through a review of records and self-administered questionnaires in a case-comparison design. Prevelance rates will be calculated and a multiple logistic regression analysis computed for the independent variables that can affect reproduction.
Chung, Yuh-Jin; Jung, Woo-Chul
2017-01-01
In the distribution service industry, sales people often experience multiple occupational stressors such as excessive emotional labor, workplace mistreatment, and job insecurity. The present study aimed to explore the associations of these stressors with depressive symptoms among women sales workers at a clothing shopping mall in Korea. A cross sectional study was conducted on 583 women who consist of clothing sales workers and manual workers using a structured questionnaire to assess demographic factors, occupational stressors, and depressive symptoms. Multiple regression analyses were performed to explore the association of these stressors with depressive symptoms. Scores for job stress subscales such as job demand, job control, and job insecurity were higher among sales workers than among manual workers (p < 0.01). The multiple regression analysis revealed the association between occupation and depressive symptoms after controlling for age, educational level, cohabiting status, and occupational stressors (sβ = 0.08, p = 0.04). A significant interaction effect between occupation and social support was also observed in this model (sβ = −0.09, p = 0.02). The multiple regression analysis stratified by occupation showed that job demand, job insecurity, and workplace mistreatment were significantly associated with depressive symptoms in both occupations (p < 0.05), although the strength of statistical associations were slightly different. We found negative associations of social support (sβ = −0.22, p < 0.01) and emotional effort (sβ = −0.17, p < 0.01) with depressive symptoms in another multiple regression model for sales workers. Emotional dissonance (sβ = 0.23, p < 0.01) showed positive association with depressive symptoms in this model. The result of this study indicated that reducing occupational stressors would be effective for women sales workers to prevent depressive symptoms. In particular, promoting social support could be the most effective way to promote women sales workers’ mental health. PMID:29168777
Chung, Yuh-Jin; Jung, Woo-Chul; Kim, Hyunjoo; Cho, Seong-Sik
2017-11-23
In the distribution service industry, sales people often experience multiple occupational stressors such as excessive emotional labor, workplace mistreatment, and job insecurity. The present study aimed to explore the associations of these stressors with depressive symptoms among women sales workers at a clothing shopping mall in Korea. A cross sectional study was conducted on 583 women who consist of clothing sales workers and manual workers using a structured questionnaire to assess demographic factors, occupational stressors, and depressive symptoms. Multiple regression analyses were performed to explore the association of these stressors with depressive symptoms. Scores for job stress subscales such as job demand, job control, and job insecurity were higher among sales workers than among manual workers ( p < 0.01). The multiple regression analysis revealed the association between occupation and depressive symptoms after controlling for age, educational level, cohabiting status, and occupational stressors (sβ = 0.08, p = 0.04). A significant interaction effect between occupation and social support was also observed in this model (sβ = -0.09, p = 0.02). The multiple regression analysis stratified by occupation showed that job demand, job insecurity, and workplace mistreatment were significantly associated with depressive symptoms in both occupations ( p < 0.05), although the strength of statistical associations were slightly different. We found negative associations of social support (sβ = -0.22, p < 0.01) and emotional effort (sβ = -0.17, p < 0.01) with depressive symptoms in another multiple regression model for sales workers. Emotional dissonance (sβ = 0.23, p < 0.01) showed positive association with depressive symptoms in this model. The result of this study indicated that reducing occupational stressors would be effective for women sales workers to prevent depressive symptoms. In particular, promoting social support could be the most effective way to promote women sales workers' mental health.
Association of abnormal plasma bilirubin with aggressive HCC phenotype
Carr, Brian I.; Guerra, Vito; Giannini, Edoardo G.; Farinati, Fabio; Ciccarese, Francesca; Rapaccini, Gian Ludovico; Marco, Maria Di; Benvegnù, Luisa; Zoli, Marco; Borzio, Franco; Caturelli, Eugenio; Chiaramonte, Maria; Trevisani, Franco
2014-01-01
Background Cirrhosis-related abnormal liver function is associated with predisposition to HCC, features in several HCC classification systems and is an HCC prognostic factor. Aims To examine the phenotypic tumor differences in HCC patients with normal or abnormal plasma bilirubin levels. Methods A 2,416 patient HCC cohort was studied and dichotomized into normal and abnormal plasma bilirubin groups. Their HCC characteristics were compared for tumor aggressiveness features, namely blood AFP levels, tumor size, presence of PVT and tumor multifocality. Results In the total cohort, elevated bilirubin levels were associated with higher AFP levels, increased PVT and multifocality and lower survival, despite similar tumor sizes. When different tumor size terciles were compared, similar results were found, even for small tumor size patients. A multiple logistic regression model for PVT or tumor multifocality showed increased OddsRatios for elevated levels of GGTP, bilirubin and AFP and for larger tumor sizes. Conclusions HCC patients with abnormal bilirubin levels had worse prognosis than patients with normal bilirubin. They also had increased incidence of PVT and tumor multifocality and higher AFP levels, in patients with both small and larger tumors. The results show an association between bilirubin levels and indices of HCC aggressiveness. PMID:24787296
Genome-wide meta-analysis uncovers novel loci influencing circulating leptin levels.
Kilpeläinen, Tuomas O; Carli, Jayne F Martin; Skowronski, Alicja A; Sun, Qi; Kriebel, Jennifer; Feitosa, Mary F; Hedman, Åsa K; Drong, Alexander W; Hayes, James E; Zhao, Jinghua; Pers, Tune H; Schick, Ursula; Grarup, Niels; Kutalik, Zoltán; Trompet, Stella; Mangino, Massimo; Kristiansson, Kati; Beekman, Marian; Lyytikäinen, Leo-Pekka; Eriksson, Joel; Henneman, Peter; Lahti, Jari; Tanaka, Toshiko; Luan, Jian'an; Del Greco M, Fabiola; Pasko, Dorota; Renström, Frida; Willems, Sara M; Mahajan, Anubha; Rose, Lynda M; Guo, Xiuqing; Liu, Yongmei; Kleber, Marcus E; Pérusse, Louis; Gaunt, Tom; Ahluwalia, Tarunveer S; Ju Sung, Yun; Ramos, Yolande F; Amin, Najaf; Amuzu, Antoinette; Barroso, Inês; Bellis, Claire; Blangero, John; Buckley, Brendan M; Böhringer, Stefan; I Chen, Yii-Der; de Craen, Anton J N; Crosslin, David R; Dale, Caroline E; Dastani, Zari; Day, Felix R; Deelen, Joris; Delgado, Graciela E; Demirkan, Ayse; Finucane, Francis M; Ford, Ian; Garcia, Melissa E; Gieger, Christian; Gustafsson, Stefan; Hallmans, Göran; Hankinson, Susan E; Havulinna, Aki S; Herder, Christian; Hernandez, Dena; Hicks, Andrew A; Hunter, David J; Illig, Thomas; Ingelsson, Erik; Ioan-Facsinay, Andreea; Jansson, John-Olov; Jenny, Nancy S; Jørgensen, Marit E; Jørgensen, Torben; Karlsson, Magnus; Koenig, Wolfgang; Kraft, Peter; Kwekkeboom, Joanneke; Laatikainen, Tiina; Ladwig, Karl-Heinz; LeDuc, Charles A; Lowe, Gordon; Lu, Yingchang; Marques-Vidal, Pedro; Meisinger, Christa; Menni, Cristina; Morris, Andrew P; Myers, Richard H; Männistö, Satu; Nalls, Mike A; Paternoster, Lavinia; Peters, Annette; Pradhan, Aruna D; Rankinen, Tuomo; Rasmussen-Torvik, Laura J; Rathmann, Wolfgang; Rice, Treva K; Brent Richards, J; Ridker, Paul M; Sattar, Naveed; Savage, David B; Söderberg, Stefan; Timpson, Nicholas J; Vandenput, Liesbeth; van Heemst, Diana; Uh, Hae-Won; Vohl, Marie-Claude; Walker, Mark; Wichmann, Heinz-Erich; Widén, Elisabeth; Wood, Andrew R; Yao, Jie; Zeller, Tanja; Zhang, Yiying; Meulenbelt, Ingrid; Kloppenburg, Margreet; Astrup, Arne; Sørensen, Thorkild I A; Sarzynski, Mark A; Rao, D C; Jousilahti, Pekka; Vartiainen, Erkki; Hofman, Albert; Rivadeneira, Fernando; Uitterlinden, André G; Kajantie, Eero; Osmond, Clive; Palotie, Aarno; Eriksson, Johan G; Heliövaara, Markku; Knekt, Paul B; Koskinen, Seppo; Jula, Antti; Perola, Markus; Huupponen, Risto K; Viikari, Jorma S; Kähönen, Mika; Lehtimäki, Terho; Raitakari, Olli T; Mellström, Dan; Lorentzon, Mattias; Casas, Juan P; Bandinelli, Stefanie; März, Winfried; Isaacs, Aaron; van Dijk, Ko W; van Duijn, Cornelia M; Harris, Tamara B; Bouchard, Claude; Allison, Matthew A; Chasman, Daniel I; Ohlsson, Claes; Lind, Lars; Scott, Robert A; Langenberg, Claudia; Wareham, Nicholas J; Ferrucci, Luigi; Frayling, Timothy M; Pramstaller, Peter P; Borecki, Ingrid B; Waterworth, Dawn M; Bergmann, Sven; Waeber, Gérard; Vollenweider, Peter; Vestergaard, Henrik; Hansen, Torben; Pedersen, Oluf; Hu, Frank B; Eline Slagboom, P; Grallert, Harald; Spector, Tim D; Jukema, J W; Klein, Robert J; Schadt, Erik E; Franks, Paul W; Lindgren, Cecilia M; Leibel, Rudolph L; Loos, Ruth J F
2016-02-01
Leptin is an adipocyte-secreted hormone, the circulating levels of which correlate closely with overall adiposity. Although rare mutations in the leptin (LEP) gene are well known to cause leptin deficiency and severe obesity, no common loci regulating circulating leptin levels have been uncovered. Therefore, we performed a genome-wide association study (GWAS) of circulating leptin levels from 32,161 individuals and followed up loci reaching P<10(-6) in 19,979 additional individuals. We identify five loci robustly associated (P<5 × 10(-8)) with leptin levels in/near LEP, SLC32A1, GCKR, CCNL1 and FTO. Although the association of the FTO obesity locus with leptin levels is abolished by adjustment for BMI, associations of the four other loci are independent of adiposity. The GCKR locus was found associated with multiple metabolic traits in previous GWAS and the CCNL1 locus with birth weight. Knockdown experiments in mouse adipose tissue explants show convincing evidence for adipogenin, a regulator of adipocyte differentiation, as the novel causal gene in the SLC32A1 locus influencing leptin levels. Our findings provide novel insights into the regulation of leptin production by adipose tissue and open new avenues for examining the influence of variation in leptin levels on adiposity and metabolic health.
Hodge, James; Chang, Howard H; Boisson, Sophie; Collin, Simon M; Peletz, Rachel; Clasen, Thomas
2016-10-01
Fecally contaminated drinking water is believed to be a major contributor to the global burden of diarrheal disease and a leading cause of mortality among young children. However, recent systematic reviews and results from blinded studies of water quality interventions have raised questions about the risk associated with fecally contaminated water, particularly as measured by thermotolerant coliform (TTC) bacteria, a WHO-approved indicator of drinking water quality. We investigated the association between TTC in drinking water and diarrhea using data from seven previous studies. We obtained individual-level data from available field studies that measured TTC levels in household-drinking water and reported prevalence of diarrhea among household members during the days prior to the visit. The combined data set included diarrhea prevalence for 26,518 individuals and 8,000 water samples from 4,017 households, yielding 45,052 observations. The odds of diarrhea increased for each log10 increase in TTC/100 mL by 18% (95% CI: 11, 26%) for children < 5 years old and 12% (95% CI: 8, 18%) for all ages. For all ages, the odds of diarrhea increased by 21%, 35% and 49% for those whose household water samples were from 11-100, 101-1,000, and > 1,000 TTC/100 mL, respectively compared to < 1 TTC/100 mL. We found no evidence of increased odds of diarrhea with contamination levels below 11 TTC/100 mL, either in adults or children. Our analysis of individual-level data shows increased risk of diarrhea with increasing levels of TTC in drinking water. These results suggest an association between fecally contaminated water and diarrheal disease and provides support for health-based targets for levels of TTC in drinking water and for interventions to improve drinking water quality to prevent diarrhea. Hodge J, Chang HH, Boisson S, Collin SM, Peletz R, Clasen T. 2016. Assessing the association between thermotolerant coliforms in drinking water and diarrhea: an analysis of individual level data from multiple studies. Environ Health Perspect 124:1560-1567; http://dx.doi.org/10.1289/EHP156.
Hodge, James; Chang, Howard H.; Boisson, Sophie; Collin, Simon M.; Peletz, Rachel; Clasen, Thomas
2016-01-01
Background: Fecally contaminated drinking water is believed to be a major contributor to the global burden of diarrheal disease and a leading cause of mortality among young children. However, recent systematic reviews and results from blinded studies of water quality interventions have raised questions about the risk associated with fecally contaminated water, particularly as measured by thermotolerant coliform (TTC) bacteria, a WHO-approved indicator of drinking water quality. Objectives: We investigated the association between TTC in drinking water and diarrhea using data from seven previous studies. Methods: We obtained individual-level data from available field studies that measured TTC levels in household-drinking water and reported prevalence of diarrhea among household members during the days prior to the visit. Results: The combined data set included diarrhea prevalence for 26,518 individuals and 8,000 water samples from 4,017 households, yielding 45,052 observations. The odds of diarrhea increased for each log10 increase in TTC/100 mL by 18% (95% CI: 11, 26%) for children < 5 years old and 12% (95% CI: 8, 18%) for all ages. For all ages, the odds of diarrhea increased by 21%, 35% and 49% for those whose household water samples were from 11–100, 101–1,000, and > 1,000 TTC/100 mL, respectively compared to < 1 TTC/100 mL. We found no evidence of increased odds of diarrhea with contamination levels below 11 TTC/100 mL, either in adults or children. Conclusions: Our analysis of individual-level data shows increased risk of diarrhea with increasing levels of TTC in drinking water. These results suggest an association between fecally contaminated water and diarrheal disease and provides support for health-based targets for levels of TTC in drinking water and for interventions to improve drinking water quality to prevent diarrhea. Citation: Hodge J, Chang HH, Boisson S, Collin SM, Peletz R, Clasen T. 2016. Assessing the association between thermotolerant coliforms in drinking water and diarrhea: an analysis of individual level data from multiple studies. Environ Health Perspect 124:1560–1567; http://dx.doi.org/10.1289/EHP156 PMID:27164618
Ferreira, Ana Paula Silva; Pegorare, Ana Beatriz Gomes de Souza; Salgado, Pedro Rippel; Casafus, Filemón Silva; Christofoletti, Gustavo
2016-01-01
The objective of this study was to investigate the effects of two programs for strengthening the pelvic floor on the urinary incontinence of patients with multiple sclerosis (MS). This is a prospective study of the clinical trial type, monitored for 6 mos, in which 24 women in the moderate stage of MS participated in a program of exercises for strengthening the pelvic floor-associated (experimental group) or not (control group) with electrotherapy. The variables analyzed were as follows: quality-of-life, overactivity of the bladder, perineal contraction, and level of anxiety and depression. The statistical procedures involved multivariate analyses of repeated measurements, with a significance of 5%. Initial homogeneity being observed in the anthropometric and clinical variables, both protocols resulted in improvements in quality-of-life (P = 0.001), overactive bladder (P = 0.001), perineal contraction (P = 0.004), and level of anxiety (P = 0.001) and depression (P = 0.001), in relation to the initial comparison. The association of electrotherapy with strengthening exercises increased the improvement of the patients regarding overactive bladder (P = 0.039) and perineal contraction (P = 0.001), in comparison with the control group. The results reinforce the benefit of exercises for strengthening the musculature of the pelvic floor in women with overactive bladder in MS and demonstrate a potential of the action when associated with electrotherapy. Complete the self-assessment activity and evaluation online at http://www.physiatry.org/JournalCME CME OBJECTIVES:: Upon completion of this article, the reader should be able to: (1) Identify common dysfunctions of the lower urinary tract in women with multiple sclerosis; (2) Discuss the relationship between quality-of-life, level of anxiety and depression, degree of perineal contraction, and overactive bladder; and (3) Recognize the benefits promoted by physical therapy for strengthening the pelvic floor in patients with multiple sclerosis. Advanced : The Association of Academic Physiatrists is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians. The Association of Academic Physiatrists designates this activity for a maximum of 1.5 AMA PRA Category 1 Credit(s). Physicians should only claim credit commensurate with the extent of their participation in the activity.
2012-01-01
Background The aim of this study was to clarify the role of global hypomethylation of repetitive elements in determining the genetic and clinical features of multiple myeloma (MM). Methods We assessed global methylation levels using four repetitive elements (long interspersed nuclear element-1 (LINE-1), Alu Ya5, Alu Yb8, and Satellite-α) in clinical samples comprising 74 MM samples and 11 benign control samples (7 cases of monoclonal gammopathy of undetermined significance (MGUS) and 4 samples of normal plasma cells (NPC)). We also evaluated copy-number alterations using array-based comparative genomic hybridization, and performed methyl-CpG binding domain sequencing (MBD-seq). Results Global levels of the repetitive-element methylation declined with the degree of malignancy of plasma cells (NPC>MGUS>MM), and there was a significant inverse correlation between the degree of genomic loss and the LINE-1 methylation levels. We identified 80 genomic loci as common breakpoints (CBPs) around commonly lost regions, which were significantly associated with increased LINE-1 densities. MBD-seq analysis revealed that average DNA-methylation levels at the CBP loci and relative methylation levels in regions with higher LINE-1 densities also declined during the development of MM. We confirmed that levels of methylation of the 5' untranslated region of respective LINE-1 loci correlated strongly with global LINE-1 methylation levels. Finally, there was a significant association between LINE-1 hypomethylation and poorer overall survival (hazard ratio 2.8, P = 0.015). Conclusion Global hypomethylation of LINE-1 is associated with the progression of and poorer prognosis for MM, possibly due to frequent copy-number loss. PMID:23259664
Holt, Nicola J
2018-01-01
To measure the immediate impact of art-making in everyday life on diverse indices of wellbeing ('in the moment' and longer term) in order to improve understanding of the psychological mechanisms by which art may improve mental health. Using the experience-sampling method, 41 artists were prompted (with a 'beep' on a handheld computer) at random intervals (10 times a day, for one week) to answer a short questionnaire. The questionnaire tracked art-making and enquired about mood, cognition and state of consciousness. This resulted in 2,495 sampled experiences, with a high response rate in which 89% of questionnaires were completed. Multi-level modelling was used to evaluate the impact of art-making on experience, with 2,495 'experiences' (experiential-level) nested within 41 participants (person-level). Recent art-making was significantly associated with experiential shifts: improvement in hedonic tone, vivid internal imagery and the flow state. Furthermore, the frequency of art-making across the week was associated with person-level measures of wellbeing: eudemonic happiness and self-regulation. Cross-level interactions, between experiential and person-level variables, suggested that hedonic tone improved more for those scoring low on eudemonic happiness, and further that, those high in eudemonic happiness were more likely to experience phenomenological features of the flow state and to experience inner dialogue while art-making. Art-making has both immediate and long-term associations with wellbeing. At the experiential level, art-making affects multiple dimensions of conscious experience: affective, cognitive and state factors. This suggests that there are multiple routes to wellbeing (improving hedonic tone, making meaning through inner dialogue and experiencing the flow state). Recommendations are made to consider these factors when both developing and evaluating public health interventions that involve participatory art.
Oe, Yukiko; Mochizuki, Kazuki; Miyauchi, Rie; Misaki, Yasumi; Kasezawa, Nobuhiko; Tohyama, Kazushige; Goda, Toshinao
2015-01-01
Inflammation has been suggested to play an important role in age-related chronic diseases and disability, and it is associated with nutritional status including obesity and malnutrition. While numerous studies have examined the validity of inflammatory markers in the population studies in Caucasian elderly people, very little information is available for the factors affecting inflammatory markers in Asian elderly people. Among inflammatory markers frequently used for the studies of aging, tumor necrosis factor α (TNF-α) is produced mainly by macrophages, and contributes to production of interleukin-6 (IL-6) and C-reactive protein (CRP), thus directing a chronic inflammatory process in the body. In the present study, we examined the associations between plasma TNF-α level and several factors related to nutrition status, including BMI, albumin, and energy intake in community-dwelling Japanese elderly. We conducted a cross-sectional study of 390 men and women aged 70-86 y (average 73.5 y), who participated in health check-ups. Associations between plasma TNF-α levels, other clinical parameters, and lifestyle factors were analyzed using Spearman's rank correlation coefficient analysis and multiple linear regression analysis. In elderly men, plasma TNF-α level was positively associated with age, white blood cell count, monocyte count, plasma CRP level, serum creatinine, ureic acid, and triacylglycerol levels, and negatively associated with albumin/globulin ratio, eGFR, and serum HDL-cholesterol level. In elderly women, plasma TNF-α level was positively associated with age, plasma CRP level, and serum triacylglycerol level, and negatively associated with serum albumin and HDL-cholesterol levels. The results of this study suggest that plasma TNF-α is associated with inflammation and insulin resistance in both Japanese elderly men and women, and a prominent association of TNF-α with malnutrition status was observed in elderly women.
Stellwagen, Kurt K; Kerig, Patricia K
2013-10-01
This study examined the association of ringleader bullying with psychopathic traits and theory of mind among 100 youth aged 10-15 (62 boys and 38 girls) receiving inpatient psychiatric services at a state facility. Results of hierarchical multiple regression analyses indicated a positive association between ringleader bullying and psychopathic narcissism, and a significant interaction effect between narcissism and theory of mind. More specifically, narcissism moderated the relationship between theory of mind and ringleader bullying such that theory of mind was positively associated with ringleader bullying when levels of narcissism were high, and theory of mind was negatively associated ringleader bullying when levels of narcissism were low. The discussion of these results focuses on the importance of developing effective treatment techniques for youth whose bullying behavior is associated with narcissistic features and social acuity.
NASA Astrophysics Data System (ADS)
Xu, Haiying; Yuan, Yang; Yu, Youlong; Xu, Kebin; Xu, Yuhuan
1990-08-01
This paper presents a real time holographic associative memory implemented with photorefractive KNSBN:Co crystal as the memory element and a liquid crystal electrooptic switch array as the reflective thresholding device. The experiment stores and recalls two images and shows that the system has real-time multiple-image storage and recall functions. An associative memory with a dynamic threshold level to decide the closest match of an incomplete input is proposed.
Christoffersen, T; Emaus, N; Dennison, E; Furberg, A-S; Gracia-Marco, L; Grimnes, G; Nilsen, O A; Vlachopoulos, D; Winther, A; Ahmed, L A
2018-02-01
Childhood fracture may predict persistent skeletal fragility, but it may also reflect high physical activity which is beneficial to bone development. We observe a difference in the relationship between previous fracture and bone outcome across physical activity level and sex. Further elaboration on this variation is needed. Childhood fracture may be an early marker of skeletal fragility, or increased levels of physical activity (PA), which are beneficial for bone mineral accrual. This study investigated the association between a previous history of childhood fracture and adolescent bone mineral outcomes by various PA levels. We recruited 469 girls and 492 boys aged 15-18 years to this study. We assessed PA levels by questionnaire and measured areal bone mineral density (aBMD) and bone mineral content (BMC) using dual-energy X-ray absorptiometry (DXA) at arm, femoral neck (FN), total hip (TH), and total body (TB) and calculated bone mineral apparent density (BMAD, g/cm 3 ). Fractures from birth to time of DXA measurements were retrospectively recorded. We analyzed differences among participants with and without fractures using independent sample t test. Multiple linear regression was used to examine the association between fractures and aBMD and BMC measurements according to adolescent PA. Girls with and without a previous history of fracture had similar BMC, aBMD, and BMAD at all sites. In multiple regression analyses stratified by physical activity intensity (PAi), there was a significant negative association between fracture and aBMD-TH and BMC-FN yet only in girls reporting low PAi. There was a significant negative association between forearm fractures, BMAD-FN, and BMAD-arm among vigorously active boys. Our findings indicate a negative association between childhood fractures and aBMD/BMC in adolescent girls reporting low PAi. In boys, such an association appears only in vigorously active participants with a history of forearm fractures.
Isolation with Migration Models for More Than Two Populations
Hey, Jody
2010-01-01
A method for studying the divergence of multiple closely related populations is described and assessed. The approach of Hey and Nielsen (2007, Integration within the Felsenstein equation for improved Markov chain Monte Carlo methods in population genetics. Proc Natl Acad Sci USA. 104:2785–2790) for fitting an isolation-with-migration model was extended to the case of multiple populations with a known phylogeny. Analysis of simulated data sets reveals the kinds of history that are accessible with a multipopulation analysis. Necessarily, processes associated with older time periods in a phylogeny are more difficult to estimate; and histories with high levels of gene flow are particularly difficult with more than two populations. However, for histories with modest levels of gene flow, or for very large data sets, it is possible to study large complex divergence problems that involve multiple closely related populations or species. PMID:19955477
Isolation with migration models for more than two populations.
Hey, Jody
2010-04-01
A method for studying the divergence of multiple closely related populations is described and assessed. The approach of Hey and Nielsen (2007, Integration within the Felsenstein equation for improved Markov chain Monte Carlo methods in population genetics. Proc Natl Acad Sci USA. 104:2785-2790) for fitting an isolation-with-migration model was extended to the case of multiple populations with a known phylogeny. Analysis of simulated data sets reveals the kinds of history that are accessible with a multipopulation analysis. Necessarily, processes associated with older time periods in a phylogeny are more difficult to estimate; and histories with high levels of gene flow are particularly difficult with more than two populations. However, for histories with modest levels of gene flow, or for very large data sets, it is possible to study large complex divergence problems that involve multiple closely related populations or species.
Shen, Minxue; Tan, Hongzhuan; Zhou, Shujin; Retnakaran, Ravi; Smith, Graeme N.; Davidge, Sandra T.; Trasler, Jacquetta; Walker, Mark C.; Wen, Shi Wu
2016-01-01
Background It has been reported that higher folate intake from food and supplementation is associated with decreased blood pressure (BP). The association between serum folate concentration and BP has been examined in few studies. We aim to examine the association between serum folate and BP levels in a cohort of young Chinese women. Methods We used the baseline data from a pre-conception cohort of women of childbearing age in Liuyang, China, for this study. Demographic data were collected by structured interview. Serum folate concentration was measured by immunoassay, and homocysteine, blood glucose, triglyceride and total cholesterol were measured through standardized clinical procedures. Multiple linear regression and principal component regression model were applied in the analysis. Results A total of 1,532 healthy normotensive non-pregnant women were included in the final analysis. The mean concentration of serum folate was 7.5 ± 5.4 nmol/L and 55% of the women presented with folate deficiency (< 6.8 nmol/L). Multiple linear regression and principal component regression showed that serum folate levels were inversely associated with systolic and diastolic BP, after adjusting for demographic, anthropometric, and biochemical factors. Conclusions Serum folate is inversely associated with BP in non-pregnant women of childbearing age with high prevalence of folate deficiency. PMID:27182603
Reflections on Native Ethnography by a Nurse Researcher.
Abdulrehman, Munib Said
2017-03-01
There are benefits and challenges associated with conducting research in a familiar setting, especially when the researcher is more an insider than an outsider. The aim of this article is to explore the author's experience as a native scholar conducting ethnographic research among the Swahili peoples of Lamu, Kenya. This article focuses on methodological issues related to conducting ethnographic research among the author's own people, including examining the issues of anthropological reflexivity as a native ethnographer and highlighting the author's experiences embodying multiple identities. Native ethnographers must consider the challenges associated with negotiating multiple roles in the research setting, especially in the presence of sociocultural factors such as gender stratification, complex kinship networks, socioeconomic hierarchies, illiteracy, and poverty. Embracing rather than being confused by the multiple levels of understanding native researchers bring to studies of their communities opens up new avenues of research and possibilities.
Clinical and biological features of multiple myeloma involving the gastrointestinal system.
Talamo, Giampaolo; Cavallo, Federica; Zangari, Maurizio; Barlogie, Bart; Lee, Choon-Kee; Pineda-Roman, Mauricio; Kiwan, Elias; Krishna, Somashekar; Tricot, Guido
2006-07-01
We report 24 cases of multiple myeloma (MM) with involvement of the gastrointestinal (GI) system. We found a strong association with high A lactate dehydrogenase levels, plasmablastic morphology, and A unfavorable karyotype. GI involvement at the time of initial diagnosis was much rarer than later in the course of the disease. The A median survival after diagnosis of GI involvement was 7 months. Among 13 patients treated with stem cell transplantation, the response rate was 92%, and median progression-free survival was 4 months. We conclude that MM involving the GI system is associated with adverse biological features and with short-lasting remissions, even after A high-dose chemotherapy.
Wang, W; Huang, S; Hou, W; Liu, Y; Fan, Q; He, A; Wen, Y; Hao, J; Guo, X; Zhang, F
2017-10-01
Several genome-wide association studies (GWAS) of bone mineral density (BMD) have successfully identified multiple susceptibility genes, yet isolated susceptibility genes are often difficult to interpret biologically. The aim of this study was to unravel the genetic background of BMD at pathway level, by integrating BMD GWAS data with genome-wide expression quantitative trait loci (eQTLs) and methylation quantitative trait loci (meQTLs) data METHOD: We employed the GWAS datasets of BMD from the Genetic Factors for Osteoporosis Consortium (GEFOS), analysing patients' BMD. The areas studied included 32 735 femoral necks, 28 498 lumbar spines, and 8143 forearms. Genome-wide eQTLs (containing 923 021 eQTLs) and meQTLs (containing 683 152 unique methylation sites with local meQTLs) data sets were collected from recently published studies. Gene scores were first calculated by summary data-based Mendelian randomisation (SMR) software and meQTL-aligned GWAS results. Gene set enrichment analysis (GSEA) was then applied to identify BMD-associated gene sets with a predefined significance level of 0.05. We identified multiple gene sets associated with BMD in one or more regions, including relevant known biological gene sets such as the Reactome Circadian Clock (GSEA p-value = 1.0 × 10 -4 for LS and 2.7 × 10 -2 for femoral necks BMD in eQTLs-based GSEA) and insulin-like growth factor receptor binding (GSEA p-value = 5.0 × 10 -4 for femoral necks and 2.6 × 10 -2 for lumbar spines BMD in meQTLs-based GSEA). Our results provided novel clues for subsequent functional analysis of bone metabolism, and illustrated the benefit of integrating eQTLs and meQTLs data into pathway association analysis for genetic studies of complex human diseases. Cite this article : W. Wang, S. Huang, W. Hou, Y. Liu, Q. Fan, A. He, Y. Wen, J. Hao, X. Guo, F. Zhang. Integrative analysis of GWAS, eQTLs and meQTLs data suggests that multiple gene sets are associated with bone mineral density. Bone Joint Res 2017;6:572-576. © 2017 Wang et al.
Multiple sclerosis lesions affect intrinsic functional connectivity of the spinal cord.
Conrad, Benjamin N; Barry, Robert L; Rogers, Baxter P; Maki, Satoshi; Mishra, Arabinda; Thukral, Saakshi; Sriram, Subramaniam; Bhatia, Aashim; Pawate, Siddharama; Gore, John C; Smith, Seth A
2018-06-01
Patients with multiple sclerosis present with focal lesions throughout the spinal cord. There is a clinical need for non-invasive measurements of spinal cord activity and functional organization in multiple sclerosis, given the cord's critical role in the disease. Recent reports of spontaneous blood oxygenation level-dependent fluctuations in the spinal cord using functional MRI suggest that, like the brain, cord activity at rest is organized into distinct, synchronized functional networks among grey matter regions, likely related to motor and sensory systems. Previous studies looking at stimulus-evoked activity in the spinal cord of patients with multiple sclerosis have demonstrated increased levels of activation as well as a more bilateral distribution of activity compared to controls. Functional connectivity studies of brain networks in multiple sclerosis have revealed widespread alterations, which may take on a dynamic trajectory over the course of the disease, with compensatory increases in connectivity followed by decreases associated with structural damage. We build upon this literature by examining functional connectivity in the spinal cord of patients with multiple sclerosis. Using ultra-high field 7 T imaging along with processing strategies for robust spinal cord functional MRI and lesion identification, the present study assessed functional connectivity within cervical cord grey matter of patients with relapsing-remitting multiple sclerosis (n = 22) compared to a large sample of healthy controls (n = 56). Patient anatomical images were rated for lesions by three independent raters, with consensus ratings revealing 19 of 22 patients presented with lesions somewhere in the imaged volume. Linear mixed models were used to assess effects of lesion location on functional connectivity. Analysis in control subjects demonstrated a robust pattern of connectivity among ventral grey matter regions as well as a distinct network among dorsal regions. A gender effect was also observed in controls whereby females demonstrated higher ventral network connectivity. Wilcoxon rank-sum tests detected no differences in average connectivity or power of low frequency fluctuations in patients compared to controls. The presence of lesions was, however, associated with local alterations in connectivity with differential effects depending on columnar location. The patient results suggest that spinal cord functional networks are generally intact in relapsing-remitting multiple sclerosis but that lesions are associated with focal abnormalities in intrinsic connectivity. These findings are discussed in light of the current literature on spinal cord functional MRI and the potential neurological underpinnings.
Taïeb, David; Yang, Chunzhang; Delenne, Blandine; Zhuang, Zhengping; Barlier, Anne; Sebag, Fréderic; Pacak, Karel
2013-05-01
Molecular genetic research has so far resulted in the identification of 10 well-characterized susceptibility genes for hereditary pheochromocytoma (PHEO) or paraganglioma (PGL). Recently, a new syndrome characterized by multiple PGLs and somatostatinomas associated with congenital polycythemia due to somatic mutations in HIF2A has been reported. The aim of the study was to define the genetic defect in a new case of bilateral PHEO and multiple PGLs associated with congenital polycythemia. A female patient presented with neonatal polycythemia (treated by phlebotomies, 1 session approximately every 4 mo), mildly enlarged cerebral ventricles, and bilateral PHEO and multiple PGLs. There was no family history of any neuroendocrine tumor or polycythemia. Surgical removal of the tumors only temporarily normalized plasma erythropoietin (Epo) levels and discontinued phlebotomies. No germline mutations were initially detected in the SDHB, SDHC, SDHD, VHL, and PHD2 genes, known to be associated with polycythemia. The PHEOs presented with a typical noradrenergic biochemical phenotype. A heterozygous missense mutation (c.1589C>T) was identified in exon 12 of HIF2A, resulting in an alanine 530 substitution in the HIF-2α protein with valine (A530V). This somatic mutation was detected in the tissue from 1 PHEO and 1 PGL, with no HIF2A germline mutation found. This mutation led to stabilization of HIF-2α and hence a gain-of-function phenotype, as in previously published studies. This case represents the first association of a somatic HIF2A gain-of-function mutation with PHEO and congenital polycythemia, and it alerts physicians to perform proper genetic screening in patients presenting with multiple norepinephrine-producing PHEOs and polycythemia. This report also extends the previous findings of a new syndrome of only multiple PGLs, somatostatinomas, and polycythemia to multiple PHEOs.
Shaw, Emily E; Schultz, Aaron P; Sperling, Reisa A; Hedden, Trey
2015-10-01
Intrinsic functional connectivity MRI has become a widely used tool for measuring integrity in large-scale cortical networks. This study examined multiple cortical networks using Template-Based Rotation (TBR), a method that applies a priori network and nuisance component templates defined from an independent dataset to test datasets of interest. A priori templates were applied to a test dataset of 276 older adults (ages 65-90) from the Harvard Aging Brain Study to examine the relationship between multiple large-scale cortical networks and cognition. Factor scores derived from neuropsychological tests represented processing speed, executive function, and episodic memory. Resting-state BOLD data were acquired in two 6-min acquisitions on a 3-Tesla scanner and processed with TBR to extract individual-level metrics of network connectivity in multiple cortical networks. All results controlled for data quality metrics, including motion. Connectivity in multiple large-scale cortical networks was positively related to all cognitive domains, with a composite measure of general connectivity positively associated with general cognitive performance. Controlling for the correlations between networks, the frontoparietal control network (FPCN) and executive function demonstrated the only significant association, suggesting specificity in this relationship. Further analyses found that the FPCN mediated the relationships of the other networks with cognition, suggesting that this network may play a central role in understanding individual variation in cognition during aging.
Association between prolonged breast-feeding and early childhood caries: a hierarchical approach.
