Genome-wide Association Analysis Reveals Putative Alzheimer's Disease Susceptibility Loci in Addition to APOE

PubMed Central

Bertram, Lars; Lange, Christoph; Mullin, Kristina; Parkinson, Michele; Hsiao, Monica; Hogan, Meghan F.; Schjeide, Brit M.M.; Hooli, Basavaraj; DiVito, Jason; Ionita, Iuliana; Jiang, Hongyu; Laird, Nan; Moscarillo, Thomas; Ohlsen, Kari L.; Elliott, Kathryn; Wang, Xin; Hu-Lince, Diane; Ryder, Marie; Murphy, Amy; Wagner, Steven L.; Blacker, Deborah; Becker, K. David; Tanzi, Rudolph E.

2008-01-01

Alzheimer's disease (AD) is a genetically complex and heterogeneous disorder. To date four genes have been established to either cause early-onset autosomal-dominant AD (APP, PSEN1, and PSEN21–4) or to increase susceptibility for late-onset AD (APOE5). However, the heritability of late-onset AD is as high as 80%,6 and much of the phenotypic variance remains unexplained to date. We performed a genome-wide association (GWA) analysis using 484,522 single-nucleotide polymorphisms (SNPs) on a large (1,376 samples from 410 families) sample of AD families of self-reported European descent. We identified five SNPs showing either significant or marginally significant genome-wide association with a multivariate phenotype combining affection status and onset age. One of these signals (p = 5.7 × 10−14) was elicited by SNP rs4420638 and probably reflects APOE-ɛ4, which maps 11 kb proximal (r2 = 0.78). The other four signals were tested in three additional independent AD family samples composed of nearly 2700 individuals from almost 900 families. Two of these SNPs showed significant association in the replication samples (combined p values 0.007 and 0.00002). The SNP (rs11159647, on chromosome 14q31) with the strongest association signal also showed evidence of association with the same allele in GWA data generated in an independent sample of ∼1,400 AD cases and controls (p = 0.04). Although the precise identity of the underlying locus(i) remains elusive, our study provides compelling evidence for the existence of at least one previously undescribed AD gene that, like APOE-ɛ4, primarily acts as a modifier of onset age. PMID:18976728

Genotypic variability-based genome-wide association study identifies non-additive loci HLA-C and IL12B for psoriasis.

PubMed

Wei, Wen-Hua; Massey, Jonathan; Worthington, Jane; Barton, Anne; Warren, Richard B

2018-03-01

Genome-wide association studies (GWASs) have identified a number of loci for psoriasis but largely ignored non-additive effects. We report a genotypic variability-based GWAS (vGWAS) that can prioritize non-additive loci without requiring prior knowledge of interaction types or interacting factors in two steps, using a mixed model to partition dichotomous phenotypes into an additive component and non-additive environmental residuals on the liability scale and then the Levene's (Brown-Forsythe) test to assess equality of the residual variances across genotype groups genome widely. The vGWAS identified two genome-wide significant (P < 5.0e-08) non-additive loci HLA-C and IL12B that were also genome-wide significant in an accompanying GWAS in the discovery cohort. Both loci were statistically replicated in vGWAS of an independent cohort with a small sample size. HLA-C and IL12B were reported in moderate gene-gene and/or gene-environment interactions in several occasions. We found a moderate interaction with age-of-onset of psoriasis, which was replicated indirectly. The vGWAS also revealed five suggestive loci (P < 6.76e-05) including FUT2 that was associated with psoriasis with environmental aspects triggered by virus infection and/or metabolic factors. Replication and functional investigation are needed to validate the suggestive vGWAS loci.

Exploring matrix effects and quantifying organic additives in hydraulic fracturing associated fluids using liquid chromatography electrospray ionization mass spectrometry.

PubMed

Nell, Marika; Helbling, Damian E

2018-05-23

Hydraulic fracturing (HF) operations utilize millions of gallons of water amended with chemical additives including biocides, corrosion inhibitors, and surfactants. Fluids injected into the subsurface return to the surface as wastewaters, which contain a complex mixture of additives, transformation products, and geogenic chemical constituents. Quantitative analytical methods are needed to evaluate wastewater disposal alternatives or to conduct adequate exposure assessments. However, our narrow understanding of how matrix effects change the ionization efficiency of target analytes limits the quantitative analysis of polar to semi-polar HF additives by means of liquid chromatography electrospray ionization mass spectrometry (LC-ESI-MS). To address this limitation, we explored the ways in which matrix chemistry influences the ionization of seventeen priority HF additives with a modified standard addition approach. We then used the data to quantify HF additives in HF-associated fluids. Our results demonstrate that HF additives generally exhibit suppressed ionization in HF-associated fluids, though HF additives that predominantly form sodiated adducts exhibit significantly enhanced ionization in produced water samples, which is largely the result of adduct shifting. In a preliminary screening, we identified glutaraldehyde and 2-butoxyethanol along with homologues of benzalkonium chloride (ADBAC), polyethylene glycol (PEG), and polypropylene glycol (PPG) in HF-associated fluids. We then used matrix recovery factors to provide the first quantitative measurements of individual homologues of ADBAC, PEG, and PPG in HF-associated fluids ranging from mg L-1 levels in hydraulic fracturing fluid to low μg L-1 levels in PW samples. Our approach is generalizable across sample types and shale formations and yields important data to evaluate wastewater disposal alternatives or implement exposure assessments.

Mining, Validation, and Clinical Significance of Colorectal Cancer (CRC)-Associated lncRNAs.

PubMed

Sun, Xiangwei; Hu, Yingying; Zhang, Liang; Hu, Changyuan; Guo, Gangqiang; Mao, Chenchen; Xu, Jianfeng; Ye, Sisi; Huang, Guanli; Xue, Xiangyang; Guo, Aizhen; Shen, Xian

2016-01-01

Colorectal cancer (CRC) is one of the deadliest tumours, but its pathogenesis remains unclear. The involvement of differentially expressed long non-coding RNAs (lncRNAs) in CRC tumorigenesis makes them suitable tumour biomarkers. Here, we screened 150 cases of CRC and 85 cases of paracancerous tissues in the GEO database for differentially expressed lncRNAs. The levels of lncRNA candidates in 84 CRC and paracancerous tissue samples were validated by qRT-PCR and their clinical significance was analyzed. We identified 15 lncRNAs with differential expression in CRC tumours; among them, AK098081 was significantly up-regulated, whereas AK025209, BC040303, BC037331, AK026659, and CR749831 were down-regulated in CRC. In a receiver operating characteristic curve analysis, the area under the curve for the six lncRNAs was 0.914. High expression of AK098081 and low expression of BC040303, CR749831, and BC037331 indicated poor CRC differentiation. CRC patients with lymph node metastasis had lower expression of BC037331. In addition, the group with high AK098081 expression presented significantly lower overall survival and disease-free survival rates than the low-expression group, confirming AK098081 as an independent risk factor for CRC patients. In conclusion, we have identified multiple CRC-associated lncRNAs from microarray expression profiles that can serve as novel biomarkers for the diagnosis and prognosis of CRC.

The association of genome-wide significant spirometric loci with chronic obstructive pulmonary disease susceptibility.

PubMed

Castaldi, Peter J; Cho, Michael H; Litonjua, Augusto A; Bakke, Per; Gulsvik, Amund; Lomas, David A; Anderson, Wayne; Beaty, Terri H; Hokanson, John E; Crapo, James D; Laird, Nan; Silverman, Edwin K

2011-12-01

Two recent metaanalyses of genome-wide association studies conducted by the CHARGE and SpiroMeta consortia identified novel loci yielding evidence of association at or near genome-wide significance (GWS) with FEV(1) and FEV(1)/FVC. We hypothesized that a subset of these markers would also be associated with chronic obstructive pulmonary disease (COPD) susceptibility. Thirty-two single-nucleotide polymorphisms (SNPs) in or near 17 genes in 11 previously identified GWS spirometric genomic regions were tested for association with COPD status in four COPD case-control study samples (NETT/NAS, the Norway case-control study, ECLIPSE, and the first 1,000 subjects in COPDGene; total sample size, 3,456 cases and 1,906 controls). In addition to testing the 32 spirometric GWS SNPs, we tested a dense panel of imputed HapMap2 SNP markers from the 17 genes located near the 32 GWS SNPs and in a set of 21 well studied COPD candidate genes. Of the previously identified GWS spirometric genomic regions, three loci harbored SNPs associated with COPD susceptibility at a 5% false discovery rate: the 4q24 locus including FLJ20184/INTS12/GSTCD/NPNT, the 6p21 locus including AGER and PPT2, and the 5q33 locus including ADAM19. In conclusion, markers previously associated at or near GWS with spirometric measures were tested for association with COPD status in data from four COPD case-control studies, and three loci showed evidence of association with COPD susceptibility at a 5% false discovery rate.

Genome-wide significant risk associations for mucinous ovarian carcinoma.