Nunes, Ana Margarida Melo; Alves, Claudia Maria Coelho; Borba de Araújo, Fernando; Ortiz, Tânia Mara Lopes; Ribeiro, Marizélia Rodrigues Costa; Silva, Antônio Augusto Moura da; Ribeiro, Cecília Claudia Costa
2012-12-01
This study was conducted to investigate the association between prolonged breastfeeding and early childhood caries(ECC) with adjustment for important confounders, using hieraschical approach. This retrospective cohort study involved 260 low-income children (18-42 months). The number of decayed teeth was used as a measure of caries. Following a theoretical framework, the hierarchical model was built in a forward fashion, by adding the following levels in succession: level 1: age; level 2: social variables; level 3: health variables; level 4: behavioral variables; level 5: oral hygiene-related variables; level 6: oral hygiene quality measured by visible plaque; and level 7: contamination by mutans streptococci. Sequential forward multiple Poisson regression analysis was employed. Breast-feeding was not a risk factor for ECC after adjustment for some confounders (incidence density ratio, 1.15; 95% confidence interval, 0.84-1.59, P = 0.363). Prolonged breast-feeding was not a risk factor for ECC while age, high sucrose comption between main meals and the quality of oral higiene were associated with disease in children. © 2012 John Wiley & Sons A/S.
The Associations of Serum Lipids with Vitamin D Status.
Wang, Ying; Si, Shaoyan; Liu, Junli; Wang, Zongye; Jia, Haiying; Feng, Kai; Sun, Lili; Song, Shu Jun
2016-01-01
Vitamin D deficiency has been associated with some disorders including cardiovascular diseases. Dyslipidemia is a major risk factor for cardiovascular diseases. However, data about the relationships between vitamin D and lipids are inconsistent. The relationship of vitamin D and Atherogenic Index of Plasma (AIP), as an excellent predictor of level of small and dense LDL, has not been reported. The objective of this study was to investigate the effects of vitamin D status on serum lipids in Chinese adults. The study was carried out using 1475 participants from the Center for Physical Examination, 306 Hospital of PLA in Beijing, China. Fasting blood samples were collected and serum concentrations of 25(OH)D, total cholesterol (TC), triglyceride (TG), high density lipoprotein cholesterol (HDL-C) and low density lipoprotein cholesterol (LDL-C) were measured. AIP was calculated based on the formula: log [TG/HDL-C]. Multiple linear regression analysis was used to estimate the associations between serum 25(OH)D and lipids. The association between the occurrences of dyslipidemias and vitamin D levels was assessed by multiple logistic regression analysis. Confounding factors, age and BMI, were used for the adjustment. The median of serum 25(OH)D concentration was 47 (27-92.25) nmol/L in all subjects. The overall percentage of 25(OH)D ≦ 50 nmol/L was 58.5% (males 54.4%, females 63.7%). The serum 25(OH)D levels were inversely associated with TG (β coefficient = -0.24, p < 0.001) and LDL-C (β coefficient = -0.34, p < 0.001) and positively associated with TC (β coefficient = 0.35, p < 0.002) in men. The associations between serum 25(OH)D and LDL-C (β coefficient = -0.25, p = 0.01) and TC (β coefficient = 0.39, p = 0.001) also existed in women. The serum 25(OH)D concentrations were negatively associated with AIP in men (r = -0.111, p < 0.01) but not in women. In addition, vitamin D deficient men had higher AIP values than vitamin D sufficient men. Furthermore, the occurrences of dyslipidemias (reduced HDL-C, elevated TG and elevated AIP) correlated with lower 25(OH)D levels in men, whereas the higher TC and LDL-C associated with higher 25(OH)D levels in women. It seems that the serum 25(OH)D levels are closely associated with the serum lipids and AIP. Vitamin D deficiency may be associated with the increased risk of dyslipidemias, especially in men. The association between vitamin D status and serum lipids may differ by genders.
Diversity in Pathways to Common Childhood Disruptive Behavior Disorders
Martel, Michelle M.; Nikolas, Molly; Jernigan, Katherine; Friderici, Karen; Nigg, Joel T.
2014-01-01
Oppositional-Defiant Disorder (ODD) and Attention-Deficit/Hyperactivity Disorder (ADHD) are highly comorbid, a phenomenon thought to be due to shared etiological factors and mechanisms. Little work has attempted to chart multiple-level-of-analysis pathways (i.e., simultaneously including biological, environmental, and trait influences) to ODD and ADHD, the goal of the present investigation. 559 children/adolescents (325 boys) between the ages of 6 and 18 participated in a multi-stage, comprehensive diagnostic procedure. 148 were classified as ODD; 309 were classified as ADHD, based on parent, teacher, and clinician ratings. Children provided buccal or salivary samples of DNA, assayed for select markers in DRD4 and 5HTT. Parents completed the Alabama Parenting Questionnaire and the California Q-Sort. Children completed the Child Perception of Interparental Conflict Scale. Correlational associations consistent with multiple-level-of-analysis pathways to ODD and ADHD emerged. For ODD, children with the short allele of the 5HTT promoter polymorphism had higher neuroticism and ODD symptoms regardless of level of self-blame in relation to inter-parental conflict, whereas children without this allele had more ODD symptoms only in the context of more self-blame for inter-parental conflict. For ADHD (and ODD), children homozygous for the long allele of DRD4 120bp insertion polymorphism had lower conscientiousness when exposed to inconsistent parenting, whereas children without this genotype were more resilient to effects of inconsistent discipline on conscientiousness. Thus, ODD and ADHD appear to demonstrate somewhat distinct correlational associations between etiological factors and mechanisms consistent with pathway models using a multiple-level-of-analysis approach. PMID:22584505
Rink, Elizabeth; FourStar, Kristofer; Anastario, Michael P
2017-01-01
We examined the relationship between American Indian men's attitudes toward pregnancy prevention, STI/HIV prevention, and sexual risk behavior. Attention was given to: (1) attitudes and intentions to use condoms and sexual risk behavior; (2) STI/HIV prevention characteristics and sexual risk behavior; (3) attitudes toward abstinence and monogamy and sexual risk behavior; and (4) decision-making in relationships and sexual risk behavior. Our sample included 120 heterosexual American Indian men aged 18 to 24 living on a reservation. Data were collected during in-depth interviews. A community-based participatory research framework was used to ensure the relevancy and acceptability of the study given the sensitivity of the topic. Results demonstrated that attitudinal factors were associated with sexual risk behavior, particularly inconsistent condom use. Attitudes associated with consistent condom use suggested greater levels of positive dispositions toward prevention and intention to use condoms. Consistent condom use was associated with more cautious attitudes toward sex with multiple sex partners. Study results suggested that American Indian men who reported sex with multiple partners exhibited a set of attitudes and beliefs toward pregnancy prevention and STI/HIV prevention that corresponded with a disposition resulting from their behaviors, in that engaging in sexual risk behavior elevated their levels of risk perception. Our findings suggest that heterosexual American Indian men living in rural environments need sexual and reproductive health programs and clinical services that address differing attitudes toward condom use within the context of multiple sex partners and sexual risk behavior. © 2015 National Rural Health Association.
Prognostic Value of microRNA-9 in Various Cancers: a Meta-analysis.
Zhang, Yunyuan; Zhou, Jun; Sun, Meiling; Sun, Guirong; Cao, Yongxian; Zhang, Haiping; Tian, Runhua; Zhou, Lan; Duan, Liang; Chen, Xian; Lun, Limin
2017-07-01
Recently, there are more and more evidences from studies have revealed the association between microRNA-9 (miR-9) expression and outcome in multiple cancers, but inconsistent results have also been reported. It is necessary to rationalize a meta analysis of all available data to clarify the prognostic role of miR-9. Eligible studies were selected through multiple search strategies and the quality was assessed by MOOSE. Data was extracted from studies according to the key statistics index. All analyses were performed using STATA software. Twenty studies were selected in the meta-analysis to evaluate the prognostic role of miR-9 in multiple tumors. MiR-9 expression level was an independent prognostic biomarker for OS in tumor patients using multivariate and univariate analyses. High expression levels of miR-9 was demonstrated to associated with poor overall survival (OS) (HR = 2.23, 95 % CI: 1.56-3.17, P < 0.05) and recurrence free survival/progress free survival (RFS/PFS) (HR = 2.08, 95 % CI: 1.33-3.27, P < 0.05). Subgroup analysis showed that residence region (China and Japan), sample size, cancer type (solid or leukemia), follow-up months and analysis method (qPCR) did not alter the predictive value of miR-9 on OS in various cancers. Furthermore, no significant associations were detected for miR-9 expression and lymph node metastasis or distant metastasis. The present results suggest that promoted miR-9 expression is associated with poor OS in patients with general cancers.
McFall, Allison M.; Solomon, Sunil S.; Srikrishnan, Aylur K.; Vasudevan, Canjeevaram K.; Anand, Santhanam; Celentano, David D.; Mehta, Shruti H.; Kumar, Suresh; Lucas, Gregory M.
2017-01-01
People who inject drugs (PWID) in India are at high risk for HIV, with women being at elevated risk. Using a socio-ecological framework, this study assessed whether factors associated with HIV transmission risk behaviors differed across men and women PWID. Data for this cross-sectional study were collected from 6449 PWID in 7 cities in Northeast India. Men (n = 5653) and women (n = 796) PWID were recruited using respondent-driven sampling (RDS). We assessed sex differences in two recent HIV transmission risk behaviors: multiple sex partners and needle/syringe sharing. We used multi-level logistic regression models, which incorporated sampling weights and random intercepts for city, to assess factors associated with these HIV risks, separately among men and women. The prevalence of HIV was significantly higher among women than men (53% vs 18.4%, p<0.01). Nearly 13% of men and 8% of women (p = .30) had multiple partners. Employment in men and relationship status and stigma in women were significantly associated with multiple partners. Approximately 25% of men and 19% of women engaged in needle sharing (p = .16). Younger age in women and depression symptoms in men were significantly associated with increased risk for sharing needles. We found that sexual and drug related risk behaviors were common among PWID in Northeast India, and there were differences between men and women in the socio-ecologic correlates of these behaviors. Contextually-integrated and gender-specific HIV prevention and intervention efforts are needed that consider factors at individual, interpersonal- and community-levels that uniquely impact HIV risks among PWID. PMID:28099458
NASA Technical Reports Server (NTRS)
Shum, C. K.
1999-01-01
The Earth's modem climate change has been characterized by interlinked changes in temperature, CO2, ice sheets and sea level. Global sea level change is a critical indicator for study of contemporary climate change. Sea level rise appears to have accelerated since the ice sheet retreats have stopped some 5000 years ago and it is estimated that the sea level rise has been approx. 15 cm over the last century. Contemporary radar altimeters represent the only technique capable of monitoring global sea level change with accuracy approaching 1 mm/yr and with a temporal scale of days and a spatial scale of 100 km or longer. This report highlights the major accomplishments of the TOPEX/POSEIDON (T/P) Extended Mission and Jason-1 science investigation. The primary objectives of the investigation include the calibration and improvement of T/P and Jason-1 altimeter data for global sea level change and coastal tide and circulation studies. The scientific objectives of the investigation include: (1) the calibration and improvement of T/P and Jason-1 data as a reference measurement system for the accurate cross-linking with other altimeter systems (Seasat, Geosat, ERS-1, ERS-2, GFO-1, and Envisat), (2) the improved determination and the associated uncertainties of the long-term (15-year) global mean sea level change using multiple altimeters, (3) the characterization of the sea level change by analyses of independent data, including tide gauges, sea surface temperature, and (4) the improvement coastal radar altimetry for studies including coastal ocean tide modeling and coastal circulation. Major accomplishments of the investigation include the development of techniques for low-cost radar altimeter absolute calibration (including the associated GPS-buoy technology), coastal ocean tide modeling, and the linking of multiple altimeter systems and the resulting determination of the 15-year (1985-1999) global mean sea level variations. The current rate of 15-year sea level rise observed by multiple satellite altimetry is +2.3 +/- 1.2 mm/yr, which is in general agreement with the analysis of sparsely distributed tide gauge measurements for the same data span, and represents the first such determination of sea level change in its kind.
Nomoto, Hiroshi; Baba, Hajime; Satomura, Emi; Maeshima, Hitoshi; Takebayashi, Naoko; Namekawa, Yuki; Suzuki, Toshihito; Arai, Heii
2015-03-04
Brain-derived neurotrophic factor (BDNF) is a member of the neurotrophin family of growth factors. Previous studies have demonstrated lower serum BDNF levels in patients with major depressive disorder (MDD) and reported an association between BDNF levels and depression-related personality traits in healthy subjects. The aim of the present study was to explore for a possible association between peripheral BDNF levels and personality traits in patients with MDD. In this cross-sectional study, a total of 123 inpatients with MDD (Diagnostic and Statistical Manual for Mental Disorders, 4th edition) at the Juntendo University Koshigaya Hospital were recruited. Serum levels of BDNF were measured. Personality traits were assessed using the 125-item short version of the Temperament and Character Inventory (TCI). Multiple regression analysis adjusted for age, sex, body mass index, dose of antidepressant, and depression severity showed that TCI Self-Directedness (SD) scores were negatively associated with serum BDNF levels (β = -0.23, p = 0.026). MDD patients who have low SD did not show the reduction in serum BDNF levels that is normally associated with depressive state. Our findings suggest that depression-related biological changes may not occur in these individuals.
Weyland, Patricia G.; Grant, William B.; Howie-Esquivel, Jill
2014-01-01
Serum 25-hydroxyvitamin D (25(OH)D) levels have been found to be inversely associated with both prevalent and incident cardiovascular disease (CVD) risk factors; dyslipidemia, hypertension and diabetes mellitus. This review looks for evidence of a causal association between low 25(OH)D levels and increased CVD risk. We evaluated journal articles in light of Hill’s criteria for causality in a biological system. The results of our assessment are as follows. Strength of association: many randomized controlled trials (RCTs), prospective and cross-sectional studies found statistically significant inverse associations between 25(OH)D levels and CVD risk factors. Consistency of observed association: most studies found statistically significant inverse associations between 25(OH)D levels and CVD risk factors in various populations, locations and circumstances. Temporality of association: many RCTs and prospective studies found statistically significant inverse associations between 25(OH)D levels and CVD risk factors. Biological gradient (dose-response curve): most studies assessing 25(OH)D levels and CVD risk found an inverse association exhibiting a linear biological gradient. Plausibility of biology: several plausible cellular-level causative mechanisms and biological pathways may lead from a low 25(OH)D level to increased risk for CVD with mediators, such as dyslipidemia, hypertension and diabetes mellitus. Experimental evidence: some well-designed RCTs found increased CVD risk factors with decreasing 25(OH)D levels. Analogy: the association between serum 25(OH)D levels and CVD risk is analogous to that between 25(OH)D levels and the risk of overall cancer, periodontal disease, multiple sclerosis and breast cancer. Conclusion: all relevant Hill criteria for a causal association in a biological system are satisfied to indicate a low 25(OH)D level as a CVD risk factor. PMID:25184368
Mendel, Peter; Weinberg, Daniel A; Gall, Elizabeth M; Leuschner, Kristin J; Kahn, Katherine L
2014-02-01
Strengthening capacity across the healthcare system for improvement is critical to ensuring that past efforts and investments establish a foundation for sustaining progress in patient safety. The objective of this analysis was to identify key system capacity issues for sustainability from evaluation of the Action Plan to prevent healthcare-associated infections, a major national initiative launched by the US Department of Health and Human Services in 2009. The analysis involves the review and synthesis of results across the components of a 3-year evaluation of the Action Plan, as described in the evaluation framework and detailed in separate analyses elsewhere in this special issue. Data collection methods included interviews with government and private stakeholders, document and literature reviews, and observations of meetings and conferences at multiple time points. Key developments in healthcare-associated infection prevention system capacity were extracted on the basis of "major activities" identified through multiple methods and organized into the level of progress based on perspectives of multiple stakeholders. Activities within each level were then examined and compared according to our evaluation's framework of 4 system functions and 5 system properties. Key system capacity and sustainability issues for the Action Plan to be addressed centered on coordination and alignment (among participating agencies, with other federal initiatives, and across levels of healthcare), infrastructure for data and accountability (including more efficient technologies and unintended consequences), cultural embedding of prevention practices, and uncertainty and variability in resources. Sustainability depends on improvements across system functions and properties and how they reinforce each other. Change is more robust if different system elements support and incentivize behavior in similar directions.
Factors associated with suicidal ideation: the role of context.
Han, Sehee; Lee, Hee-Sun
2013-06-01
No previous study could be found that examined the longitudinal association between suicidal ideation and the factors associated with it and that considered both individual and contextual characteristics simultaneously. This study examined whether variation in suicidal ideation is attributable to the administrative-area level and examined suicidal ideation and the factors associated with it at multiple levels, especially focusing on social capital. Longitudinal data of 5222 individuals and 2741 households in 25 administrative areas from the Wave 1 and Wave 2 of the Seoul Welfare Panel Study were used. In the study, 2.7% of variation in suicidal ideation was attributable to the administrative area. The results also suggested that perceived helpfulness at individual level (odds ratio (OR) = 0.60; 95% confidence interval (CI) = 0.43, 0.83) and organizational participation at administrative-area level were associated with suicidal ideation (OR = 0.73; 95% CI = 0.53, 0.99). Policy makers should consider laying down policies aimed at preventing suicide at administrative-area level as suicidal ideation of individuals is different between administrative areas. However, it should also be recognized that directing attention solely at administrative-area level is not efficient, as only small variations in suicidal ideation are attributable to this level. Decision makers need to consider policies promoting social capital, as it may play a role in reducing suicide risk.
Jarrah, Mohamad I; Mhaidat, Nizar M; Alzoubi, Karem H; Alrabadi, Nasr; Alsatari, Enas; Khader, Yousef; Bataineh, Moath F
2018-01-01
Decreased levels of vitamin D were associated with increased risk of multiple diseases, including cardiovascular diseases. However, there seem to be some discrepancies among the results obtained from different studies. The aim of the present study was to explore the importance of having sufficient serum levels of vitamin D in reducing the incidence and the progression of coronary artery stenosis and ischemic heart disease (IHD). Serum levels of vitamin D were measured using radioimmunoassay in 186 Jordanian patients who underwent investigative coronary catheterization. Of these patients, 133 were suffering from coronary artery stenosis. The association between vitamin D levels, coronary stenosis and many risk factors was determined using SPSS software. Interestingly, the current results did not show an association between vitamin D abnormalities and the incidence or the reoccurrence of coronary artery stenosis. Moreover, significant differences were detected in the prevalence of vitamin D abnormalities based on the patient's gender, and there was a significant association between vitamin D abnormalities and both body mass index and dyslipidemia. However, current results did not show any significant association with other risk factors for IHD. For instance, no association was found with smoking, hypertension, diabetes mellitus, stable and unstable angina or with acute recent myocardial infarction.
Auditing the multiply-related concepts within the UMLS.
Mougin, Fleur; Grabar, Natalia
2014-10-01
This work focuses on multiply-related Unified Medical Language System (UMLS) concepts, that is, concepts associated through multiple relations. The relations involved in such situations are audited to determine whether they are provided by source vocabularies or result from the integration of these vocabularies within the UMLS. We study the compatibility of the multiple relations which associate the concepts under investigation and try to explain the reason why they co-occur. Towards this end, we analyze the relations both at the concept and term levels. In addition, we randomly select 288 concepts associated through contradictory relations and manually analyze them. At the UMLS scale, only 0.7% of combinations of relations are contradictory, while homogeneous combinations are observed in one-third of situations. At the scale of source vocabularies, one-third do not contain more than one relation between the concepts under investigation. Among the remaining source vocabularies, seven of them mainly present multiple non-homogeneous relations between terms. Analysis at the term level also shows that only in a quarter of cases are the source vocabularies responsible for the presence of multiply-related concepts in the UMLS. These results are available at: http://www.isped.u-bordeaux2.fr/ArticleJAMIA/results_multiply_related_concepts.aspx. Manual analysis was useful to explain the conceptualization difference in relations between terms across source vocabularies. The exploitation of source relations was helpful for understanding why some source vocabularies describe multiple relations between a given pair of terms. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.
Emotional Desensitization to Violence Contributes to Adolescents' Violent Behavior.
Mrug, Sylvie; Madan, Anjana; Windle, Michael
2016-01-01
Many adolescents are exposed to violence in their schools, communities and homes. Exposure to violence at high levels or across multiple contexts has been linked with emotional desensitization, indicated by low levels of internalizing symptoms. However, the long-term consequences of such desensitization are unknown. This study examined emotional desensitization to violence, together with externalizing problems, as mediators of the relationship between exposure to violence in pre-adolescence and violent behavior in late adolescence. A community sample of youth (N = 704; 48% female; 76% African American, 22% Caucasian) reported on their exposure to violence in multiple settings at ages 11, 13 and 18. Internalizing and externalizing problems were assessed at ages 11 and 13; violent behavior was measured at age 18. Structural Equation Modeling showed that exposure to high levels of violence at age 11 was associated with lower levels of internalizing problems (quadratic effect) at age 13, as was exposure to violence across multiple contexts (linear effect). In turn, fewer internalizing problems and more externalizing problems at age 13 predicted more violent behavior at age 18. The results suggest that emotional desensitization to violence in early adolescence contributes to serious violence in late adolescence.
Emotional Desensitization to Violence Contributes to Adolescents’ Violent Behavior
Mrug, Sylvie; Madan, Anjana; Windle, Michael
2015-01-01
Many adolescents are exposed to violence in their schools, communities and homes. Exposure to violence at high levels or across multiple contexts has been linked with emotional desensitization, indicated by low levels of internalizing symptoms. However, the long-term consequences of such desensitization are unknown. This study examined emotional desensitization to violence, together with externalizing problems, as mediators of the relationship between exposure to violence in pre-adolescence and violent behavior in late adolescence. A community sample of youth (N=704; 48% female; 76% African American, 22% Caucasian) reported on their exposure to violence in multiple settings at ages 11, 13 and 18. Internalizing and externalizing problems were assessed at ages 11 and 13; violent behavior was measured at age 18. Structural Equation Modeling showed that exposure to high levels of violence at age 11 was associated with lower levels of internalizing problems (quadratic effect) at age 13, as was exposure to violence across multiple contexts (linear effect). In turn, fewer internalizing problems and more externalizing problems at age 13 predicted more violent behavior at age 18. The results suggest that emotional desensitization to violence in early adolescence contributes to serious violence in late adolescence. PMID:25684447
Behavioral and psychosocial factors associated with suicidal ideation among adolescents.
Lee, GyuYoung; Ham, Ok Kyung
2018-04-10
Suicidal ideation poses a serious threat to the well-being of adolescents and is the strongest risk factor for suicide. Indeed, Korea ranks first among Organisation for Economic Cooperation and Development countries regarding the age-standardized suicide rates. In the present study, we examined multiple levels of factors associated with the suicidal ideation of adolescents in Korea by applying the Ecological Models of Health Behavior. A cross-sectional study was conducted with a convenience sample of 860 adolescents. The instruments included the Beck Depression Inventory and the Adolescent Mental Health and Problem Behavior Questionnaire. The data were analyzed using hierarchical multiple regression. Sixteen percent of participants reported suicidal ideation. Intrapersonal (sleep disturbance, Internet game addiction, destructive behavior, and depressive symptoms) and interpersonal factors (family conflicts and peer victimization) were associated with suicidal ideation. Because multiple factors were associated with suicidal ideation among adolescents, both intrapersonal (sleep disturbance, Internet game addiction, and depression) and interpersonal factors (family conflicts and peer problems) should be considered in the development of suicide-prevention programs. These programs could include campaigns changing the norms (permissive attitudes toward school violence) and the development of strict and rigorous school non-violence policies. © 2018 John Wiley & Sons Australia, Ltd.
Pelé, Fabienne; Bajeux, Emma; Gendron, Hélène; Monfort, Christine; Rouget, Florence; Multigner, Luc; Viel, Jean-François; Cordier, Sylvaine
2013-12-02
Environmental exposures, including dietary contaminants, may influence the developing immune system. This study assesses the association between maternal pre-parturition consumption of seafood and wheeze, eczema, and food allergy in preschool children. Fish and shellfish were studied separately as they differ according to their levels of omega-3 polyunsaturated fatty acids (which have anti-allergic properties) and their levels of contaminants. The PELAGIE cohort included 3421 women recruited at the beginning of pregnancy. Maternal fish and shellfish intake was measured at inclusion by a food frequency questionnaire. Wheeze, eczema, and food allergy were evaluated by a questionnaire completed by the mother when the child was 2 years old (n = 1500). Examination of the associations between seafood intake and outcomes took major confounders into account. Complementary sensitivity analyses with multiple imputation enabled us to handle missing data, due mostly to attrition. Moderate maternal pre-parturition fish intake (1 to 4 times a month) was, at borderline significance, associated with a lower risk of wheeze (adjusted OR = 0.69 (0.45-1.05)) before age 2, compared with low intake (< once/month). This result was not, however, consistent: after multiple imputation, the adjusted OR was 0.86 (0.63-1.17). Shellfish intake at least once a month was associated with a higher risk of food allergy before age 2 (adjusted OR = 1.62 (1.11-2.37)) compared to low or no intake (< once/month). Multiple imputation confirmed this association (adjusted OR = 1.52 (1.05-2.21)). This study suggests that maternal pre-parturition shellfish consumption may increase the risk of food allergy. Further large-scale epidemiologic studies are needed to corroborate these results, identify the contaminants or components of shellfish responsible for the effects observed, determine the persistence of the associations seen at age 2, and investigate potential associations with health effects observable at later ages, such as allergic asthma.
Piao, Hui-Hong; He, Jiajia; Zhang, Keqin; Tang, Zihui
2015-01-01
Our research aims to investigate the associations between education level and osteoporosis (OP) in Chinese postmenopausal women. A large-scale, community-based, cross-sectional study was conducted to examine the associations between education level and OP. A self-reported questionnaire was used to access the demographical information and medical history of the participants. A total of 1905 postmenopausal women were available for data analysis in this study. Multiple regression models controlling for confounding factors to include education level were performed to investigate the relationship with OP. The prevalence of OP was 28.29% in our study sample. Multivariate linear regression analyses adjusted for relevant potential confounding factors detected significant associations between education level and T-score (β = 0.025, P-value = 0.095, 95% CI: -0.004-0.055 for model 1; and β = 0.092, P-value = 0.032, 95% CI: 0.008-0.175 for model 2). Multivariate logistic regression analyses detected significant associations between education level and OP in model 1 (P-value = 0.070 for model 1, Table 5), while no significant associations was reported in model 2 (P value = 0.131). In participants with high education levels, the OR for OP was 0.914 (95% CI: 0.830-1.007). The findings indicated that education level was independently and significantly associated with OP. The prevalence of OP was more frequent in Chinese postmenopausal women with low educational status.
Khalili, Mohammad; Eghtesadi, Shahryar; Mirshafiey, Abbas; Eskandari, Ghazaleh; Sanoobar, Meisam; Sahraian, Mohamad Ali; Motevalian, Abbas; Norouzi, Abbas; Moftakhar, Shirin; Azimi, Amirreza
2014-01-01
Multiple sclerosis is a neurodegenerative and demyelinating disease of central nervous system. High levels of oxidative stress are associated with inflammation and play an important role in pathogenesis of multiple sclerosis. This double-blind, randomized controlled clinical study was carried out to determine the effect of daily consumption of lipoic acid on oxidative stress among multiple sclerosis patients. A total of 52 relapsing-remitting multiple sclerosis patients, aged 18-50 years with Expanded Disability Status Scale ≤5.5 were assigned to consume either lipoic acid (1200 mg/day) or placebo capsules for 12 weeks. Fasting blood samples were collected before the first dose taken and 12 hours after the last. Dietary intakes were obtained by using 3-day dietary records. Consumption of lipoic acid resulted in a significant improvement of total antioxidant capacity (TAC) in comparison to the placebo group (P = 0.004). Although a significant change of TAC (-1511 mmol/L, P = 0.001) was found within lipoic acid group, other markers of oxidative stress including superoxide dismutase activity, glutathione peroxidase activity, and malondialdehyde levels were not affected by lipoic acid consumption. These results suggest that 1200 mg of lipoic acid improves serum TAC among multiple sclerosis patients but does not affect other markers of oxidative stress.
Wei, Shu; Hua, Hai-Rong; Chen, Qian-Quan; Zhang, Ying; Chen, Fei; Li, Shu-Qing; Li, Fan; Li, Jia-Li
2017-03-18
Brain development and aging are associated with alterations in multiple epigenetic systems, including DNA methylation and demethylation patterns. Here, we observed that the levels of the 5-hydroxymethylcytosine (5hmC) ten-eleven translocation (TET) enzyme-mediated active DNA demethylation products were dynamically changed and involved in postnatal brain development and aging in tree shrews ( Tupaia belangeri chinensis ). The levels of 5hmC in multiple anatomic structures showed a gradual increase throughout postnatal development, whereas a significant decrease in 5hmC was found in several brain regions in aged tree shrews, including in the prefrontal cortex and hippocampus, but not the cerebellum. Active changes in Tet mRNA levels indicated that TET2 and TET3 predominantly contributed to the changes in 5hmC levels. Our findings provide new insight into the dynamic changes in 5hmC levels in tree shrew brains during postnatal development and aging processes.
Hypochondriasis and somatization: two distinct aspects of somatoform disorders?
Leibbrand, R; Hiller, W; Fichter, M M
2000-01-01
We investigated boundaries and overlap between somatization and hypochondriasis on different levels of psychopathology: (1) comorbidity between hypochondriasis and somatization on the level of diagnoses in the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV; American Psychiatric Association, 1994): (2) comorbidity with other mental disorders; (3) differences in clinical characteristics: and (4) overlap on the level of psychometric measures. The sample consisted of 120 psycho somatic inpatients. Somatoform, hypochondriacal, and depressive symptomatology, cognitions about body and health, and further aspects of general symptomatology were investigated. Diagnoses of Axis I and II were based on DSM-IV Our results suggest a large overlap on the level of DSM-IV-diagnoses: only 3 of 31 hypochondriacal patients had no multiple somatoform symptoms, while 58 of 86 patients with multiple somatoform symptoms had no hypochondriasis. However, the overlap between hypochondriacal and somatization symptomatology on the level of psychometric measurement is only moderate, indicating that hypochondriasis is a markedly distinct aspect of somatoform disorders.
Factors associated with recovery from acute optic neuritis in patients with multiple sclerosis.
Malik, Muhammad Taimur; Healy, Brian C; Benson, Leslie A; Kivisakk, Pia; Musallam, Alexander; Weiner, Howard L; Chitnis, Tanuja
2014-06-17
To identify clinical and demographic features associated with the severity and recovery from acute optic neuritis (AON) episodes in patients with multiple sclerosis (MS). Adult (n = 253) and pediatric (n = 38) patients whose first symptom was AON were identified from our MS database. Severity measured by loss of visual acuity (mild attack ≤20/40, moderate attack 20/50-20/190, and severe attack ≥20/200) and recovery in visual acuity at 1 year after the attack (complete recovery ≤20/20, fair recovery 20/40, and poor recovery ≥20/50) were recorded. Demographic and clinical features associated with attack severity and recovery were identified using proportional odds logistic regression. For another group of patients, blood samples were available within 6 months of an AON attack. In this group, the impact of vitamin D level on the severity/recovery was also assessed. Men (adjusted odds ratio [OR] = 2.28, p = 0.03) and subjects with severe attacks (adjusted OR = 5.24, p < 0.001) had worse recovery. AON severity was similar between the pediatric and adult subjects, but recovery was significantly better in pediatric subjects in the unadjusted analysis (p = 0.041) and the analysis adjusted for sex (p = 0.029). Season-adjusted vitamin D level was significantly associated with attack severity (OR for 10-U increase in vitamin D level = 0.47; 95% confidence interval: 0.32, 0.68; p < 0.001). Vitamin D level was not associated with recovery from the attack (p = 0.98) in univariate analysis or after accounting for attack severity (p = 0.10). Vitamin D levels affect AON severity, whereas younger age, attack severity, and male sex affect AON recovery. Underlying mechanisms and potential therapeutic targets may identify new measures to mitigate disability accrual in MS. © 2014 American Academy of Neurology.
Werling, Donna M; Brand, Harrison; An, Joon-Yong; Stone, Matthew R; Zhu, Lingxue; Glessner, Joseph T; Collins, Ryan L; Dong, Shan; Layer, Ryan M; Markenscoff-Papadimitriou, Eirene; Farrell, Andrew; Schwartz, Grace B; Wang, Harold Z; Currall, Benjamin B; Zhao, Xuefang; Dea, Jeanselle; Duhn, Clif; Erdman, Carolyn A; Gilson, Michael C; Yadav, Rachita; Handsaker, Robert E; Kashin, Seva; Klei, Lambertus; Mandell, Jeffrey D; Nowakowski, Tomasz J; Liu, Yuwen; Pochareddy, Sirisha; Smith, Louw; Walker, Michael F; Waterman, Matthew J; He, Xin; Kriegstein, Arnold R; Rubenstein, John L; Sestan, Nenad; McCarroll, Steven A; Neale, Benjamin M; Coon, Hilary; Willsey, A Jeremy; Buxbaum, Joseph D; Daly, Mark J; State, Matthew W; Quinlan, Aaron R; Marth, Gabor T; Roeder, Kathryn; Devlin, Bernie; Talkowski, Michael E; Sanders, Stephan J
2018-05-01
Genomic association studies of common or rare protein-coding variation have established robust statistical approaches to account for multiple testing. Here we present a comparable framework to evaluate rare and de novo noncoding single-nucleotide variants, insertion/deletions, and all classes of structural variation from whole-genome sequencing (WGS). Integrating genomic annotations at the level of nucleotides, genes, and regulatory regions, we define 51,801 annotation categories. Analyses of 519 autism spectrum disorder families did not identify association with any categories after correction for 4,123 effective tests. Without appropriate correction, biologically plausible associations are observed in both cases and controls. Despite excluding previously identified gene-disrupting mutations, coding regions still exhibited the strongest associations. Thus, in autism, the contribution of de novo noncoding variation is probably modest in comparison to that of de novo coding variants. Robust results from future WGS studies will require large cohorts and comprehensive analytical strategies that consider the substantial multiple-testing burden.
Serum growth differentiation factor 15 levels in newly diagnosed multiple myeloma patients.
Tarkun, Pinar; Birtas Atesoglu, Elif; Mehtap, Ozgur; Musul, Mahmut Mert; Hacihanefioglu, Abdullah
2014-01-01
Multiple myeloma (MM) is a hematological cancer associated with increased clonal malignant plasma cells. Growth differentiation factor 15 (GDF 15) is a protein that is highly expressed in the bone marrow mesenchymal stem cells of patients with MM. This study investigated whether the clinical stage of the disease, treatment response and survival are affected by pretreatment serum GDF 15 levels. Serum GDF 15 levels were measured in 35 newly diagnosed MM patients and 27 healthy controls. The correlation between serum GDF 15 levels and various clinical and laboratory parameters was analyzed. The study demonstrated significantly higher levels of GDF 15 in MM patients. There was a negative correlation between GDF 15 levels, hemoglobin and albumin levels, and a positive correlation between GDF 15 levels, CRP, creatinine, β-2-microglobulin and stage. GDF 15 levels were lower in patients who could receive autologous stem cell transplantation compared to other groups, representing a statistically significant difference. However, in the survival analyses, GDF 15 level did not have an impact on survival. High serum levels of GDF 15 may indicate a poor treatment response. Our study supports the prognostic value of GDF 15 in MM. © 2013 S. Karger AG, Basel.
Curtis, Ross E; Kim, Seyoung; Woolford, John L; Xu, Wenjie; Xing, Eric P
2013-03-21
Association analysis using genome-wide expression quantitative trait locus (eQTL) data investigates the effect that genetic variation has on cellular pathways and leads to the discovery of candidate regulators. Traditional analysis of eQTL data via pairwise statistical significance tests or linear regression does not leverage the availability of the structural information of the transcriptome, such as presence of gene networks that reveal correlation and potentially regulatory relationships among the study genes. We employ a new eQTL mapping algorithm, GFlasso, which we have previously developed for sparse structured regression, to reanalyze a genome-wide yeast dataset. GFlasso fully takes into account the dependencies among expression traits to suppress false positives and to enhance the signal/noise ratio. Thus, GFlasso leverages the gene-interaction network to discover the pleiotropic effects of genetic loci that perturb the expression level of multiple (rather than individual) genes, which enables us to gain more power in detecting previously neglected signals that are marginally weak but pleiotropically significant. While eQTL hotspots in yeast have been reported previously as genomic regions controlling multiple genes, our analysis reveals additional novel eQTL hotspots and, more interestingly, uncovers groups of multiple contributing eQTL hotspots that affect the expression level of functional gene modules. To our knowledge, our study is the first to report this type of gene regulation stemming from multiple eQTL hotspots. Additionally, we report the results from in-depth bioinformatics analysis for three groups of these eQTL hotspots: ribosome biogenesis, telomere silencing, and retrotransposon biology. We suggest candidate regulators for the functional gene modules that map to each group of hotspots. Not only do we find that many of these candidate regulators contain mutations in the promoter and coding regions of the genes, in the case of the Ribi group, we provide experimental evidence suggesting that the identified candidates do regulate the target genes predicted by GFlasso. Thus, this structured association analysis of a yeast eQTL dataset via GFlasso, coupled with extensive bioinformatics analysis, discovers a novel regulation pattern between multiple eQTL hotspots and functional gene modules. Furthermore, this analysis demonstrates the potential of GFlasso as a powerful computational tool for eQTL studies that exploit the rich structural information among expression traits due to correlation, regulation, or other forms of biological dependencies.
Pendergrass, Sarah A.; Brown-Gentry, Kristin; Dudek, Scott; Frase, Alex; Torstenson, Eric S.; Goodloe, Robert; Ambite, Jose Luis; Avery, Christy L.; Buyske, Steve; Bůžková, Petra; Deelman, Ewa; Fesinmeyer, Megan D.; Haiman, Christopher A.; Heiss, Gerardo; Hindorff, Lucia A.; Hsu, Chu-Nan; Jackson, Rebecca D.; Kooperberg, Charles; Le Marchand, Loic; Lin, Yi; Matise, Tara C.; Monroe, Kristine R.; Moreland, Larry; Park, Sungshim L.; Reiner, Alex; Wallace, Robert; Wilkens, Lynn R.; Crawford, Dana C.; Ritchie, Marylyn D.
2013-01-01
Using a phenome-wide association study (PheWAS) approach, we comprehensively tested genetic variants for association with phenotypes available for 70,061 study participants in the Population Architecture using Genomics and Epidemiology (PAGE) network. Our aim was to better characterize the genetic architecture of complex traits and identify novel pleiotropic relationships. This PheWAS drew on five population-based studies representing four major racial/ethnic groups (European Americans (EA), African Americans (AA), Hispanics/Mexican-Americans, and Asian/Pacific Islanders) in PAGE, each site with measurements for multiple traits, associated laboratory measures, and intermediate biomarkers. A total of 83 single nucleotide polymorphisms (SNPs) identified by genome-wide association studies (GWAS) were genotyped across two or more PAGE study sites. Comprehensive tests of association, stratified by race/ethnicity, were performed, encompassing 4,706 phenotypes mapped to 105 phenotype-classes, and association results were compared across study sites. A total of 111 PheWAS results had significant associations for two or more PAGE study sites with consistent direction of effect with a significance threshold of p<0.01 for the same racial/ethnic group, SNP, and phenotype-class. Among results identified for SNPs previously associated with phenotypes such as lipid traits, type 2 diabetes, and body mass index, 52 replicated previously published genotype–phenotype associations, 26 represented phenotypes closely related to previously known genotype–phenotype associations, and 33 represented potentially novel genotype–phenotype associations with pleiotropic effects. The majority of the potentially novel results were for single PheWAS phenotype-classes, for example, for CDKN2A/B rs1333049 (previously associated with type 2 diabetes in EA) a PheWAS association was identified for hemoglobin levels in AA. Of note, however, GALNT2 rs2144300 (previously associated with high-density lipoprotein cholesterol levels in EA) had multiple potentially novel PheWAS associations, with hypertension related phenotypes in AA and with serum calcium levels and coronary artery disease phenotypes in EA. PheWAS identifies associations for hypothesis generation and exploration of the genetic architecture of complex traits. PMID:23382687
Internet use and loneliness in older adults.
Sum, Shima; Mathews, R Mark; Hughes, Ian; Campbell, Andrew
2008-04-01
Use of the Internet by seniors as a communication technology may lead to changes in older adult social relationships. This study used an online questionnaire to survey 222 Australians over 55 years of age on Internet use. Respondents primarily used the Internet for communication, seeking information, and commercial purposes. The results showed negative correlations between loneliness and well-being. Multiple regression analyses revealed that greater use of the Internet as a communication tool was associated with a lower level of social loneliness. In contrast, greater use of the Internet to find new people was associated with a higher level of emotional loneliness.
Elevated visfatin/pre-B-cell colony-enhancing factor plasma concentration in ischemic stroke.
Lu, Li-Fen; Yang, Sheng-Shan; Wang, Chao-Ping; Hung, Wei-Chin; Yu, Teng-Hung; Chiu, Cheng-An; Chung, Fu-Mei; Shin, Shyi-Jang; Lee, Yau-Jiunn
2009-01-01
Visfatin/pre-B-cell colony-enhancing factor is a cytokine that is expressed as a protein in several tissues (e.g., liver, skeletal muscle, immune cells), including adipose tissue, and is reported to stimulate inflammatory cytokine expressions and promote vascular smooth cell maturation. Visfatin may act as a proinflammatory cytokine and be involved in the process of atherosclerosis. In this study, we investigated whether plasma visfatin levels were altered in patients with ischemic stroke. Plasma visfatin concentrations were measured through enzyme immunoassays in patients with ischemic stroke and in control subjects without stroke. The mean plasma concentration of visfatin in the 120 patients with ischemic stroke was significantly higher than that of the 120 control subjects without stroke (51.5 +/- 48.4 v 23.0 +/- 23.9 ng/mL, P < .001). Multiple logistic regression analysis confirmed plasma visfatin to be an independent factor associated with ischemic stroke. Increasing concentrations of visfatin were independently and significantly associated with a higher risk of ischemic stroke when concentrations were analyzed as both a quartile and a continuous variable. The multiple logistic regression analysis-adjusted odds ratios and 95% confidence intervals for ischemic stroke in the second, third, and fourth quartiles were 2.3 (0.7-7.7), 6.9 (2.2-23.3), and 20.1 (4.9-97.7), respectively. Plasma visfatin concentration was positively associated with high-sensitivity C-reactive protein levels and negatively associated with low-density lipoprotein cholesterol. Our results indicate that higher visfatin levels are associated with ischemic stroke in the Chinese population.
Glutamatergic system abnormalities in posttraumatic stress disorder.
Nishi, Daisuke; Hashimoto, Kenji; Noguchi, Hiroko; Hamazaki, Kei; Hamazaki, Tomohito; Matsuoka, Yutaka
2015-12-01
Accumulating evidence suggests involvement of the glutamatergic system in the biological mechanisms of posttraumatic stress disorder (PTSD), but few studies have demonstrated an association between glutamatergic system abnormalities and PTSD diagnosis or severity. We aimed to examine whether abnormalities in serum glutamate and in the glutamine/glutamate ratio were associated with PTSD diagnosis and severity in severely injured patients at risk for PTSD and major depressive disorder (MDD). This is a nested case-control study in TPOP (Tachikawa project for prevention of posttraumatic stress disorder with polyunsaturated fatty acid) trial. Diagnosis and severity of PTSD were assessed 3 months after the accidents using the Clinician-Administered PTSD Scale. The associations of glutamate levels and the glutamine/glutamate ratio with diagnosis and severity of PTSD and MDD were investigated by univariate and multiple linear regression analyses. Ninety-seven of 110 participants (88 %) completed assessments at 3 months. Serum glutamate levels were significantly higher for participants with full or partial PTSD than for participants without PTSD (p = 0.049) and for participants with MDD than for participants without MDD (p = 0.048). Multiple linear regression analyses showed serum glutamate levels were significantly positively associated with PTSD severity (p = 0.02) and MDD severity (p = 0.03). The glutamine/glutamate ratio was also significantly inversely associated with PTSD severity (p = 0.03), but not with MDD severity (p = 0.07). These findings suggest that the glutamatergic system may play a major role in the pathogenesis of PTSD and the need for new treatments targeting the glutamatergic system to be developed for PTSD.
Viral MicroRNAs Repress the Cholesterol Pathway, and 25-Hydroxycholesterol Inhibits Infection.
Serquiña, Anna K P; Kambach, Diane M; Sarker, Ontara; Ziegelbauer, Joseph M
2017-07-11
From various screens, we found that Kaposi's sarcoma-associated herpesvirus (KSHV) viral microRNAs (miRNAs) target several enzymes in the mevalonate/cholesterol pathway. 3-Hydroxy-3-methylglutaryl-coenzyme A (CoA) synthase 1 (HMGCS1), 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR [a rate-limiting step in the mevalonate pathway]), and farnesyl-diphosphate farnesyltransferase 1 (FDFT1 [a committed step in the cholesterol branch]) are repressed by multiple KSHV miRNAs. Transfection of viral miRNA mimics in primary endothelial cells (human umbilical vein endothelial cells [HUVECs]) is sufficient to reduce intracellular cholesterol levels; however, small interfering RNAs (siRNAs) targeting only HMGCS1 did not reduce cholesterol levels. This suggests that multiple targets are needed to perturb this tightly regulated pathway. We also report here that cholesterol levels were decreased in de novo -infected HUVECs after 7 days. This reduction is at least partially due to viral miRNAs, since the mutant form of KSHV lacking 10 of the 12 miRNA genes had increased cholesterol compared to wild-type infections. We hypothesized that KSHV is downregulating cholesterol to suppress the antiviral response by a modified form of cholesterol, 25-hydroxycholesterol (25HC). We found that the cholesterol 25-hydroxylase (CH25H) gene, which is responsible for generating 25HC, had increased expression in de novo -infected HUVECs but was strongly suppressed in long-term latently infected cell lines. We found that 25HC inhibits KSHV infection when added exogenously prior to de novo infection. In conclusion, we found that multiple KSHV viral miRNAs target enzymes in the mevalonate pathway to modulate cholesterol in infected cells during latency. This repression of cholesterol levels could potentially be beneficial to viral infection by decreasing the levels of 25HC. IMPORTANCE A subset of viruses express unique microRNAs (miRNAs), which act like cellular miRNAs to generally repress host gene expression. A cancer virus, Kaposi's sarcoma-associated herpesvirus (KSHV, or human herpesvirus 8 [HHV-8]), encodes multiple miRNAs that repress gene expression of multiple enzymes that are important for cholesterol synthesis. In cells with these viral miRNAs or with natural infection, cholesterol levels are reduced, indicating these viral miRNAs decrease cholesterol levels. A modified form of cholesterol, 25-hydroxycholesterol, is generated directly from cholesterol. Addition of 25-hydroxycholesterol to primary cells inhibited KSHV infection of cells, suggesting that viral miRNAs may decrease cholesterol levels to decrease the concentration of 25-hydroxycholesterol and to promote infection. These results suggest a new virus-host relationship and indicate a previously unidentified viral strategy to lower cholesterol levels. Copyright © 2017 Serquiña et al.
Association between serum osteocalcin level and blood pressure in a Chinese population.
Xu, Yiting; Ma, Xiaojing; Xiong, Qin; Hu, Xiang; Zhang, Xueli; Yuan, Yeqing; Bao, Yuqian
2018-04-01
This observational study investigated the association between serum osteocalcin level and blood pressure in a Chinese population. A total of 2241 subjects (909 men and 1,332 women; age, 24-78 years) from Shanghai communities were recruited. Subjects were divided into non-hypertensive and hypertensive groups according to diagnosis of hypertension based on the 1999 World Health Organization-International Society of Hypertension Guidelines. Serum osteocalcin levels were measured using an electrochemiluminescence immunoassay. Men in the hypertensive group showed lower serum osteocalcin level compared with those in the non-hypertensive group, [16.37 (13.34-20.11) ng/mL versus 17.01 (14.23-20.79) ng/mL, p = .039]. No difference in serum osteocalcin level was found between the two groups of women (p = .675). An inverse association was observed between serum osteocalcin level and systolic blood pressure (SBP) in men (p = .004), but serum osteocalcin level was not associated with diastolic blood pressure (DBP) in men (p = .472). No associations were detected between serum osteocalcin level and SBP or DBP in women (SBP: p = .108; DBP: p = .575). A multiple stepwise regression analysis showed an inverse association between serum osteocalcin level and SBP in men after adjusting for age, smoking status, family history of hypertension, and lipid and C-reactive protein levels (standardized β = -0.074, p = .023), but the association disappeared after adjustment for body mass index, waist circumference, blood glucose, and homeostasis model assessment of insulin resistance (p = .327). Serum osteocalcin level was not independently associated with blood pressure in a Chinese population.
Presneill, J J; Waring, P M; Layton, J E; Maher, D W; Cebon, J; Harley, N S; Wilson, J W; Cade, J F
2000-07-01
To define the circulating levels of granulocyte colony-stimulating factor (G-CSF) and granulocyte-macrophage colony-stimulating factor (GM-CSF) during critical illness and to determine their relationship to the severity of illness as measured by the Acute Physiology and Chronic Health Evaluation (APACHE) II score, the development of multiple organ dysfunction, or mortality. Prospective cohort study. University hospital intensive care unit. A total of 82 critically ill adult patients in four clinically defined groups, namely septic shock (n = 29), sepsis without shock (n = 17), shock without sepsis (n = 22), and nonseptic, nonshock controls (n = 14). None. During day 1 of septic shock, peak plasma levels of G-CSF, interleukin (IL)-6, and leukemia inhibitory factor (LIF), but not GM-CSF, were greater than in sepsis or shock alone (p < .001), and were correlated among themselves (rs = 0.44-0.77; p < .02) and with the APACHE II score (rs = 0.25-0.40; p = .03 to .18). G-CSF, IL-6, and UF, and sepsis, shock, septic shock, and APACHE II scores were strongly associated with organ dysfunction or 5-day mortality by univariate analysis. However, multiple logistic regression analysis showed that only septic shock remained significantly associated with organ dysfunction and only APACHE II scores and shock with 5-day mortality. Similarly, peak G-CSF, IL-6, and LIF were poorly predictive of 30-day mortality. Plasma levels of G-CSF, IL-6, and LIF are greatly elevated in critical illness, including septic shock, and are correlated with one another and with the severity of illness. However, they are not independently predictive of mortality, or the development of multiple organ dysfunction. GM-CSF was rarely elevated, suggesting different roles for G-CSF and GM-CSF in human septic shock.
HbA1c Predicts Time to Diagnosis of Type 1 Diabetes in Children at Risk.
Helminen, Olli; Aspholm, Susanna; Pokka, Tytti; Hautakangas, Milla-Riikka; Haatanen, Nora; Lempainen, Johanna; Ilonen, Jorma; Simell, Olli; Knip, Mikael; Veijola, Riitta
2015-05-01
Prediction of type 1 diabetes is based on the detection of multiple islet autoantibodies in subjects who are at increased genetic risk. Prediction of the timing of diagnosis is challenging, however. We assessed the utility of HbA1c levels in predicting the clinical disease in genetically predisposed children with multiple autoantibodies. Cord blood samples from 168,055 newborn infants were screened for class II HLA genotypes in Finland, and 14,876 children with increased genetic risk for type 1 diabetes were invited to participate in regular follow-ups, including screening for diabetes-associated autoantibodies. When two or more autoantibodies were detected, HbA1c levels were analyzed at each visit. During follow-up, multiple (two or more) autoantibodies developed in 466 children; type 1 diabetes was diagnosed in 201 of these children (43%, progressors), while 265 children remained disease free (nonprogressors) by December 2011. A 10% increase in HbA1c levels in samples obtained 3-12 months apart predicted the diagnosis of clinical disease (hazard ratio [HR] 5.7 [95% CI 4.1-7.9]) after a median time of 1.1 years (interquartile range [IQR] 0.6-3.1 years) from the observed rise of HbA1c. If the HbA1c level was ≥5.9% (41 mmol/mol) in two consecutive samples, the median time to diagnosis was 0.9 years (IQR 0.3-1.5, HR 11.9 [95% CI 8.8-16.0]). In conclusion, HbA1c is a useful biochemical marker when predicting the time to diagnosis of type 1 diabetes in children with multiple autoantibodies. © 2015 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.
Relation of Urinary Calcium and Magnesium Excretion to Blood Pressure
Kesteloot†, Hugo; Tzoulaki, Ioanna; Brown, Ian J.; Chan, Queenie; Wijeyesekera, Anisha; Ueshima, Hirotsugu; Zhao, Liancheng; Dyer, Alan R.; Unwin, Robert J.; Stamler, Jeremiah; Elliott, Paul
2011-01-01
Data indicate an inverse association between dietary calcium and magnesium intakes and blood pressure (BP); however, much less is known about associations between urinary calcium and magnesium excretion and BP in general populations. The authors assessed the relation of BP to 24-hour excretion of calcium and magnesium in 2 cross-sectional studies. The International Study of Macro- and Micro-Nutrients and Blood Pressure (INTERMAP) comprised 4,679 persons aged 40–59 years from 17 population samples in China, Japan, the United Kingdom, and the United States, and the International Cooperative Study on Salt, Other Factors, and Blood Pressure (INTERSALT) comprised 10,067 persons aged 20–59 years from 52 samples around the world. Timed 24-hour urine collections, BP measurements, and nutrient data from four 24-hour dietary recalls (INTERMAP) were collected. In multiple linear regression analyses, urinary calcium excretion was directly associated with BP. After adjustment for multiple confounders (including weight, height, alcohol intake, calcium intake, urinary sodium level, and urinary potassium intake), systolic BP was 1.9 mm Hg higher per each 4.1 mmol per 24 hours (2 standard deviations) of higher urinary calcium excretion (associations were smaller for diastolic BP) in INTERMAP. Qualitatively similar associations were observed in INTERSALT analyses. Associations between magnesium excretion and BP were small and nonsignificant for most of the models examined. The present data suggest that altered calcium homoeostasis, as exhibited by increased calcium excretion, is associated with higher BP levels. PMID:21624957
Girard, Lisa-Christine; Côté, Sylvana M; de Lauzon-Guillain, Blandine; Dubois, Lise; Falissard, Bruno; Forhan, Anne; Doyle, Orla; Bernard, Jonathan Y; Heude, Barbara; Saurel-Cubizolles, Marie-Josephe; Kaminski, Monique; Boivin, Michel; Tremblay, Richard E
2016-01-01
Breastfeeding is associated with multiple domains of health for both mothers and children. Nevertheless, breastfeeding initiation is low within certain developed countries. Furthermore, comparative studies of initiation rates using harmonised data across multiple regions is scarce. The aim of the present study was to investigate and compare individual-level determinants of breastfeeding initiation using two French-speaking cohorts. Participants included ~ 3,900 mothers enrolled in two cohort studies in Canada and France. Interviews, questionnaires, and medical records were utilised to collect information on maternal, family, and medical factors associated with breastfeeding initiation. Rates of breastfeeding initiation were similar across cohorts, slightly above 70%. Women in both Canada and France who had higher levels of maternal education, were born outside of their respective countries and who did not smoke during pregnancy were more likely to initiate breastfeeding with the cohort infant. Notably, cohort effects of maternal education at the university level were found, whereby having 'some university' was not statistically significant for mothers in France. Further, younger mothers in Canada, who delivered by caesarean section and who had previous children, had reduced odds of breastfeeding initiation. These results were not found for mothers in France. While some similar determinants were observed, programming efforts to increase breastfeeding initiation should be tailored to the characteristics of specific geographical regions which may be heavily impacted by the social, cultural and political climate of the region, in addition to individual and family level factors.
The Associative Structure of Memory for Multi-Element Events
2013-01-01
The hippocampus is thought to be an associative memory “convergence zone,” binding together the multimodal elements of an experienced event into a single engram. This predicts a degree of dependency between the retrieval of the different elements comprising an event. We present data from a series of studies designed to address this prediction. Participants vividly imagined a series of person–location–object events, and memory for these events was assessed across multiple trials of cued retrieval. Consistent with the prediction, a significant level of dependency was found between the retrieval of different elements from the same event. Furthermore, the level of dependency was sensitive both to retrieval task, with higher dependency during cued recall than cued recognition, and to subjective confidence. We propose a simple model, in which events are stored as multiple pairwise associations between individual event elements, and dependency is captured by a common factor that varies across events. This factor may relate to between-events modulation of the strength of encoding, or to a process of within-event “pattern completion” at retrieval. The model predicts the quantitative pattern of dependency in the data when changes in the level of guessing with retrieval task and confidence are taken into account. Thus, we find direct behavioral support for the idea that memory for complex multimodal events depends on the pairwise associations of their constituent elements and that retrieval of the various elements corresponding to the same event reflects a common factor that varies from event to event. PMID:23915127
Spencer, Monique E; Jain, Alka; Matteini, Amy; Beamer, Brock A; Wang, Nae-Yuh; Leng, Sean X; Punjabi, Naresh M; Walston, Jeremy D; Fedarko, Neal S
2010-08-01
Neopterin, a GTP metabolite expressed by macrophages, is a marker of immune activation. We hypothesize that levels of this serum marker alter with donor age, reflecting increased chronic immune activation in normal aging. In addition to age, we assessed gender, race, body mass index (BMI), and percentage of body fat (%fat) as potential covariates. Serum was obtained from 426 healthy participants whose age ranged from 18 to 87 years. Anthropometric measures included %fat and BMI. Neopterin concentrations were measured by competitive ELISA. The paired associations between neopterin and age, BMI, or %fat were analyzed by Spearman's correlation or by linear regression of log-transformed neopterin, whereas overall associations were modeled by multiple regression of log-transformed neopterin as a function of age, gender, race, BMI, %fat, and interaction terms. Across all participants, neopterin exhibited a positive association with age, BMI, and %fat. Multiple regression modeling of neopterin in women and men as a function of age, BMI, and race revealed that each covariate contributed significantly to neopterin values and that optimal modeling required an interaction term between race and BMI. The covariate %fat was highly correlated with BMI and could be substituted for BMI to yield similar regression coefficients. The association of age and gender with neopterin levels and their modification by race, BMI, or %fat reflect the biology underlying chronic immune activation and perhaps gender differences in disease incidence, morbidity, and mortality.
Serum Metabolomic Profiling in Acute Alcoholic Hepatitis Identifies Multiple Dysregulated Pathways
Rachakonda, Vikrant; Gabbert, Charles; Raina, Amit; Bell, Lauren N.; Cooper, Sara; Malik, Shahid; Behari, Jaideep
2014-01-01
Background and Objectives While animal studies have implicated derangements of global energy homeostasis in the pathogenesis of acute alcoholic hepatitis (AAH), the relevance of these findings to the development of human AAH remains unclear. Using global, unbiased serum metabolomics analysis, we sought to characterize alterations in metabolic pathways associated with severe AAH and identify potential biomarkers for disease prognosis. Methods This prospective, case-control study design included 25 patients with severe AAH and 25 ambulatory patients with alcoholic cirrhosis. Serum samples were collected within 24 hours of the index clinical encounter. Global, unbiased metabolomics profiling was performed. Patients were followed for 180 days after enrollment to determine survival. Results Levels of 234 biochemicals were altered in subjects with severe AAH. Random-forest analysis, principal component analysis, and integrated hierarchical clustering methods demonstrated that metabolomics profiles separated the two cohorts with 100% accuracy. Severe AAH was associated with enhanced triglyceride lipolysis, impaired mitochondrial fatty acid beta oxidation, and upregulated omega oxidation. Low levels of multiple lysolipids and related metabolites suggested decreased plasma membrane remodeling in severe AAH. While most measured bile acids were increased in severe AAH, low deoxycholate and glycodeoxycholate levels indicated intestinal dysbiosis. Several changes in substrate utilization for energy homeostasis were identified in severe AAH, including increased glucose consumption by the pentose phosphate pathway, altered tricarboxylic acid (TCA) cycle activity, and enhanced peptide catabolism. Finally, altered levels of small molecules related to glutathione metabolism and antioxidant vitamin depletion were observed in patients with severe AAH. Univariable logistic regression revealed 15 metabolites associated with 180-day survival in severe AAH. Conclusion Severe AAH is characterized by a distinct metabolic phenotype spanning multiple pathways. Metabolomics profiling revealed a panel of biomarkers for disease prognosis, and future studies are planned to validate these findings in larger cohorts of patients with severe AAH. PMID:25461442
Gross, Erin L.; Beall, Clifford J.; Kutsch, Stacey R.; Firestone, Noah D.; Leys, Eugene J.; Griffen, Ann L.
2012-01-01
Dental caries in very young children may be severe, result in serious infection, and require general anesthesia for treatment. Dental caries results from a shift within the biofilm community specific to the tooth surface, and acidogenic species are responsible for caries. Streptococcus mutans, the most common acid producer in caries, is not always present and occurs as part of a complex microbial community. Understanding the degree to which multiple acidogenic species provide functional redundancy and resilience to caries-associated communities will be important for developing biologic interventions. In addition, microbial community interactions in health and caries pathogenesis are not well understood. The purpose of this study was to investigate bacterial community profiles associated with the onset of caries in the primary dentition. In a combination cross-sectional and longitudinal design, bacterial community profiles at progressive stages of caries and over time were examined and compared to those of health. 16S rRNA gene sequencing was used for bacterial community analysis. Streptococcus mutans was the dominant species in many, but not all, subjects with caries. Elevated levels of S. salivarius, S. sobrinus, and S. parasanguinis were also associated with caries, especially in subjects with no or low levels of S. mutans, suggesting these species are alternative pathogens, and that multiple species may need to be targeted for interventions. Veillonella, which metabolizes lactate, was associated with caries and was highly correlated with total acid producing species. Among children without previous history of caries, Veillonella, but not S. mutans or other acid-producing species, predicted future caries. Bacterial community diversity was reduced in caries as compared to health, as many species appeared to occur at lower levels or be lost as caries advanced, including the Streptococcus mitis group, Neisseria, and Streptococcus sanguinis. This may have implications for bacterial community resilience and the restoration of oral health. PMID:23091642
Abraham, Kristen M; Stein, Catherine H
2012-10-01
Guided by a life course perspective, the current study examined whether emerging adults with and without mothers with affective disorders viewed their relationships with their mothers differently, and whether aspects of the emerging adult-mother relationship were associated with reports of caregiving for mothers. Reports from emerging adults with mothers with affective disorders (n = 46) were compared to reports from emerging adults with mothers without mental illness (n = 64). Results indicated that emerging adults with mothers with affective disorders reported significantly lower levels of affection, felt obligation, reciprocity, and future caregiving intentions, and significantly higher levels of role reversal in their relationships with their mothers. Reported current caregiving levels did not differ between emerging adults with and without mothers with affective disorders. Hierarchical multiple regression analyses generally indicated higher levels of felt obligation were associated with higher levels of caregiving, regardless of maternal mental health status. Results and future research directions are discussed from a life course perspective. © 2012 American Orthopsychiatric Association.
Plasma ghrelin levels and polymorphisms of ghrelin gene in Chinese obese children and adolescents.
Zhu, J F; Liang, L; Zou, C C; Fu, J F
2010-09-01
To evaluate the role of fasting plasma ghrelin levels [ln(ghrelin)] and polymorphisms of ghrelin gene in Chinese obese children. Genotyping for ghrelin polymorphism was performed in 230 obese and 100 normal weight children. Among them, plasma ghrelin levels were measured in 91 obese and 23 health subjects. (1) Bivariate correlation analysis showed the ln(ghrelin) was inversely correlated with abnormality of glucose metabolism (r = -0.240, P = 0.023). Stepwise multiple regression analysis showed that abnormality of glucose metabolism was an independent determinant of plasma ghrelin levels (P = 0.023). (2) There was no difference in frequency of Leu72Met polymorphisms between obese and control groups (36.09 vs. 41.00%). Ghrelin is associated with obesity in childhood, especially associated with the glucose homeostasis. Lower ghrelin levels might be a result of obesity, but not a cause of obesity. The Leu72Met polymorphism of ghrelin gene is not associated with obesity and metabolic syndrome in Chinese children.
Federal Register 2010, 2011, 2012, 2013, 2014
2011-07-14
...] Draft Environmental Impact Statement and Habitat Conservation Plan for Commercial Wind Energy... regional- level construction, operation, and maintenance associated with multiple commercial wind energy...; Attention: Laila Lienesch; Facsimile: 505/248-6922 (Attention: Laila Lienesch); E-Mail: WindEnergy...
The relationship between environmental conditions and human health varies by environmental domain and urbanicity. To account for multiple ambient environmental conditions, we constructed an Environmental Quality Index (EQI) for health research. We used U.S. county level data rep...
Stress and the multiple-role woman: taking a closer look at the "superwoman".
Sumra, Monika K; Schillaci, Michael A
2015-01-01
In the academic literature there is debate as to whether women who engage in multiple social roles experience more or less stress than women in fewer roles. For the present research we examined the relationship between levels of engagement in seven distinct roles and perceived stress and life satisfaction in a small non-random sample of women in North America (N = 308). We did not find a significant correlation between role engagement and perceived stress, though we did find a small but significant positive correlation between role engagement and life satisfaction. Similarly, in a subset of the participants (N = 31), there was not a significant relationship between the level of role engagement and physiological stress as measured by hair or urinary cortisol levels. We found a significant negative correlation between perceived stress and life satisfaction, and role satisfaction. The results from multiple regression models did not identify the level of role engagement as a significant predictor of either perceived stress or life satisfaction. Role satisfaction in addition to several life style variables such as the frequency of sex and exercise were identified as significant predictors of both outcome variables. We also examined the popularized notion of the "superwoman", which we defined as women who fell within the 4th quartile of role engagement, or those engaged in the wife/mother/worker/homemaker role combination. Based on popular discourses surrounding the superwoman we expected that superwomen would exhibit higher levels of perceived stress. Our results revealed that superwomen do not experience a significantly higher level of perceived stress than non-superwomen. The results of our study therefore suggest that multiple role engagement in women, even at a relatively high level as experienced by "superwomen", is not associated with significantly higher stress, or reduced life satisfaction.
Tipping points? Curvilinear associations between activity level and mental development in toddlers.
Flom, Megan; Cohen, Madeleine; Saudino, Kimberly J
2017-05-01
The Theory of Optimal Stimulation (Zentall & Zentall, Psychological Bulletin, 94, 1983, 446) posits that the relation between activity level (AL) and cognitive performance follows an inverted U shape where midrange AL predicts better cognitive performance than AL at the extremes. We explored this by fitting linear and quadratic models predicting mental development from AL assessed via multiple methods (parent ratings, observations, and actigraphs) and across multiple situations (laboratory play, laboratory test, home) in over 600 twins (2- and 3-year olds). Only observed AL in the laboratory was curvilinearly related to mental development scores. Results replicated across situations, age, and twin samples, providing strong support for the optimal stimulation model for this measure of AL in early childhood. Different measures of AL provide different information. Observations of AL which include both qualitative and quantitative aspects of AL within structured situations are able to capture beneficial aspects of normative AL as well as detriments of both low and high AL. © 2016 Association for Child and Adolescent Mental Health.
Multiple determinants of the abortion care experience: from the patient's perspective.
Taylor, Diana; Postlethwaite, Debbie; Desai, Sheila; James, E Angel; Calhoun, Amanda W; Sheehan, Katharine; Weitz, Tracy A
2013-01-01
Because of the highly stigmatized nature of abortion care delivery and the restriction of abortion provision in most states, little is known about abortion care quality beyond procedural safety. This study examined which aspects of abortion care contributed to patient experiences. Data from a prospective, observational study of 9087 women aged 16 to 44 years, from 22 clinics across California, who responded to a postprocedure survey, were analyzed using mixed-effects logistic regression. Patient experience scores were very high (mean overall satisfaction = 9.4 [0-10 scale]) for all clinicians trained in abortion provision (physicians, nurse practitioners, nurse-midwives, and physician assistants). Multiple patient factors (pain rating, expectations of care, sociodemographics) and clinic-level factors (timely care, treatment by clinicians and staff) were significantly associated with patient experience. Study findings demonstrated that clinic environment, treatment by clinical staff, and managed pain levels contributed to a patient's experience of abortion care, whereas clinician type was not significantly associated.
Calçada, Dulce; Vianello, Dario; Giampieri, Enrico; Sala, Claudia; Castellani, Gastone; de Graaf, Albert; Kremer, Bas; van Ommen, Ben; Feskens, Edith; Santoro, Aurelia; Franceschi, Claudio; Bouwman, Jildau
2014-01-01
Aging is a biological process characterized by the progressive functional decline of many interrelated physiological systems. In particular, aging is associated with the development of a systemic state of low-grade chronic inflammation (inflammaging), and with progressive deterioration of metabolic function. Systems biology has helped in identifying the mediators and pathways involved in these phenomena, mainly through the application of high-throughput screening methods, valued for their molecular comprehensiveness. Nevertheless, inflammation and metabolic regulation are dynamical processes whose behavior must be understood at multiple levels of biological organization (molecular, cellular, organ, and system levels) and on multiple time scales. Mathematical modeling of such behavior, with incorporation of mechanistic knowledge on interactions between inflammatory and metabolic mediators, may help in devising nutritional interventions capable of preventing, or ameliorating, the age-associated functional decline of the corresponding systems. Copyright © 2014 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.
Setoguchi, Soko; Zhu, Ying; Jalbert, Jessica J; Williams, Lauren A; Chen, Chih-Ying
2014-05-01
Linking patient registries with administrative databases can enhance the utility of the databases for epidemiological and comparative effectiveness research. However, registries often lack direct personal identifiers, and the validity of record linkage using multiple indirect personal identifiers is not well understood. Using a large contemporary national cardiovascular device registry and 100% Medicare inpatient data, we linked hospitalization-level records. The main outcomes were the validity measures of several deterministic linkage rules using multiple indirect personal identifiers compared with rules using both direct and indirect personal identifiers. Linkage rules using 2 or 3 indirect, patient-level identifiers (ie, date of birth, sex, admission date) and hospital ID produced linkages with sensitivity of 95% and specificity of 98% compared with a gold standard linkage rule using a combination of both direct and indirect identifiers. Ours is the first large-scale study to validate the performance of deterministic linkage rules without direct personal identifiers. When linking hospitalization-level records in the absence of direct personal identifiers, provider information is necessary for successful linkage. © 2014 American Heart Association, Inc.
Gans, Itai; Jain, Amit; Sirisreetreerux, Norachart; Haut, Elliott R; Hasenboehler, Erik A
2017-01-01
The risk of postoperative surgical site infection after long bone fracture fixation can be decreased with appropriate antibiotic use. However, there is no agreement on the superiority of a single- or multiple-dose perioperative regimen of antibiotic prophylaxis. The purpose of this study is to determine the following: 1) What are the current practice patterns of orthopaedic trauma surgeons in using perioperative antibiotics for closed long bone fractures? 2) What is the current knowledge of published antibiotic prophylaxis guidelines among orthopaedic trauma surgeons? 3) Are orthopaedic surgeons willing to change their current practices? A questionnaire was distributed via email between September and December 2015 to 955 Orthopaedic Trauma Association members, of whom 297 (31%) responded. Most surgeons (96%) use cefazolin as first-line infection prophylaxis. Fifty-nine percent used a multiple-dose antibiotic regimen, 39% used a single-dose regimen, and 2% varied this decision according to patient factors. Thirty-six percent said they were unfamiliar with Centers for Disease Control and Prevention (CDC) antibiotic prophylaxis guidelines; only 30% were able to select the correct CDC recommendation from a multiple-choice list. However, 44% of surgeons said they followed CDC recommendations. Fifty-six percent answered that a single-dose antibiotic prophylaxis regimen was not inferior to a multiple-dose regimen. If a level-I study comparing a single preoperative dose versus multiple perioperative antibiotic dosing regimen for treatment of closed long bone fractures were published, most respondents (64%) said they would fully follow these guidelines, and 22% said they would partially change their practice to follow these guidelines. There is heterogeneity in the use of single- versus multiple-dose antibiotic prophylaxis for surgical repair of closed long bone fractures. Many surgeons were unsure of current evidence-based recommendations regarding perioperative antibiotic use. Most respondents indicated they would be receptive to high-level evidence regarding the single- versus multiple-dose perioperative prophylactic antibiotics for the treatment of closed long bone fractures.
Resilience and Associated Factors among Mainland Chinese Women Newly Diagnosed with Breast Cancer.