PubMed

Kelemen, Linda E; Lawrenson, Kate; Tyrer, Jonathan; Li, Qiyuan; Lee, Janet M; Seo, Ji-Heui; Phelan, Catherine M; Beesley, Jonathan; Chen, Xiaoqing; Spindler, Tassja J; Aben, Katja K H; Anton-Culver, Hoda; Antonenkova, Natalia

2015-08-01

Genome-wide association studies have identified several risk associations for ovarian carcinomas but not for mucinous ovarian carcinomas (MOCs). Our analysis of 1,644 MOC cases and 21,693 controls with imputation identified 3 new risk associations: rs752590 at 2q13 (P = 3.3 × 10(-8)), rs711830 at 2q31.1 (P = 7.5 × 10(-12)) and rs688187 at 19q13.2 (P = 6.8 × 10(-13)). We identified significant expression quantitative trait locus (eQTL) associations for HOXD9 at 2q31.1 in ovarian (P = 4.95 × 10(-4), false discovery rate (FDR) = 0.003) and colorectal (P = 0.01, FDR = 0.09) tumors and for PAX8 at 2q13 in colorectal tumors (P = 0.03, FDR = 0.09). Chromosome conformation capture analysis identified interactions between the HOXD9 promoter and risk-associated SNPs at 2q31.1. Overexpressing HOXD9 in MOC cells augmented the neoplastic phenotype. These findings provide the first evidence for MOC susceptibility variants and insights into the underlying biology of the disease.

Genome-wide association study of CSF levels of 59 alzheimer's disease candidate proteins: significant associations with proteins involved in amyloid processing and inflammation.

PubMed

Kauwe, John S K; Bailey, Matthew H; Ridge, Perry G; Perry, Rachel; Wadsworth, Mark E; Hoyt, Kaitlyn L; Staley, Lyndsay A; Karch, Celeste M; Harari, Oscar; Cruchaga, Carlos; Ainscough, Benjamin J; Bales, Kelly; Pickering, Eve H; Bertelsen, Sarah; Fagan, Anne M; Holtzman, David M; Morris, John C; Goate, Alison M

2014-10-01

Cerebrospinal fluid (CSF) 42 amino acid species of amyloid beta (Aβ42) and tau levels are strongly correlated with the presence of Alzheimer's disease (AD) neuropathology including amyloid plaques and neurodegeneration and have been successfully used as endophenotypes for genetic studies of AD. Additional CSF analytes may also serve as useful endophenotypes that capture other aspects of AD pathophysiology. Here we have conducted a genome-wide association study of CSF levels of 59 AD-related analytes. All analytes were measured using the Rules Based Medicine Human DiscoveryMAP Panel, which includes analytes relevant to several disease-related processes. Data from two independently collected and measured datasets, the Knight Alzheimer's Disease Research Center (ADRC) and Alzheimer's Disease Neuroimaging Initiative (ADNI), were analyzed separately, and combined results were obtained using meta-analysis. We identified genetic associations with CSF levels of 5 proteins (Angiotensin-converting enzyme (ACE), Chemokine (C-C motif) ligand 2 (CCL2), Chemokine (C-C motif) ligand 4 (CCL4), Interleukin 6 receptor (IL6R) and Matrix metalloproteinase-3 (MMP3)) with study-wide significant p-values (p<1.46×10-10) and significant, consistent evidence for association in both the Knight ADRC and the ADNI samples. These proteins are involved in amyloid processing and pro-inflammatory signaling. SNPs associated with ACE, IL6R and MMP3 protein levels are located within the coding regions of the corresponding structural gene. The SNPs associated with CSF levels of CCL4 and CCL2 are located in known chemokine binding proteins. The genetic associations reported here are novel and suggest mechanisms for genetic control of CSF and plasma levels of these disease-related proteins. Significant SNPs in ACE and MMP3 also showed association with AD risk. Our findings suggest that these proteins/pathways may be valuable therapeutic targets for AD. Robust associations in cognitively normal

The evidence for clinically significant bias in plasma glucose between liquid and lyophilized citrate buffer additive.

PubMed

Juricic, Gordana; Saracevic, Andrea; Kopcinovic, Lara Milevoj; Bakliza, Ana; Simundic, Ana-Maria

2016-12-01

Citrate buffer additive has been suggested to be of supreme performance in inhibiting glycolysis. However, there is little evidence in the literature regarding the comparability of glucose concentrations in liquid and lyophilized citrate buffer containing tubes. The aim of this study was to compare glucose concentrations in tubes containing liquid (Glucomedics) and lyophilized citrate buffer (Terumo VENOSAFE™ Glycemia) additive, measured immediately after centrifugation. Blood was collected from forty volunteers into both Glucomedics and Venosafe Glycemia tubes. Blood was centrifuged within 15min from venipuncture and glucose concentration was measured immediately after centrifugation, on the Abbott Architect analyzer. Differences between glucose concentrations in Glucomedics and Terumo tubes were tested using the paired t-test. Mean bias was calculated and compared to recommended quality specification for glucose (i.e. 2.2%). Glucose concentration in Terumo tubes was 3.4% lower than in Glucomedics tubes (P<0.001). The mean bias was clinically significant. There is a clinically significant difference between glucose concentrations in liquid and lyophilized citrate buffer additive tubes (Glucomedics vs. Terumo tubes) measured immediately after centrifugation. This difference may affect the patient outcome due to the misclassification of diabetes. Copyright © 2016 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

Are Mammographically Occult Additional Tumors Identified More Than 2 Cm Away From the Primary Breast Cancer on MRI Clinically Significant?

PubMed

Goodman, Sarah; Mango, Victoria; Friedlander, Lauren; Desperito, Elise; Wynn, Ralph; Ha, Richard

2018-06-08

To evaluate the clinical significance of mammographically occult additional tumors identified more than 2cm away from the primary breast cancer on preoperative magnetic resonance imaging (MRI). An Institutional Review Board approved review of consecutive preoperative breast MRIs performed from 1/1/08 to 12/31/14, yielded 667 patients with breast cancer. These patients underwent further assessment to identify biopsy proven mammographically occult breast tumors located more than 2cm away from the edge of the primary tumor. Additional MRI characteristics of the primary and secondary tumors and pathology were reviewed. Statistical analysis was performed using SPSS (v. 24). Of 667 patients with breast cancer, 129 patients had 150 additional ipsilateral mammographically occult tumors that were more than 2cm away from the edge of the primary tumor. One hundred twelve of 129 (86.8%) patients had one additional tumor and 17/129 (13.2%) had two or more additional tumors. In 71/129 (55.0%), additional tumors were located in a different quadrant and in 58/129 (45.0%) additional tumors were in the same quadrant but ≥2cm away. Overall, primary tumor size was significantly larger (mean 1.87± 1.25 cm) than the additional tumors (mean 0.79 ± 0.61cm, p < 0.001). However, in 20/129 (15.5%) the additional tumor was larger and in 26/129 (20.2%) the additional tumor was ≥1cm. The primary tumor was significantly more likely to be invasive (81.4%, 105/129) compared to additional tumors (70%, 105/150, p = 0.03). In 9/129 (7.0%) patients, additional tumors yielded unsuspected invasive cancer orhigher tumor grade. The additional tumor was more likely to be nonmass lesion type (37.3% vs 24% p = 0.02) and focus lesion type (10% vs 0.08%, p < 0.001) compared to primary tumor. Mammographically occult additional tumors identified more than 2cm away from the primary breast tumor on MRI are unlikely to be surgically treated if undiagnosed and may be clinically significant. Copyright �

Enlarged leukocyte referent libraries can explain additional variance in blood-based epigenome-wide association studies.

PubMed

Kim, Stephanie; Eliot, Melissa; Koestler, Devin C; Houseman, Eugene A; Wetmur, James G; Wiencke, John K; Kelsey, Karl T

2016-09-01

We examined whether variation in blood-based epigenome-wide association studies could be more completely explained by augmenting existing reference DNA methylation libraries. We compared existing and enhanced libraries in predicting variability in three publicly available 450K methylation datasets that collected whole-blood samples. Models were fit separately to each CpG site and used to estimate the additional variability when adjustments for cell composition were made with each library. Calculation of the mean difference in the CpG-specific residual sums of squares error between models for an arthritis, aging and metabolic syndrome dataset, indicated that an enhanced library explained significantly more variation across all three datasets (p < 10(-3)). Pathologically important immune cell subtypes can explain important variability in epigenome-wide association studies done in blood.

Significant Association of Urinary Toxic Metals and Autism-Related Symptoms—A Nonlinear Statistical Analysis with Cross Validation

PubMed Central

Adams, James; Kruger, Uwe; Geis, Elizabeth; Gehn, Eva; Fimbres, Valeria; Pollard, Elena; Mitchell, Jessica; Ingram, Julie; Hellmers, Robert; Quig, David; Hahn, Juergen

2017-01-01

Introduction A number of previous studies examined a possible association of toxic metals and autism, and over half of those studies suggest that toxic metal levels are different in individuals with Autism Spectrum Disorders (ASD). Additionally, several studies found that those levels correlate with the severity of ASD. Methods In order to further investigate these points, this paper performs the most detailed statistical analysis to date of a data set in this field. First morning urine samples were collected from 67 children and adults with ASD and 50 neurotypical controls of similar age and gender. The samples were analyzed to determine the levels of 10 urinary toxic metals (UTM). Autism-related symptoms were assessed with eleven behavioral measures. Statistical analysis was used to distinguish participants on the ASD spectrum and neurotypical participants based upon the UTM data alone. The analysis also included examining the association of autism severity with toxic metal excretion data using linear and nonlinear analysis. “Leave-one-out” cross-validation was used to ensure statistical independence of results. Results and Discussion Average excretion levels of several toxic metals (lead, tin, thallium, antimony) were significantly higher in the ASD group. However, ASD classification using univariate statistics proved difficult due to large variability, but nonlinear multivariate statistical analysis significantly improved ASD classification with Type I/II errors of 15% and 18%, respectively. These results clearly indicate that the urinary toxic metal excretion profiles of participants in the ASD group were significantly different from those of the neurotypical participants. Similarly, nonlinear methods determined a significantly stronger association between the behavioral measures and toxic metal excretion. The association was strongest for the Aberrant Behavior Checklist (including subscales on Irritability, Stereotypy, Hyperactivity, and Inappropriate

Insertion/Deletion Within the KDM6A Gene Is Significantly Associated With Litter Size in Goat

PubMed Central

Cui, Yang; Yan, Hailong; Wang, Ke; Xu, Han; Zhang, Xuelian; Zhu, Haijing; Liu, Jinwang; Qu, Lei; Lan, Xianyong; Pan, Chuanying

2018-01-01

A previous whole-genome association analysis identified lysine demethylase 6A (KDM6A), which encodes a type of histone demethylase, as a candidate gene associated to goat fecundity. KDM6A gene knockout mouse disrupts gametophyte development, suggesting that it has a critical role in reproduction. In this study, goat KDM6A mRNA expression profiles were determined, insertion/deletion (indel) variants in the gene identified, indel variants effect on KDM6A gene expression assessed, and their association with first-born litter size analyzed in 2326 healthy female Shaanbei white cashmere goats. KDM6A mRNA was expressed in all tissues tested (heart, liver, spleen, lung, kidney, muscle, brain, skin and testis); the expression levels in testes at different developmental stages [1-week-old (wk), 2, 3 wk, 1-month-old (mo), 1.5 and 2 mo] indicated a potential association with the mitosis-to-meiosis transition, implying that KDM6A may have an essential role in goat fertility. Meanwhile, two novel intronic indels of 16 bp and 5 bp were identified. Statistical analysis revealed that only the 16 bp indel was associated with first-born litter size (P < 0.01), and the average first-born litter size of individuals with an insertion/insertion genotype higher than that of those with the deletion/deletion genotype (P < 0.05). There was also a significant difference in genotype distributions of the 16 bp indel between mothers of single-lamb and multi-lamb litters in the studied goat population (P = 0.001). Consistently, the 16 bp indel also had a significant effect on KDM6A gene expression. Additionally, there was no significant linkage disequilibrium (LD) between these two indel loci, consistent with the association analysis results. Together, these findings suggest that the 16 bp indel in KDM6A may be useful for marker-assisted selection (MAS) of goats. PMID:29616081

Selective neurocognitive deficits and poor life functioning are associated with significant depressive symptoms in alcoholism-HIV infection comorbidity.

PubMed

Sassoon, Stephanie A; Rosenbloom, Margaret J; Fama, Rosemary; Sullivan, Edith V; Pfefferbaum, Adolf

2012-09-30

Alcoholism, HIV, and depressive symptoms frequently co-occur and are associated with impairment in cognition and life function. We administered the Beck Depression Inventory-II (BDI-II), measures of life function, and neurocognitive tests to 67 alcoholics, 56 HIV+ patients, 63 HIV+ alcoholics, and 64 controls to examine whether current depressive symptom level (significant, BDI-II>14 vs. minimal, BDI-II<14) was associated with poorer cognitive or psychosocial function in alcoholism-HIV comorbidity. Participants with significant depressive symptoms demonstrated slower manual motor speed and poorer visuospatial memory than those with minimal depressive symptoms. HIV patients with depressive symptoms showed impaired manual motor speed. Alcoholics with depressive symptoms showed impaired visuospatial memory. HIV+ alcoholics with depressive symptoms reported the poorest quality of life; alcoholics with depressive symptoms, irrespective of HIV status, had poorest life functioning. Thus, significant depressive symptoms were associated with poorer selective cognitive and life functioning in alcoholism and in HIV infection, even though depressive symptoms had neither synergistic nor additive effects on cognition in alcoholism-HIV comorbidity. The results suggest the relevance of assessing and treating current depressive symptoms to reduce cognitive compromise and functional disability in HIV infection, alcoholism, and their comorbidity. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

In vitro bioassays reveal that additives are significant contributors to the toxicity of commercial household pesticides.

PubMed

van de Merwe, Jason P; Neale, Peta A; Melvin, Steven D; Leusch, Frederic D L

2018-06-01

Pesticides commonly used around households can contain additives of unknown concentrations and toxicity. Given the likelihood of these chemicals washing into urban waterways, it is important to understand the effects that these additives may have on aquatic organisms. The aim of this study was to compare the toxicity of commercially available household pesticides to that of the active ingredient(s) alone. The toxicity of five household pesticides (three herbicides and two insecticides) was investigated using a bacterial cytotoxicity bioassay and an algal photosynthesis bioassay. The commercial products were up to an order of magnitude more toxic than the active ingredient(s) alone. In addition, two commercial products with the same listed active ingredients in the same ratio had a 600× difference in potency. These results clearly demonstrate that additives in commercial formulations are significant contributors to the toxicity of household pesticides. The toxicity of pesticides in aquatic systems is therefore likely underestimated by conventional chemical monitoring and risk assessment when only the active ingredients are considered. Regulators and customers should require more clarity from pesticide manufacturers about the nature and concentrations of not only the active ingredients, but also additives used in commercial formulations. In addition, monitoring programmes and chemical risk assessments schemes should develop a structured approach to assessing the toxic effects of commercial formulations, including additives, rather than simply those of the listed active ingredients. Copyright © 2018. Published by Elsevier B.V.

The significance of FM associations for women with FM.

PubMed

Juuso, Päivi; Söderberg, Siv; Olsson, Malin; Skär, Lisa

2014-01-01

Living with fibromyalgia (FM) means living with a long-term pain syndrome that is invisible to others. Support and understanding from others seem to be important to managing the affected daily life. The aim of this study was to describe the significance of FM associations for women with FM. Data collection was carried out through focus group discussions with seventeen women with FM. Data were analyzed through thematic content analysis. The findings show that women experienced associations for people with FM as important as they gave access to contacts with others with similar experiences. Their need of togetherness was fulfilled at the association and they described being strengthened by the support received. Because of the lack of information and knowledge about FM, the association was described as an important venue for getting and mediating information about the illness. At the association the women seem to be empowered, which increases their ability to manage their daily lives despite the limitations imposed by FM. Healthcare personnel could not satisfy the women's needs and to manage to support women with FM. There is a need for communication based on a shared understanding between the women and healthcare personnel. This study highlighted the need for communication based on a shared understanding between people with chronic illness and healthcare personnel to support and strengthen women with FM in their daily lives. The FM associations meet the needs for togetherness, confirmation, and information that the women with FM in this study described and healthcare personnel could not satisfy. Healthcare personnel can learn from FM associations how to empower women with FM in their everyday lives.

Significant associations between driver gene mutations and DNA methylation alterations across many cancer types

PubMed Central

Chen, Yun-Ching; Margolin, Gennady

2017-01-01

Recent evidence shows that mutations in several driver genes can cause aberrant methylation patterns, a hallmark of cancer. In light of these findings, we hypothesized that the landscapes of tumor genomes and epigenomes are tightly interconnected. We measured this relationship using principal component analyses and methylation-mutation associations applied at the nucleotide level and with respect to genome-wide trends. We found that a few mutated driver genes were associated with genome-wide patterns of aberrant hypomethylation or CpG island hypermethylation in specific cancer types. In addition, we identified associations between 737 mutated driver genes and site-specific methylation changes. Moreover, using these mutation-methylation associations, we were able to distinguish between two uterine and two thyroid cancer subtypes. The driver gene mutation–associated methylation differences between the thyroid cancer subtypes were linked to differential gene expression in JAK-STAT signaling, NADPH oxidation, and other cancer-related pathways. These results establish that driver gene mutations are associated with methylation alterations capable of shaping regulatory network functions. In addition, the methodology presented here can be used to subdivide tumors into more homogeneous subsets corresponding to underlying molecular characteristics, which could improve treatment efficacy. PMID:29125844

Pathogen and Particle Associations in Wastewater: Significance and Implications for Treatment and Disinfection Processes.