Wu, Zijing; Liu, Ye; Li, Xuelian; Li, Xiaohan
2016-01-01
Resilience is the individual's ability to bounce back from trauma. It has been studied for some time in the U.S., but few studies in China have addressed this important construct. In mainland China, relatively little is known about the resilience of patients in clinical settings, especially among patients with breast cancer. In this study, we aimed to evaluate the level of resilience and identify predictors of resilience among mainland Chinese women newly diagnosed with breast cancer. A cross-sectional descriptive study was conducted with 213 mainland Chinese women newly diagnosed with breast cancer between November 2014 and June 2015. Participants were assessed with the Connor-Davidson Resilience Scale (CD-RISC), Social Support Rating Scale (SSRS), Medical Coping Modes Questionnaire (MCMQ, including 3 subscales: confrontation, avoidance, and acceptance-resignation), Herth Hope Index (HHI), and demographic and disease-related information. Descriptive statistics, bivariate analyses and multiple stepwise regression were conducted to explore predictors for resilience. The average score for CD-RISC was 60.97, ranging from 37 to 69. Resilience was positively associated with educational level, family income, time span after diagnosis, social support, confrontation, avoidance, and hope. However, resilience was negatively associated with age, body mass index (BMI), and acceptance-resignation. Multiple stepwise regression analysis indicated that hope (β = 0.343, P<0.001), educational level of junior college or above (β = 0.272, P<0.001), educational level of high school (β = 0.235, P<0.001), avoidance (β = 0.220, P<0.001), confrontation (β = 0.187, P = 0.001), and age (β = -0.108, P = 0.037) significantly affected resilience and explained 50.1% of the total variance in resilience. Women with newly diagnosed breast cancer from mainland China demonstrated particularly low resilience level, which was predicted by hope educational level, avoidance, confrontation, and age.
Zhao, Jinying; An, Qiang; Goldberg, Jack; Quyyumi, Arshed A; Vaccarino, Viola
2015-09-01
Endothelial dysfunction assessed by brachial artery flow-mediated dilation (FMD) is a marker of early atherosclerosis. Glucocorticoid receptor gene (NR3C1) regulates many biological processes, including stress response, behavioral, cardiometabolic and immunologic functions. Genetic variants in NR3C1 have been associated with atherosclerosis and related risk factors. This study investigated the association of NR3C1 promoter methylation with FMD, independent of genetic and family-level environmental factors. We studied 84 middle-aged, male-male monozygotic twin pairs recruited from the Vietnam Era Twin Registry. Brachial artery FMD was measured by ultrasound. DNA methylation levels at 22 CpG residues in the NR3C1 exon 1F promoter region were quantified by bisulfite pyrosequencing in genomic DNA isolated from peripheral blood leukocytes. Co-twin control analyses were conducted to examine the association of methylation variation with FMD, adjusting for smoking, physical activity, body mass index, lipids, blood pressure, fasting glucose, and depressive symptoms. Multiple testing was corrected using the false discovery rate. Mean methylation level across the 22 studied CpG sites was 2.02%. Methylation alterations at 12 out of the 22 CpG residues were significantly associated with FMD. On average, a 1% increase in the intra-pair difference in mean DNA methylation was associated with 2.83% increase in the intra-pair difference in FMD (95% CI: 1.46-4.20; P < 0.0001) after adjusting for risk factors and multiple testing. Methylation variation in NR3C1 exon 1F promoter significantly influences subclinical atherosclerosis, independent of genetic, early family environmental and other risk factors. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.
Zhang, Xinyan; Li, Bingzong; Han, Huiying; Song, Sha; Xu, Hongxia; Hong, Yating; Yi, Nengjun; Zhuang, Wenzhuo
2018-05-10
Multiple myeloma (MM), like other cancers, is caused by the accumulation of genetic abnormalities. Heterogeneity exists in the patients' response to treatments, for example, bortezomib. This urges efforts to identify biomarkers from numerous molecular features and build predictive models for identifying patients that can benefit from a certain treatment scheme. However, previous studies treated the multi-level ordinal drug response as a binary response where only responsive and non-responsive groups are considered. It is desirable to directly analyze the multi-level drug response, rather than combining the response to two groups. In this study, we present a novel method to identify significantly associated biomarkers and then develop ordinal genomic classifier using the hierarchical ordinal logistic model. The proposed hierarchical ordinal logistic model employs the heavy-tailed Cauchy prior on the coefficients and is fitted by an efficient quasi-Newton algorithm. We apply our hierarchical ordinal regression approach to analyze two publicly available datasets for MM with five-level drug response and numerous gene expression measures. Our results show that our method is able to identify genes associated with the multi-level drug response and to generate powerful predictive models for predicting the multi-level response. The proposed method allows us to jointly fit numerous correlated predictors and thus build efficient models for predicting the multi-level drug response. The predictive model for the multi-level drug response can be more informative than the previous approaches. Thus, the proposed approach provides a powerful tool for predicting multi-level drug response and has important impact on cancer studies.
Nishitani, Naoko; Sakakibara, Hisataka
2014-01-01
Relationships between work-related psychological and physical stress responses and counts of white blood cells (WBCs), neutrophils, and lymphocytes were investigated in 101 daytime workers. Counts of WBCs and neutrophils were positively associated with smoking and inversely correlated with high density lipoprotein (HDL)-cholesterol levels. Additionally, general fatigue score as measured by the profile of mood state was positively correlated with WBC and neutrophil counts whereas lymphocyte counts was not significantly associated with fatigue score. Multiple regression analysis showed that WBC count was significantly related to general fatigue, age, and HDL-cholesterol levels. Neutrophil count was significantly related to HDL-cholesterol levels and fatigue score. Among various psychological stress response variables, general fatigue may be a key determinant of low-grade inflammation as represented by increases of WBC and neutrophil counts.
Toemen, L; Gishti, O; Vogelezang, S; Gaillard, R; Hofman, A; Franco, O H; Felix, J F; Jaddoe, V W V
2015-07-01
High body mass index is associated with increased C-reactive protein levels in childhood and adulthood. Little is known about the associations of detailed adiposity measures with C-reactive protein levels in childhood. We examined the associations of general and abdominal adiposity measures with C-reactive protein levels at school age. To gain insight into the direction of causality, we used genetic risk scores based on known genetic variants in adults as proxies for child adiposity measures and C-reactive protein levels. Within a population-based cohort study among 4338 children at the median age of 6.2 years, we measured body mass index, fat mass percentage, android/gynoid fat mass ratio and preperitoneal abdominal fat mass. We also measured C-reactive protein blood levels and defined increased levels as ⩾3.0 mg l(-1). Single-nucleotide polymorphisms (SNPs) for the weighted genetic risk scores were extracted from large genome-wide association studies on adult body mass index, waist-hip ratio and C-reactive protein levels. All fat mass measures were associated with increased C-reactive protein levels, even after adjusting for multiple confounders. Fat mass percentage was most strongly associated with increased C-reactive protein levels (odds ratio 1.46 (95% confidence interval 1.30-1.65) per increase standard deviation scores in fat mass percentage). The association was independent of body mass index. The genetic risk score based on adult body mass index SNPs, but not adult waist-hip ratio SNPs, tended to be associated with increased C-reactive protein levels at school age. The genetic risk score based on adult C-reactive protein level SNPs was not associated with adiposity measures at school age. Our results suggest that higher general and abdominal fat mass may lead to increased C-reactive protein levels at school age. Further studies are needed to replicate these results and explore the causality and long-term consequences.
Evaluating Reported Candidate Gene Associations with Polycystic Ovary Syndrome
Pau, Cindy; Saxena, Richa; Welt, Corrine Kolka
2013-01-01
Objective To replicate variants in candidate genes associated with PCOS in a population of European PCOS and control subjects. Design Case-control association analysis and meta-analysis. Setting Major academic hospital Patients Women of European ancestry with PCOS (n=525) and controls (n=472), aged 18 to 45 years. Intervention Variants previously associated with PCOS in candidate gene studies were genotyped (n=39). Metabolic, reproductive and anthropomorphic parameters were examined as a function of the candidate variants. All genetic association analyses were adjusted for age, BMI and ancestry and were reported after correction for multiple testing. Main Outcome Measure Association of candidate gene variants with PCOS. Results Three variants, rs3797179 (SRD5A1), rs12473543 (POMC), and rs1501299 (ADIPOQ), were nominally associated with PCOS. However, they did not remain significant after correction for multiple testing and none of the variants replicated in a sufficiently powered meta-analysis. Variants in the FBN3 gene (rs17202517 and rs73503752) were associated with smaller waist circumferences and variant rs727428 in the SHBG gene was associated with lower SHBG levels. Conclusion Previously identified variants in candidate genes do not appear to be associated with PCOS risk. PMID:23375202
Glaser, Karen; Evandrou, Maria; Tomassini, Cecilia
2006-01-01
We investigated the relationship between intensive multiple role occupancy and one key dimension of well-being, social participation (i.e., frequency of participation in social and leisure activities and meeting friends or relatives). Moreover, we examined gender differences in the association between individual, spousal and couple intensive multiple role commitments and individual social participation. Our research is based on a sample of mid-life wives (45-59) and their husbands from the 2000 British Household Panel Study (BHPS). Our findings show that, among wives whose husbands were providing care to a dependent for 20 or more hours a week, there was a negative association with social and leisure activity participation, whereas husbands' level of participation in social and leisure activities was higher if their wives were in full-time paid work. We also found lower odds of meeting friends or relatives among wives and husbands in full-time employment, and higher odds of meeting friends and relatives among wives providing care for 20 or more hours a week. Our results will aid policy thinking in addressing how people can be best supported to balance work and family commitments in order to optimize different dimensions of well-being in later life and help alleviate the pressures associated with multiple-role occupancy in mid-life.
Safety and Pharmacokinetics of Multiple Dose myo-Inositol in Preterm Infants
Phelps, Dale L.; Ward, Robert M.; Williams, Rick L.; Nolen, Tracy L.; Watterberg, Kristi L.; Oh, William; Goedecke, Michael; Ehrenkranz, Richard A.; Fennell, Timothy; Poindexter, Brenda B.; Cotten, C. Michael; Hallman, Mikko; Frantz, Ivan D.; Faix, Roger G.; Zaterka-Baxter, Kristin M.; Das, Abhik; Ball, M. Bethany; Lacy, Conra Backstrom; Walsh, Michele C.; Carlo, Waldemar A.; Sánchez, Pablo J.; Bell, Edward F.; Shankaran, Seetha; Carlton, David P.; Chess, Patricia R.; Higgins, Rosemary D.
2016-01-01
BACKGROUND Preterm infants with RDS given inositol had reduced BPD, death and severe ROP. We assessed the safety and pharmacokinetics(PK) of daily inositol to select a dose providing serum levels previously associated with benefit, and to learn if accumulation occurred when administered throughout the normal period of retinal vascularization. METHODS Infants ≤29wks GA (n=122, 14 centers) were randomized and treated with placebo or inositol at 10, 40 or 80mg/kg/day. Intravenous administration converted to enteral when feedings were established, and continued to the first of 10 weeks, 34weeks PMA or discharge. Serum collection employed a sparse sampling population PK design. Inositol urine losses and feeding intakes were measured. Safety was prospectively monitored. RESULTS At 80mg/kg/day mean serum levels reached 140mg/L, similar to Hallman’s findings. Levels declined after 2 weeks, converging in all groups by 6 wks. Analyses showed a mean volume of distribution 0.657 L/kg, clearance 0.058 L/kg/hr, and half-life 7.90 hr. Adverse events and co-morbidities were fewer in the inositol groups, but not significantly so. CONCLUSIONS Multiple dose inositol at 80mg/kg/day was not associated with increased adverse events, achieves previously effective serum levels, and is appropriate for investigation in a Phase 3 trial. PMID:27074126
Tang, Zhenwu; Chai, Miao; Cheng, Jiali; Jin, Jing; Yang, Yufei; Nie, Zhiqiang; Huang, Qifei; Li, Yanhua
2017-04-01
We collected street dust from Huainan, a typical coal-mining city in China, to investigate the contamination features and health risks of heavy metals. Concentrations of Co, Cr, Cu, Pb, As, and Sb were generally low to moderate, while pollution levels of Cd and Hg were moderate to high. Concentrations of Cd and Hg were associated with considerable health risks at 64.3% and 58.6% of sites, respectively. In particular, about a fifth of samples had associated high risks as a result of Hg contamination levels. Relative to other urban areas, the street dust from the mining area had no more severe metal pollution, which might be partly attributed to the deposition of coal dust onto street dusts. A source assessment indicated that metals in dust form Huainan were mainly derived from vehicular-related activities, industrial emissions, weathering of coal dust and natural soils, and coal combustion. Although the health risk levels from exposure to individual metals in dusts were low, the non-carcinogenic risks from multiple metals to local children exceeded the acceptable level (1.0), suggesting that the overall risk from exposure to multiple metals in dust is concerning. Copyright © 2016 Elsevier Inc. All rights reserved.
Olson, Sheryl L; Ceballo, Rosario; Park, Curie
2002-12-01
Examined proximal and contextual factors most strongly related to externalizing behavior among young children growing up in low-income, mother-headed families. Participants were 50 low-income single mothers and their preschool-age children who were visited twice in the home setting. Measures of proximal (low levels of supportive parenting, high levels of punitive disciplinary practices, low levels of maternal emotional well-being) and contextual (low maternal support, high levels of family stress) risk were assessed in relation to maternal reports of child externalizing behavior and an index of negative child behavior during a clean-up task. Child defiance during the clean-up task was highly associated with punitive maternal control in the same situation but had no other direct correlates. However, multiple risk factors representing both proximal and contextual variables were associated with variations in children's behavior problem scores. Mothers of children with high behavior problem scores reported lower feelings of self-efficacy in handling child care and emotional stressors, more frequent use of punitive child disciplinary practices, and lower feelings of satisfaction with the quality of their supportive resources than others. Maternal self-evaluations of coping efficacy mediated the relation between perceived support and child behavior problems, suggesting that constructs of personal control are important to represent in future studies of highly stressed parents.
Romeo, Stefano; Yin, Wu; Kozlitina, Julia; Pennacchio, Len A.; Boerwinkle, Eric; Hobbs, Helen H.; Cohen, Jonathan C.
2008-01-01
The relative activity of lipoprotein lipase (LPL) in different tissues controls the partitioning of lipoprotein-derived fatty acids between sites of fat storage (adipose tissue) and oxidation (heart and skeletal muscle). Here we used a reverse genetic strategy to test the hypothesis that 4 angiopoietin-like proteins (ANGPTL3, -4, -5, and -6) play key roles in triglyceride (TG) metabolism in humans. We re-sequenced the coding regions of the genes encoding these proteins and identified multiple rare nonsynonymous (NS) sequence variations that were associated with low plasma TG levels but not with other metabolic phenotypes. Functional studies revealed that all mutant alleles of ANGPTL3 and ANGPTL4 that were associated with low plasma TG levels interfered either with the synthesis or secretion of the protein or with the ability of the ANGPTL protein to inhibit LPL. A total of 1% of the Dallas Heart Study population and 4% of those participants with a plasma TG in the lowest quartile had a rare loss-of-function mutation in ANGPTL3, ANGPTL4, or ANGPTL5. Thus, ANGPTL3, ANGPTL4, and ANGPTL5, but not ANGPTL6, play nonredundant roles in TG metabolism, and multiple alleles at these loci cumulatively contribute to variability in plasma TG levels in humans. PMID:19075393
Chromosome 15q25.1 genetic markers associated with level of response to alcohol in humans.
Joslyn, Geoff; Brush, Gerry; Robertson, Margaret; Smith, Tom L; Kalmijn, Jelger; Schuckit, Marc; White, Raymond L
2008-12-23
As with other genetically complex common psychiatric and medical conditions, multiple genetic and environmental components contribute to alcohol use disorders (AUDs), which can confound attempts to identify genetic components. Intermediate phenotypes are often more closely correlated with underlying biology and have often proven invaluable in genetic studies. Level of response (LR) to alcohol is an intermediate phenotype for AUDs, and individuals with a low LR are at increased risk. A high rate of concurrent alcohol and nicotine use and dependence suggests that these conditions may share biochemical and genetic mechanisms. Genetic association studies indicate that a genetic locus, which includes the CHRNA5-CHRNA3-CHRNB4 gene cluster, plays a role in nicotine consumption and dependence. Genetic association with alcohol dependence was also recently shown. We show here that two of the markers from the nicotine studies also show an association (multiple testing corrected P < 0.025) with several LR phenotypes in a sample of 367 siblings. Additional markers in the region were analyzed and shown to be located in a 250-kb expanse of high linkage disequilibrium containing three additional genes. These findings indicate that LR intermediate phenotypes have utility in genetic approaches to AUDs and will prove valuable in the identification of other genetic loci conferring susceptibility to AUDs.
Koutsis, G; Panas, M; Giogkaraki, E; Karadima, G; Sfagos, C; Vassilopoulos, D
2009-02-01
Elevated ApoA1 levels have been associated with decreased dementia risk. The A-allele of the APOA1 -75G/A promoter polymorphism has been associated with elevated ApoA1 levels. We sought to investigate the effect of the APOA1 -75G/A promoter polymorphism on cognitive performance in patients with multiple sclerosis (MS). A total of 138 patients with MS and 43 controls were studied and underwent neuropsychological assessment with Rao's Brief Repeatable Battery and the Stroop test. All patients were genotyped for APOA1. APOA1 A-allele carriers displayed superior overall cognitive performance compared with non-carriers (P 0.008) and had a three-fold decrease in the relative risk of overall cognitive impairment (OR 0.29, 95% CI 0.11-0.74). Regarding performance on individual cognitive domains, although APOA1 A-allele carriers performed better than non-carriers on all tests, this was significant only for semantic verbal fluency and the Stroop interference task (P 0.036 and 0.018, respectively). We found an association of the APOA1 -75G/A promoter polymorphism with cognitive performance in MS. This effect was most prominent on semantic verbal fluency and the Stroop interference task.
Polymorphism of the renalase gene in gestational diabetes mellitus.
Fatima, Syeda Sadia; Jamil, Zehra; Alam, Faiza; Malik, Hajira Zafar; Madhani, Sarosh Irfan; Ahmad, Muhammad Saad; Shabbir, Tayyab; Rehmani, Muhammed Noman; Rabbani, Amna
2017-01-01
Renalase is considered as a novel candidate gene for type 2 diabetes. In this study, we aimed to investigate the relationship of serum renalase and two single nucleotide polymorphisms with gestational diabetes mellitus. One hundred and ninety-eight normotensive pregnant females (n = 99 gestational diabetes mellitus; n = 99 euglycemic pregnant controls) were classified according to the International Association of the Diabetes and Pregnancy Study criteria. Fasting and 2-h post glucose load blood levels and anthropometric assessment was performed. Serum renalase was measured using enzyme-linked immunosorbent assay, whereas DNA samples were genotyped for renalase single nucleotide polymorphisms rs2576178 and rs10887800 using Polymerase chain reaction-Restriction fragment length polymorphism method. In an age-matched case control study, no difference was observed in the serum levels of renalase (p > 0.05). The variant rs10887800 showed an association with gestational diabetes mellitus and remained significant after multiple adjustments (p < 0.05), whereas rs2576178 showed weak association (p = 0.030) that was lost after multiple adjustments (p = 0.09). We inferred a modest association of the rs10887800 polymorphism with gestational diabetes. Although gestational diabetes mellitus is self-reversible, yet presence of this minor G allele might predispose to metabolic syndrome phenotypes in near the future.
Hirschler, Valeria; González, Claudio; Maccallini, Gustavo; Molinari, Claudia; Castano, Luis
2017-07-08
To determine the association between nontraditional risk factors such as magnesium and uric acid with blood pressure (BP) in Indigenous children. A total of 263 school-aged indigenous children living at high altitude were enrolled in a cross-sectional study in November 2011. Prehypertension (preHTN) and hypertension (HTN) were defined by systolic and/or diastolic BP ≥ 90th to <95th percentile or ≥95th percentile respectively, according to age, sex, and height. The prevalence of preHTN and HTN was 13.7 and 8.3%, respectively. Low magnesium levels were identified in 21.7% (57/263): 28.1% (16/57) of the children with low magnesium levels had preHTN versus 9.7% (20/206) with normal magnesium values. Furthermore, 21.8% (12/57) of the children with low magnesium levels had HTN versus 4.5% (20/206) with normal magnesium values. There was a significant association between mean arterial pressure and magnesium (r = -026), uric acid (r = 0.20), phosphorus (r = -0.17), z-BMI (r = 0.22), potassium (r = -0.10), HOMA-IR (r = 0.17), calcium (r = -0.10), and sodium (r = -0.13). Multiple linear regression analysis showed that mean arterial pressure was associated significantly and directly with BMI, age, gender, and uric acid; and inversely with magnesium, adjusted for sodium, calcium, phosphorus, potassium, and HOMA-IR (R 2 = 0.43). Furthermore, multiple logistic regression analyses showed that magnesium (OR = 0.015) and uric acid (OR = 2.95) were significantly associated with preHTN. Similar results were obtained when preHTN was replaced by HTN. Our results indicate that HTN was associated inversely with magnesium and positively with uric acid in indigenous school children. © 2017 Wiley Periodicals, Inc.
Wang, Ke-Sheng; Liu, Xuefeng; Ategbole, Muyiwa; Xie, Xin; Liu, Ying; Xu, Chun; Xie, Changchun; Sha, Zhanxin
2017-01-01
Objective: Screening for colorectal cancer (CRC) can reduce disease incidence, morbidity, and mortality. However, few studies have investigated the urban-rural differences in social and behavioral factors influencing CRC screening. The objective of the study was to investigate the potential factors across urban-rural groups on the usage of CRC screening. Methods: A total of 38,505 adults (aged ≥40 years) were selected from the 2009 California Health Interview Survey (CHIS) data - the latest CHIS data on CRC screening. The weighted generalized linear mixed-model (WGLIMM) was used to deal with this hierarchical structure data. Weighted simple and multiple mixed logistic regression analyses in SAS ver. 9.4 were used to obtain the odds ratios (ORs) and their 95% confidence intervals (CIs). Results: The overall prevalence of CRC screening was 48.1% while the prevalence in four residence groups - urban, second city, suburban, and town/rural, were 45.8%, 46.9%, 53.7% and 50.1%, respectively. The results of WGLIMM analysis showed that there was residence effect (p<0.0001) and residence groups had significant interactions with gender, age group, education level, and employment status (p<0.05). Multiple logistic regression analysis revealed that age, race, marital status, education level, employment stats, binge drinking, and smoking status were associated with CRC screening (p<0.05). Stratified by residence regions, age and poverty level showed associations with CRC screening in all four residence groups. Education level was positively associated with CRC screening in second city and suburban. Infrequent binge drinking was associated with CRC screening in urban and suburban; while current smoking was a protective factor in urban and town/rural groups. Conclusions: Mixed models are useful to deal with the clustered survey data. Social factors and behavioral factors (binge drinking and smoking) were associated with CRC screening and the associations were affected by living areas such as urban and rural regions. PMID:28952708
Wang, Ke-Sheng; Liu, Xuefeng; Ategbole, Muyiwa; Xie, Xin; Liu, Ying; Xu, Chun; Xie, Changchun; Sha, Zhanxin
2017-09-27
Objective: Screening for colorectal cancer (CRC) can reduce disease incidence, morbidity, and mortality. However, few studies have investigated the urban-rural differences in social and behavioral factors influencing CRC screening. The objective of the study was to investigate the potential factors across urban-rural groups on the usage of CRC screening. Methods: A total of 38,505 adults (aged ≥40 years) were selected from the 2009 California Health Interview Survey (CHIS) data - the latest CHIS data on CRC screening. The weighted generalized linear mixed-model (WGLIMM) was used to deal with this hierarchical structure data. Weighted simple and multiple mixed logistic regression analyses in SAS ver. 9.4 were used to obtain the odds ratios (ORs) and their 95% confidence intervals (CIs). Results: The overall prevalence of CRC screening was 48.1% while the prevalence in four residence groups - urban, second city, suburban, and town/rural, were 45.8%, 46.9%, 53.7% and 50.1%, respectively. The results of WGLIMM analysis showed that there was residence effect (p<0.0001) and residence groups had significant interactions with gender, age group, education level, and employment status (p<0.05). Multiple logistic regression analysis revealed that age, race, marital status, education level, employment stats, binge drinking, and smoking status were associated with CRC screening (p<0.05). Stratified by residence regions, age and poverty level showed associations with CRC screening in all four residence groups. Education level was positively associated with CRC screening in second city and suburban. Infrequent binge drinking was associated with CRC screening in urban and suburban; while current smoking was a protective factor in urban and town/rural groups. Conclusions: Mixed models are useful to deal with the clustered survey data. Social factors and behavioral factors (binge drinking and smoking) were associated with CRC screening and the associations were affected by living areas such as urban and rural regions. Creative Commons Attribution License
Patel, Chirag J; Manrai, Arjun K; Corona, Erik; Kohane, Isaac S
2017-02-01
It is hypothesized that environmental exposures and behaviour influence telomere length, an indicator of cellular ageing. We systematically associated 461 indicators of environmental exposures, physiology and self-reported behaviour with telomere length in data from the US National Health and Nutrition Examination Survey (NHANES) in 1999-2002. Further, we tested whether factors identified in the NHANES participants are also correlated with gene expression of telomere length modifying genes. We correlated 461 environmental exposures, behaviours and clinical variables with telomere length, using survey-weighted linear regression, adjusting for sex, age, age squared, race/ethnicity, poverty level, education and born outside the USA, and estimated the false discovery rate to adjust for multiple hypotheses. We conducted a secondary analysis to investigate the correlation between identified environmental variables and gene expression levels of telomere-associated genes in publicly available gene expression samples. After correlating 461 variables with telomere length, we found 22 variables significantly associated with telomere length after adjustment for multiple hypotheses. Of these varaibales, 14 were associated with longer telomeres, including biomarkers of polychlorinated biphenyls([PCBs; 0.1 to 0.2 standard deviation (SD) increase for 1 SD increase in PCB level, P < 0.002] and a form of vitamin A, retinyl stearate. Eight variables associated with shorter telomeres, including biomarkers of cadmium, C-reactive protein and lack of physical activity. We could not conclude that PCBs are correlated with gene expression of telomere-associated genes. Both environmental exposures and chronic disease-related risk factors may play a role in telomere length. Our secondary analysis found no evidence of association between PCBs/smoking and gene expression of telomere-associated genes. All correlations between exposures, behaviours and clinical factors and changes in telomere length will require further investigation regarding biological influence of exposure. © The Author 2016. Published by Oxford University Press on behalf of the International Epidemiological Association
Multiple Myeloma Index for Risk of Infection.
T, Valkovic; V, Gacic; A, Nacinovic-Duletic
2018-01-01
Based on our earlier research into the main characteristics and risk factors for infections in hospitalized patients with multiple myeloma, we created the numerical Multiple Myeloma Index for Risk of Infection (MMIRI) to predict infection in myeloma patients. The included factors that could influence the pathogenesis and incidence of infections were sex, performance status, Durie Salmon stage of disease, International Staging System, serum creatinine level, immune paresis, neutropenia, serum ferritin level, the presence of any catheters, disease duration, stable/progressive disease, and type of therapy. For each of these parameters, the strength of association with infection was statistically estimated and specific number of points was assigned to each of these parameters, proportional to the strength of the association. When designing the MMIRI, we included only those parameters that we determined were pathophysiologically associated with the infection. After further statistical analysis, we identified an optimal cutoff score of 6 or above as indicating a significant risk for infection, with a sensitivity of 93.2% and specificity of 80.2%. The scoring system in the retrospective receiver operating characteristic analysis showed an area under the curve of 0.918. The potential value of the MMIRI is the possibility of identifying those patients who would benefit from the prophylactic administration of antibiotics and other anti-infective measures while minimizing the contribution to antibiotic resistance related to the overuse of these drugs. As far as we know, this index represents the first attempt to create such an instrument for predicting the occurrence of infections in myeloma patients.
De Riccardis, L; Buccolieri, A; Muci, M; Pitotti, E; De Robertis, F; Trianni, G; Manno, D; Maffia, M
2018-05-01
Although many studies have been carried out in order to understand the implication of copper (Cu) in the pathogenesis of multiple sclerosis (MS), the exact role that this metal plays in the disease is not still clear. Because of the lack of information in this subject, the present study compared the serum and cerebrospinal (CSF) levels of copper in MS patients in respect to a control group, matched for age and sex, finding a significant increase of metal concentrations, in both biological fluids of MS subjects. To confirm the possible impairment of Cu metabolism, we analyzed ceruloplasmin (Cp) level and activity, seeing as this protein is an established peripheral marker in diseases associated with Cu imbalance. By comparing these two parameters between control and MS subjects, we found an increase of Cp levels, associated with a decrease in Cp activity, in the second group. By analysing these data, free copper levels were calculated, significantly increased in serum of MS subjects; the increase in free copper could be one of the predisposing factors responsible for the Cu altered levels in CSF of MS patients. At the same time, this alteration could be attributable to the inability to incorporate Cu by Cp, probably due to the high oxidative environment found in serum of MS patients. Overall, all these copper alterations may play a role in MS pathogenesis. Copyright © 2018 Elsevier B.V. All rights reserved.
The association between subgingival periodontal pathogens and systemic inflammation.
Winning, Lewis; Patterson, Christopher C; Cullen, Kathy M; Stevenson, Kathryn A; Lundy, Fionnuala T; Kee, Frank; Linden, Gerard J
2015-09-01
To investigate associations between periodontal disease pathogens and levels of systemic inflammation measured by C-reactive protein (CRP). A representative sample of dentate 60-70-year-old men in Northern Ireland had a comprehensive periodontal examination. Men taking statins were excluded. Subgingival plaque samples were analysed by quantitative real time PCR to identify the presence of Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis, Treponema denticola and Tannerella forsythia. High-sensitivity CRP (mg/l) was measured from fasting blood samples. Multiple linear regression analysis was performed using log-transformed CRP concentration as the dependent variable, with the presence of each periodontal pathogen as predictor variables, with adjustment for various potential confounders. A total of 518 men (mean age 63.6 SD 3.0 years) were included in the analysis. Multiple regression analysis showed that body mass index (p < 0.001), current smoking (p < 0.01), the detectable presence of P. gingivalis (p < 0.01) and hypertension (p = 0.01), were independently associated with an increased CRP. The detectable presence of P. gingivalis was associated with a 20% (95% confidence interval 4-35%) increase in CRP (mg/l) after adjustment for all other predictor variables. In these 60-70-year-old dentate men, the presence of P. gingivalis in subgingival plaque was significantly associated with a raised level of C-reactive protein. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
Trade-offs and synergies between carbon storage and livelihood benefits from forest commons.
Chhatre, Ashwini; Agrawal, Arun
2009-10-20
Forests provide multiple benefits at local to global scales. These include the global public good of carbon sequestration and local and national level contributions to livelihoods for more than half a billion users. Forest commons are a particularly important class of forests generating these multiple benefits. Institutional arrangements to govern forest commons are believed to substantially influence carbon storage and livelihood contributions, especially when they incorporate local knowledge and decentralized decision making. However, hypothesized relationships between institutional factors and multiple benefits have never been tested on data from multiple countries. By using original data on 80 forest commons in 10 countries across Asia, Africa, and Latin America, we show that larger forest size and greater rule-making autonomy at the local level are associated with high carbon storage and livelihood benefits; differences in ownership of forest commons are associated with trade-offs between livelihood benefits and carbon storage. We argue that local communities restrict their consumption of forest products when they own forest commons, thereby increasing carbon storage. In showing rule-making autonomy and ownership as distinct and important institutional influences on forest outcomes, our results are directly relevant to international climate change mitigation initiatives such as Reduced Emissions from Deforestation and Forest Degradation (REDD) and avoided deforestation. Transfer of ownership over larger forest commons patches to local communities, coupled with payments for improved carbon storage can contribute to climate change mitigation without adversely affecting local livelihoods.
Peng, Rui; Li, Yan
2017-08-01
The current study was designed to investigate the association between serum thyroid hormones and thyroid-stimulating hormone (TSH) levels with lipid profile in depressive disorder. A total of 370 depressive individuals aged 18 years and above were recruited in this cross-section study. All participants underwent a Structured Clinical Interview for DSM-IV (SCID) and recorded the duration of their symptoms. The serum levels of total cholesterol (TCH), triglyceride (TG), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), lipoprotein A (Lp(a)), high-sensitivity C-reactive protein (hsCRP), free thyroxine (FT4), free triiodothyronine (FT3) and TSH levels were determined and the ratios of TCH/HDL-C were assessed. Depressed subjects with a symptom duration ≥3 years had higher TG levels, increased TCH/HDL-C ratios and lower levels of HDL-C, FT4 and TSH compared with depressive patients with a symptom duration <3 years. Correlation analysis displayed that TSH is positively and significantly associated with TCH and LDL-C (p<0.05); the above FT4 and FT3 are negatively, significantly and respectively associated with TCH/HDL-C (p<0.05) and TCH, HDL-C, LDL-C (p<0.05). Multiple linear regression analysis indicated that serum TG and TSH levels are associated with depressive symptom duration. According to our results,These findings indicate that low serum TSH levels are associated with lipid profile, TG and TSH levels have significant association with symptom duration in depressive patients. Copyright © 2017. Published by Elsevier B.V.
Association between insulin and executive functioning in alcohol dependence: a pilot study.
Han, Changwoo; Bae, Hwallip; Won, Sung-Doo; Lim, Jaeyoung; Kim, Dai-Jin
2015-01-01
Alcohol dependence is a disorder ascribable to multiple factors and leads to cognitive impairment. Given that insulin dysregulation can cause cognitive impairment, patients with alcohol dependence are likely to develop insulin dysregulation such as that in diabetes. The purposes of this study are to identify an association between cognitive functioning and insulin and to investigate insulin as the biomarker of cognitive functioning in alcohol-dependent patients. Serum insulin levels were measured and cognitive functions were assessed in 45 patients with chronic alcoholism. The Korean version of the Consortium to Establish a Registry for Alzheimer's Disease (CERAD-K), a battery of cognitive function tests, was used to assess cognitive functioning. Serum insulin levels were not significantly correlated with most CERAD-K scores, but there was a significant negative correlation with scores on the Trail Making Test B, which is designed to measure executive functioning. Lower serum insulin levels were associated with slower executive functioning responses on the Trail Making Test B, suggesting that executive functioning may be in proportion to serum insulin levels. Thus, in patients with alcohol dependence, insulin level is associated with cognitive functioning. In addition, the present findings suggest that insulin level is a potential biomarker for determining cognitive functioning.
Out, Dorothée; Hall, Rosalie J.; Granger, Douglas A.; Page, Gayle G.; Woods, Stephanie J.
2012-01-01
This study evaluated individual differences in levels of C-reactive protein (CRP) measured in saliva, cross-sectionally and prospectively, in relation to systemic inflammation and risk for cardiovascular disease (CVD). Plasma and saliva samples, later assayed for CRP, were collected multiple times from an ethnically diverse group of women seeking help from domestic violence crisis shelters-agencies (N = 107; mean age at study start = 34 years). Plasma and saliva CRP levels were moderately associated cross-sectionally and across two years. There were indications that saliva CRP levels were, on average, higher in the morning than evening. Higher levels of saliva and plasma CRP were associated with a higher body mass index, but did not differ between women who did and did not smoke. Salivary CRP reliably discriminated between high and low levels of plasma CRP, using a clinically relevant cutoff point of 3 mg/L, recommended by the American Heart Association. Results build upon an emerging literature suggesting that under specific conditions levels of CRP in saliva may reflect low-grade inflammation and have the potential to serve as a screen for CVD risk status. PMID:22326517
Inverse associations of total and decaffeinated coffee with liver enzyme levels in NHANES 1999–2010
Xiao, Qian; Sinha, Rashmi; Graubard, Barry I.; Freedman, Neal D.