PubMed

Chahal, C; van den Akker, B; Young, F; Franco, C; Blackbeard, J; Monis, P

2016-01-01

Disinfection guidelines exist for pathogen inactivation in potable water and recycled water, but wastewater with high numbers of particles can be more difficult to disinfect, making compliance with the guidelines problematic. Disinfection guidelines specify that drinking water with turbidity ≥1 Nephelometric Turbidity Units (NTU) is not suitable for disinfection and therefore not fit for purpose. Treated wastewater typically has higher concentrations of particles (1-10NTU for secondary treated effluent). Two processes widely used for disinfecting wastewater are chlorination and ultraviolet radiation. In both cases, particles in wastewater can interfere with disinfection and can significantly increase treatment costs by increasing operational expenditure (chemical demand, power consumption) or infrastructure costs by requiring additional treatment processes to achieve the required levels of pathogen inactivation. Many microorganisms (viruses, bacteria, protozoans) associate with particles, which can allow them to survive disinfection processes and cause a health hazard. Improved understanding of this association will enable development of cost-effective treatment, which will become increasingly important as indirect and direct potable reuse of wastewater becomes more widespread in both developed and developing countries. This review provides an overview of wastewater and associated treatment processes, the pathogens in wastewater, the nature of particles in wastewater and how they interact with pathogens, and how particles can impact disinfection processes. Copyright © 2016 Elsevier Inc. All rights reserved.

Genome-wide significant risk associations for mucinous ovarian carcinoma

PubMed Central

Kelemen, Linda E.; Lawrenson, Kate; Tyrer, Jonathan; Li, Qiyuan; M. Lee, Janet; Seo, Ji-Heui; Phelan, Catherine M.; Beesley, Jonathan; Chen, Xiaoqin; Spindler, Tassja J.; Aben, Katja K.H.; Anton-Culver, Hoda; Antonenkova, Natalia; Baker, Helen; Bandera, Elisa V.; Bean, Yukie; Beckmann, Matthias W.; Bisogna, Maria; Bjorge, Line; Bogdanova, Natalia; Brinton, Louise A.; Brooks-Wilson, Angela; Bruinsma, Fiona; Butzow, Ralf; Campbell, Ian G.; Carty, Karen; Chang-Claude, Jenny; Chen, Y. Ann; Chen, Zhihua; Cook, Linda S.; Cramer, Daniel W.; Cunningham, Julie M.; Cybulski, Cezary; Dansonka-Mieszkowska, Agnieszka; Dennis, Joe; Dicks, Ed; Doherty, Jennifer A.; Dörk, Thilo; du Bois, Andreas; Dürst, Matthias; Eccles, Diana; Easton, Douglas T.; Edwards, Robert P.; Eilber, Ursula; Ekici, Arif B.; Engelholm, Svend Aage; Fasching, Peter A.; Fridley, Brooke L.; Gao, Yu-Tang; Gentry-Maharaj, Aleksandra; Giles, Graham G.; Glasspool, Rosalind; Goode, Ellen L.; Goodman, Marc T.; Grownwald, Jacek; Harrington, Patricia; Harter, Philipp; Hasmad, Hanis Nazihah; Hein, Alexander; Heitz, Florian; Hildebrandt, Michelle A.T.; Hillemanns, Peter; Hogdall, Estrid; Hogdall, Claus; Hosono, Satoyo; Iversen, Edwin S.; Jakubowska, Anna; Jensen, Allan; Ji, Bu-Tian; Karlan, Beth Y; Kellar, Melissa; Kelley, Joseph L.; Kiemeney, Lambertus A.; Krakstad, Camilla; Kjaer, Susanne K.; Kupryjanczyk, Jolanta; Lambrechts, Diether; Lambrechts, Sandrina; Le, Nhu D.; Lee, Alice W.; Lele, Shashi; Leminen, Arto; Lester, Jenny; Levine, Douglas A.; Liang, Dong; Lissowska, Jolanta; Lu, Karen; Lubinski, Jan; Lundvall, Lene; Massuger, Leon F.A.G.; Matsuo, Keitaro; McGuire, Valerie; McLaughlin, John R.; McNeish, Iain; Menon, Usha; Modugno, Francesmary; Moes-Sosnowska, Joanna; Moysich, Kirsten B.; Narod, Steven A.; Nedergaard, Lotte; Ness, Roberta B.; Nevanlinna, Heli; Azmi, Mat Adenan Noor; Odunsi, Kunle; Olson, Sara H.; Orlow, Irene; Orsulic, Sandra; Weber, Rachel Palmieri; Paul, James; Pearce, Celeste Leigh; Pejovic, Tanja; Pelttari, Liisa M.; Permuth-Wey, Jennifer; Pike, Malcolm C.; Poole, Elizabeth M.; Ramus, Susan J.; Risch, Harvey A.; Rosen, Barry; Rossing, Mary Anne; Rothstein, Joseph H.; Rudolph, Anja; Runnebaum, Ingo B.; Rzepecka, Iwona K.; Salvesen, Helga B.; Schildkraut, Joellen M.; Schwaab, Ira; Shu, Xiao-Ou; Shvetsov, Yurii B; Siddiqui, Nadeem; Sieh, Weiva; Song, Honglin; Southey, Melissa C.; Sucheston, Lara; Tangen, Ingvild L.; Teo, Soo-Hwang; Terry, Kathryn L.; Thompson, Pamela J; Tworoger, Shelley S.; van Altena, Anne M.; Van Nieuwenhuysen, Els; Vergote, Ignace; Vierkant, Robert A.; Wang-Gohrke, Shan; Walsh, Christine; Wentzensen, Nicolas; Whittemore, Alice S.; Wicklund, Kristine G.; Wilkens, Lynne R.; Wlodzimierz, Sawicki; Woo, Yin-Ling; Wu, Xifeng; Wu, Anna H.; Yang, Hannah; Zheng, Wei; Ziogas, Argyrios; Sellers, Thomas A.; Freedman, Matthew L.; Chenevix-Trench, Georgia; Pharoah, Paul D.; Gayther, Simon A.; Berchuck, Andrew

2015-01-01

Genome-wide association studies have identified several risk associations for ovarian carcinomas (OC) but not for mucinous ovarian carcinomas (MOC). Genotypes from OC cases and controls were imputed into the 1000 Genomes Project reference panel. Analysis of 1,644 MOC cases and 21,693 controls identified three novel risk associations: rs752590 at 2q13 (P = 3.3 × 10−8), rs711830 at 2q31.1 (P = 7.5 × 10−12) and rs688187 at 19q13.2 (P = 6.8 × 10−13). Expression Quantitative Trait Locus (eQTL) analysis in ovarian and colorectal tumors (which are histologically similar to MOC) identified significant eQTL associations for HOXD9 at 2q31.1 in ovarian (P = 4.95 × 10−4, FDR = 0.003) and colorectal (P = 0.01, FDR = 0.09) tumors, and for PAX8 at 2q13 in colorectal tumors (P = 0.03, FDR = 0.09). Chromosome conformation capture analysis identified interactions between the HOXD9 promoter and risk SNPs at 2q31.1. Overexpressing HOXD9 in MOC cells augmented the neoplastic phenotype. These findings provide the first evidence for MOC susceptibility variants and insights into the underlying biology of the disease. PMID:26075790

Significant obesity-associated gene expression changes occur in the stomach but not intestines in obese mice.

PubMed

Chen, Jing; Chen, Lihong; Sanseau, Philippe; Freudenberg, Johannes M; Rajpal, Deepak K

2016-05-01

The gastrointestinal (GI) tract can have significant impact on the regulation of the whole-body metabolism and may contribute to the development of obesity and diabetes. To systemically elucidate the role of the GI tract in obesity, we performed a transcriptomic analysis in different parts of the GI tract of two obese mouse models: ob/ob and high-fat diet (HFD) fed mice. Compared to their lean controls, significant changes in the gene expression were observed in both obese mouse groups in the stomach (ob/ob: 959; HFD: 542). In addition, these changes were quantitatively much higher than in the intestine. Despite the difference in genetic background, the two mouse models shared 296 similar gene expression changes in the stomach. Among those genes, some had known associations to obesity, diabetes, and insulin resistance. In addition, the gene expression profiles strongly suggested an increased gastric acid secretion in both obese mouse models, probably through an activation of the gastrin pathway. In conclusion, our data reveal a previously unknown dominant connection between the stomach and obesity in murine models extensively used in research. © 2016 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.