2014-01-01
Background Coffee may have hepatoprotective effects and higher coffee consumption has been associated inversely with levels of liver enzymatic markers. However, it is unclear whether decaffeinated coffee is also associated with liver enzymes. Methods The study population included 27,793 participants, age 20 or older, in the US National Health and Nutrition Examination Survey (1999–2010). Coffee intake was evaluated by 24-hour dietary recall. Serum levels of aminotransferase (ALT), aminotransferase (AST), alkaline phosphatase (ALP) and gamma glutamyl transaminase (GGT) were measured. We examined the relationship between coffee intake and enzymatic levels using weighted multiple variable logistic (abnormally elevated levels of enzymes) and linear regression (continuous enzymatic levels). Results Total coffee consumption was inversely associated with abnormal levels of all four liver enzymes and continuous levels of AST, ALP and GGT. Compared to those reporting no coffee consumption, participants reporting ≥3 cups per day had an odds ratio (OR) (95% confidence interval (CI)) of 0.75 (0.63, 0.89)), 0.82 (0.68, 0.98), 0.73 (0.55, 0.95) and 0.69 (0.57, 0.83) for abnormal levels of ALT, AST, ALP and GGT, respectively. Similar inverse associations were found with decaffeinated coffee intake and abnormal levels of ALT (OR≥2 vs 0 cup/d: 0.62 (0.41, 0.94)), AST (0.74 (0.49, 1.11)), and GGT (0.70, 0.49–1.00). Conclusion Higher intakes of coffee, regardless of its caffeine content, were associated with lower levels of liver enzymes. PMID:25124935
Lorente, Leonardo; Martín, María M; Pérez-Cejas, Antonia; Ramos, Luis; Argueso, Mónica; Solé-Violán, Jordi; Cáceres, Juan J; Jiménez, Alejandro; García-Marín, Victor
2018-04-16
Apoptotic changes after cerebral hemorrhage in brain samples of humans have been found. Caspase-cleaved cytokeratin (CCCK)-18 could be detected in the bloodstream during apoptosis. Higher circulating CCCK-18 levels have been associated with 6-month mortality in patients with basal ganglia hemorrhage. The aim of our study was to determine whether there is an association between serum CCCK-18 levels and early mortality of spontaneous intracerebral hemorrhage (SIH) patients. We performed an observational, prospective and multicentre study. There were included patients with severe SIH defined as Glasgow Coma Scale (GCS) lower than 9. We determined serum CCCK-18 levels at the severe SIH diagnosis moment. We found that non-surviving SIH patients (n = 46) showed lower GCS, and higher serum CCCK-18 levels and APACHE-II score than survivor ones (n = 54). In ROC analysis was found that the area under the curve of serum CCCK-18 levels for 30-day mortality prediction was 90% (95% CI 82-95%; p < 0.001). In the multiple logistic regression analysis, we found an association between serum CCCK-18 levels and 30-day mortality (OR 1.034; 95% CI 1.013-1.055; p = 0.002). The novel finding of our study was that there is an association between high serum CCCK-18 levels and 30-day mortality in severe SIH patients.
Bokhari, Syed Akhtar H; Khan, Ayyaz A; Butt, Arshad K; Hanif, Mohammad; Izhar, Mateen; Tatakis, Dimitris N; Ashfaq, Mohammad
2014-11-01
Few studies have examined the relationship of individual periodontal parameters with individual systemic biomarkers. This study assessed the possible association between specific clinical parameters of periodontitis and systemic biomarkers of coronary heart disease risk in coronary heart disease patients with periodontitis. Angiographically proven coronary heart disease patients with periodontitis (n = 317), aged >30 years and without other systemic illness were examined. Periodontal clinical parameters of bleeding on probing (BOP), probing depth (PD), and clinical attachment level (CAL) and systemic levels of high-sensitivity C-reactive protein (CRP), fibrinogen (FIB) and white blood cells (WBC) were noted and analyzed to identify associations through linear and stepwise multiple regression analyses. Unadjusted linear regression showed significant associations between periodontal and systemic parameters; the strongest association (r = 0.629; p < 0.001) was found between BOP and CRP levels, the periodontal and systemic inflammation marker, respectively. Stepwise regression analysis models revealed that BOP was a predictor of systemic CRP levels (p < 0.0001). BOP was the only periodontal parameter significantly associated with each systemic parameter (CRP, FIB, and WBC). In coronary heart disease patients with periodontitis, BOP is strongly associated with systemic CRP levels; this association possibly reflects the potential significance of the local periodontal inflammatory burden for systemic inflammation. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
Sinha, Shivani; Saxena, Sandeep; Prasad, Senthamizh; Mahdi, Abbas Ali; Bhasker, Shashi Kumar; Das, Siddharth; Krasnik, Vladimir; Caprnda, Martin; Opatrilova, Radka; Kruzliak, Peter
2017-05-01
To study the association of serum levels of anti-myeloperoxidase (MPO) antibody with retinal photoreceptor ellipsoid zone (EZ) disruption in diabetic retinopathy. Consecutive patients with type 2 DM [diabetes mellitus with no retinopathy (NODR; n=20); non-proliferative diabetic retinopathy (NPDR; n=18); proliferative diabetic retinopathy (PDR; n=16)] and healthy controls (n=20) between the ages of 40 and 65years were included. Disruption of EZ was graded by spectral domain optical coherence tomography as no disruption of EZ and disrupted EZ. The serum levels of anti-MPO antibody was analyzed using standard protocol. Association between the variables was evaluated using multiple regression analysis. A significant difference was found between the serum levels of anti-MPO antibody in various study groups (p<0.001). A positive association was found between EZ disruption and levels of anti-MPO antibody [adjusted odd's ratio (AOR)=1.079, CI 1.010-1.124, p=0.04]. A significant positive correlation was found between logMAR visual acuity and grade of disruption (AOR=1.008, CI 1.006-5.688, p=0.04). An increased serum anti-MPO antibody levels is associated with retinal photoreceptor EZ disruption and decreased visual acuity in diabetic retinopathy. Copyright © 2017 Elsevier Inc. All rights reserved.
USDA-ARS?s Scientific Manuscript database
Microbial ecologists are intensely interested in the processes governing microbial community assembly, progress has been limited by a lack of studies that span multiple geographical scales and levels of biological organization. High throughput sequencing was used to characterize foliar fungal endoph...
Using Multilevel Modeling in Language Assessment Research: A Conceptual Introduction
ERIC Educational Resources Information Center
Barkaoui, Khaled
2013-01-01
This article critiques traditional single-level statistical approaches (e.g., multiple regression analysis) to examining relationships between language test scores and variables in the assessment setting. It highlights the conceptual, methodological, and statistical problems associated with these techniques in dealing with multilevel or nested…
Hypothalamic vitamin D improves glucose homeostasis and reduces weight
USDA-ARS?s Scientific Manuscript database
Despite clear associations between vitamin D deficiency and obesity and/or type 2 diabetes, a causal relationship is not established. Vitamin D receptors (VDRs) are found within multiple tissues, including the brain. Given the importance of the brain in controlling both glucose levels and body weigh...
Association between obesity-related biomarkers and cognitive and motor development in infants.
Camargos, Ana Cristina R; Mendonça, Vanessa A; Oliveira, Katherine S C; de Andrade, Camila Alves; Leite, Hércules Ribeiro; da Fonseca, Sueli Ferreira; Vieira, Erica Leandro Marciano; Teixeira Júnior, Antônio Lúcio; Lacerda, Ana Cristina Rodrigues
2017-05-15
This study aimed to verify the association between obesity-related biomarkers and cognitive and motor development in infants between 6 and 24 months of age. A cross-sectional study was conducted with 50 infants and plasma levels of leptin, adiponectin, resistin, soluble tumor necrosis factor receptors 1 and 2 (sTNFR1 and sTNFR2), chemokines, brain-derived neurotrophic factor (BDNF), serum cortisol and redox status were measured. The Bayley-III test was utilized to evaluate cognitive and motor development, and multiple linear stepwise regression models were performed to verify the association between selected biomarkers and cognitive and motor development. A significant association was found among plasma leptin and sTNFR1 levels with cognitive composite scores, and these two independents variables together explained 37% of the variability of cognitive composite scores (p=0.001). Only plasma sTNFR1 levels were associated and explained 24% of the variability of motor composite scores (p=0.003). Plasma levels of sTNFR1 were associated with the increase in cognitive and motor development scores in infants between 6 and 24 months of age through a mechanism not directly related to excess body weight. Moreover, increase in plasma levels of leptin reduced the cognitive development in this age range. Copyright © 2017 Elsevier B.V. All rights reserved.
Heitz, Ulrike; Papmeyer, Martina; Studerus, Erich; Egloff, Laura; Ittig, Sarah; Andreou, Christina; Vogel, Tobias; Borgwardt, Stefan; Graf, Marc; Eckert, Anne; Riecher-Rössler, Anita
2018-06-25
Brain-derived neurotrophic factor (BDNF) is involved in numerous cognitive processes. Since cognitive deficits are a core feature of psychotic disorders, the investigation of BDNF levels in psychosis and their correlation with cognition has received increased attention. However, there are no studies investigating BDNF levels in individuals with an at-risk mental state (ARMS) for psychosis. Hence, the aims of the present study were: (1) assessing peripheral BDNF levels across different (potential) stages of psychosis; (2) investigating their association with cognition. Plasma and serum BDNF levels and neuropsychological performance were assessed in 16 ARMS, six first-episode psychosis (FEP), and 11 chronic schizophrenia (CS) patients. Neuropsychological assessment covered intelligence, verbal memory, working memory, attention and executive functioning. Both plasma and serum BDNF levels were highest in CS, intermediate in FEP and lowest in ARMS. Multiple regression analysis revealed a significant positive association of plasma BDNF levels with planning ability across all groups. The lower peripheral BDNF levels in ARMS compared to FEP and CS might point towards an important drop of this neurotrophin prior to the onset of frank psychosis. The associations of peripheral BDNF with planning-abilities match previous findings.
Cardiac angiogenic imbalance leads to peripartum cardiomyopathy.
Patten, Ian S; Rana, Sarosh; Shahul, Sajid; Rowe, Glenn C; Jang, Cholsoon; Liu, Laura; Hacker, Michele R; Rhee, Julie S; Mitchell, John; Mahmood, Feroze; Hess, Philip; Farrell, Caitlin; Koulisis, Nicole; Khankin, Eliyahu V; Burke, Suzanne D; Tudorache, Igor; Bauersachs, Johann; del Monte, Federica; Hilfiker-Kleiner, Denise; Karumanchi, S Ananth; Arany, Zoltan
2012-05-09
Peripartum cardiomyopathy (PPCM) is an often fatal disease that affects pregnant women who are near delivery, and it occurs more frequently in women with pre-eclampsia and/or multiple gestation. The aetiology of PPCM, and why it is associated with pre-eclampsia, remain unknown. Here we show that PPCM is associated with a systemic angiogenic imbalance, accentuated by pre-eclampsia. Mice that lack cardiac PGC-1α, a powerful regulator of angiogenesis, develop profound PPCM. Importantly, the PPCM is entirely rescued by pro-angiogenic therapies. In humans, the placenta in late gestation secretes VEGF inhibitors like soluble FLT1 (sFLT1), and this is accentuated by multiple gestation and pre-eclampsia. This anti-angiogenic environment is accompanied by subclinical cardiac dysfunction, the extent of which correlates with circulating levels of sFLT1. Exogenous sFLT1 alone caused diastolic dysfunction in wild-type mice, and profound systolic dysfunction in mice lacking cardiac PGC-1α. Finally, plasma samples from women with PPCM contained abnormally high levels of sFLT1. These data indicate that PPCM is mainly a vascular disease, caused by excess anti-angiogenic signalling in the peripartum period. The data also explain how late pregnancy poses a threat to cardiac homeostasis, and why pre-eclampsia and multiple gestation are important risk factors for the development of PPCM.
Cardiac Angiogenic Imbalance Leads to Peri-partum Cardiomyopathy
Patten, Ian S.; Rana, Sarosh; Shahul, Sajid; Rowe, Glenn C; Jang, Cholsoon; Liu, Laura; Hacker, Michele R.; Rhee, Julie S.; Mitchell, John; Mahmood, Feroze; Hess, Phil; Farrell, Caitlin; Koulisis, Nicole; Khankin, Eliyahu V; Burke, Suzanne D.; Tudorache, Igor; Bauersachs, Johann; del Monte, Federica; Hilfiker-Kleiner, Denise; Karumanchi, S. Ananth; Arany, Zoltan
2012-01-01
Peri-partum cardiomyopathy (PPCM) is a frequently fatal disease that affects women near delivery, and occurs more frequently in women with pre-eclampsia and/or multiple gestation. The etiology of PPCM, or why it associates with pre-eclampsia, remains unknown. We show here that PPCM is associated with a systemic angiogenic imbalance, accentuated by pre-eclampsia. Mice that lack cardiac PGC-1α, a powerful regulator of angiogenesis, develop profound PPCM. Importantly, the PPCM is entirely rescued by pro-angiogenic therapies. In humans, the placenta in late gestation secretes VEGF inhibitors like soluble Flt1 (sFlt1), and this is accentuated by multiple gestation and pre-eclampsia. This anti-angiogenic environment is accompanied by sub-clinical cardiac dysfunction, the extent of which correlates with circulating levels of sFlt1. Exogenous sFlt1 alone caused diastolic dysfunction in wildtype mice, and profound systolic dysfunction in mice lacking cardiac PGC-1α. Finally, plasma samples from women with PPCM contained abnormally high levels of sFlt1. These data strongly suggest that PPCM is in large part a vascular disease, caused by excess anti-angiogenic signaling in the peri-partum period. The data also explain how late pregnancy poses a threat to cardiac homeostasis, and why pre-eclampsia and multiple gestation are important risk factors for the development of PPCM. PMID:22596155
Barbieri, Magali; Egidi, Viviana; Demuru, Elena; Frova, Luisa; Meslé, France; Pappagallo, Marilena
2018-01-01
Objectives We investigate the reporting of obesity on death certificates in three countries (France, Italy, and the United States) with different levels of prevalence, and we examine which causes are frequently associated with obesity. Methods We use cause-of-death data for all deaths at ages 50–89 in 2010–2011. Since obesity may not be the underlying cause (UC) of death, we compute age- and sex- standardized death rates considering all mentions of obesity (multiple causes or MC). We use cluster analyses to identify patterns of cause-of-death combinations. Results Obesity is selected as UC in no more than 20% of the deaths with a mention of obesity. Mortality levels, whether measured from the UC or the MC, are weakly related to levels of prevalence. Patterns of cause-of-death combinations are similar across the countries. In addition to strong links with cardiovascular diseases and diabetes, we identify several less familiar associations. Conclusions Considering all mentions on the deaths certificates reduces the underestimation of obesity-related mortality based on the UC only. It also enables us to describe the various mortality patterns involving obesity. PMID:28497238
Barbieri, Magali; Désesquelles, Aline; Egidi, Viviana; Demuru, Elena; Frova, Luisa; Meslé, France; Pappagallo, Marilena
2017-07-01
We investigate the reporting of obesity on death certificates in three countries (France, Italy, and the United States) with different levels of prevalence, and we examine which causes are frequently associated with obesity. We use cause-of-death data for all deaths at ages 50-89 in 2010-2011. Since obesity may not be the underlying cause (UC) of death, we compute age- and sex-standardized death rates considering all mentions of obesity (multiple causes or MC). We use cluster analyses to identify patterns of cause-of-death combinations. Obesity is selected as UC in no more than 20% of the deaths with a mention of obesity. Mortality levels, whether measured from the UC or the MC, are weakly related to levels of prevalence. Patterns of cause-of-death combinations are similar across the countries. In addition to strong links with cardiovascular diseases and diabetes, we identify several less familiar associations. Considering all mentions on the deaths certificates reduces the underestimation of obesity-related mortality based on the UC only. It also enables us to describe the various mortality patterns involving obesity.
Self-reported levels of education and disability progression in multiple sclerosis.
D'hooghe, M B; Haentjens, P; Van Remoortel, A; De Keyser, J; Nagels, G
2016-12-01
The purpose of our study is to investigate whether socioeconomic indicators such as education, financial concerns, employment, and living status are associated with disease progression in relapsing-onset and progressive-onset Multiple Sclerosis (MS). We performed a cross-sectional survey among individuals with MS, registered by the Flemish MS society and included socioeconomic indicators. A Cox proportional hazard regression was performed with the time from MS onset and from birth to reach an ambulatory disability milestone corresponding to Expanded Disability Status Scale (EDSS) 6 (requiring a cane) as outcome measure, adjusted for gender, age at MS onset, and immunomodulatory treatment. Among the participants with relapsing-onset MS, subjects reporting education for more than 12 years had a reduced risk of reaching EDSS 6 compared to subjects reporting education for less than 12 years [HR from onset 0.68 (95% CI 0.49-0.95); HR from birth 0.71 (95% CI 0.51-0.99)]. In progressive-onset MS, longer education was associated with an increased hazard to reach EDSS 6 [HR from onset 1.25 (95% CI 0.91-1.70); HR from birth 1.39 (95% CI 1.02-1.90)]. Our study shows an association of self-reported levels of education with disability progression in MS, with the highest level being protective in relapsing-onset MS. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
Adolescent Physical Activity: Moderation of Individual Factors by Neighborhood Environment.
D'Angelo, Heather; Fowler, Stephanie L; Nebeling, Linda C; Oh, April Y
2017-06-01
Less than a third of U.S. adolescents meet federal physical activity (PA) guidelines. Understanding correlates of PA at multiple levels of the Social Ecological Model could improve PA interventions among youth. This study examines (1) associations between factors across the Social Ecological Model including psychosocial factors, perceived neighborhood physical and social environment characteristics, and adolescent moderate to vigorous PA (MVPA) and (2) whether perceived neighborhood characteristics moderate associations between psychosocial factors and MVPA. A national sample of adolescents (aged 12-17 years) in the 2014 Family Life, Activity, Sun, Health, and Eating Study was used to examine associations between psychosocial characteristics, perceived neighborhood social and physical characteristics, and self-reported weekly minutes of MVPA. Analyses were conducted in 2015. Interaction terms between psychosocial and neighborhood variables were added to multiple linear regression models to examine moderation hypotheses. Significant two-way interactions revealed that neighborhoods with features perceived as supportive of PA strengthened several psychosocial-MVPA associations. The positive associations between MVPA and friend norms, friend support, and attitudes were strengthened for adolescents living in neighborhoods with high versus low PA resource availability (all p<0.05). Furthermore, the association between controlled and autonomous motivation and MVPA was strengthened under conditions of shops/stores near (versus distant from) adolescents' homes (p<0.05). The association between some psychosocial factors and adolescent MVPA may be environment dependent. Neighborhood physical and social environments supportive of PA are important to consider when developing targeted PA interventions and may strengthen the association between psychosocial-level factors and adolescent MVPA. Copyright © 2017 American Journal of Preventive Medicine. All rights reserved.
White Matter Tract Injury is Associated with Deep Gray Matter Iron Deposition in Multiple Sclerosis.
Bergsland, Niels; Tavazzi, Eleonora; Laganà, Maria Marcella; Baglio, Francesca; Cecconi, Pietro; Viotti, Stefano; Zivadinov, Robert; Baselli, Giuseppe; Rovaris, Marco
2017-01-01
With respect to healthy controls (HCs), increased iron concentrations in the deep gray matter (GM) and decreased white matter (WM) integrity are common findings in multiple sclerosis (MS) patients. The association between these features of the disease remains poorly understood. We investigated the relationship between deep iron deposition in the deep GM and WM injury in associated fiber tracts in MS patients. Sixty-six MS patients (mean age 50.0 years, median Expanded Disability Status Scale 5.25, mean disease duration 19.1 years) and 29 HCs, group matched for age and sex were imaged on a 1.5T scanner. Susceptibility-weighted imaging and diffusion tensor imaging (DTI) were used for assessing high-pass filtered phase values in the deep GM and normal appearing WM (NAWM) integrity in associated fiber tracts, respectively. Correlation analyses investigated the associations between filtered phase values (suggestive of iron content) and WM damage. Areas indicative of increased iron levels were found in the left and right caudates as well as in the left thalamus. MS patients presented with decreased DTI-derived measures of tissue integrity in the associated WM tracts. Greater mean, axial and radial diffusivities were associated with increased iron levels in all three GM areas (r values .393 to .514 with corresponding P values .003 to <.0001). Global NAWM diffusivity measures were not related to mean filtered phase values within the deep GM. Increased iron concentration in the deep GM is associated with decreased tissue integrity of the connected WM in MS patients. Copyright © 2016 by the American Society of Neuroimaging.
Prevalence and risk factors related to preterm birth in Brazil.
Leal, Maria do Carmo; Esteves-Pereira, Ana Paula; Nakamura-Pereira, Marcos; Torres, Jacqueline Alves; Theme-Filha, Mariza; Domingues, Rosa Maria Soares Madeira; Dias, Marcos Augusto Bastos; Moreira, Maria Elizabeth; Gama, Silvana Granado
2016-10-17
The rate of preterm birth has been increasing worldwide, including in Brazil. This constitutes a significant public health challenge because of the higher levels of morbidity and mortality and long-term health effects associated with preterm birth. This study describes and quantifies factors affecting spontaneous and provider-initiated preterm birth in Brazil. Data are from the 2011-2012 "Birth in Brazil" study, which used a national population-based sample of 23,940 women. We analyzed the variables following a three-level hierarchical methodology. For each level, we performed non-conditional multiple logistic regression for both spontaneous and provider-initiated preterm birth. The rate of preterm birth was 11.5 %, (95 % confidence 10.3 % to 12.9 %) 60.7 % spontaneous - with spontaneous onset of labor or premature preterm rupture of membranes - and 39.3 % provider-initiated, with more than 90 % of the last group being pre-labor cesarean deliveries. Socio-demographic factors associated with spontaneous preterm birth were adolescent pregnancy, low total years of schooling, and inadequate prenatal care. Other risk factors were previous preterm birth (OR 3.74; 95 % CI 2.92-4.79), multiple pregnancy (OR 16.42; 95 % CI 10.56-25.53), abruptio placentae (OR 2.38; 95 % CI 1.27-4.47) and infections (OR 4.89; 95 % CI 1.72-13.88). In contrast, provider-initiated preterm birth was associated with private childbirth healthcare (OR 1.47; 95 % CI 1.09-1.97), advanced-age pregnancy (OR 1.27; 95 % CI 1.01-1.59), two or more prior cesarean deliveries (OR 1.64; 95 % CI 1.19-2.26), multiple pregnancy (OR 20.29; 95 % CI 12.58-32.72) and any maternal or fetal pathology (OR 6.84; 95 % CI 5.56-8.42). The high proportion of provider-initiated preterm birth and its association with prior cesarean deliveries and all of the studied maternal/fetal pathologies suggest that a reduction of this type of prematurity may be possible. The association of spontaneous preterm birth with socially-disadvantaged groups reaffirms that the reduction of social and health inequalities should continue to be a national priority.
Software engineering the mixed model for genome-wide association studies on large samples.
Zhang, Zhiwu; Buckler, Edward S; Casstevens, Terry M; Bradbury, Peter J
2009-11-01
Mixed models improve the ability to detect phenotype-genotype associations in the presence of population stratification and multiple levels of relatedness in genome-wide association studies (GWAS), but for large data sets the resource consumption becomes impractical. At the same time, the sample size and number of markers used for GWAS is increasing dramatically, resulting in greater statistical power to detect those associations. The use of mixed models with increasingly large data sets depends on the availability of software for analyzing those models. While multiple software packages implement the mixed model method, no single package provides the best combination of fast computation, ability to handle large samples, flexible modeling and ease of use. Key elements of association analysis with mixed models are reviewed, including modeling phenotype-genotype associations using mixed models, population stratification, kinship and its estimation, variance component estimation, use of best linear unbiased predictors or residuals in place of raw phenotype, improving efficiency and software-user interaction. The available software packages are evaluated, and suggestions made for future software development.
Social identity continuity and mental health among Syrian refugees in Turkey.
Smeekes, Anouk; Verkuyten, Maykel; Çelebi, Elif; Acartürk, Ceren; Onkun, Samed
2017-10-01
Building upon social psychological work on social identity and mental health, this study among Syrian refugees in Turkey examined the importance of multiple group memberships and identity continuity for mental health and well-being. A survey study was conducted among the very difficult to reach population of Syrian refugees (N = 361). With path analysis in AMOS the associations were examined between multiple group memberships, social identity continuity and mental health and psychological well-being. Indicate that belonging to multiple groups before migration was related to a higher likelihood of having preserved group memberships after migration (i.e., sense of social identity continuity), which, in turn, predicted greater life satisfaction and lower levels of depression. Multiple group membership, however, was also directly related to higher depression. Findings are discussed in relation to the importance of multiple group membership and feelings of identity continuity for refugees.
Blanco-Muñoz, Julia; Morales, Magally Mayanin; Lacasaña, Marina; Aguilar-Garduño, Clemente; Bassol, Susana; Cebrián, Mariano E
2010-07-01
Studies on experimental animals have found that organophosphate (OP) pesticides may act as endocrine disruptors; however, their effects on the human hormonal profile have not yet been adequately characterized. We evaluate the association between exposure to OP pesticides, measured through dialkyl phosphate (DAP) metabolites urinary levels, and the male hormone profile. A cross-sectional study was performed in 104 floriculturists of Morelos, Mexico. A structured questionnaire was applied to get information on sociodemographic characteristics, anthropometry, clinical history, alcohol and tobacco consumption, and work history. DAP metabolites [dimethylphosphate (DMP), dimethylthiophosphate, dimethyldithiophosphate, diethylphosphate (DEP), diethylthiophosphate (DETP) and diethyldithiophosphate] were determined using gas-liquid chromatography. Serum levels of FSH, LH, prolactin, testosterone, inhibin B and estradiol were determined using enzyme-linked immunosorbent assay. Multiple linear regression was used to study the association between DAP metabolite levels and male hormonal profile. Data were adjusted by p,p'-dichlorodiphenyldichloroethene serum levels and other potential confounders. There was a negative association between inhibin B and urinary levels of DMP, DEP, DETP and total DAP metabolites. DEP levels were negatively associated with serum FSH concentrations, but marginally and positively associated with those of testosterone. DETP was marginally associated with lower LH serum levels. There were no other significant associations among OP metabolites and serum hormone levels. Inhibin B and FSH vary according to levels of DAP metabolites in men occupationally exposed to OP pesticides. These results suggest that OP pesticides could act as endocrine disruptors in humans; however, most hormonal values fell within the wide normal range and associations were small. There is, therefore, a need for further investigation to elucidate their biological and clinical relevance.
Han, M A; Kim, K S; Park, J; Kang, M G; Ryu, S Y
2009-10-01
To investigate the association between level of physical activity and poor self-rated health in Korean adults. A cross-sectional study was conducted on 7,800 adults aged > or =19 years who completed the Health Interview and the Health Behavior Surveys, issued during the Third National Health and Nutrition Examination Survey (2005). The association between self-rated health and physical activity was tested using Chi-squared test. Multiple logistic regression analysis was used to calculate the odds ratios of poor self-rated health for different levels of physical activity after adjusting for physical and chronic medical conditions. The prevalence of poor self-rated health was significantly lower as the level of physical activity increased, and odds ratios for poor self-rated health were significantly lower for higher levels of physical activity after adjusting for age, marital status, educational status, smoking, alcohol consumption, and the number of physical impairments and chronic medical conditions. The association was similar in different age groups and among healthy respondents and respondents with physical impairments or chronic medical conditions. Physical activity was positively associated with self-rated health in Koreans. The independent association between a lower level of physical activity and poor self-rated health supports public health programmes that encourage regular physical activity.
Readiness to change as a moderator of outcome in transdiagnostic treatment
BOSWELL, JAMES F.; SAUER, SHANNON E.; GALLAGHER, MATTHEW W.; DELGADO, NICOLE; BARLOW, DAVID H.
2012-01-01
Initial symptom severity is a client characteristic associated with psychotherapy outcome, although this relationship is not well-understood. Readiness to change is a factor that may influence this relationship. This study tested readiness as a moderator of the relationship between initial severity and symptom change. Data were derived from an RCT examining the efficacy of a transdiagnostic CBT treatment. Readiness was assessed with the URICA, and symptom and functioning outcomes were assessed. Multiple regression models indicated that severity was associated with less overall change, yet readiness moderated this relationship. At higher levels of readiness, the effect of initial severity on outcome was essentially reversed; for clients with higher initial readiness, higher levels of severity were associated with greater change. PMID:22607634
Ribbons, Karen; Lea, Rodney; Schofield, Peter W; Lechner-Scott, Jeannette
2017-01-01
Neurological and psychological symptoms in multiple sclerosis can affect cognitive function. The objective of this study was to explore the relationship between psychological measures and cognitive performance in a patient cohort. In 322 multiple sclerosis patients, psychological symptoms were measured using the Depression Anxiety and Stress Scale, and cognitive function was evaluated using Audio Recorded Cognitive Screen. Multifactor linear regression analysis, accounting for all clinical covariates, found that anxiety was the only psychological measure to remain a significant predictor of cognitive performance (p<0.001), particularly memory function (p<0.001). Further prospective studies are required to determine whether treatment of anxiety improves cognitive impairment.
[High Risk Sex Behaviors and Associated Factors in Young Men in Chengdu].
2015-11-01
To determine the prevalence of high risk sex behaviors and associated factors in 18-34 years old men in Chengdu. Methods An anonymous questionnaire survey was conducted in 18-34 years old men selected by multi-stage random sampling in Chengdu. Data of 1536 respondents who reported having sex contacts were analyzed. 23.6% of respondents had multiple sex partners in the past 12 months; 11.8% were involved commercial sex; 9.0% had group sex; 4. 7% had anal sex; 15.6% had never used a condom; 37.7% had sex under the influence of alcohol or drugs. Logistic regression analysis revealed that marital status [married, standardized partial regression coefficient (B) = -0.086, P<0.05] , level of education (bachelor or above, B= -0.063, P<0.05), frequency of exposure to pornography (B=0.058, P<0.05), childhood sexual abuse (B= 0.042, P<0.05), first sexual intercourse at an earlier age (B=0.162, P<0.05), frequency of sex under the influence of alcohol or drugs (B=0.054, P<0.05) were significant predictors of having multiple sexual partners. Sexual orientation, age, smoking, alcohol abuse, drug use, anxiety, depression, childhood physical abuse did not appear to be significant factors associated with having multiple sexual partners. Having multiple sexual partners is the main high risk sex behavior of young men in Chengdu. Childhood sexual abuse and early start of sexual intercourse are the major predictors of having multiple sexual partners.
Magnitude of income-related disparities in adverse perinatal outcomes.
Shankardass, Ketan; O'Campo, Patricia; Dodds, Linda; Fahey, John; Joseph, Ks; Morinis, Julia; Allen, Victoria M
2014-03-04
To assess and compare multiple measurements of socioeconomic position (SEP) in order to determine the relationship with adverse perinatal outcomes across various contexts. A birth registry, the Nova Scotia Atlee Perinatal Database, was confidentially linked to income tax and related information for the year in which delivery occurred. Multiple logistic regression was used to examine odds ratios between multiple indicators of SEP and multiple adverse perinatal outcomes in 117734 singleton births between 1988 and 2003. Models for after tax family income were also adjusted for neighborhood deprivation to gauge the relative magnitude of effects related to SEP at both levels. Effects of SEP were stratified by single- versus multiple-parent family composition, and by urban versus rural location of residence. The risk of small for gestational age and spontaneous preterm birth was higher across all the indicators of lower SEP, while risk for large for gestational age was lower across indicators of lower SEP. Higher risk of postneonatal death was demonstrated for several measures of lower SEP. Higher material deprivation in the neighborhood of residence was associated with increased risk for perinatal death, small for gestational age birth, and iatrogenic and spontaneous preterm birth. Family composition and urbanicity were shown to modify the association between income and some perinatal outcomes. This study highlights the importance of understanding the definitions of SEP and the mechanisms that lead to the association between income and poor perinatal outcomes, and broadening the types of SEP measures used in some cases.
Magnitude of income-related disparities in adverse perinatal outcomes
2014-01-01
Background To assess and compare multiple measurements of socioeconomic position (SEP) in order to determine the relationship with adverse perinatal outcomes across various contexts. Methods A birth registry, the Nova Scotia Atlee Perinatal Database, was confidentially linked to income tax and related information for the year in which delivery occurred. Multiple logistic regression was used to examine odds ratios between multiple indicators of SEP and multiple adverse perinatal outcomes in 117734 singleton births between 1988 and 2003. Models for after tax family income were also adjusted for neighborhood deprivation to gauge the relative magnitude of effects related to SEP at both levels. Effects of SEP were stratified by single- versus multiple-parent family composition, and by urban versus rural location of residence. Results The risk of small for gestational age and spontaneous preterm birth was higher across all the indicators of lower SEP, while risk for large for gestational age was lower across indicators of lower SEP. Higher risk of postneonatal death was demonstrated for several measures of lower SEP. Higher material deprivation in the neighborhood of residence was associated with increased risk for perinatal death, small for gestational age birth, and iatrogenic and spontaneous preterm birth. Family composition and urbanicity were shown to modify the association between income and some perinatal outcomes. Conclusions This study highlights the importance of understanding the definitions of SEP and the mechanisms that lead to the association between income and poor perinatal outcomes, and broadening the types of SEP measures used in some cases. PMID:24589212
Attrition Bias Related to Missing Outcome Data: A Longitudinal Simulation Study.
Lewin, Antoine; Brondeel, Ruben; Benmarhnia, Tarik; Thomas, Frédérique; Chaix, Basile
2018-01-01
Most longitudinal studies do not address potential selection biases due to selective attrition. Using empirical data and simulating additional attrition, we investigated the effectiveness of common approaches to handle missing outcome data from attrition in the association between individual education level and change in body mass index (BMI). Using data from the two waves of the French RECORD Cohort Study (N = 7,172), we first examined how inverse probability weighting (IPW) and multiple imputation handled missing outcome data from attrition in the observed data (stage 1). Second, simulating additional missing data in BMI at follow-up under various missing-at-random scenarios, we quantified the impact of attrition and assessed how multiple imputation performed compared to complete case analysis and to a perfectly specified IPW model as a gold standard (stage 2). With the observed data in stage 1, we found an inverse association between individual education and change in BMI, with complete case analysis, as well as with IPW and multiple imputation. When we simulated additional attrition under a missing-at-random pattern (stage 2), the bias increased with the magnitude of selective attrition, and multiple imputation was useless to address it. Our simulations revealed that selective attrition in the outcome heavily biased the association of interest. The present article contributes to raising awareness that for missing outcome data, multiple imputation does not do better than complete case analysis. More effort is thus needed during the design phase to understand attrition mechanisms by collecting information on the reasons for dropout.
Ward, Michael M
2004-08-15
To determine if socioeconomic status, as measured by education level, is associated with mortality due to systemic lupus erythematosus (SLE), and to determine if these associations differ among ethnic groups. Sex- and race-specific mortality rates due to SLE by education level were computed for persons age 25-64 years using US Multiple Causes of Death data from 1994 to 1997. SLE-specific mortality rates were compared with all-cause mortality rates in 1997 to determine if the association between education level and mortality in SLE was similar to that in other causes of death. Among whites, the risk of death due to SLE was significantly higher among those with lower levels of education, and the risk gradient closely paralleled the 1997 all-cause mortality risks by education level. However, in African American women and men and Asian/Pacific Islander women, the risk of death due to SLE was lower among those with lower education levels, contrary to the associations between education level and all-cause mortality in these groups. Comparing the distribution of education levels among deaths due to SLE and all deaths in 1997, persons with lower education levels were underrepresented among deaths due to SLE in African Americans and Asian/Pacific Islanders. Among whites, higher education levels are associated with lower mortality due to SLE. These associations were not present in ethnic minorities, likely due to underascertainment of deaths due to SLE in less-well educated persons. This underascertainment may be due to underreporting of SLE on death certificates, but may also represent underdiagnosis of SLE in ethnic minorities with low education levels.
Romero-Moreno, R; Losada, A; Márquez-González, M; Mausbach, B T
2016-11-01
Despite the robust associations between stressors and anxiety in dementia caregiving, there is a lack of research examining which factors contribute to explain this relationship. This study was designed to test a multiple mediation model of behavioral and psychological symptoms of dementia (BPSD) and anxiety that proposes higher levels of rumination and experiential avoidance and lower levels of leisure satisfaction as potential mediating variables. The sample consisted of 256 family caregivers. In order to test a simultaneously parallel multiple mediation model of the BPSD to anxiety pathway, a PROCESS method was used and bias-corrected and accelerated bootstrapping method was used to test confidence intervals. Higher levels of stressors significantly predicted anxiety. Greater stressors significantly predicted higher levels of rumination and experiential avoidance, and lower levels of leisure satisfaction. These three coping variables significantly predicted anxiety. Finally, rumination, experiential avoidance, and leisure satisfaction significantly mediated the link between stressors and anxiety. The explained variance for the final model was 47.09%. Significant contrasts were found between rumination and leisure satisfaction, with rumination being a significantly higher mediator. The results suggest that caregivers' experiential avoidance, rumination, and leisure satisfaction may function as mechanisms through which BPSD influence on caregivers' anxiety. Training caregivers in reducing their levels of experiential avoidance and rumination by techniques that foster their ability of acceptance of their negative internal experiences, and increase their level of leisure satisfaction, may be helpful to reduce their anxiety symptoms developed by stressors.