The antibiotic resistome of swine manure is significantly altered by association with the Musca domestica larvae gut microbiome

PubMed Central

Wang, Hang; Sangwan, Naseer; Li, Hong-Yi; Su, Jian-Qiang; Oyang, Wei-Yin; Zhang, Zhi-Jian; Gilbert, Jack A; Zhu, Yong-Guan; Ping, Fan; Zhang, Han-Luo

2017-01-01

The overuse of antibiotics as veterinary feed additives is potentially contributing to a significant reservoir of antibiotic resistance in agricultural farmlands via the application of antibiotic-contaminated manure. Vermicomposting of swine manure using housefly larvae is a promising biotechnology for waste reduction and control of antibiotic pollution. To determine how vermicomposting influences antibiotic resistance traits in swine manure, we explored the resistome and associated bacterial community dynamics during larvae gut transit over 6 days of treatment. In total, 94 out of 158 antibiotic resistance genes (ARGs) were significantly attenuated (by 85%), while 23 were significantly enriched (3.9-fold) following vermicomposting. The manure-borne bacterial community showed a decrease in the relative abundance of Bacteroidetes, and an increase in Proteobacteria, specifically Ignatzschineria, following gut transit. ARG attenuation was significantly correlated with changes in microbial community succession, especially reduction in Clostridiales and Bacteroidales. Six genomes were assembled from the manure, vermicompost (final product) and gut samples, including Pseudomonas, Providencia, Enterococcus, Bacteroides and Alcanivorax. Transposon-linked ARGs were more abundant in gut-associated bacteria compared with those from manure and vermicompost. Further, ARG-transposon gene cassettes had a high degree of synteny between metagenomic assemblies from gut and vermicompost samples, highlighting the significant contribution of gut microbiota through horizontal gene transfer to the resistome of vermicompost. In conclusion, the larvae gut microbiome significantly influences manure-borne community succession and the antibiotic resistome during animal manure processing. PMID:27458785

The antibiotic resistome of swine manure is significantly altered by association with the Musca domestica larvae gut microbiome.

PubMed

Wang, Hang; Sangwan, Naseer; Li, Hong-Yi; Su, Jian-Qiang; Oyang, Wei-Yin; Zhang, Zhi-Jian; Gilbert, Jack A; Zhu, Yong-Guan; Ping, Fan; Zhang, Han-Luo

2017-01-01

The overuse of antibiotics as veterinary feed additives is potentially contributing to a significant reservoir of antibiotic resistance in agricultural farmlands via the application of antibiotic-contaminated manure. Vermicomposting of swine manure using housefly larvae is a promising biotechnology for waste reduction and control of antibiotic pollution. To determine how vermicomposting influences antibiotic resistance traits in swine manure, we explored the resistome and associated bacterial community dynamics during larvae gut transit over 6 days of treatment. In total, 94 out of 158 antibiotic resistance genes (ARGs) were significantly attenuated (by 85%), while 23 were significantly enriched (3.9-fold) following vermicomposting. The manure-borne bacterial community showed a decrease in the relative abundance of Bacteroidetes, and an increase in Proteobacteria, specifically Ignatzschineria, following gut transit. ARG attenuation was significantly correlated with changes in microbial community succession, especially reduction in Clostridiales and Bacteroidales. Six genomes were assembled from the manure, vermicompost (final product) and gut samples, including Pseudomonas, Providencia, Enterococcus, Bacteroides and Alcanivorax. Transposon-linked ARGs were more abundant in gut-associated bacteria compared with those from manure and vermicompost. Further, ARG-transposon gene cassettes had a high degree of synteny between metagenomic assemblies from gut and vermicompost samples, highlighting the significant contribution of gut microbiota through horizontal gene transfer to the resistome of vermicompost. In conclusion, the larvae gut microbiome significantly influences manure-borne community succession and the antibiotic resistome during animal manure processing.

Ventilator-associated pneumonia: clinical significance and implications for nursing.

PubMed

Grap, M J; Munro, C L

1997-01-01

Pneumonia is the second most common nosocomial infection in the United States and the leading cause of death from nosocomial infections. Intubation and mechanical ventilation greatly increase the risk of bacterial pneumonia. Ventilator-associated pneumonia (VAP) occurs in a patient treated with mechanical ventilation, and it is neither present nor developing at the time of intubation; it is a serious problem--with significant morbidity and mortality rates. Aspiration of bacteria from the oropharynx, leakage of contaminated secretions around the endotracheal tube, patient position, and cross-contamination from respiratory equipment and health care providers are important factors in the development of VAP. Nurses caring for patients treated with mechanical ventilation must recognize risk factors and include strategies for reducing these factors as part of their nursing care. This article summarizes the literature related to VAP: its incidence, associated factors, diagnosis, and current therapies, with an emphasis on nursing implications in the care of these patients.

Genetic variants in a haplotype block spanning IDE are significantly associated with plasma Abeta42 levels and risk for Alzheimer disease.

PubMed

Ertekin-Taner, Nilüfer; Allen, Mariet; Fadale, Daniel; Scanlin, Leah; Younkin, Linda; Petersen, Ronald C; Graff-Radford, Neill; Younkin, Steven G

2004-04-01

Risk for late onset Alzheimer disease (LOAD) and plasma amyloid beta levels (Abeta42; encoded by APP), an intermediate phenotype for LOAD, show linkage to chromosome 10q. Several strong candidate genes (VR22, PLAU, IDE) lie within the 1-lod support interval for linkage. Others have independently identified haplotypes in the chromosome 10q region harboring IDE that show highly significant association with intermediate AD phenotypes and with risk for AD. To pursue these associations, we analyzed the same haplotypes for association with plasma Abeta42 in 24 extended LOAD families and for association with LOAD in two independent case-control series. One series (MCR, 188 age-matched case-control pairs) did not show association (p=0.64) with the six haplotypes in the 276-kb region spanning three genes (IDE, KNSL1, and HHEX) previously shown to associate with LOAD. The other series (MCJ, 109 age-matched case-control pairs) showed significant (p=0.003) association with these haplotypes. In the MCJ series, the H4 (odds ratio [OR]=5.1, p=0.003) and H2(H7) haplotypes (OR=0.60, p=0.04) had the same effects previously reported. In this series, the H8 haplotype (OR=2.7, p=0.098) also had an effect similar as in one previous case control series but not in others. In the extended families, the H8 haplotype was associated with significantly elevated plasma Abeta42 (p=0.02). In addition, the H5(H10) haplotype, which is associated with reduced risk for AD in the other study is associated with reduced plasma Abeta42 (p=0.007) in our family series. These results provide strong evidence for pathogenic variant(s) in the 276-kb region harboring IDE that influence intermediate AD phenotypes and risk for AD. Copyright 2004 Wiley-Liss, Inc.

[The Additional Role of Symptom-Reflux Association Analysis of Diagnosis of Gastroesophageal Reflux Disease Using Bravo Capsule pH Test].

PubMed

Jung, Kyoungwon; Park, Moo In; Park, Seun Ja; Moon, Won; Kim, Sung Eun; Kim, Jae Hyun

2017-10-25

Since the development of ambulatory esophageal pH monitoring test to diagnose gastroesophageal reflux disease (GERD), several parameters have been introduced. The aim of this study was to assess whether using the symptom index (SI), symptom sensitivity index (SSI), and symptom association probability (SAP), in addition to the DeMeester score (DS), would be useful for interpreting the Bravo pH monitoring test. A retrospective study, which included 68 patients with reflux symptoms refractory to proton pump inhibitor (PPI) therapy who underwent a Bravo capsule pH test between October 2006 and May 2015, was carried out. Acid reflux parameters and symptom reflux association parameters were analyzed. The median percent time of total pH<4 and DS were 2.90% (interquartile range [IQR] 1.13-6.03%) and 11.10 (IQR 4.90-22.80), respectively. According to the analysis of the day-to-day variation in percent time of total pH<4 (r=0.724) and DS (r=0.537), there was a significant correlation between Day 1 and Day 2. The positive rate of Bravo test according to DS was 27 (39.7%). Although thirty patients experienced symptoms during the test, there were no significant differences of reflux parameters compared with other patients. In the symptom group, 7 patients (23.3%) were identified as having negative DS and an abnormal symptom-related index. There were no significant test-related complications. In addition to the analysis of traditional acid parameters of the Bravo capsule pH test, diagnosis of GERD, including reflux hypersensitivity, can be improved by performing an analysis of the symptom-reflux association and of the day-to-day variation.

Ultimate strength performance of tankers associated with industry corrosion addition practices

NASA Astrophysics Data System (ADS)

Kim, Do Kyun; Kim, Han Byul; Zhang, Xiaoming; Li, Chen Guang; Paik, Jeom Kee

2014-09-01

In the ship and offshore structure design, age-related problems such as corrosion damage, local denting, and fatigue damage are important factors to be considered in building a reliable structure as they have a significant influence on the residual structural capacity. In shipping, corrosion addition methods are widely adopted in structural design to prevent structural capacity degradation. The present study focuses on the historical trend of corrosion addition rules for ship structural design and investigates their effects on the ultimate strength performance such as hull girder and stiffened panel of double hull oil tankers. Three types of rules based on corrosion addition models, namely historic corrosion rules (pre-CSR), Common Structural Rules (CSR), and harmonised Common Structural Rules (CSRH) are considered and compared with two other corrosion models namely UGS model, suggested by the Union of Greek Shipowners (UGS), and Time-Dependent Corrosion Wastage Model (TDCWM). To identify the general trend in the effects of corrosion damage on the ultimate longitudinal strength performance, the corrosion addition rules are applied to four representative sizes of double hull oil tankers namely Panamax, Aframax, Suezmax, and VLCC. The results are helpful in understanding the trend of corrosion additions for tanker structures

Periodontitis is associated with significant hepatic fibrosis in patients with non-alcoholic fatty liver disease.