Kallaur, Ana Paula; Oliveira, Sayonara Rangel; Simão, Andréa Name Colado; Alfieri, Daniela Frizon; Flauzino, Tamires; Lopes, Josiane; de Carvalho Jennings Pereira, Wildea Lice; de Meleck Proença, Caio; Borelli, Sueli Donizete; Kaimen-Maciel, Damacio Ramón; Maes, Michael; Reiche, Edna Maria Vissoci
2017-05-01
Inflammation is the driving force for brain injury in patients with multiple sclerosis (MS). The objective of the present study is to delineate the serum cytokine profile in patients with progressive MS in a Southern Brazilian population compared with healthy controls and patients with relapsing-remitting MS (RRMS) and its associations with disease progression and disability. We included 32 patients with progressive MS, 126 with RRMS, and 40 healthy controls. The patients were evaluated using the Expanded Disability Status Scale (EDSS) and magnetic resonance imaging (MRI) with gadolinium. Serum interleukin (IL)-1β, IL-6, IL-12, tumor necrosis factor (TNF)-α, interferon (IFN)-γ, IL-10, IL-4, and IL-17 levels were assessed using an enzyme-linked immunosorbent assay. IL-1β, IL-6, TNF-α, IFN-γ, IL-17, IL-4, and IL-10 levels were higher in progressive MS than in controls. Increased IL-1β and IFN-γ and decreased IL-12 and IL-4 levels were found in progressive MS compared with RRMS. Patients with progressive MS with disease progression presented higher TNF-α, IFN-γ, and IL-10 levels than those without disease progression. Patients with progressive MS with disease progression showed a higher frequency of positive gadolinium-enhanced lesions in MRI; higher TNF-α, IFN-γ, and IL-17 levels; and decreased IL-12 levels compared with RRMS patients with progression. There was a significant inverse correlation between IL-10 levels and EDSS score in patients with progressive MS. The results underscore the complex cytokine network imbalance exhibited by progressive MS patients and show the important involvement of TNF-α, IFN-γ, and IL-17 in the pathophysiology and progression of the disease. Moreover, serum IL-10 levels were inversely associated with disability in patients with progressive MS.
Zeng, Yanni; Navarro, Pau; Fernandez-Pujals, Ana M; Hall, Lynsey S; Clarke, Toni-Kim; Thomson, Pippa A; Smith, Blair H; Hocking, Lynne J; Padmanabhan, Sandosh; Hayward, Caroline; MacIntyre, Donald J; Wray, Naomi R; Deary, Ian J; Porteous, David J; Haley, Chris S; McIntosh, Andrew M
2017-02-15
Genome-wide association studies (GWASs) of major depressive disorder (MDD) have identified few significant associations. Testing the aggregation of genetic variants, in particular biological pathways, may be more powerful. Regional heritability analysis can be used to detect genomic regions that contribute to disease risk. We integrated pathway analysis and multilevel regional heritability analyses in a pipeline designed to identify MDD-associated pathways. The pipeline was applied to two independent GWAS samples [Generation Scotland: The Scottish Family Health Study (GS:SFHS, N = 6455) and Psychiatric Genomics Consortium (PGC:MDD) (N = 18,759)]. A polygenic risk score (PRS) composed of single nucleotide polymorphisms from the pathway most consistently associated with MDD was created, and its accuracy to predict MDD, using area under the curve, logistic regression, and linear mixed model analyses, was tested. In GS:SFHS, four pathways were significantly associated with MDD, and two of these explained a significant amount of pathway-level regional heritability. In PGC:MDD, one pathway was significantly associated with MDD. Pathway-level regional heritability was significant in this pathway in one subset of PGC:MDD. For both samples the regional heritabilities were further localized to the gene and subregion levels. The NETRIN1 signaling pathway showed the most consistent association with MDD across the two samples. PRSs from this pathway showed competitive predictive accuracy compared with the whole-genome PRSs when using area under the curve statistics, logistic regression, and linear mixed model. These post-GWAS analyses highlight the value of combining multiple methods on multiple GWAS data for the identification of risk pathways for MDD. The NETRIN1 signaling pathway is identified as a candidate pathway for MDD and should be explored in further large population studies. Copyright © 2016 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.
Naaijen, J; Bralten, J; Poelmans, G; Glennon, J C; Franke, B; Buitelaar, J K
2017-01-10
Attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorders (ASD) often co-occur. Both are highly heritable; however, it has been difficult to discover genetic risk variants. Glutamate and GABA are main excitatory and inhibitory neurotransmitters in the brain; their balance is essential for proper brain development and functioning. In this study we investigated the role of glutamate and GABA genetics in ADHD severity, autism symptom severity and inhibitory performance, based on gene set analysis, an approach to investigate multiple genetic variants simultaneously. Common variants within glutamatergic and GABAergic genes were investigated using the MAGMA software in an ADHD case-only sample (n=931), in which we assessed ASD symptoms and response inhibition on a Stop task. Gene set analysis for ADHD symptom severity, divided into inattention and hyperactivity/impulsivity symptoms, autism symptom severity and inhibition were performed using principal component regression analyses. Subsequently, gene-wide association analyses were performed. The glutamate gene set showed an association with severity of hyperactivity/impulsivity (P=0.009), which was robust to correcting for genome-wide association levels. The GABA gene set showed nominally significant association with inhibition (P=0.04), but this did not survive correction for multiple comparisons. None of single gene or single variant associations was significant on their own. By analyzing multiple genetic variants within candidate gene sets together, we were able to find genetic associations supporting the involvement of excitatory and inhibitory neurotransmitter systems in ADHD and ASD symptom severity in ADHD.
Kesby, James P; Turner, Karly M; Alexander, Suzanne; Eyles, Darryl W; McGrath, John J; Burne, Thomas H J
2017-11-01
Epidemiological evidence suggests that developmental vitamin D (DVD) deficiency is a risk factor for neuropsychiatric disorders, such as schizophrenia. DVD deficiency in rats is associated with altered brain structure and adult behaviours indicating alterations in dopamine and glutamate signalling. Developmental alterations in dopamine neurotransmission have also been observed in DVD-deficient rats but a comprehensive assessment of brain neurochemistry has not been undertaken. Thus, the current study determined the regional concentrations of dopamine, noradrenaline, serotonin, glutamine, glutamate and γ-aminobutyric acid (GABA), and associated metabolites, in DVD-deficient neonates. Sprague-Dawley rats were fed a vitamin D deficient diet or control diet six weeks prior to mating until birth and housed under UVB-free lighting conditions. Neurotransmitter concentration was assessed by high-performance liquid chromatography on post-mortem neonatal brain tissue. Ubiquitous reductions in the levels of glutamine (12-24%) were observed in DVD-deficient neonates compared with control neonates. Similarly, in multiple brain regions DVD-deficient neonates had increased levels of noradrenaline and serine compared with control neonates. In contrast, increased levels of dopamine and decreased levels of serotonin in DVD-deficient neonates were limited to striatal subregions compared with controls. Our results confirm that DVD deficiency leads to changes in multiple neurotransmitter systems in the neonate brain. Importantly, this regionally-based assessment in DVD-deficient neonates identified both widespread neurotransmitter changes (glutamine/noradrenaline) and regionally selective neurotransmitter changes (dopamine/serotonin). Thus, vitamin D may have both general and local actions depending on the neurotransmitter system being investigated. Taken together, these data suggest that DVD deficiency alters neurotransmitter systems relevant to schizophrenia in the developing rat brain. Copyright © 2017 ISDN. All rights reserved.
Changes in Th17 cells function after nanocurcumin use to treat multiple sclerosis.
Dolati, Sanam; Ahmadi, Majid; Rikhtegar, Reza; Babaloo, Zohreh; Ayromlou, Hormoz; Aghebati-Maleki, Leili; Nouri, Mohammad; Yousefi, Mehdi
2018-05-28
MS is a chronic inflammatory disease that causes to brain inflammation and Th17 cells are considered to be important in multiple sclerosis pathogenesis. In the current study, we aimed to identify nanocurcumin effects on Th17 cells frequency, cytokines secretion, and expression of transcription factor of patients with relapsing-remitting multiple sclerosis (RRMS). In this study we investigated frequency of Th17 lymphocytes; the expression of transcription factor, associated cytokines and the concentration of them in 35 healthy controls, and from 25 patients at baseline and after 6 months of nanocurcumin treatment and also from 25 patients whose received placebo by flowcytometry, real-time PCR and ELISA, respectively. Our analysis revealed that the proportions of Th17 were increased dramatically, along with increases in the levels of IL-17A, IL-23, and RORγt expression in MS patients in compared with healthy control group. Post-treatment evaluation of the nanocurcumin group revealed a significant decrease in Th17 associated parameters such as Th17 frequency (p = 0.029), expression levels of RORγt (p < 0.0001) and IL-17 (p = 0.0044) and also secretion level of IL-17 (p = 0.0011), but IL-23 mRNA expression levels and IL-23 concentration were not influenced by nanocurcumin. However, in the placebo group there is no significant changes in these factors. Our study suggests that the increase in proportion of Th17 cells might contribute to the pathogenesis of RRMS. The results of the current work indicated that nanocurcumin is able to restore the dysregulated of Th17 cells in MS patients. Copyright © 2018 Elsevier B.V. All rights reserved.
Borgquist, Ola; Wise, Matt P; Nielsen, Niklas; Al-Subaie, Nawaf; Cranshaw, Julius; Cronberg, Tobias; Glover, Guy; Hassager, Christian; Kjaergaard, Jesper; Kuiper, Michael; Smid, Ondrej; Walden, Andrew; Friberg, Hans
2017-08-01
Dysglycemia and glycemic variability are associated with poor outcomes in critically ill patients. Targeted temperature management alters blood glucose homeostasis. We investigated the association between blood glucose concentrations and glycemic variability and the neurologic outcomes of patients randomized to targeted temperature management at 33°C or 36°C after cardiac arrest. Post hoc analysis of the multicenter TTM-trial. Primary outcome of this analysis was neurologic outcome after 6 months, referred to as "Cerebral Performance Category." Thirty-six sites in Europe and Australia. All 939 patients with out-of-hospital cardiac arrest of presumed cardiac cause that had been included in the TTM-trial. Targeted temperature management at 33°C or 36°C. Nonparametric tests as well as multiple logistic regression and mixed effects logistic regression models were used. Median glucose concentrations on hospital admission differed significantly between Cerebral Performance Category outcomes (p < 0.0001). Hyper- and hypoglycemia were associated with poor neurologic outcome (p = 0.001 and p = 0.054). In the multiple logistic regression models, the median glycemic level was an independent predictor of poor Cerebral Performance Category (Cerebral Performance Category, 3-5) with an odds ratio (OR) of 1.13 in the adjusted model (p = 0.008; 95% CI, 1.03-1.24). It was also a predictor in the mixed model, which served as a sensitivity analysis to adjust for the multiple time points. The proportion of hyperglycemia was higher in the 33°C group compared with the 36°C group. Higher blood glucose levels at admission and during the first 36 hours, and higher glycemic variability, were associated with poor neurologic outcome and death. More patients in the 33°C treatment arm had hyperglycemia.
2010-01-01
Multiple Sclerosis (MS) patients present a decrease of antioxidants and neuroprotective and immunoregulatory vitamins and an increase of total homocysteine (tHcy), cholesterol (CHL), HDL-cholesterol, and of cellular stress markers, variably associated with the different phases of the disease. We compared the blood levels of uric acid, folic acid, vitamins B12, A, and E, tHcy, CHL, HDL-cholesterol, and triglycerides in forty MS patients during a phase of clinical inactivity with those of eighty healthy controls, matched for age and sex. We found higher levels of tHcy (p = 0.032) and of HDL-cholesterol (p = 0.001) and lower levels of vitamin E (p = 0.001) and the ratio vitamin E/CHL (p = 0.001) in MS patients. In conclusion, modifications of some biochemical markers of cell damage were detected in MS patients during a phase of clinical inactivity. PMID:20163740
Inducible and reversible phenotypes in a novel mouse model of Friedreich’s Ataxia
Gao, Kun; Swarup, Vivek; Versano, Revital; Dong, Hongmei; Jordan, Maria C
2017-01-01
Friedreich's ataxia (FRDA), the most common inherited ataxia, is caused by recessive mutations that reduce the levels of frataxin (FXN), a mitochondrial iron binding protein. We developed an inducible mouse model of Fxn deficiency that enabled us to control the onset and progression of disease phenotypes by the modulation of Fxn levels. Systemic knockdown of Fxn in adult mice led to multiple phenotypes paralleling those observed in human patients across multiple organ systems. By reversing knockdown after clinical features appear, we were able to determine to what extent observed phenotypes represent reversible cellular dysfunction. Remarkably, upon restoration of near wild-type FXN levels, we observed significant recovery of function, associated pathology and transcriptomic dysregulation even after substantial motor dysfunction and pathology were observed. This model will be of broad utility in therapeutic development and in refining our understanding of the relative contribution of reversible cellular dysfunction at different stages in disease. PMID:29257745
Chou, Wen-Jiun; Liu, Tai-Ling; Yang, Pinchen; Yen, Cheng-Fang; Hu, Huei-Fan
2018-01-01
To examine the prevalence rates of bullying involvement and their correlates in adolescents diagnosed with ADHD in Taiwan. Bullying involvement, family and ADHD characteristics, the levels of behavioral inhibition system (BIS) and behavioral approach system (BAS), and psychiatric comorbidity were assessed in 287 adolescents with ADHD. The multiple regression analysis was used to examine the correlate of bullying victimization and perpetration. The prevalence rates of the pure victims, pure perpetrators, and victim-perpetrators were 14.6%, 8.4%, and 5.6%, respectively. Young age, a high BIS score, autism spectrum disorders, and low satisfaction with family relationships were associated with severe bullying victimization. A high score of fun seeking on the BAS and low satisfaction with family relationships were associated with severe bullying perpetration. A high proportion of adolescents with ADHD are involved in bullying. Multiple factors are associated with bullying involvement in adolescents with ADHD.
Analyses of arsenic (As) species in body fluids and tissues of individuals chronically exposed to inorganic arsenic (iAs) provide essential information about the exposure level and pattern of iAs metabolism. This information facilitates the risk assessment of disorders associated...
Employment Experiences of Black and White Veterans with Service-Connected Disabilities
ERIC Educational Resources Information Center
Murphy, Sharon Y.
2014-01-01
The study examined the association between race and employment experiences among Veterans with disability to determine if employment experience differed for White and Black Veterans in the labor market. The research revealed typical characteristics of employment experiences, which suggest that work is completed at multiple levels, based on…
Multiple drivers, including nutrient loading and climate change, affect the Narragansett Bay ecosystem in Rhode Island/Massachusetts, USA. Managers are interested in understanding the timing and magnitude of these effects, and ecosystem responses to restoration actions. To provid...
Conducting Multilevel Analyses in Medical Education
ERIC Educational Resources Information Center
Zyphur, Michael J.; Kaplan, Seth A.; Islam, Gazi; Barsky, Adam P.; Franklin, Michael S.
2008-01-01
A significant body of education literature has begun using multilevel statistical models to examine data that reside at multiple levels of analysis. In order to provide a primer for medical education researchers, the current work gives a brief overview of some issues associated with multilevel statistical modeling. To provide an example of this…
Multi-scale Homogenization of Caddisfly Metacomminities in Human-modified Landscapes
NASA Astrophysics Data System (ADS)
Simião-Ferreira, Juliana; Nogueira, Denis Silva; Santos, Anna Claudia; De Marco, Paulo; Angelini, Ronaldo
2018-04-01
The multiple scale of stream networks spatial organization reflects the hierarchical arrangement of streams habitats with increasingly levels of complexity from sub-catchments until entire hydrographic basins. Through these multiple spatial scales, local stream habitats form nested subsets of increasingly landscape scale and habitat size with varying contributions of both alpha and beta diversity for the regional diversity. Here, we aimed to test the relative importance of multiple nested hierarchical levels of spatial scales while determining alpha and beta diversity of caddisflies in regions with different levels of landscape degradation in a core Cerrado area in Brazil. We used quantitative environmental variables to test the hypothesis that landscape homogenization affects the contribution of alpha and beta diversity of caddisflies to regional diversity. We found that the contribution of alpha and beta diversity for gamma diversity varied according to landscape degradation. Sub-catchments with more intense agriculture had lower diversity at multiple levels, markedly alpha and beta diversities. We have also found that environmental predictors mainly associated with water quality, channel size, and habitat integrity (lower scores indicate stream degradation) were related to community dissimilarity at the catchment scale. For an effective management of the headwater biodiversity of caddisfly, towards the conservation of these catchments, heterogeneous streams with more pristine riparian vegetation found within the river basin need to be preserved in protected areas. Additionally, in the most degraded areas the restoration of riparian vegetation and size increase of protected areas will be needed to accomplish such effort.
Factors Influencing Amount of Weekly Exercise Time in Colorectal Cancer Survivors.
Chou, Yun-Jen; Lai, Yeur-Hur; Lin, Been-Ren; Liang, Jin-Tung; Shun, Shiow-Ching
Performing regular exercise of at least 150 minutes weekly has benefits for colorectal cancer survivors. However, barriers inhibit these survivors from performing regular exercise. The aim of this study was to explore exercise behaviors and significant factors influencing weekly exercise time of more than 150 minutes in colorectal cancer survivors. A cross-sectional study design was used to recruit participants in Taiwan. Guided by the ecological model of health behavior, exercise barriers were assessed including intrapersonal, interpersonal, and environment-related barriers. A multiple logistic regression was used to explore the factors associated with the amount of weekly exercise. Among 321 survivors, 57.0% of them had weekly exercise times of more than 150 minutes. The results identified multiple levels of significant factors related to weekly exercise times including intrapersonal factors (occupational status, functional status, pain, interest in exercise, and beliefs about the importance of exercise) and exercise barriers related to environmental factors (lack of time and bad weather). No interpersonal factors were found to be significant. Colorectal cancer survivors experienced low levels of physical and psychological distress. Multiple levels of significant factors related to exercise time including intrapersonal factors as well as exercise barriers related to environmental factors should be considered. Healthcare providers should discuss with their patients how to perform exercise programs; the discussion should address multiple levels of the ecological model such as any pain problems, functional status, employment status, and time limitations, as well as community environment.
Rural-urban analyses of health-related quality of life among people with multiple sclerosis.
Buchanan, Robert J; Zhu, Li; Schiffer, Randolph; Radin, Dagmar; James, Wesley
2008-01-01
Health-related quality of life (HRQOL) is a multi-dimensional construct including aspects of life quality or function that are affected by physical health and symptoms, psychosocial factors, and psychiatric conditions. HRQOL gives a broader measure of the burden of disease than physical impairment or disability levels. To identify factors associated with HRQOL among people with multiple sclerosis (MS) utilizing the SF-8 Health Survey. Data presented in this study were collected in a survey of 1,518 people with MS living in all 50 states. The survey sample was randomly selected from the database of the National Multiple Sclerosis Society, using ZIP codes to recruit the survey sample. A multiple linear regression model was employed to analyze the survey data, with the Physical Component Summary and the Mental Component Summary of the SF-8 the dependent variables. Independent variables were demographic characteristics, MS-disease characteristics, and health services utilized. People with MS in rural areas tended to report lower physically related HRQOL. Worsening MS symptoms were associated with reduced physical and mental dimensions of HRQOL. In addition, people with MS who received a diagnosis of depression tended to have reduced physical and mental dimensions of HRQOL. Receiving MS care at an MS clinic was associated with better physically related HRQOL, while having a neurologist as principal care physician was associated with better mental-related HRQOL. The challenge is to increase the access that people living with MS in rural areas have to MS-focused specialty care.
Solanky, Bhavana S.; Muhlert, Nils; Tur, Carmen; Edden, Richard A. E.; Wheeler-Kingshott, Claudia A. M.; Miller, David H.; Thompson, Alan J.; Ciccarelli, Olga
2015-01-01
Neurodegeneration is thought to be the major cause of ongoing, irreversible disability in progressive stages of multiple sclerosis. Gamma-aminobutyric acid is the principle inhibitory neurotransmitter in the brain. The aims of this study were to investigate if gamma-aminobutyric acid levels (i) are abnormal in patients with secondary progressive multiple sclerosis compared with healthy controls; and (ii) correlate with physical and cognitive performance in this patient population. Thirty patients with secondary progressive multiple sclerosis and 17 healthy control subjects underwent single-voxel MEGA-PRESS (MEscher-GArwood Point RESolved Spectroscopy) magnetic resonance spectroscopy at 3 T, to quantify gamma-aminobutyric acid levels in the prefrontal cortex, right hippocampus and left sensorimotor cortex. All subjects were assessed clinically and underwent a cognitive assessment. Multiple linear regression models were used to compare differences in gamma-aminobutyric acid concentrations between patients and controls adjusting for age, gender and tissue fractions within each spectroscopic voxel. Regression was used to examine the relationships between the cognitive function and physical disability scores specific for these regions with gamma-aminobuytric acid levels, adjusting for age, gender, and total N-acetyl-aspartate and glutamine-glutamate complex levels. When compared with controls, patients performed significantly worse on all motor and sensory tests, and were cognitively impaired in processing speed and verbal memory. Patients had significantly lower gamma-aminobutyric acid levels in the hippocampus (adjusted difference = −0.403 mM, 95% confidence intervals −0.792, −0.014, P = 0.043) and sensorimotor cortex (adjusted difference = −0.385 mM, 95% confidence intervals −0.667, −0.104, P = 0.009) compared with controls. In patients, reduced motor function in the right upper and lower limb was associated with lower gamma-aminobutyric acid concentration in the sensorimotor cortex. Specifically for each unit decrease in gamma-aminobutyric acid levels (in mM), there was a predicted −10.86 (95% confidence intervals −16.786 to −4.482) decrease in grip strength (kg force) (P < 0.001) and −8.74 (95% confidence intervals −13.943 to −3.015) decrease in muscle strength (P < 0.006). This study suggests that reduced gamma-aminobutyric acid levels reflect pathological abnormalities that may play a role in determining physical disability. These abnormalities may include decreases in the pre- and postsynaptic components of gamma-aminobutyric acid neurotransmission and in the density of inhibitory neurons. Additionally, the reduced gamma-aminobutyric acid concentration may contribute to the neurodegenerative process, resulting in increased firing of axons, with consequent increased energy demands, which may lead to neuroaxonal degeneration and loss of the compensatory mechanisms that maintain motor function. This study supports the idea that modulation of gamma-aminobutyric acid neurotransmission may be an important target for neuroprotection in multiple sclerosis. See De Stefano and Giorgio (doi:10.1093/brain/awv213) for a scientific commentary on this article. PMID:26304151
Heidary, Masoumeh; Rakhshi, Nahid; Pahlevan Kakhki, Majid; Behmanesh, Mehrdad; Sanati, Mohammad Hossein; Sanadgol, Nima; Kamaladini, Hossein; Nikravesh, Abbas
2014-08-15
IL-1B is released by monocytes, astrocytes and brain endothelial cells and seems to be involved in inflammatory reactions of the central nervous system (CNS) in multiple sclerosis (MS). This study aims to evaluate the expression level of IL-1B mRNA in peripheral blood mononuclear cells (PBMCs), genotype the rs16944 SNP and find out the role of this SNP on the expression level of IL-1B in MS patients. We found that the expression level of IL-1B in MS patients increased 3.336 times more than controls in PBMCs but the rs16944 SNP in the promoter region of IL-1B did not affect the expression level of this gene and there was not association of this SNP with MS in the examined population. Also, our data did not reveal any correlation between normalized expressions of IL-1B gene with age of participants, age of onset, and disease duration. Copyright © 2014 Elsevier B.V. All rights reserved.
Alwan, Heba; Viswanathan, Bharathi; Rousson, Valentin; Paccaud, Fred; Bovet, Pascal
2011-10-11
We examined the associations between substance use (cigarette smoking, alcohol drinking, and cannabis use) and psychosocial characteristics at the individual and family levels among adolescents of the Seychelles, a rapidly developing small island state in the African region. A school survey was conducted in a representative sample of 1432 students aged 11-17 years from all secondary schools. Data came from a self-administered anonymous questionnaire conducted along a standard methodology (Global School-based Health Survey, GSHS). Risk behaviors and psychosocial characteristics were dichotomized. Association analyses were adjusted for a possible classroom effect. The prevalence of cigarette smoking, alcohol drinking and cannabis use was higher in boys than in girls and increased with age. Age-adjusted and multivariate analyses showed that several individual level characteristics (e.g. suicidal ideation and truancy) and family level characteristics (e.g. poor parental monitoring) were associated with substance use among students. Our results suggest that health promotion programs should simultaneously address multiple risk behaviors and take into account a wide range of psychosocial characteristics of the students at the individual and family levels.
Neighborhood Racial Composition, Racial Discrimination, and Depressive Symptoms in African Americans
Lambert, Sharon F.; Evans, Michele K.; Zonderman, Alan B.
2015-01-01
While evidence indicates that experienced racial discrimination is associated with increased depressive symptoms for African Americans, there is little research investigating predictors of experienced racial discrimination. This paper examines neighborhood racial composition and sociodemographic factors as antecedents to experienced racial discrimination and resultant levels of depressive symptoms among African American adults. The sample included 505 socioeconomically-diverse African American adults from Baltimore, MD. Study data were obtained via self-report and geocoding of participant addresses based on 2010 census data. Study hypotheses were tested using multiple pathways within a longitudinal Structural Equation Model. Experienced racial discrimination was positively associated with age and sex such that older individuals and males experienced increased levels of racial discrimination. In addition, the percentage of White individuals residing in a neighborhood was positively associated with levels of experienced racial discrimination for African American neighborhood residents. Experienced racial discrimination was positively associated with later depressive symptoms. Neighborhood-level contextual factors such as neighborhood racial composition and individual differences in sociodemographic characteristics appear to play an important role in the experience of racial discrimination and the etiology of depression in African American adults. PMID:24969707
English, Devin; Lambert, Sharon F; Evans, Michele K; Zonderman, Alan B
2014-12-01
While evidence indicates that experienced racial discrimination is associated with increased depressive symptoms for African Americans, there is little research investigating predictors of experienced racial discrimination. This paper examines neighborhood racial composition and sociodemographic factors as antecedents to experienced racial discrimination and resultant levels of depressive symptoms among African American adults. The sample included 505 socioeconomically-diverse African American adults from Baltimore, MD. Study data were obtained via self-report and geocoding of participant addresses based on 2010 census data. Study hypotheses were tested using multiple pathways within a longitudinal Structural Equation Model. Experienced racial discrimination was positively associated with age and sex such that older individuals and males experienced increased levels of racial discrimination. In addition, the percentage of White individuals residing in a neighborhood was positively associated with levels of experienced racial discrimination for African American neighborhood residents. Experienced racial discrimination was positively associated with later depressive symptoms. Neighborhood-level contextual factors such as neighborhood racial composition and individual differences in sociodemographic characteristics appear to play an important role in the experience of racial discrimination and the etiology of depression in African American adults.
Multiple cutaneous hemangiomas in a patient with combined pituitary hormone deficiency.
Aykut, Ayca; Ozen, Samim; Sımsek, Damla Gokşen; Onay, Huseyin; Cogulu, Ozgur; Darcan, Sukran; Ozkinay, Ferda
2014-01-01
Combined pituitary hormone deficiency (CPHD) refers to a rare heterogeneous group of conditions in which there is a deficiency in at least two anterior pituitary hormones. Patients with POU1F1 mutations show a combined pituitary deficiency with low or absent levels of growth hormone, prolactin, and thyroid-stimulating hormone. In this study, a 7-month-old girl with a CPHD is presented. She had facial dysmorphologic features, hypertrichosis, and hypotonia. Additionally, she also presented with multiple cutaneous hemangioma that until now has not been reported in association with this disorder.
Maternal characteristics associated with vaccination of young children.
Luman, Elizabeth T; McCauley, Mary Mason; Shefer, Abigail; Chu, Susan Y
2003-05-01
Mothers can be instrumental in gaining access to vaccination services for their children. This study examines maternal characteristics associated with vaccination in US preschool children. We analyzed data from 21 212 children aged 19 to 35 months in the National Immunization Survey. Bivariate and multivariate analyses were used to identify maternal characteristics associated with completion of all recommended vaccinations in these children. Factors most strongly associated with undervaccination included having mothers who were black; had less than a high school education; were divorced, separated, or widowed; had multiple children; were eligible for the Special Supplemental Nutrition Program for Women, Infants and Children (WIC) but not participating; or had incomes below 50% of the federal poverty level. Because most mothers play an important role in their children's vaccination, it is important to address maternal concerns and barriers when developing public health interventions for promoting childhood vaccinations. Encouraging eligible women and their children to participate in the WIC program and providing support and encouragement for immunization to mothers with multiple children may improve early childhood vaccination coverage.
How Team-Level and Individual-Level Conflict Influences Team Commitment: A Multilevel Investigation.
Lee, Sanghyun; Kwon, Seungwoo; Shin, Shung J; Kim, MinSoo; Park, In-Jo
2017-01-01
We investigate how two different types of conflict (task conflict and relationship conflict) at two different levels (individual-level and team-level) influence individual team commitment. The analysis was conducted using data we collected from 193 employees in 31 branch offices of a Korean commercial bank. The relationships at multiple levels were tested using hierarchical linear modeling (HLM). The results showed that individual-level relationship conflict was negatively related to team commitment while individual-level task conflict was not. In addition, both team-level task and relationship conflict were negatively associated with team commitment. Finally, only team-level relationship conflict significantly moderated the relationship between individual-level relationship conflict and team commitment. We further derive theoretical implications of these findings.
How Team-Level and Individual-Level Conflict Influences Team Commitment: A Multilevel Investigation
Lee, Sanghyun; Kwon, Seungwoo; Shin, Shung J.; Kim, MinSoo; Park, In-Jo
2018-01-01
We investigate how two different types of conflict (task conflict and relationship conflict) at two different levels (individual-level and team-level) influence individual team commitment. The analysis was conducted using data we collected from 193 employees in 31 branch offices of a Korean commercial bank. The relationships at multiple levels were tested using hierarchical linear modeling (HLM). The results showed that individual-level relationship conflict was negatively related to team commitment while individual-level task conflict was not. In addition, both team-level task and relationship conflict were negatively associated with team commitment. Finally, only team-level relationship conflict significantly moderated the relationship between individual-level relationship conflict and team commitment. We further derive theoretical implications of these findings. PMID:29387033
Role of hormonal levels on hospital mortality for male patients with severe traumatic brain injury.
Hohl, Alexandre; Ronsoni, Marcelo Fernando; Debona, Rodrigo; Ben, Juliana; Schwarzbold, Marcelo Liborio; Diaz, Alexandre Paim; Thais, Maria Emília Rodrigues de Oliveira; Linhares, Marcelo Neves; Latini, Alexandra; Prediger, Rui Daniel; Pizzol, Felipe Dal; Walz, Roger
2014-01-01
Changes in hormone blood levels during the acute phase of traumatic brain injury (TBI) have been described in the literature. The objective was to investigate the association among several hormones plasma levels in the acute phase of severe TBI and the hospital mortality rate of male patients. The independent association among plasma levels of TSH, LH, FSH, GH, free T4, cortisol, IGF-1 and total testosterone was measured 10 hours and 30 hours after severe TBI and the hospital mortality of 60 consecutive male patients was evaluated. At least one hormonal level abnormality was demonstrated in 3.6-73.1% of patients. The multiple logistic regressions showed a trend for an independent association among hospital mortality and normal or elevated LH levels measured at 10 hours (OR = 3.7, 95% CI = 0.8-16.3, p = 0.08) and 30 hours (OR = 3.9, 95% CI = 0.9-16.7, p = 0.06). Admission with abnormal pupils and a lower Glasgow Coma Score also were independently associated with hospital mortality. The hormonal changes are frequent in the acute phase of severe TBI. The hormones plasma levels, excepting the LH, are not highly consistent with the hospital mortality of male patients.
Consumer product exposures associated with urinary phthalate levels in pregnant women
Buckley, Jessie P.; Palmieri, Rachel T.; Matuszewski, Jeanine M.; Herring, Amy H.; Baird, Donna D.; Hartmann, Katherine E.; Hoppin, Jane A.
2012-01-01
Human phthalate exposure is ubiquitous, but little is known regarding predictors of urinary phthalate levels. To explore this, 50 pregnant women aged 18–38 years completed two questionnaires on potential phthalate exposures and provided a first morning void. Urine samples were analyzed for 12 phthalate metabolites. Associations with questionnaire items were evaluated via Wilcoxon tests and t-tests, and r-squared values were calculated in multiple linear regression models. Few measured factors were statistically significantly associated with phthalate levels. Individuals who used nail polish had higher levels of mono-butyl phthalate (p=0.048) than non-users. Mono-benzyl phthalate levels were higher among women who used eye makeup (p=0.034) or used makeup on a regular basis (p=0.004). Women who used cologne or perfume had higher levels of di-(2-ethylhexyl) phthalate metabolites. Household products, home flooring or paneling, and other personal care products were also associated with urinary phthalates. The proportion of variance in metabolite concentrations explained by questionnaire items ranged between 0.31 for mono-ethyl phthalate and 0.42 for mono-n-methyl phthalate. Although personal care product use may be an important predictor of urinary phthalate levels, most of the variability in phthalate exposure was not captured by our relatively comprehensive set of questionnaire items. PMID:22760436
Hamilton, S; Corker, E; Weeks, C; Williams, P; Henderson, C; Pinfold, V; Rose, D; Thornicroft, G
2016-08-01
Research has found considerable variation in how far individuals with a diagnosis of mental illness experience discrimination. This study tested four hypotheses: (i) a diagnosis of schizophrenia will be associated with more discrimination than depression, anxiety or bipolar disorder; (ii) people with a history of involuntary treatment will report more discrimination than people without; (iii) higher levels of avoidance behaviour due to anticipated discrimination will be associated with higher levels of discrimination and (iv) longer time in contact with services will be associated with higher levels of discrimination. Three thousand five hundred and seventy-nine people using mental health services in England took part in structured telephone interviews about discrimination experiences. A multiple regression model found that study year, age, employment status, length of time in mental health services, disagreeing with the diagnosis, anticipating discrimination in personal relationships and feeling the need to conceal a diagnosis from others were significantly associated with higher levels of experienced discrimination. Findings suggest that discrimination is not related to specific diagnoses but rather is associated with mental health problems generally. An association between unemployment and discrimination may indicate that employment protects against experiences of discrimination, supporting efforts to improve access to employment among people with a diagnosis of mental illness.
Associations between Bisphenol A Exposure and Reproductive Hormones among Female Workers
Miao, Maohua; Yuan, Wei; Yang, Fen; Liang, Hong; Zhou, Zhijun; Li, Runsheng; Gao, Ersheng; Li, De-Kun
2015-01-01
The associations between Bisphenol-A (BPA) exposure and reproductive hormone levels among women are unclear. A cross-sectional study was conducted among female workers from BPA-exposed and unexposed factories in China. Women’s blood samples were collected for assay of follicle-stimulating hormone (FSH), luteinizing hormone (LH), 17β-Estradiol (E2), prolactin (PRL), and progesterone (PROG). Their urine samples were collected for BPA measurement. In the exposed group, time weighted average exposure to BPA for an 8-h shift (TWA8), a measure incorporating historic exposure level, was generated based on personal air sampling. Multiple linear regression analyses were used to examine linear associations between urine BPA concentration and reproductive hormones after controlling for potential confounders. A total of 106 exposed and 250 unexposed female workers were included in this study. A significant positive association between increased urine BPA concentration and higher PRL and PROG levels were observed. Similar associations were observed after the analysis was carried out separately among the exposed and unexposed workers. In addition, a positive association between urine BPA and E2 was observed among exposed workers with borderline significance, while a statistically significant inverse association between urine BPA and FSH was observed among unexposed group. The results suggest that BPA exposure may lead to alterations in female reproductive hormone levels. PMID:26506366
Associations between Bisphenol A Exposure and Reproductive Hormones among Female Workers.
Miao, Maohua; Yuan, Wei; Yang, Fen; Liang, Hong; Zhou, Zhijun; Li, Runsheng; Gao, Ersheng; Li, De-Kun
2015-10-22
The associations between Bisphenol-A (BPA) exposure and reproductive hormone levels among women are unclear. A cross-sectional study was conducted among female workers from BPA-exposed and unexposed factories in China. Women's blood samples were collected for assay of follicle-stimulating hormone (FSH), luteinizing hormone (LH), 17β-Estradiol (E2), prolactin (PRL), and progesterone (PROG). Their urine samples were collected for BPA measurement. In the exposed group, time weighted average exposure to BPA for an 8-h shift (TWA8), a measure incorporating historic exposure level, was generated based on personal air sampling. Multiple linear regression analyses were used to examine linear associations between urine BPA concentration and reproductive hormones after controlling for potential confounders. A total of 106 exposed and 250 unexposed female workers were included in this study. A significant positive association between increased urine BPA concentration and higher PRL and PROG levels were observed. Similar associations were observed after the analysis was carried out separately among the exposed and unexposed workers. In addition, a positive association between urine BPA and E2 was observed among exposed workers with borderline significance, while a statistically significant inverse association between urine BPA and FSH was observed among unexposed group. The results suggest that BPA exposure may lead to alterations in female reproductive hormone levels.
Vaidya, Dhananjay; Yanek, Lisa R.; Herrera-Galeano, J. Enrique; Mathias, Rasika A.; Moy, Taryn F.; Faraday, Nauder; Becker, Lewis C.; Becker, Diane M.
2010-01-01
Von Willebrand Factor (vWF) is a plasma protein involved in thrombosis and hemostasis [1]. We examined whether common single nucleotide polymorphisms (SNPs) in the vWF gene were associated with vWF levels and platelet aggregation-related functional consequences in1230 Whites and 837 African Americans in a cross-sectional family based genetic study of platelet function. From a high-density scan, 28 SNPs with a minor allele frequency > 5% in both races were tested for association using age and sex adjusted variance components analysis in MERLIN. SNP rs216321, with the strongest association with vWF levels in biracial metaanalysis (p=9.5×10−6, Whites–p=8.1×10−4, African Americans–p=3.6×10−3), encoding a R852Q substitution in the D’D3 protein domain, demonstrated negative association with plasma vWF. The R852Q variant was recessively associated with 15.5% lower collagen-induced platelet aggregation adjusting for dose-response relationship (p=0.010, vWF-level adjusted p=0.003). Each copy of the R852Q variant was additively associated with 31% higher FVIII levels (p=0.039, vWF-adjusted p=0.033). In conclusion, this common missense polymorphism appears to have pleiotropic functional consequences. PMID:20941784
Foarde, Karin; Berry, Michael
2004-01-01
Choosing the appropriate floor surface for a school environment is a complex issue. To assist school personnel in determining which flooring is best for their school, we studied the biocontaminant levels associated with carpeted and hard surface flooring. Two schools were selected, one predominantly tiled and one predominantly carpeted, as similar as possible with the exception of their floor coverings. Neither school was a "problem" building. Multiple biocontaminants were measured. For flooring, there were statistically significant differences for all the tested biocontaminants except fungi. The carpeted surfaces, being strong sinks, generally had higher surface loadings of the biocontaminants, while the airborne levels were significantly higher over tiled floors. Significant differences in airborne levels were found for dust mass, spores, fungi, beta-1,3 glucans, and endotoxins. The results suggest that carpet flooring was not the major contributor to airborne levels of biocontaminants in these two nonproblem schools.
Access to environmental resources and physical activity levels of adults in Hawaii.
Geller, Karly S; Nigg, Claudio R; Ollberding, Nicholas J; Motl, Robert W; Horwath, Caroline; Dishman, Rodney K
2015-03-01
Examine associations between physical activity (PA) and spatial accessibility to environmental PA resources in Hawaii. Metabolic equivalents (METs) of mild, moderate, and strenuous PA were compared for accessibility with environmental PA resources within a population-based sample of Hawaiian adults (n = 381). Multiple linear regression estimated differences in PA levels for residing further from a PA resource or residing in an area with a greater number of resources. No associations were found in the total sample. Analyses within subsamples stratified by ethnicity revealed that greater spatial accessibility to a PA resource was positively associated with strenuous PA among Caucasians (P = .04) but negatively associated with moderate PA among Native Hawaiians (P = .00). The lack of association in the total sample may be a consequence of Hawaii's unique environment. Results of stratified sample analyses are unique, providing groundwork for future examinations within parallel environments and among similar ethnic groups. © 2012 APJPH.
Big five personality and residential mobility: a state-level analysis of the USA.
McCann, Stewart J H
2015-01-01
Relations of the state-aggregated Big Five personality scores of 619,397 residents to four 2005 state-level residential mobility criteria were examined with the 50 states as cases. Multiple regression controlling for five state demographic variables showed (a) higher state neuroticism was strongly associated with lower mobility, lower same-county mobility, and lower between-county mobility; (b) higher state extraversion was associated with lower mobility and lower same-county mobility, but only with neuroticism and/or conscientiousness controlled; and (c) conscientiousness was related to same-residence, same-county, and different-county mobility, but only without demographic variables controlled. Discussion is grounded in the dangers of cross-level speculation and the potential of a basic assumption of geographical psychology that an area's aggregate position on a dispositional variable is associated there with behavioral and psychological tendencies related to that variable.
Quality control and conduct of genome-wide association meta-analyses.
Winkler, Thomas W; Day, Felix R; Croteau-Chonka, Damien C; Wood, Andrew R; Locke, Adam E; Mägi, Reedik; Ferreira, Teresa; Fall, Tove; Graff, Mariaelisa; Justice, Anne E; Luan, Jian'an; Gustafsson, Stefan; Randall, Joshua C; Vedantam, Sailaja; Workalemahu, Tsegaselassie; Kilpeläinen, Tuomas O; Scherag, André; Esko, Tonu; Kutalik, Zoltán; Heid, Iris M; Loos, Ruth J F
2014-05-01
Rigorous organization and quality control (QC) are necessary to facilitate successful genome-wide association meta-analyses (GWAMAs) of statistics aggregated across multiple genome-wide association studies. This protocol provides guidelines for (i) organizational aspects of GWAMAs, and for (ii) QC at the study file level, the meta-level across studies and the meta-analysis output level. Real-world examples highlight issues experienced and solutions developed by the GIANT Consortium that has conducted meta-analyses including data from 125 studies comprising more than 330,000 individuals. We provide a general protocol for conducting GWAMAs and carrying out QC to minimize errors and to guarantee maximum use of the data. We also include details for the use of a powerful and flexible software package called EasyQC. Precise timings will be greatly influenced by consortium size. For consortia of comparable size to the GIANT Consortium, this protocol takes a minimum of about 10 months to complete.
Quality control and conduct of genome-wide association meta-analyses
Winkler, Thomas W; Day, Felix R; Croteau-Chonka, Damien C; Wood, Andrew R; Locke, Adam E; Mägi, Reedik; Ferreira, Teresa; Fall, Tove; Graff, Mariaelisa; Justice, Anne E; Luan, Jian'an; Gustafsson, Stefan; Randall, Joshua C; Vedantam, Sailaja; Workalemahu, Tsegaselassie; Kilpeläinen, Tuomas O; Scherag, André; Esko, Tonu; Kutalik, Zoltán; Heid, Iris M; Loos, Ruth JF
2014-01-01
Rigorous organization and quality control (QC) are necessary to facilitate successful genome-wide association meta-analyses (GWAMAs) of statistics aggregated across multiple genome-wide association studies. This protocol provides guidelines for [1] organizational aspects of GWAMAs, and for [2] QC at the study file level, the meta-level across studies, and the meta-analysis output level. Real–world examples highlight issues experienced and solutions developed by the GIANT Consortium that has conducted meta-analyses including data from 125 studies comprising more than 330,000 individuals. We provide a general protocol for conducting GWAMAs and carrying out QC to minimize errors and to guarantee maximum use of the data. We also include details for use of a powerful and flexible software package called EasyQC. For consortia of comparable size to the GIANT consortium, the present protocol takes a minimum of about 10 months to complete. PMID:24762786
Social Support and Mental Health in LGBTQ Adolescents: A review of the literature.
McDonald, Kari
2018-01-01
LGBTQ adolescents experience higher rates of mental health disorders than their heterosexual peers. The purpose of this systematic review of the literature was to examine studies evaluating social support and its effects on mental health in the LGBTQ adolescent population. Higher levels of social support were associated with positive self-esteem. Lack of social support (or low social support) was associated with higher levels of depression, anxiety, alcohol or drug misuse, risky sexual behaviors, shame, and low self-esteem. Interdisciplinary research teams from multiple and diverse professions could provide valuable insight supporting the development of inclusive and comprehensive interventions programs for this population.
Vuorijoki, Linda; Tiwari, Arjun; Kallio, Pauli; Aro, Eva-Mari
2017-05-01
Iron-sulfur (Fe-S) clusters are protein-bound cofactors associated with cellular electron transport and redox sensing, with multiple specific functions in oxygen-evolving photosynthetic cyanobacteria. The aim here was to elucidate protein-level effects of the transcriptional repressor SufR involved in the regulation of Fe-S cluster biogenesis in the cyanobacterium Synechocystis sp. PCC 6803. The approach was to quantitate 94 pre-selected target proteins associated with various metabolic functions using SRM in Synechocystis. The evaluation was conducted in response to sufR deletion under different iron conditions, and complemented with EPR analysis on the functionality of the photosystems I and II as well as with RT-qPCR to verify the effects of SufR also on transcript level. The results on both protein and transcript levels show that SufR acts not only as a repressor of the suf operon when iron is available but also has other direct and indirect functions in the cell, including maintenance of the expression of pyruvate:ferredoxin oxidoreductase NifJ and other Fe-S cluster proteins under iron sufficient conditions. Furthermore, the results imply that in the absence of iron the suf operon is repressed by some additional regulatory mechanism independent of SufR. The study demonstrates that Fe-S cluster metabolism in Synechocystis is stringently regulated, and has complex interactions with multiple primary functions in the cell, including photosynthesis and central carbon metabolism. The study provides new insight into the regulation of Fe-S cluster biogenesis via suf operon, and the associated wide-ranging protein-level changes in photosynthetic cyanobacteria. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.
Ye, Zusen; Zhang, Zhizhong; Zhang, Hao; Hao, Yonggang; Zhang, Jun; Liu, Wenhua; Xu, Gelin; Liu, Xinfeng
2017-03-01
Our objective is to investigate whether C-reactive protein (CRP) and homocysteine (Hcy) levels in the acute phase of large-artery atherosclerotic stroke predict long-term functional disability and recurrent vascular events. Patients with first-ever large-artery atherosclerotic ischemic stroke were prospectively registered in the Nanjing Stroke Registry Program between January 2012 and June 2014. Venous blood samples were collected within 2 weeks after the index stroke. Patients were followed up for 1 year. The Kaplan-Meier method was performed in survival analysis. Multiple logistic regression analysis and Cox proportional hazard model were applied to identify predictors of functional disability and recurrent vascular events, respectively. A total of 625 eligible patients (458 males) were evaluated. During the 1-year follow-up period, 63 patients suffered recurrent vascular events. An elevated CRP level is an independent predictor of poor functional disability at 1 year (P for trend = .002), in both males (P for trend = .017) and females (P for trend = .042). Hcy showed no relationship with functional disability. No significant relationship between CRP and Hcy levels and recurrent vascular events was found in total patients in multiple models. Stratified by sex, high Hcy levels were associated with recurrent vascular events in females (P for trend = .036) but not in males. Elevated CRP levels are associated with poor functional disability in patients with large-artery atherosclerotic stroke at 1 year, and Hcy is a relatively moderate predictor of recurrent vascular events in female patients with large-artery atherosclerotic stroke at 1 year. Copyright © 2017 National Stroke Association. Published by Elsevier Inc. All rights reserved.
Hormone-Related Pathways and Risk of Breast Cancer Subtypes in African American Women
Haddad, Stephen A.; Lunetta, Kathryn L.; Ruiz-Narváez, Edward A.; Bensen, Jeannette T.; Hong, Chi-Chen; Sucheston-Campbell, Lara E.; Yao, Song; Bandera, Elisa V.; Rosenberg, Lynn; Haiman, Christopher A.; Troester, Melissa A.; Ambrosone, Christine B.; Palmer, Julie R.
2016-01-01
Purpose We sought to investigate genetic variation in hormone pathways in relation to risk of overall and subtype-specific breast cancer in women of African ancestry (AA). Methods Genotyping and imputation yielded data on 143,934 SNPs in 308 hormone-related genes for 3663 breast cancer cases (1098 ER-, 1983 ER+, 582 ER unknown) and 4687 controls from the African American Breast Cancer Epidemiology and Risk (AMBER) Consortium. AMBER includes data from four large studies of AA women: the Carolina Breast Cancer Study, the Women's Circle of Health Study, the Black Women's Health Study, and the Multiethnic Cohort Study. Pathway- and gene-based analyses were conducted, and single SNP tests were run for the top genes. Results There were no strong associations at the pathway level. The most significantly associated genes were GHRH, CALM2, CETP, and AKR1C1 for overall breast cancer (gene-based nominal p ≤0.01); NR0B1, IGF2R, CALM2, CYP1B1, and GRB2 for ER+ breast cancer (p ≤0.02); and PGR, MAPK3, MAP3K1, and LHCGR for ER- disease (p ≤0.02). Single-SNP tests for SNPs with pairwise linkage disequilibrium r2 <0.8 in the top genes identified 12 common SNPs (in CALM2, CETP, NR0B1, IGF2R, CYP1B1, PGR, MAPK3, and MAP3K1) associated with overall or subtype-specific breast cancer after gene-level correction for multiple testing. Rs11571215 in PGR (progesterone receptor) was the SNP most strongly associated with ER- disease. Conclusion We identified eight genes in hormone pathways that contain common variants associated with breast cancer in AA women after gene-level correction for multiple testing. PMID:26458823
Rodilla, Enrique; Pérez-Lahiguera, Francisco; Costa, José A; González, Carmen; Miralles, Amparo; Moral, Desamparados; Pascual, José María
2009-01-17
The aim of the study was to assess the association of serum uric acid levels with microalbuminuria -urinary albumin excretion (UAE)> or = 30mg/24h-. Cross-sectional study in 429 (220 women) hypertensive, non diabetic, never treated patients (mean age: 47 years) with glomerular filtration rate > or =60ml/min/1.73m(2). The prevalence of microalbuminuria was 20.5%; 18% had hyperuricemia and 47% fulfilled the criteria for metabolic syndrome (MS). Baseline UAE correlated in the unvaried analysis to diastolic blood pressure, waist circumference, high-density lipoprotein cholesterol and uric acid. In multiple linear regression models, only MS (beta=0.113; p=0.03), and serum uric acid values (beta=0.04; p=0.05) were independently associated with logUAE, after adjustment for age and sex. Hyperuricemia (serum uric acid level > or =7.0mg/dl for men and > or =6.5mg/dl for women; odds ratio=2.18; 95% confidence interval, 1.21-3.92; p=0.010), and MS (odds ratio=2.16; 95% confidence interval, 1.32-3.53; p=0.002) were independently associated with a higher risk of microalbuminuria in multiple logistic regression analyses. The prevalence of microalbuminuria was 45.8% in patients with coexistent MS and hyperuricemia, as compared to 13.6% in hypertensive patients without it (p<0.001). In patients with concomitant MS and hyperuricemia the probability of being microalbuminuric was 3.7 times higher than in patients without those factors. Serum uric acid level is associated with microalbuminuria. Coexistence of MS and hyperuricemia in hypertensive patients increases almost 4 times the odds of being microalbuminuric.
Charbonneau, Bridget; Maurer, Matthew J.; Fredericksen, Zachary S.; Zent, Clive S.; Link, Brian K.; Novak, Anne J.; Ansell, Stephen M.; Weiner, George J.; Wang, Alice H.; Witzig, Thomas E.; Dogan, Ahmet; Slager, Susan L.; Habermann, Thomas M.; Cerhan, James R.
2013-01-01
The complement pathway plays a central role in innate immunity, and also functions as a regulator of the overall immune response. We evaluated whether polymorphisms in complement genes are associated with event-free survival (EFS) in follicular (FL) and diffuse large B-cell (DLBCL) lymphoma. We genotyped 167 single nucleotide polymorphisms (SNPs) from 30 complement pathway genes in a prospective cohort study of newly diagnosed FL (N=107) and DLBCL (N=82) patients enrolled at the Mayo Clinic from 2002–2005. Cox regression was used to estimate Hazard Ratios (HRs) for individual SNPs with EFS, adjusting for FLIPI or IPI and treatment. For gene-level analyses, we used a principal components based gene-level test. In gene-level analyses for FL EFS, CFH (p=0.009), CD55 (p=0.006), CFHR5 (p=0.01), C9 (p=0.02), CFHR1 (p=0.03), and CD46 (p=0.03) were significant at p<0.05, and these genes remained noteworthy after accounting for multiple testing (q<0.15). SNPs in CFH, CFHR1, and CFHR5 showed stronger associations among patients receiving any rituximab, while SNPs from CD55 and CD46 showed stronger associations among patients who were observed. For DLBCL, only CLU (p=0.001) and C7 (p=0.03) were associated with EFS, but did not remain noteworthy after accounting for multiple testing (q>0.15). Genes from the Regulators of Complement Activation (CFH, CD55, CFHR1, CFHR5, CD46) at 1q32-q32.1, along with C9, were associated with FL EFS after adjusting for clinical variables, and if replicated, these findings add further support for the role of host innate immunity in FL prognosis. PMID:22718493
Single vs. multiple sets of resistance exercise for muscle hypertrophy: a meta-analysis.
Krieger, James W
2010-04-01
Previous meta-analyses have compared the effects of single to multiple sets on strength, but analyses on muscle hypertrophy are lacking. The purpose of this study was to use multilevel meta-regression to compare the effects of single and multiple sets per exercise on muscle hypertrophy. The analysis comprised 55 effect sizes (ESs), nested within 19 treatment groups and 8 studies. Multiple sets were associated with a larger ES than a single set (difference = 0.10 +/- 0.04; confidence interval [CI]: 0.02, 0.19; p = 0.016). In a dose-response model, there was a trend for 2-3 sets per exercise to be associated with a greater ES than 1 set (difference = 0.09 +/- 0.05; CI: -0.02, 0.20; p = 0.09), and a trend for 4-6 sets per exercise to be associated with a greater ES than 1 set (difference = 0.20 +/- 0.11; CI: -0.04, 0.43; p = 0.096). Both of these trends were significant when considering permutation test p values (p < 0.01). There was no significant difference between 2-3 sets per exercise and 4-6 sets per exercise (difference = 0.10 +/- 0.10; CI: -0.09, 0.30; p = 0.29). There was a tendency for increasing ESs for an increasing number of sets (0.24 for 1 set, 0.34 for 2-3 sets, and 0.44 for 4-6 sets). Sensitivity analysis revealed no highly influential studies that affected the magnitude of the observed differences, but one study did slightly influence the level of significance and CI width. No evidence of publication bias was observed. In conclusion, multiple sets are associated with 40% greater hypertrophy-related ESs than 1 set, in both trained and untrained subjects.
Individual- and Structural-Level Risk Factors for Suicide Attempts Among Transgender Adults.
Perez-Brumer, Amaya; Hatzenbuehler, Mark L; Oldenburg, Catherine E; Bockting, Walter
2015-01-01
This study assessed individual (ie, internalized transphobia) and structural forms of stigma as risk factors for suicide attempts among transgender adults. Internalized transphobia was assessed through a 26-item scale including four dimensions: pride, passing, alienation, and shame. State-level structural stigma was operationalized as a composite index, including density of same-sex couples; proportion of Gay-Straight Alliances per public high school; 5 policies related to sexual orientation discrimination; and aggregated public opinion toward homosexuality. Multivariable logistic generalized estimating equation models assessed associations of interest among an online sample of transgender adults (N = 1,229) representing 48 states and the District of Columbia. Lower levels of structural stigma were associated with fewer lifetime suicide attempts (AOR 0.96, 95% CI 0.92-0.997), and a higher score on the internalized transphobia scale was associated with greater lifetime suicide attempts (AOR 1.18, 95% CI 1.04-1.33). Addressing stigma at multiple levels is necessary to reduce the vulnerability of suicide attempts among transgender adults.
Collins, Charles R; Neal, Jennifer Watling; Neal, Zachary P
2014-12-01
Collective efficacy is defined as residents' perceived collective capacity to take coordinated and interdependent action on issues that affect their lives. This study explored factors associated with neighborhood collective efficacy among residents. Utilizing a national sample of 4,120 urban households provided by Annie E. Casey Foundation's Making Connection Initiative, we investigated the mediating role of residents' perceptions of bonding social capital (i.e. reciprocity, trust, and shared norms) in the association between civic engagement and collective efficacy. Multiple regression analyses revealed that civic engagement and bonding social capital were both directly related to collective efficacy. Additionally, bonding social capital partially mediated the relationship between civic engagement and collective efficacy. Specifically, residents who reported greater levels of civic engagement also reported higher levels of bonding social capital. In turn, residents who reported higher levels of bonding social capital also reported higher levels of neighborhood collective efficacy. We discuss implications of these findings for researchers and practitioners interested in associations of neighborhood collective efficacy.
Fjell, Ylva; Alexanderson, Kristina; Nordenmark, Mikael; Bildt, Carina
2008-01-01
The aim of the present study was to analyze the association between number of working hours, the level of perceived physical strain, work-home interface and musculoskeletal pain and fatigue among women and men employed in the public sector. Cross-sectional data from 1,180 employees (86% women) in 49 public workplaces in 2002-2003 were analyzed. Odds ratios (OR) with 95% confidence intervals (CIs) were used as measures of the associations. The analyses showed differences as well as similarities between women and men. Overall the women reported higher levels of perceived physical strain relative to total workload. A high level of physical strain was strongly associated with musculoskeletal pain and fatigue. Nevertheless, no detrimental effects were observed on health of high total working hours which indicates that a large number of total working hours might be balanced by accompanying multiple roles or many responsibilities and therefore not be generally regarded as risk factors for ill health.
McKay, Gareth J; Loane, Edward; Nolan, John M; Patterson, Christopher C; Meyers, Kristin J; Mares, Julie A; Yonova-Doing, Ekaterina; Hammond, Christopher J; Beatty, Stephen; Silvestri, Giuliana
2013-01-01
Objective To investigate association of scavenger receptor class B, member 1 (SCARB1) genetic variants with serum carotenoid levels of lutein (L) and zeaxanthin (Z) and macular pigment optical density (MPOD). Design A cross-sectional study of healthy adults aged 20-70. Participants 302 participants recruited following local advertisement. Methods MPOD was measured by customized heterochromatic flicker photometry. Fasting blood samples were taken for serum L and Z measurement by HPLC and lipoprotein analysis by spectrophotometric assay. Forty-seven single nucleotide polymorphisms (SNPs) across SCARB1 were genotyped using Sequenom technology. Association analyses were performed using PLINK to compare allele and haplotype means, with adjustment for potential confounding and correction for multiple comparisons by permutation testing. Replication analysis was performed in the TwinsUK and CAREDS cohorts. Main outcome measures Odds ratios (ORs) for macular pigment optical density area, serum lutein and zeaxanthin concentrations associated with genetic variations in SCARB1 and interactions between SCARB1 and sex. Results Following multiple regression analysis with adjustment for age, body mass index, sex, high-density lipoprotein cholesterol (HDLc), low-density lipoprotein cholesterol (LDLc), triglycerides, smoking, dietary L and Z levels, 5 SNPs were significantly associated with serum L concentration and 1 SNP with MPOD (P<0.01). Only the association between rs11057841 and serum L withstood correction for multiple comparisons by permutation testing (P<0.01) and replicated in the TwinsUK cohort (P=0.014). Independent replication was also observed in the CAREDS cohort with rs10846744 (P=2×10−4), a SNP in high linkage disequilibrium with rs11057841 (r2=0.93). No significant interactions by sex were found. Haplotype analysis revealed no stronger association than obtained with single SNP analyses. Conclusions Our study has identified association between rs11057841 and serum L concentration (24% increase per T allele) in healthy subjects, independent of potential confounding factors. Our data supports further evaluation of the role for SCARB1 in the transport of macular pigment and the possible modulation of AMD risk through combating the effects of oxidative stress within the retina. PMID:23562302
Association of Depressed Mood With Herpes Simplex Virus-2 Immunoglobulin-G Levels in Pregnancy.
Hsu, Pao-Chu; Yolken, Robert H; Postolache, Teodor T; Beckie, Theresa M; Munro, Cindy L; Groer, Maureen W
2016-10-01
Depressed mood is common in pregnancy, is associated with stress, and could result in immune suppression that may lead to latent herpes viral reactivation. This study investigated whether depressed mood is associated with higher herpes viral IgG levels in pregnant women. Complete cross-sectional data from 247 pregnant women were available for this substudy. The data included demographics, scores on the Perceived Stress Scale and Profile of Mood States (POMS), and a panel of serum IgG levels for human herpesviruses. Only the herpes simplex virus type 2 (HSV-2) (genital herpes) IgG level was associated with Perceived Stress Scale and POMS-Depression/Dejection (POMS-D) score. Hierarchical multiple regression analysis was used to examine the association of POMS-D with herpesviral IgG levels adjusting for demographic variables. In the final model, African American race (β = .251, p < .001), older age (β = .199, p = .002), single marital status (β = -.304, p < .001), and depressed mood (β = .122, p = .04) were associated with HSV-2 IgG levels. In logistic regression, the strongest correlates of HSV IgG positivity were single marital status, followed by POMS-D scores and African American race. Genital herpes is a concern in pregnancy. Antibody titers may indicate asymptomatic viral shedding, viral reactivation, or primary viral infection. Antibody levels may be higher because of the immune changes during pregnancy and potential immune effects of depressed mood causing reactivation of latent HSV-2.
Incentives and other factors associated with employee participation in health risk assessments.
Taitel, Michael S; Haufle, Vincent; Heck, Debi; Loeppke, Ronald; Fetterolf, Donald
2008-08-01
Investigate factors associated with employee participation rates in health risk assessments. This cross-sectional study using multiple regression analyzed data from 124 employers with 882,275 eligible employees who completed 344,825 health and productivity assessments (HPAs). Incentive value and Communications and Organizational Commitment Level (Com/Org Level) were the strongest predictors of HPA completion rates. Employer size and a Gateway Model were also significant predictors. In addition, a correlation of variables showed other important relationships. To achieve a 50% HPA completion rate, employers with a low Com/Org Level will need an incentive value of approximately $120 whereas employers with a high Com/Org Level only need approximately $40--a difference of $80 dollars. This applied study offers empirical evidence to help employers increase their employees' participation in health risk assessments.
Riley, Richard D; Ensor, Joie; Jackson, Dan; Burke, Danielle L
2017-01-01
Many meta-analysis models contain multiple parameters, for example due to multiple outcomes, multiple treatments or multiple regression coefficients. In particular, meta-regression models may contain multiple study-level covariates, and one-stage individual participant data meta-analysis models may contain multiple patient-level covariates and interactions. Here, we propose how to derive percentage study weights for such situations, in order to reveal the (otherwise hidden) contribution of each study toward the parameter estimates of interest. We assume that studies are independent, and utilise a decomposition of Fisher's information matrix to decompose the total variance matrix of parameter estimates into study-specific contributions, from which percentage weights are derived. This approach generalises how percentage weights are calculated in a traditional, single parameter meta-analysis model. Application is made to one- and two-stage individual participant data meta-analyses, meta-regression and network (multivariate) meta-analysis of multiple treatments. These reveal percentage study weights toward clinically important estimates, such as summary treatment effects and treatment-covariate interactions, and are especially useful when some studies are potential outliers or at high risk of bias. We also derive percentage study weights toward methodologically interesting measures, such as the magnitude of ecological bias (difference between within-study and across-study associations) and the amount of inconsistency (difference between direct and indirect evidence in a network meta-analysis).
Alcohol Use Problems and Sexual Risk among Young Adult African American Mothers
Swartzendruber, Andrea; Sales, Jessica M.; Rose, Eve S.; DiClemente, Ralph J.
2015-01-01
Studies have documented high levels of alcohol use and sexual risk among young mothers. We examined parenting satisfaction and self-efficacy in relation to alcohol use problems and sexual risk among 346 young African American women enrolled in an HIV prevention trial, 41% (n=141) of whom were mothers. Among mothers, greater parenting satisfaction was associated with a reduced likelihood of problematic alcohol use, having multiple sex partners, and testing positive for Trichomonas vaginalis. Relative to non-parenting women, mothers reported lower condom use. Compared to non-parenting women, mothers with the highest parenting satisfaction reported fewer alcohol use problems; mothers with the lowest parenting satisfaction reported lower condom use and were more likely to have multiple partners and test positive for T. vaginalis. Parenting self-efficacy was not associated with the outcomes examined. Future research investigating relationships between parenting satisfaction, alcohol use and sexual risk may be useful for improving multiple maternal health outcomes. PMID:26499334
Multiple Classes of Environmental Chemicals are Associated ...
Biomonitoring of human tissues and fluids has shown that virtually all individuals, worldwide, carry a “body burden” of synthetic chemicals (Thornton et al. 2002; CDC 2009). Although the measurement of an environmental chemical in a person’s tissues or fluids is an indication of exposure, it does not by itself mean that the chemical or the exposure concentration is sufficient to cause a disease or an adverse effect. However, since humans are exposed to multiple chemicals, there may be a combination effect (e.g., additive, synergistic) on health risks associated with exposure even at low levels (Kortenkamp 2008). Further, biomonitoring studies show that humans carry a body burden of multiple classes of contaminants which are often not studied together. We used the 2003-2006 National Health and Nutrition Examination Survey to evaluate the relationship between alanine aminotransferase (ALT) and 53 environmental contaminants across six classes (metals; perfluorinated compounds [PFCs]; phthalates; phenols; coplanar and non-dioxin-like polychlorinated biphenyls [PCBs]) using a novel method.
Reinke, Wendy M; Herman, Keith C; Stormont, Melissa; Newcomer, Lori; David, Kimberly
2013-11-01
Many school-based interventions to promote student mental health rely on teachers as implementers. Thus, understanding the interplay between the multiple domains of fidelity to the intervention and intervention support systems such as coaching and teacher implementation of new skills is an important aspect of implementation science. This study describes a systematic process for assessing multiple domains of fidelity. Data from a larger efficacy trial of the Incredible Years Teacher Classroom Management (IY TCM) program are utilized. Data on fidelity to the IY TCM workshop training sessions and onsite weekly coaching indicate that workshop leaders and the IY TCM coach implemented the training and coaching model with adequate adherence. Further, workshop leaders' ratings of engagement were associated with teacher implementation of specific praise, following training on this content. Lastly, the IY TCM coach differentiation of teacher exposure to coaching was evaluated and found to be associated with teacher implementation of classroom management practices and student disruptive behavior.
Morinaga, Jun; Zhao, Jiabin; Endo, Motoyoshi; Kadomatsu, Tsuyoshi; Miyata, Keishi; Sugizaki, Taichi; Okadome, Yusuke; Tian, Zhe; Horiguchi, Haruki; Miyashita, Kazuya; Maruyama, Nobuhiro; Mukoyama, Masashi; Oike, Yuichi
2018-01-01
Angiopoietin-like proteins (ANGPTLs) 3, 4, and 8 reportedly contribute to progression of metabolic disease, a risk factor for cardiovascular disease (CVD). The purpose of this study was to investigate whether circulating ANGPTL levels are associated with CVD risk after adjustment for potential confounding factors. We conducted a single center, cross-sectional study of 988 Japanese subjects undergoing routine health checks. Serum ANGPTL3, 4, and 8 levels were measured using an enzyme-linked immunosorbent assay. Using multiple regression analysis we evaluated potential association of circulating ANGPTL3, 4, and 8 levels with general medical status including age, sex, smoking, drinking, obesity, hypertension, impaired glycometabolism, dyslipidemia, hyperuricemia, hepatic impairment, chronic kidney disease, anemia, cardiac abnormality, and inflammation. Circulating ANGPTL3 levels were relatively high in health-related categories of hepatic impairment and inflammation. Circulating ANGPTL4 levels were also significantly high in impaired glycometabolism or hepatic impairment but decreased in inflammation. Finally, increased ANGPTL8 levels were observed in obesity, impaired glycometabolism and dyslipidemia. Particularly, increased levels of circulating ANGPTL8 were positively correlated with circulating triglycerides and LDL-cholesterol levels and inversely correlated with circulating HDL-cholesterol levels. Circulating ANGPTL3, 4, and 8 levels reflect some risk factors for CVD development.
2015-01-01
Introduction. There is an increasing body of literature relating musculoskeletal diseases to both job physical exposures and psychosocial outcomes. Relationships between job physical exposure measures and psychosocial factors have not been well examined or quantified. These exploratory analyses evaluate relationships between quantified exposures and psychosocial outcomes. Methods. Individualized quantification of duration, repetition, and force and composite scores of the Strain Index (SI) and the Threshold Limit Value for Hand Activity Level (TLV for HAL) were compared to 10 psychosocial measures. Relationships and predicted probabilities were assessed using ordered logistic regression. Analyses were adjusted for age, BMI, and gender. Results and Discussion. Among 1834 study participants there were multiple statistically significant relationships. In general, as duration, repetition, and force increased, psychosocial factors worsened. However, general health and mental exhaustion improved with increasing job exposures. Depression was most strongly associated with increased repetition, while physical exhaustion was most strongly associated with increased force. SI and TLV for HAL were significantly related to multiple psychosocial factors. These relationships persisted after adjustment for strong confounders. Conclusion. This study quantified multiple associations between job physical exposures and occupational and nonoccupational psychosocial factors. Further research is needed to quantify the impacts on occupational health outcomes. PMID:26557686
Coelho, Andreia; Dias, Alexandra; Morais, Anabela; Nunes, Baltazar; Ferreira, Emanuel; Picanço, Isabel; Faustino, Paula; Lavinha, João
2014-03-01
Chronic haemolysis stands out as one of the hallmarks of sickle cell anaemia, a clinically heterogeneous autosomal recessive monogenic anaemia. However, the genetic architecture of this sub-phenotype is still poorly understood. Here, we report the results of an association study between haemolysis biomarkers (serum LDH, total bilirubin and reticulocyte count) and the inheritance of 41 genetic variants of ten candidate genes in a series of 99 paediatric SS patients (median current age of 9.9 yr) followed up in two general hospitals in Greater Lisboa area (median follow-up per patient of 5.0 yr). Although in a large number of tests a seemingly significant (i.e. P < 0.05) association was observed, the following ones were confirmed upon correction for multiple comparisons: (i) an increased serum LDH level was associated with haplotype 7 within VCAM1 gene; (ii) a lower total bilirubin was associated with the 3.7-kb deletion at HBA gene, rs2070744_T allele at NOS3 gene, and haplotype 9 within VCAM1 promoter; and (iii) a diminished reticulocyte count was associated with the 3.7-kb deletion at HBA, whereas an increased count was associated with rs1984112_G allele at CD36 gene. On the whole, our findings suggest a complex genetic architecture for the sickle cell anaemia haemolysis process involving multiple pathways, namely control of vascular cell adhesion, NO synthesis and erythrocyte volume and haemoglobinisation. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
Trinh, Oanh Thi Hoang; Oh, Juhwan; Choi, Sugy; To, Kien Gia; Van Do, Dung
2016-01-01
Understanding factors associated with domestic violence-supportive attitudes among Vietnamese women is important for designing effective policies to prevent this behavior. Previous studies have largely overlooked risk factors associated with domestic violence-supportive attitudes by women in Vietnam. This paper explores and identifies socioeconomic factors that contribute to domestic violence-supportive attitudes among Vietnamese women using data from the Multiple Indicator Cluster Surveys (MICS). Secondary data from two cross-sectional studies (MICS 3, 2006, and MICS 4, 2011) with representative samples (9,471 and 11,663 women, respectively) in Vietnam were analyzed. The prevalence of supportive attitudes toward domestic violence and associations with age, residence region, area, education level, household wealth index, ethnicity, and marital status were estimated using descriptive statistics and multivariate Poisson models, giving estimates of relative risk. Overall, the prevalence of acceptance of domestic violence declined between 2006 and 2011 in Vietnam (65.1% vs. 36.1%). Socioeconomic factors associated with women's condoning of domestic violence were age, wealth, education level, and living area. In particular, younger age and low educational attainment were key factors associated with violence-supportive attitudes, and these associations have become stronger over time. Higher educational attainment in women is an important predictor of women's attitudes toward domestic violence. To date, Doi Moi and the Vietnamese government's commitment to the Millennium Development Goals may have positively contributed to lowering the acceptance of domestic violence. Tailored interventions that focus on education will be important in further changing attitudes toward domestic violence.
Ghrelin level negatively predicts quality of life in obese women.