PubMed

Alazawi, William; Bernabe, Eduardo; Tai, David; Janicki, Tomasz; Kemos, Polychronis; Samsuddin, Salma; Syn, Wing-Kin; Gillam, David; Turner, Wendy

2017-01-01

Non-alcoholic fatty liver disease (NAFLD) has a bidirectional association with metabolic syndrome. It affects up to 30% of the general population, 70% of individuals with diabetes and 90% with obesity. The main histological hallmark of progressive NAFLD is fibrosis. There is a bidirectional epidemiological link between periodontitis and metabolic syndrome. NAFLD, periodontitis and diabetes share common risk factors, are characterised by inflammation and associated with changes in commensal bacteria. Therefore we tested the hypothesis that periodontitis is associated with NAFLD and with significant fibrosis in two study groups. We analyzed data from a population-based survey and a patient-based study. NHANES III participants with abdominal ultrasound and sociodemographic, clinical, and oral examination data were extracted and appropriate weighting applied. In a separate patient-based study, consenting patients with biopsy-proved NAFLD (or with liver indices too mild to justify biopsy) underwent dental examination. Basic Periodontal Examination score was recorded. In NHANES, periodontitis was significantly associated with steatosis in 8172 adults even after adjusting for sociodemographic factors. However, associations were fully explained after accounting for features of metabolic syndrome. In the patient-based study, periodontitis was significantly more common in patients with biopsy-proven NASH and any fibrosis (F0-F4) than without NASH (p = 0.009). Periodontitis was more common in patients with NASH and significant fibrosis (F2-4) than mild or no fibrosis (F0-1, p = 0.04). Complementary evidence from an epidemiological survey and a clinical study show that NAFLD is associated with periodontitis and that the association is stronger with significant liver fibrosis.

Inactivation of Hippo Pathway Is Significantly Associated with Poor Prognosis in Hepatocellular Carcinoma.

PubMed

Sohn, Bo Hwa; Shim, Jae-Jun; Kim, Sang-Bae; Jang, Kyu Yun; Kim, Soo Mi; Kim, Ji Hoon; Hwang, Jun Eul; Jang, Hee-Jin; Lee, Hyun-Sung; Kim, Sang-Cheol; Jeong, Woojin; Kim, Sung Soo; Park, Eun Sung; Heo, Jeonghoon; Kim, Yoon Jun; Kim, Dae-Ghon; Leem, Sun-Hee; Kaseb, Ahmed; Hassan, Manal M; Cha, Minse; Chu, In-Sun; Johnson, Randy L; Park, Yun-Yong; Lee, Ju-Seog

2016-03-01

The Hippo pathway is a tumor suppressor in the liver. However, the clinical significance of Hippo pathway inactivation in HCC is not clearly defined. We analyzed genomic data from human and mouse tissues to determine clinical relevance of Hippo pathway inactivation in HCC. We analyzed gene expression data from Mst1/2(-/-) and Sav1(-/-) mice and identified a 610-gene expression signature reflecting Hippo pathway inactivation in the liver [silence of Hippo (SOH) signature]. By integrating gene expression data from mouse models with those from human HCC tissues, we developed a prediction model that could identify HCC patients with an inactivated Hippo pathway and used it to test its significance in HCC patients, via univariate and multivariate Cox analyses. HCC patients (National Cancer Institute cohort, n = 113) with the SOH signature had a significantly poorer prognosis than those without the SOH signature [P < 0.001 for overall survival (OS)]. The significant association of the signature with poor prognosis was further validated in the Korean (n = 100, P = 0.006 for OS) and Fudan University cohorts (n = 242, P = 0.001 for OS). On multivariate analysis, the signature was an independent predictor of recurrence-free survival (HR, 1.6; 95% confidence interval, 1.12-2.28: P = 0.008). We also demonstrated significant concordance between the SOH HCC subtype and the hepatic stem cell HCC subtype that had been identified in a previous study (P < 0.001). Inactivation of the Hippo pathway in HCC is significantly associated with poor prognosis. ©2015 American Association for Cancer Research.

Event-level relationship between methamphetamine use significantly associated with non-adherence to pharmacologic trial medications in event-level analyses.

PubMed

Hermanstyne, Keith A; Santos, Glenn-Milo; Vittinghoff, Eric; Santos, Deirdre; Colfax, Grant; Coffin, Phillip

2014-10-01

Methamphetamine use has been previously associated with poor medication adherence, but, to date, there have been no studies that have conducted event-level analyses on correlates of medication adherence in studies of pharmacologic agents for methamphetamine dependence. We pooled data from two previous, randomized controlled trials (using bupropion and mirtazapine, respectively) for methamphetamine dependence and used a mixed effects logistic model to examine correlates of daily opening of the medication event monitoring system (MEMS) cap as a repeated measure. We explored whether periods of observed methamphetamine use via urine testing were associated with study medication adherence based on MEMS cap openings. We found a significant negative association between methamphetamine-urine positivity and event-level study medication adherence as measured by MEMS cap openings (AOR: 0.69; 95% CI: 0.49-0.98). In addition, age (AOR: 1.07; 95% CI: 1.02-1.11) and depressive symptoms (AOR: 0.78; 95% CI: 0.64-0.90) were significantly associated with adherence. Finally, participants were more likely to open their study medication bottles on days when they presented for in-person urine testing. Our event-level analysis shows that methamphetamine use can be associated with reduced medication adherence as measured by MEMS cap openings in pharmacologic trials, which corroborates prior research. These findings may suggest that medication adherence support in pharmacologic trials among methamphetamine users may be needed to improve study compliance and could be targeted towards periods of time when there are more likely to not open their study medication pill bottles. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Significance of genetic variants in DLC1 and their association with hepatocellular carcinoma

PubMed Central

XIE, CHENG-RONG; SUN, HONG-GUANG; SUN, YU; ZHAO, WEN-XIU; ZHANG, SHENG; WANG, XIAO-MIN; YIN, ZHEN-YU

2015-01-01

DLC1 has been shown to be downregulated or absent in hepatocellular carcinoma (HCC) and is associated with tumorigenesis and development. However, only a small number of studies have focused on genetic variations of DLC1. The present study performed exon sequencing for the DLC1 gene in HCC tissue samples from 105 patients to identify functional genetic variation of DLC1 and its association with HCC susceptibility, clinicopathological features and prognosis. A novel missense mutation and four non-synonymous single nucleotide polymorphisms (SNPs; rs3816748, rs11203495, rs3816747 and rs532841) were identified. A significant correlation of rs3816747 polymorphisms with HCC susceptibility was identified. Compared to individuals with the GG genotype of rs3816747, those with the GA (odds ratio (OR)=0.486; P=0.037) or GA+AA genotype (OR=0.51; P=0.039) were associated with a significantly decreased HCC risk. Furthermore, patients with the GC+CC genotype of rs3816748, the TC+CC genotype of rs11203495 or the GA+AA genotype of rs3816747 had small-sized tumors compared with those carrying the wild-type genotype. No significant association of DLC1 SNPs with the patients' prognosis was found. These results indicated that genetic variations in the DLC1 gene may confer a risk for HCC. PMID:26095787

The Unique and Additive Associations of Family Functioning and Parenting Practices with Disordered Eating Behaviors in Diverse Adolescents

PubMed Central

Berge, Jerica M.; Wall, Melanie; Larson, Nicole; Eisenberg, Marla E.; Loth, Katie A.; Neumark-Sztainer, Dianne

2012-01-01

Objective To examine the unique and additive associations of family functioning and parenting practices with adolescent disordered eating behaviors (i.e., dieting, unhealthy weight control behaviors, binge eating). Methods Data from EAT (Eating and Activity in Teens) 2010, a population-based study assessing eating and activity among racially/ethnically and socio-economically diverse adolescents (n = 2,793; mean age = 14.4, SD = 2.0; age range = 11–19) was used. Logistic regression models were used to examine associations between adolescent dieting and disordered eating behaviors and family functioning and parenting variables, including interactions. All analyses controlled for demographics and body mass index. Results Higher family functioning, parent connection, and parental knowledge about child’s whereabouts (e.g. who child is with, what they are doing, where they are at) were significantly associated with lower odds of engaging in dieting and disordered eating behaviors in adolescents, while parent psychological control was associated with greater odds of engaging in dieting and disordered eating behaviors. Although the majority of interactions were non-significant, parental psychological control moderated the protective relationship between family functioning and disordered eating behaviors in adolescent girls. Conclusions Clinicians and health care providers may want to discuss the importance of balancing specific parenting behaviors, such as increasing parent knowledge about child whereabouts while decreasing psychological control in order to enhance the protective relationship between family functioning and disordered eating behaviors in adolescents. PMID:23196919

Sniffing out significant "Pee values": genome wide association study of asparagus anosmia.

PubMed

Markt, Sarah C; Nuttall, Elizabeth; Turman, Constance; Sinnott, Jennifer; Rimm, Eric B; Ecsedy, Ethan; Unger, Robert H; Fall, Katja; Finn, Stephen; Jensen, Majken K; Rider, Jennifer R; Kraft, Peter; Mucci, Lorelei A

2016-12-13

 To determine the inherited factors associated with the ability to smell asparagus metabolites in urine.  Genome wide association study.  Nurses' Health Study and Health Professionals Follow-up Study cohorts.  6909 men and women of European-American descent with available genetic data from genome wide association studies.  Participants were characterized as asparagus smellers if they strongly agreed with the prompt "after eating asparagus, you notice a strong characteristic odor in your urine," and anosmic if otherwise. We calculated per-allele estimates of asparagus anosmia for about nine million single nucleotide polymorphisms using logistic regression. P values <5×10 -8 were considered as genome wide significant.  58.0% of men (n=1449/2500) and 61.5% of women (n=2712/4409) had anosmia. 871 single nucleotide polymorphisms reached genome wide significance for asparagus anosmia, all in a region on chromosome 1 (1q44: 248139851-248595299) containing multiple genes in the olfactory receptor 2 (OR2) family. Conditional analyses revealed three independent markers associated with asparagus anosmia: rs13373863, rs71538191, and rs6689553.  A large proportion of people have asparagus anosmia. Genetic variation near multiple olfactory receptor genes is associated with the ability of an individual to smell the metabolites of asparagus in urine. Future replication studies are necessary before considering targeted therapies to help anosmic people discover what they are missing. 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.

The functional significance of EEG microstates--Associations with modalities of thinking.

PubMed

Milz, P; Faber, P L; Lehmann, D; Koenig, T; Kochi, K; Pascual-Marqui, R D

2016-01-15

. Contrary to associations suggested by previous reports, parameters were increased for class A during visualization, and class B during verbalization. In line with previous reports, microstate D parameters were increased during no-task resting compared to the three internal, goal-directed tasks. Topographic differences between conditions included particular sub-regions of components of the metabolic default mode network. Modality-specific personal parameters did not consistently correlate with microstate parameters except verbal cognitive style which correlated negatively with microstate class A duration and positively with class C occurrence. This is the first study that aimed to induce EEG microstate class parameter changes based on their hypothesized functional significance. Beyond the associations of microstate classes A and B with visual and verbal processing, respectively, our results suggest that a finely-tuned interplay between all four EEG microstate classes is necessary for the continuous formation of visual and verbal thoughts. Our results point to the possibility that the EEG microstate classes may represent the head-surface measured activity of intra-cortical sources primarily exhibiting inhibitory functions. However, additional studies are needed to verify and elaborate on this hypothesis. Copyright © 2015 Elsevier Inc. All rights reserved.

Addition of sodium caseinate to skim milk increases nonsedimentable casein and causes significant changes in rennet-induced gelation, heat stability, and ethanol stability.

PubMed

Lin, Yingchen; Kelly, Alan L; O'Mahony, James A; Guinee, Timothy P

2017-02-01

The protein content of skim milk was increased from 3.3 to 4.1% (wt/wt) by the addition of a blend of skim milk powder and sodium caseinate (NaCas), in which the weight ratio of skim milk powder to NaCas was varied from 0.8:0.0 to 0.0:0.8. Addition of NaCas increased the levels of nonsedimentable casein (from ∼6 to 18% of total casein) and calcium (from ∼36 to 43% of total calcium) and reduced the turbidity of the fortified milk, to a degree depending on level of NaCas added. Rennet gelation was adversely affected by the addition of NaCas at 0.2% (wt/wt) and completely inhibited at NaCas ≥0.4% (wt/wt). Rennet-induced hydrolysis was not affected by added NaCas. The proportion of total casein that was nonsedimentable on centrifugation (3,000 × g, 1 h, 25°C) of the rennet-treated milk after incubation for 1 h at 31°C increased significantly on addition of NaCas at ≥0.4% (wt/wt). Heat stability in the pH range 6.7 to 7.2 and ethanol stability at pH 6.4 were enhanced by the addition of NaCas. It is suggested that the negative effect of NaCas on rennet gelation is due to the increase in nonsedimentable casein, which upon hydrolysis by chymosin forms into small nonsedimentable particles that physically come between, and impede the aggregation of, rennet-altered para-casein micelles, and thereby inhibit the development of a gel network. Copyright © 2017 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

A genome scan revealed significant associations of growth traits with a major QTL and GHR2 in tilapia

PubMed Central

Liu, Feng; Sun, Fei; Xia, Jun Hong; Li, Jian; Fu, Gui Hong; Lin, Grace; Tu, Rong Jian; Wan, Zi Yi; Quek, Delia; Yue, Gen Hua

2014-01-01

Growth is an important trait in animal breeding. However, the genetic effects underpinning fish growth variability are still poorly understood. QTL mapping and analysis of candidate genes are effective methods to address this issue. We conducted a genome-wide QTL analysis for growth in tilapia. A total of 10, 7 and 8 significant QTLs were identified for body weight, total length and standard length at 140 dph, respectively. The majority of these QTLs were sex-specific. One major QTL for growth traits was identified in the sex-determining locus in LG1, explaining 71.7%, 67.2% and 64.9% of the phenotypic variation (PV) of body weight, total length and standard length, respectively. In addition, a candidate gene GHR2 in a QTL was significantly associated with body weight, explaining 13.1% of PV. Real-time qPCR revealed that different genotypes at the GHR2 locus influenced the IGF-1 expression level. The markers located in the major QTL for growth traits could be used in marker-assisted selection of tilapia. The associations between GHR2 variants and growth traits suggest that the GHR2 gene should be an important gene that explains the difference in growth among tilapia species. PMID:25435025

Additional Guidance on Prevention of Significant Deterioration (PSD) Regulations

EPA Pesticide Factsheets

This document may be of assistance in applying the New Source Review (NSR) air permitting regulations including the Prevention of Significant Deterioration (PSD) requirements. This document is part of the NSR Policy and Guidance Database. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

Dieting and encouragement to diet by significant others: associations with disordered eating in young adults

PubMed Central

Eisenberg, Marla E.; Berge, Jerica M.; Neumark-Sztainer, Dianne

2013-01-01

Purpose Examine the role of perceived significant other's modeling or encouragement of dieting in young adults' disordered eating behaviors. Design Online survey data were collected (2008–2009) as part of an ongoing study examining weight and related issues in young people. Setting Participants were originally recruited as students at middle and high schools in Minnesota (1998–1999). Subjects 1,030 young adults (mean age 25.3, 55% female, 50% white) with significant others. Measures Participants were asked if their significant other diets or encourages them to diet. Behaviors included unhealthy weight control, extreme weight control, and binge eating. Analysis General linear models estimated the predicted probability of using each behavior across levels of significant other's dieting or encouraging dieting, stratifying by gender and adjusting for demographics and BMI. Results Perceived dieting and encouragement to diet by significant others were common. Disordered eating behaviors were positively associated with significant other's dieting and encouragement to diet, particularly for females. In models including both perceived dieting and encouragement, encouragement remained significantly associated with disordered eating. For example, women's binge eating was almost doubled if their significant other encouraged dieting “very much” (25.5%) compared to “not at all” (13.6%, p=.015). Conclusion There is a strong association between disordered eating behaviors and perceived modeling and encouragement to diet by significant others in young adulthood. PMID:23398133

Significant factors associated with fatal outcome in emergency open surgery for perforated peptic ulcer.

PubMed

Testini, Mario; Portincasa, Piero; Piccinni, Giuseppe; Lissidini, Germana; Pellegrini, Fabio; Greco, Luigi

2003-10-01

To evaluate the main factors associated with mortality in patients undergoing surgery for perforated peptic ulcer referred to an academic department of general surgery in a large southern Italian city. One hundred and forty-nine consecutive patients (M:F ratio=110:39, mean age 52 yrs, range 16-95) with peptic ulcer disease were investigated for clinical history (including age, sex, previous history of peptic ulcer, associated diseases, delayed abdominal surgery, ulcer site, operation type, shock on admission, postoperative general complications, and intra-abdominal and/or wound infections), serum analyses and radiological findings. The overall mortality rate was 4.0%. Among all factors, an age above 65 years, one or more associated diseases, delayed abdominal surgery, shock on admission, postoperative abdominal complications and/or wound infections, were significantly associated (chi2) with increased mortality in patients undergoing surgery (0.0001significantly associated with fatal outcomes and need careful evaluation within the general workup of patients admitted for perforated peptic ulcer.

Genome-wide association study for rotator cuff tears identifies two significant single-nucleotide polymorphisms.