Lu, P H; Song, Y L; Hsu, C H
2017-02-01
A cross-sectional cohort study was conducted to investigate whether ghrelin level in obese women predicts the quality of life (QOL). A total of 307 subjects fulfilled the criteria: (1) age between 20 and 65 years old, (2) body mass index ≥27 kg/m 2 (3) waist circumference ≥80 cm were enrolled in the study. All subjects were assigned to one of the plasma ghrelin level categories according to the quartiles. The median of age and BMI of the 307 obese women were 45 ± 18 years and 29.9 ± 4.1 kg/m 2 , respectively. The main outcome evaluated is the associations of plasma ghrelin level and QOL, which were evaluated using multiple linear regression analysis. Results of linear trend test show significant statistical difference in plasma lipoproteins (triglyceride, cholesterol, HDL-cholestero and LDL-cholesterol = and levels of obesity-related hormone peptides, including leptin, adiponectin, insulin among quartiles of ghrelin. Multiple liner regression analysis of serum obesity-related hormone peptide level and QOL using stepwise method shows ghrelin concentration was the only predictor of QOL, including PCS-12 level (β = -0.18, p = 0.001), MCS-12 level (β = -0.14, p = 0.009), WHOQOL-BREF scores: physical (β = -0.13, p = 0.03), psychological (β = -0.16, p = 0.007), social (β = -0.21, p = < 0.001), and environmental (β = -0.22, p = <0.001), after adjusting other factors for obese female subjects. This study demonstrated that ghrelin concentration is strongly associated with QOL level among obese women. Hence, ghrelin concentration might be a valuable marker to be monitored in obese women.
The importance of personality and life-events in anxious depression: from trait to state anxiety.
van der Veen, Date C; van Dijk, Silvia D M; Comijs, Hannie C; van Zelst, Willeke H; Schoevers, Robert A; Oude Voshaar, Richard C
2017-11-01
Anxious depression is associated with severe impairment and bad prognoses. We hypothesize that recent life-events are associated with more anxiety in late-life depression and that this is conditional upon the level of certain personality traits. Baseline data of the Netherlands Study of Depression in Older Persons (NESDO) were used. In 333 patients (≥60 years) suffering from a major depressive disorder, anxiety was assessed with the BAI, personality traits with the NEO-FFI and the Mastery Scale, and life-events with the Brugha questionnaire. Multiple linear regression analyses were applied with anxiety severity as dependent and life-events and personality traits as independent variables. 147 patients (44.1%) had recently experienced one or more life-events. The presence of a life-event is not associated with anxiety (p = .161) or depression severity (p = .440). However, certain personality traits interacted with life-events in explaining anxiety severity. Stratified analyses showed that life-events were associated with higher anxiety levels in case of high levels of neuroticism and openness and low levels of conscientiousness or mastery. In the face of a life-event, personality traits may play a central role in increased anxiety levels in late-life depression.
Gonzales, Nancy A.; Fuligni, Andrew J.
2014-01-01
School bullying incidents, particularly experiences with victimization, are a significant social and health concern among adolescents. The current study extended past research by examining the daily peer victimization experiences of Mexican-American adolescents and examining how chronic (mean-level) and episodic (daily-level) victimization incidents at school are associated with psychosocial, physical and school adjustment. Across a two-week span, 428 ninth and tenth grade Mexican-American students (51 % female) completed brief checklists every night before going to bed. Hierarchical linear model analyses revealed that, at the individual level, Mexican-American adolescents’ who reported more chronic peer victimization incidents across the two-weeks also reported heightened distress and academic problems. After accounting for adolescent’s mean levels of peer victimization, daily victimization incidents were associated with more school adjustment problems (i.e., academic problems, perceived role fulfillment as a good student). Additionally, support was found for the mediation model in which distress accounts for the mean-level association between peer victimization and academic problems. The results from the current study revealed that everyday peer victimization experiences among Mexican-American high school students have negative implications for adolescents’ adjustment, across multiple domains. PMID:23238764
2010-01-01
Background Advanced HIV infection can result in lipoatrophy and wasting, even in the absence of ongoing opportunistic infections, suggesting that HIV may directly affect adipose tissue amount and distribution. Methods We assessed the relationship of fat (measured using anthropometry, DEXA, MRI scans) or markers related to glucose and lipid metabolism with viral load in a cross-sectional sample of 83 antiretroviral-naïve HIV-1-infected South African women. A multivariable linear model was fitted to log10VL to assess the combined effect of these variables. Results In addition to higher T cell activation, women with viral load greater than the population median had lower waist circumference, body mass index and subcutaneous abdominal fat, as well as lower serum leptin. We demonstrate that leptin serum levels are inversely associated with viral replication, independent of the amount of adipose tissue. This association is maintained after adjusting for multiple variables associated with disease progression (i.e., cellular activation and innate immunity effector levels). Conclusions Our results demonstrate that serum leptin levels are inversely associated with viral replication, independent of disease progression: we postulate that leptin may affect viral replication. PMID:20822522
Degarege, A; Animut, A; Medhin, G; Legesse, M; Erko, B
2014-06-01
In this cross-sectional study, the associations between helminth infections and ABO blood group, anaemia and undernutrition were investigated in 480 febrile outpatients who visited Dore Bafeno Health Centre, southern Ethiopia, in December 2010. Stool specimens were processed using the Kato-Katz method and examined for intestinal helminth infections. Haemoglobin level was measured using a HemoCue machine and blood group was determined using an antisera haemagglutination test. Nutritional status of the study participants was assessed using height and weight measurements. Among the study participants, 50.2% were infected with intestinal helminths. Ascaris lumbricoides (32.7%), Trichuris trichiura (12.7%), Schistosoma mansoni (11.9%) and hookworm (11.0%) were the most frequently diagnosed helminths. The odds of infection and mean eggs per gram of different intestinal helminth species were comparable between the various blood groups. Among individuals who were infected with intestinal helminth(s), the mean haemoglobin level was significantly lower in individuals harbouring three or more helminth species and blood type AB compared to cases with double or single helminth infection and blood type O, respectively. The odds of being underweight was significantly higher in A. lumbricoides and T. trichiura infected individuals of age ≤ 5 and ≥ 20 years, respectively, when compared to individuals of the matching age group without intestinal helminths. In conclusion, infection with multiple intestinal helminths was associated with lower haemoglobin level, which was more severe in individuals with blood type AB. Future studies should focus on mechanisms by which blood group AB exacerbates the helminth-related reduction in mean haemoglobin level.
Girard, Lisa-Christine; Côté, Sylvana M.; de Lauzon-Guillain, Blandine; Dubois, Lise; Falissard, Bruno; Forhan, Anne; Doyle, Orla; Bernard, Jonathan Y.; Heude, Barbara; Saurel-Cubizolles, Marie-Josephe; Kaminski, Monique; Boivin, Michel; Tremblay, Richard E.
2016-01-01
Background Breastfeeding is associated with multiple domains of health for both mothers and children. Nevertheless, breastfeeding initiation is low within certain developed countries. Furthermore, comparative studies of initiation rates using harmonised data across multiple regions is scarce. Objective The aim of the present study was to investigate and compare individual-level determinants of breastfeeding initiation using two French-speaking cohorts. Methods Participants included ~ 3,900 mothers enrolled in two cohort studies in Canada and France. Interviews, questionnaires, and medical records were utilised to collect information on maternal, family, and medical factors associated with breastfeeding initiation. Results Rates of breastfeeding initiation were similar across cohorts, slightly above 70%. Women in both Canada and France who had higher levels of maternal education, were born outside of their respective countries and who did not smoke during pregnancy were more likely to initiate breastfeeding with the cohort infant. Notably, cohort effects of maternal education at the university level were found, whereby having ‘some university’ was not statistically significant for mothers in France. Further, younger mothers in Canada, who delivered by caesarean section and who had previous children, had reduced odds of breastfeeding initiation. These results were not found for mothers in France. Conclusions and Implications for Practice While some similar determinants were observed, programming efforts to increase breastfeeding initiation should be tailored to the characteristics of specific geographical regions which may be heavily impacted by the social, cultural and political climate of the region, in addition to individual and family level factors. PMID:27902741
Onyango, Patrick Ogola; Gesquiere, Laurence R.; Altmann, Jeanne; Alberts, Susan C.
2012-01-01
Testosterone (T) is often positively associated with male sexual behavior and negatively associated with paternal care. These associations have primarily been demonstrated in species where investment in paternal care begins well after mating activity is complete, when offspring are hatched or born. Different patterns may emerge in studies of species where investment in mating and paternal care overlap temporally, for instance in non-seasonal breeders in which males mate with multiple females sequentially and may simultaneously have multiple offspring of different ages. In a 9-year data set on levels of T in male baboons, fecal concentrations of T (fT) were positively associated with both mate guarding (“consortship”) – a measure of current reproductive activity – and with the number of immature offspring a male had in his social group – a measure of past reproductive activity and an indicator of likely paternal behavior. To further examine the relationship between T and potential paternal behavior, we next drew on an intensive 8-month study of male behavior, and found that fathers were more likely to be in close proximity to their offspring than expected by chance. Because male baboons are known to provide paternal care, and because time in proximity to offspring would facilitate such care, this suggests that T concentrations in wild male baboons may be associated with both current reproductive activity and with current paternal behavior. These results are consistent with the predicted positive association between T a mating effort but not nd with a negative association between T a paternal care; in male baboons, high levels of nd T occur in males that are differentially associating with their offspring. PMID:23206991
Watanabe, Kazuhiro; Otsuka, Yasumasa; Inoue, Akiomi; Sakurai, Kenji; Ui, Akiko; Nakata, Akinori
2016-08-01
Physical inactivity is one of the major risk factors for dyslipidemia and coronary heart disease. Job resources have been identified as determinants of employees' vigor and physical activity habits. Our first purpose was to comprehensively analyze the series of relationships of job resources, through vigor and exercise habit (i.e., one aspect of physical activity), to serum lipid levels in a sample of Japanese employees in a manufacturing company. Our second purpose was to investigate sex differences in these relationships using a multiple-group path analysis. Data were collected from 4543 employees (men = 4018, women = 525) during a medical checkup conducted in February and March 2012. Job resources (job control, skill utilization, suitable jobs, and meaningfulness of work), vigor, exercise habit, triglyceride, high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) were measured cross-sectionally. Job resources and vigor were positively associated with exercise habit in both sexes. Exercise habit was inversely associated with triglyceride (-0.03 in men and -0.01 in women, ps < 0.05) and LDL-C (-0.07 in both sexes, ps < 0.05). HDL-C was positively associated with exercise habit (0.03 in both sexes, ps < 0.05). There was no significant difference by sex in path coefficients, except for the covariance between suitable jobs and meaningfulness of work. Higher levels of job resources were associated with greater vigor, leading to exercise habit, which in turn, improved serum lipid levels. Longitudinal studies are required to demonstrate causality.
Yorkston, Kathryn M; Baylor, Carolyn; Amtmann, Dagmar
2014-01-01
Individuals with multiple sclerosis (MS) are at risk for communication problems that may restrict their ability to take participation in important life roles such as maintenance of relationships, work, or household management. The aim of this project is to examine selected demographic and symptom-related variables that may contribute to participation restrictions. This examination is intended to aid clinicians in predicting who might be at risk for such restrictions and what variables may be targeted in interventions. Community-dwelling adults with MS (n=216) completed a survey either online or using paper forms. The survey included the 46-item version of the Communicative Participation Item Bank, demographics (age, sex, living situation, employment status, education, and time since onset of diagnosis of MS), and self-reported symptom-related variables (physical activity, emotional problems, fatigue, pain, speech severity, and cognitive/communication skills). In order to identify predictors of restrictions in communicative participation, these variables were entered into a backwards stepwise multiple linear regression analysis. Five variables (cognitive/communication skills, speech severity, speech usage, physical activity, and education) were statistically significant predictors of communication participation. In order to examine the relationship of communicative participation and social role variables, bivariate Spearman correlations were conducted. Results suggest only a fair to moderate relationship between communicative participation and measures of social roles. Communicative participation is a complex construct associated with a number of self-reported variables. Clinicians should be alert to risk factors for reduced communicative participation including reduced cognitive and speech skills, lower levels of speech usage, limitations in physical activities and higher levels of education. The reader will be able to: (a) describe the factors that may restrict participation in individuals with multiple sclerosis; (b) list measures of social functioning that may be pertinent in adults with multiple sclerosis; (c) discuss factors that can be used to predict communicative participation in multiple sclerosis. Copyright © 2014 Elsevier Inc. All rights reserved.
Park, Susan; Lee, Sejin; Hwang, Jinseub; Kwon, Jin-Won
2017-01-01
Background/objectives Weight perception, especially misperception, might affect health-related quality of life (HRQoL); however, related research is scarce and results remain equivocal. We examined the association between HRQoL and weight misperception by comparing obesity level as measured by body mass index (BMI) and weight perception in Korean adults. Methods Study subjects were 43 883 adults aged 19 years or older from cycles IV (2007–2009), V (2010–2012) and VI (2013–2014) of the Korean National Health and Nutrition Examination Survey. Multiple regression analyses comprising both logit and tobit models were conducted to evaluate the independent effect of obesity level as measured by BMI, weight perception and weight misperception on HRQoL after adjusting for demographics, socioeconomic status and number of chronic diseases. We also performed multiple regressions to explore the association between weight misperception and HRQoL stratified by BMI status. Results Obesity level as measured by BMI and weight perception were independently associated with low HRQoL in both separate and combined analyses. Weight misperception, including underestimation and overestimation, had a significantly negative impact on HRQoL. In subgroup analysis, subjects with BMI ranges from normal to overweight who misperceived their weight also had a high risk of low HRQoL. Overestimation of weight among obese subjects associated with low HRQoL, whereas underestimation of weight showed no significant association. Conclusions Both obesity level as measured by BMI and perceiving weight as fat were significant risk factors for low HRQoL. Subjects who incorrectly perceived their weight relative to their BMI status were more likely to report impaired HRQoL, particularly subjects with BMI in the normal to overweight range. Based on these findings, we recommend political and clinical efforts to better inform individuals about healthy weight status and promote accurate weight perception. PMID:28645975
2013-01-01
Background There are inconsistencies in the determinants of adherence to antiretrovirals (ARVs) across settings as well as a lack of studies that take into consideration factors beyond the individual level. This makes it necessary to examine factors holistically in multiple settings and populations while taking into consideration the particularities of each context, in order to understand the patterns of ARV adherence. This research explored ARV adherence and individual, relational and environmental-structural factors. Methods A cross-sectional survey was conducted from August 2008 through July 2009 among participants currently on ARVs recruited from 6 public health clinics, selected to maximize diversity in terms of caseload and location, representing the range of clinics within Rio de Janeiro city, Brazil. Multivariate logistic regression analysis was used to assess the association between our multilevel factors with ARV adherence among participants with complete cases (n = 632). Results Eighty-four percent of respondents reported adherence to all of their ARV doses in the last 4 days. Of the socio-demographic variables, those who had one child were positively associated with adherence (AOR 2.29 CI [1.33-3.94]). On the relational level, those with high social support (AOR 2.85 CI [1.50-5.41]) were positively associated with adherence to ARVs. On the environmental-structural level, we found gender was significant with women negatively associated with adherence to ARVs (AOR 0.58 CI [0.38-0.88]) while those with a high asset index (AOR 2.47 CI [1.79-3.40]) were positively associated with adherence to ARVs. Conclusions This research highlights the importance of examining the multiple levels of influence on ARV adherence. Intervention research in lower and middle-income settings should address and evaluate the impact of attending to both gender and economic inequalities to improve ARV adherence, as well as relational areas such as the provision of social support. PMID:23758780
Study of process variables associated with manufacturing hermetically-sealed nickel-cadmium cells
NASA Technical Reports Server (NTRS)
Miller, L.; Doan, D. J.; Carr, E. S.
1971-01-01
A program to determine and study the critical process variables associated with the manufacture of aerospace, hermetically-sealed, nickel-cadmium cells is described. The determination and study of the process variables associated with the positive and negative plaque impregnation/polarization process are emphasized. The experimental data resulting from the implementation of fractional factorial design experiments are analyzed by means of a linear multiple regression analysis technique. This analysis permits the selection of preferred levels for certain process variables to achieve desirable impregnated plaque characteristics.
Yan, Pi-Jun; Xu, Yong; Wan, Qin; Feng, Jian; Li, Hua; Gao, Chen-Lin; Yang, Jun; Zhong, Hai-Hua; Zhang, Zhi-Hong
2017-12-01
Inflammation has been reported to be involved in the pathogenesis of atherosclerosis. This principal objective of this study was to investigate if the secretion of neuregulin 4 (Nrg4), a soluble protein associated with metabolic syndrome and subclinical cardiovascular disease, is correlated with the inflammation marker high-sensitivity C-reactive protein (hs-CRP) in patients with newly diagnosed type 2 diabetes mellitus (nT2DM). A study group of 311 nT2DM patients was divided into three subgroups based on hs-CRP tertiles. Multiple linear regression was conducted to explore the association between plasma Nrg4 and hs-CRP levels. The nT2DM patients with the highest hs-CRP levels (>2.46 mg/L) exhibited higher atherogenic coefficients and atherogenic index of plasma (AIP) levels, but lower levels of plasma Nrg4, as compared to those with the lowest hs-CRP levels (<0.63 mg/L). Plasma Nrg4 levels were inversely associated with white blood cell count, hs-CRP, and AIP and positively associated with high-density lipoprotein cholesterol (HDL-C), before and after adjustment for age, gender, body mass index (BMI), and body fat percentage (P < 0.01 or P < 0.05). hs-CRP was the factor most strongly associated with plasma Nrg4 levels. These results indicate that lower plasma Nrg4 levels may be associated with elevated hs-CRP in nT2DM patients. It generates the hypothesis that decreased levels of Nrg4 may trigger the development of atherosclerosis through its proinflammatory effects. These findings need to be confirmed by further prospective studies.
Green, Cori M; Berkule, Samantha B; Dreyer, Benard P; Fierman, Arthur H; Huberman, Harris S; Klass, Perri E; Tomopoulos, Suzy; Yin, Hsiang Shonna; Morrow, Lesley M; Mendelsohn, Alan L
2009-09-01
To determine whether maternal literacy level accounts for associations between educational level and the cognitive home environment in low-income families. Analysis of 369 mother-infant dyads participating in a long-term study related to early child development. Urban public hospital. Low-income mothers of 6-month-old infants. Maternal literacy level was assessed using the Woodcock-Johnson III/Bateria III Woodcock-Munoz Tests of Achievement, Letter-Word Identification Test. Maternal educational level was assessed by determining the last grade that had been completed by the mother. The cognitive home environment (provision of learning materials, verbal responsivity, teaching, and shared reading) was assessed using StimQ, an office-based interview measure. In unadjusted analyses, a maternal literacy level of ninth grade or higher was associated with increases in scores for the overall StimQ and each of 4 subscales, whereas a maternal educational level of ninth grade or higher was associated with increases in scores for the overall StimQ and 3 of 4 subscales. In simultaneous multiple linear regression models including both literacy and educational levels, literacy continued to be associated with scores for the overall StimQ (adjusted mean difference, 3.7; 95% confidence interval, 1.7-5.7) and all subscales except teaching, whereas maternal educational level was no longer significantly associated with scores for the StimQ (1.8; 0.5-4.0) or any of its subscales. Literacy level may be a more specific indicator of risk than educational level in low-income families. Studies of low-income families should include direct measures of literacy. Pediatricians should develop strategies to identify mothers with low literacy levels and promote parenting behaviors to foster cognitive development in these at-risk families.
Wu, Chen; Yang, Handong; Yu, Dianke; Yang, Xiaobo; Zhang, Xiaomin; Wang, Yiqin; Sun, Jielin; Gao, Yong; Tan, Aihua; He, Yunfeng; Zhang, Haiying; Qin, Xue; Zhu, Jingwen; Li, Huaixing; Lin, Xu; Zhu, Jiang; Min, Xinwen; Lang, Mingjian; Li, Dongfeng; Zhai, Kan; Chang, Jiang; Tan, Wen; Yuan, Jing; Chen, Weihong; Wang, Youjie; Wei, Sheng; Miao, Xiaoping; Wang, Feng; Fang, Weimin; Liang, Yuan; Deng, Qifei; Dai, Xiayun; Lin, Dafeng; Huang, Suli; Guo, Huan; Lilly Zheng, S.; Xu, Jianfeng; Lin, Dongxin; Hu, Frank B.; Wu, Tangchun
2013-01-01
Plasma lipid levels are important risk factors for cardiovascular disease and are influenced by genetic and environmental factors. Recent genome wide association studies (GWAS) have identified several lipid-associated loci, but these loci have been identified primarily in European populations. In order to identify genetic markers for lipid levels in a Chinese population and analyze the heterogeneity between Europeans and Asians, especially Chinese, we performed a meta-analysis of two genome wide association studies on four common lipid traits including total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL) and high-density lipoprotein cholesterol (HDL) in a Han Chinese population totaling 3,451 healthy subjects. Replication was performed in an additional 8,830 subjects of Han Chinese ethnicity. We replicated eight loci associated with lipid levels previously reported in a European population. The loci genome wide significantly associated with TC were near DOCK7, HMGCR and ABO; those genome wide significantly associated with TG were near APOA1/C3/A4/A5 and LPL; those genome wide significantly associated with LDL were near HMGCR, ABO and TOMM40; and those genome wide significantly associated with HDL were near LPL, LIPC and CETP. In addition, an additive genotype score of eight SNPs representing the eight loci that were found to be associated with lipid levels was associated with higher TC, TG and LDL levels (P = 5.52×10-16, 1.38×10-6 and 5.59×10-9, respectively). These findings suggest the cumulative effects of multiple genetic loci on plasma lipid levels. Comparisons with previous GWAS of lipids highlight heterogeneity in allele frequency and in effect size for some loci between Chinese and European populations. The results from our GWAS provided comprehensive and convincing evidence of the genetic determinants of plasma lipid levels in a Chinese population. PMID:24386095
Mirshafiey, Abbas; Jadidi-Niaragh, Farhad
2010-06-01
Multiple sclerosis (MS) is a chronic inflammatory disease that involves central nervous system, and is generally associated with demyelination and axonal lesion. The effective factors for initiation of the inflammatory responses have not been known precisely so far. Leukotrienes (LTs) are inflammatory mediators with increased levels in the cerebrospinal fluid of MS patients and in experimental models of multiple sclerosis. Inhibition of LT receptors with specific antagonists can decrease inflammatory responses. In this review article we try to clarify the role of LT receptor antagonists and also inhibitors of enzymes which are involved in LTs generating pathway for treating multiple sclerosis as new targets for MS therapy. Moreover, we suggest that blockage of LT receptors by potent specific antagonists and/or agonists can be as a novel useful method in treatment of MS.
Williams, Ann Houston; Smith, James Travis; Hudgens, Edward E; Rhoney, Scott; Ozkaynak, Halûk; Hamilton, Robert G; Gallagher, Jane E
2011-09-01
Home exposure to allergens is an important factor in the development of sensitization and subsequent exacerbations of allergic asthma. We investigated linkages among allergen exposure, immunological measurements, and asthma by examining (1) reservoir dust allergen levels in homes, (2) associations between presence of allergens in homes and sensitization status of resident children, and (3) associations between asthma status and total IgE, atopy (by Phadiatop), and positive allergen-specific tests. The study protocol was approved by Institutional Review Boards (IRBs) of the University of North Carolina Chapel Hill; Westat, Inc.; and the US Environmental Protection Agency Human Research Protocol Office. Data were collected from questionnaires, serum analyses, and household vacuum dust. Children (n = 205) were predominately African American (AA) (85.4%) and 51.6% were asthmatic. Sera from 185 children and home dust samples (n = 141) were analyzed for total and specific IgE antibodies to allergens from cat and dog dander, cockroach, dust mites, mice, rats, and molds. Sixty percent of the homes had detectable levels of three or more dust allergens. The proportions of children with positive allergen-specific IgE tests were dust mite (32%), dog (28%), cat (23%), cockroach (18%), mouse (5%), rat (4%), and molds (24-36%). Children testing positive to a single allergen also had positive responses to other allergens. Those children with positive serum tests for cat, dog, and dust mite lived in homes with detectable levels of cat (51%), dog (90%), and dust mite (Der f 1) (92%) allergens. Correlations between children's specific IgE levels and dust levels were linearly related for dog (p < .04), but not for cat (p = .12) or dust mite (Der f 1) (p = .21). Odds ratios (95% CI) for the associations between asthma and serum-specific IgE were over 1.0 for cat, dog, dust mite (Der f 1), cockroach, and four types of molds. House dust allergen exposure levels, however, exhibited no differences between asthmatic and non-asthmatic homes. Both the co-occurrence of multiple allergens in dust and the high frequency of multiple allergen sensitizations indicate that a broad-based intervention aimed at reducing multiple allergens (pets, pests, and molds) would be more successful than any approach that aimed at reducing one type of allergen.
Holstein, Bjørn E; Currie, Candace; Boyce, Will; Damsgaard, Mogens T; Gobina, Inese; Kökönyei, Gyöngyi; Hetland, Jørn; de Looze, Margaretha; Richter, Matthias; Due, Pernille
2009-09-01
To use comparable data from many countries to examine 1) socio-economic inequality in multiple health complaints among adolescents, 2) whether the countries' absolute wealth and economic inequality was associated with symptom load among adolescents, and 3) whether the countries' absolute wealth and economic inequality explained part of the individual level socio-economic variation in health complaints. The Health Behaviour in School-aged Children (HBSC) international study from 2005/06 provided data on 204,534 11-, 13- and 15-year old students from nationally random samples of schools in 37 countries in Europe and North America. The outcome measure was prevalence of at least two daily health complaints, measured by the HBSC Symptom Check List. We included three independent variables at the individual level (sex, age group, family affluence measured by the Family Affluence Scale FAS) and two macro level measures on the country's economic situation: wealth measured by Gross National Product (GNP) and distribution of income measured by the Gini coefficient. There was a significant socio-economic variation in health complaints in 31 of the 37 countries. The overall OR (95 % CI) for 2+ daily health complaints for all countries was 1.31 (1.27-1.36) in the medium versus high FAS group and 2.07 (2.00-2.14) in the low versus high FAS group. This socio-economic gradient in health complaints attenuated somewhat in the multilevel models which included macro level data. There was no association between GNP and health complaints. The OR for high symptom load was 1.35 (1.08-1.69) per 10 % increase in Gini coefficient. The socio-economic gradient in health complaints at the individual level was somewhat attenuated in the multilevel models which included macro level data. There was a significant association between low FAS and high level of health complaints in 30 of 37 countries. Health complaints increased significantly by increasing income inequality in the country.
2013-01-01
Background Among life-style factors affecting mental health, dietary habits are becoming a public health concern in their relation to psychological distress and social capital. We examined associations between interest in dietary pattern, social capital, and psychological distress with a population-based cross-sectional study in rural Japan. Methods A total of 16,996 residents of a rural town in northern Japan aged 30–79 years participated in this questionnaire survey. The questionnaire gathered data about socio-demographic variables, psychological distress, issues related to dietary habits, including interest in dietary pattern, and the social capital factors of reciprocity and sense of community belonging. Factors related to psychological distress were analyzed by using multiple logistic regression analysis. Results A high interest in dietary pattern was significantly associated with a high level of social capital. In addition, an association between interest in dietary pattern and frequencies of intake of vegetables and fruits was confirmed. The multiple logistic regression analyses showed significant associations between interest in dietary pattern, social capital, frequency of intake of vegetables, and psychological distress after adjusting for socio-demographic variables. Low interest in dietary pattern was positively associated with psychological distress after adjusting for socio-demographic variables (OR = 2.18; 95%CI: 1.69-2.81). Low levels of both reciprocity and sense of community belonging were associated with psychological distress after adjusting for socio-demographic variables (OR = 3.46 with 95%CI of 2.10–5.71 for reciprocity, and OR = 7.42 with 95%CI of 4.64–11.87 for sense of community belonging). Conclusion Low interest in dietary pattern, low frequency of intake of vegetables, and low levels of social capital were significantly associated with psychological distress after adjusting for socio-demographic variables. PMID:24099097
Pleiotropy Analysis of Quantitative Traits at Gene Level by Multivariate Functional Linear Models
Wang, Yifan; Liu, Aiyi; Mills, James L.; Boehnke, Michael; Wilson, Alexander F.; Bailey-Wilson, Joan E.; Xiong, Momiao; Wu, Colin O.; Fan, Ruzong
2015-01-01
In genetics, pleiotropy describes the genetic effect of a single gene on multiple phenotypic traits. A common approach is to analyze the phenotypic traits separately using univariate analyses and combine the test results through multiple comparisons. This approach may lead to low power. Multivariate functional linear models are developed to connect genetic variant data to multiple quantitative traits adjusting for covariates for a unified analysis. Three types of approximate F-distribution tests based on Pillai–Bartlett trace, Hotelling–Lawley trace, and Wilks’s Lambda are introduced to test for association between multiple quantitative traits and multiple genetic variants in one genetic region. The approximate F-distribution tests provide much more significant results than those of F-tests of univariate analysis and optimal sequence kernel association test (SKAT-O). Extensive simulations were performed to evaluate the false positive rates and power performance of the proposed models and tests. We show that the approximate F-distribution tests control the type I error rates very well. Overall, simultaneous analysis of multiple traits can increase power performance compared to an individual test of each trait. The proposed methods were applied to analyze (1) four lipid traits in eight European cohorts, and (2) three biochemical traits in the Trinity Students Study. The approximate F-distribution tests provide much more significant results than those of F-tests of univariate analysis and SKAT-O for the three biochemical traits. The approximate F-distribution tests of the proposed functional linear models are more sensitive than those of the traditional multivariate linear models that in turn are more sensitive than SKAT-O in the univariate case. The analysis of the four lipid traits and the three biochemical traits detects more association than SKAT-O in the univariate case. PMID:25809955
Pleiotropy analysis of quantitative traits at gene level by multivariate functional linear models.
Wang, Yifan; Liu, Aiyi; Mills, James L; Boehnke, Michael; Wilson, Alexander F; Bailey-Wilson, Joan E; Xiong, Momiao; Wu, Colin O; Fan, Ruzong
2015-05-01
In genetics, pleiotropy describes the genetic effect of a single gene on multiple phenotypic traits. A common approach is to analyze the phenotypic traits separately using univariate analyses and combine the test results through multiple comparisons. This approach may lead to low power. Multivariate functional linear models are developed to connect genetic variant data to multiple quantitative traits adjusting for covariates for a unified analysis. Three types of approximate F-distribution tests based on Pillai-Bartlett trace, Hotelling-Lawley trace, and Wilks's Lambda are introduced to test for association between multiple quantitative traits and multiple genetic variants in one genetic region. The approximate F-distribution tests provide much more significant results than those of F-tests of univariate analysis and optimal sequence kernel association test (SKAT-O). Extensive simulations were performed to evaluate the false positive rates and power performance of the proposed models and tests. We show that the approximate F-distribution tests control the type I error rates very well. Overall, simultaneous analysis of multiple traits can increase power performance compared to an individual test of each trait. The proposed methods were applied to analyze (1) four lipid traits in eight European cohorts, and (2) three biochemical traits in the Trinity Students Study. The approximate F-distribution tests provide much more significant results than those of F-tests of univariate analysis and SKAT-O for the three biochemical traits. The approximate F-distribution tests of the proposed functional linear models are more sensitive than those of the traditional multivariate linear models that in turn are more sensitive than SKAT-O in the univariate case. The analysis of the four lipid traits and the three biochemical traits detects more association than SKAT-O in the univariate case. © 2015 WILEY PERIODICALS, INC.
Zhang, Weihua; Jernerén, Fredrik; Lehne, Benjamin C; Chen, Ming-Huei; Luben, Robert N; Johnston, Carole; Elshorbagy, Amany; Eppinga, Ruben N; Scott, William R; Adeyeye, Elizabeth; Scott, James; Böger, Rainer H; Khaw, Kay-Tee; van der Harst, Pim; Wareham, Nicholas J; Vasan, Ramachandran S; Chambers, John C; Refsum, Helga; Kooner, Jaspal S
2016-11-30
L-arginine is the essential precursor of nitric oxide, and is involved in multiple key physiological processes, including vascular and immune function. The genetic regulation of blood L-arginine levels is largely unknown. We performed a genome-wide association study (GWAS) to identify genetic factors determining serum L-arginine levels, amongst 901 Europeans and 1,394 Indian Asians. We show that common genetic variations at the KLKB1 and F12 loci are strongly associated with serum L-arginine levels. The G allele of single nucleotide polymorphism (SNP) rs71640036 (T/G) in KLKB1 is associated with lower serum L-arginine concentrations (10 µmol/l per allele copy, p=1×10 -24 ), while allele T of rs2545801 (T/C) near the F12 gene is associated with lower serum L-arginine levels (7 µmol/l per allele copy, p=7×10 -12 ). Together these two loci explain 7 % of the total variance in serum L-arginine concentrations. The associations at both loci were replicated in independent cohorts with plasma L-arginine measurements (p<0.004). The two sentinel SNPs are in nearly complete LD with the nonsynonymous SNP rs3733402 at KLKB1 and the 5'-UTR SNP rs1801020 at F12, respectively. SNPs at both loci are associated with blood pressure. Our findings provide new insight into the genetic regulation of L-arginine and its potential relationship with cardiovascular risk.
The mediator subunit Med23 contributes to controlling T-cell activation and prevents autoimmunity.
Sun, Yang; Zhu, Xiaoyan; Chen, Xufeng; Liu, Haifeng; Xu, Yu; Chu, Yajing; Wang, Gang; Liu, Xiaolong
2014-10-10
T-cell activation is critical for successful immune responses and is controlled at multiple levels. Although many changes of T-cell receptor-associated signalling molecules affect T-cell activation, the transcriptional mechanisms that control this process remain largely unknown. Here we find that T cell-specific deletion of the mediator subunit Med23 leads to hyperactivation of T cells and aged Med23-deficient mice exhibit an autoimmune syndrome. Med23 specifically and consistently promotes the transcription of multiple negative regulators of T-cell activation. In the absence of Med23, the T-cell activation threshold is lower, which results in enhanced antitumour T-cell function. Cumulatively, our data suggest that Med23 contributes to controlling T-cell activation at the transcriptional level and prevents the development of autoimmunity.
Chronic periodontitis with multiple risk factor syndrome: a case report.
Shimoe, Masayuki; Yamamoto, Tadashi; Iwamoto, Yoshihiro; Shiomi, Nobuyuki; Maeda, Hiroshi; Nishimura, Fusanori; Takashiba, Shogo
2011-07-01
Multiple risk factor syndrome is a clustering of cardiovascular risk factors, such as diabetes, dyslipidemia, hypertension, and obesity associated epidemiologically with insulin resistance. This report describes the clinical course of a patient suffering from severe periodontitis with multiple risk factor syndrome, and discusses the association between periodontal infection and systemic health. The patient had a history of type 2 diabetes, dyslipidemia, and hypertension for over 10 years. At baseline, her hemoglobin A1 c was 8.1%. However, she had no diabetic complications except periodontitis. The IgG antibody titers against Porphyromonas gingivalis FDC 381 and SU63 were elevated above the mean of healthy subjects +2 standard deviations. Intensive periodontal treatment, including periodontal surgery, was performed to reduce periodontal infection and bacteremia. Her systemic and periodontal conditions were evaluated longitudinally for 10 years. Following periodontal treatment, antibody titers against Porphyromonas gingivalis and hemoglobin A1c values were significantly improved. The other clinical data and medication for her systemic condition also remained stable during supportive periodontal therapy. However, she developed myocardial infarction, and showed continuous deterioration of hemoglobin A1 c level and periodontitis. The long-term clustering of risk factors, such as diabetes, dyslipidemia, hypertension, and periodontitis, are associated with the development of myocardial infarction. Treatment of systemic conditions in combination with comprehensive periodontal treatment is important in management of patients with multiple risk factor syndrome.
Wu, Jun; Davis-Ajami, Mary Lynn; Noxon, Virginia; Lu, Zhiqiang Kevin
2017-04-01
To determine predictors associated with the diabetes self-management education and training (DSME) venue and its impact on oral antidiabetic (OAD) medication adherence. The Medical Expenditure Panel Survey household component (MEPS-HC) data (2010-2012) identified adults with diabetes prescribed OAD medication(s) who completed a supplemental Diabetes Care Survey (DCS). Based on the DCS responses to questions about the number and type of DSME venue(s), two groups were created: (1) multiple venues (a physician or health professional plus internet and/or group classes) vs (2) single venue (physician or health professional only). The medication possession ratio (MPR) measured medication adherence, with 0.80 the cut-point defining adherent. Logistic regression examined factors associated with the DSME venue and its effect on OAD medication adherence. Of the 2119 respondents, 41.6% received DSME from multiple venues. Age (<65years), education-level (college or higher), high-income, and diet modification were significantly more likely associated with receiving DSME from multiple venues. In single vs multiple venues, medication adherence was suboptimal (mean MPR 0.66 vs 0.64, p=0.245), and venue showed no influence on adherence (OR: 0.92, 95% CI, 0.73-1.16). Sociodemographic characteristics influence where adults with diabetes receive DSME. Adding different DSME venues may not address suboptimal OAD medication adherence. Copyright © 2016 Primary Care Diabetes Europe. Published by Elsevier Ltd. All rights reserved.