PubMed

Tashjian, Robert Z; Granger, Erin K; Farnham, James M; Cannon-Albright, Lisa A; Teerlink, Craig C

2016-02-01

The precise etiology of rotator cuff disease is unknown, but prior evidence suggests a role for genetic factors. Limited data exist identifying specific genes associated with rotator cuff tearing. The purpose of this study was to identify specific genes or genetic variants associated with rotator cuff tearing by a genome-wide association study with an independent set of rotator cuff tear cases. A set of 311 full-thickness rotator cuff tear cases genotyped on the Illumina 5M single-nucleotide polymorphism (SNP) platform were used in a genome-wide association study with 2641 genetically matched white population controls available from the Illumina iControls database. Tests of association were performed with GEMMA software at 257,558 SNPs that compose the intersection of Illumina SNP platforms and that passed general quality control metrics. SNPs were considered significant if P < 1.94 × 10(-7) (Bonferroni correction: 0.05/257,558). Tests of association revealed 2 significantly associated SNPs, one occurring in SAP30BP (rs820218; P = 3.8E-9) on chromosome 17q25 and another occurring in SASH1 (rs12527089; P = 1.9E-7) on chromosome 6q24. This study represents the first attempt to identify genetic factors influencing rotator cuff tearing by a genome-wide association study using a dense/complete set of SNPs. Two SNPs were significantly associated with rotator cuff tearing, residing in SAP30BP on chromosome 17 and SASH1 on chromosome 6. Both genes are associated with the cellular process of apoptosis. Identification of potential genes or genetic variants associated with rotator cuff tearing may help in identifying individuals at risk for the development of rotator cuff tearing. Copyright © 2016 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Elsevier Inc. All rights reserved.

Congruence of Additive and Non-Additive Effects on Gene Expression Estimated from Pedigree and SNP Data

PubMed Central

Powell, Joseph E.; Henders, Anjali K.; McRae, Allan F.; Kim, Jinhee; Hemani, Gibran; Martin, Nicholas G.; Dermitzakis, Emmanouil T.; Gibson, Greg

2013-01-01

There is increasing evidence that heritable variation in gene expression underlies genetic variation in susceptibility to disease. Therefore, a comprehensive understanding of the similarity between relatives for transcript variation is warranted—in particular, dissection of phenotypic variation into additive and non-additive genetic factors and shared environmental effects. We conducted a gene expression study in blood samples of 862 individuals from 312 nuclear families containing MZ or DZ twin pairs using both pedigree and genotype information. From a pedigree analysis we show that the vast majority of genetic variation across 17,994 probes is additive, although non-additive genetic variation is identified for 960 transcripts. For 180 of the 960 transcripts with non-additive genetic variation, we identify expression quantitative trait loci (eQTL) with dominance effects in a sample of 339 unrelated individuals and replicate 31% of these associations in an independent sample of 139 unrelated individuals. Over-dominance was detected and replicated for a trans association between rs12313805 and ETV6, located 4MB apart on chromosome 12. Surprisingly, only 17 probes exhibit significant levels of common environmental effects, suggesting that environmental and lifestyle factors common to a family do not affect expression variation for most transcripts, at least those measured in blood. Consistent with the genetic architecture of common diseases, gene expression is predominantly additive, but a minority of transcripts display non-additive effects. PMID:23696747

Congruence of additive and non-additive effects on gene expression estimated from pedigree and SNP data.

PubMed

Powell, Joseph E; Henders, Anjali K; McRae, Allan F; Kim, Jinhee; Hemani, Gibran; Martin, Nicholas G; Dermitzakis, Emmanouil T; Gibson, Greg; Montgomery, Grant W; Visscher, Peter M

2013-05-01

There is increasing evidence that heritable variation in gene expression underlies genetic variation in susceptibility to disease. Therefore, a comprehensive understanding of the similarity between relatives for transcript variation is warranted--in particular, dissection of phenotypic variation into additive and non-additive genetic factors and shared environmental effects. We conducted a gene expression study in blood samples of 862 individuals from 312 nuclear families containing MZ or DZ twin pairs using both pedigree and genotype information. From a pedigree analysis we show that the vast majority of genetic variation across 17,994 probes is additive, although non-additive genetic variation is identified for 960 transcripts. For 180 of the 960 transcripts with non-additive genetic variation, we identify expression quantitative trait loci (eQTL) with dominance effects in a sample of 339 unrelated individuals and replicate 31% of these associations in an independent sample of 139 unrelated individuals. Over-dominance was detected and replicated for a trans association between rs12313805 and ETV6, located 4MB apart on chromosome 12. Surprisingly, only 17 probes exhibit significant levels of common environmental effects, suggesting that environmental and lifestyle factors common to a family do not affect expression variation for most transcripts, at least those measured in blood. Consistent with the genetic architecture of common diseases, gene expression is predominantly additive, but a minority of transcripts display non-additive effects.

The Prognostic and Clinicopathological Significance of Tumor-Associated Macrophages in Patients with Gastric Cancer: A Meta-Analysis.

PubMed

Yin, Songcheng; Huang, Jinyu; Li, Zhan; Zhang, Junyan; Luo, Jiazi; Lu, Chunyang; Xu, Hao; Xu, Huimian

2017-01-01

Comprehensive studies have investigated the prognostic and clinicopathological value of tumor-associated macrophages (TAMs) in gastric cancer patients, yet results remain controversial. Therefore, we performed a meta-analysis to clarify this issue. PubMed, Embase, and the Cochrane Library databases were searched to identify eligible studies. We extracted hazard ratios (HRs) and odds ratios (ORs) with their corresponding 95% confidence intervals (95% CIs) to estimate the effect sizes. In addition, subgroup analysis and sensitivity analysis were also conducted. A total of 19 studies involving 2242 patients were included. High generalised TAMs density was significantly associated with poor overall survival (OS) (HR 1.49, 95% CI 1.15-1.95). Subgroup analysis revealed that CD68+ TAMs had no significant effect on OS (HR 1.38, 95% CI 1.00-1.91). High M1 TAMs density was correlated with better OS (HR 0.45, 95% CI 0.32-0.65). By contrast, high density of M2 TAMs was correlated with a poor prognosis for OS (HR 1.48, 95% CI 1.25-1.75). Furthermore, high M2 TAMs density was correlated with larger tumor size, diffuse Lauren type, poor histologic differentiation, deeper tumor invasion, lymph node metastasis, and advanced TNM stage. Overall, this meta-analysis reveal that although CD68+ TAMs infiltration has the neutral prognostic effects on OS, the M1/M2 polarization of TAMs are predicative factor of prognosis in gastric cancer patients.

The significance of reduced respiratory chain enzyme activities: clinical, biochemical and radiological associations.

PubMed

Mordekar, S R; Guthrie, P; Bonham, J R; Olpin, S E; Hargreaves, I; Baxter, P S

2006-03-01

Mitochondrial diseases are an important group of neurometabolic disorders in children with varied clinical presentations and diagnosis that can be difficult to confirm. To report the significance of reduced respiratory chain enzyme (RCE) activity in muscle biopsy samples from children. Retrospective odds ratio was used to compare clinical and biochemical features, DNA studies, neuroimaging, and muscle biopsies in 18 children with and 48 without reduced RCE activity. Children with reduced RCE activity were significantly more likely to have consanguineous parents, to present with acute encephalopathy and lactic acidaemia and/or within the first year of life; to have an axonal neuropathy, CSF lactate >4 mmol/l; and/or to have signal change in the basal ganglia. There were positive associations with a maternal family history of possible mitochondrial cytopathy; a presentation with failure to thrive and lactic acidaemia, ragged red fibres, reduced fibroblast fatty acid oxidation and with an abnormal allopurinol loading test. There was no association with ophthalmic abnormalities, deafness, epilepsy or myopathy. The association of these clinical, biochemical and radiological features with reduced RCE activity suggests a possible causative link.

Significant factors associated with fatal outcome in emergency open surgery for perforated peptic ulcer

PubMed Central

Testini, Mario; Portincasa, Piero; Piccinni, Giuseppe; Lissidini, Germana; Pellegrini, Fabio; Greco, Luigi

2003-01-01

AIM: To evaluate the main factors associated with mortality in patients undergoing surgery for perforated peptic ulcer referred to an academic department of general surgery in a large southern Italian city. METHODS: One hundred and forty-nine consecutive patients (M:F ratio = 110:39, mean age 52 yrs, range 16-95) with peptic ulcer disease were investigated for clinical history (including age, sex, previous history of peptic ulcer, associated diseases, delayed abdominal surgery, ulcer site, operation type, shock on admission, postoperative general complications, and intra-abdominal and/or wound infections), serum analyses and radiological findings. RESULTS: The overall mortality rate was 4.0%. Among all factors, an age above 65 years, one or more associated diseases, delayed abdominal surgery, shock on admission, postoperative abdominal complications and/or wound infections, were significantly associated (χ2) with increased mortality in patients undergoing surgery (0.0001 < P < 0.03). CONCLUSION: Factors such as concomitant diseases, shock on admission, delayed surgery, and postoperative abdominal and wound infections are significantly associated with fatal outcomes and need careful evaluation within the general workup of patients admitted for perforated peptic ulcer. PMID:14562406

Sniffing out significant “Pee values”: genome wide association study of asparagus anosmia

PubMed Central

Markt, Sarah C; Nuttall, Elizabeth; Turman, Constance; Sinnott, Jennifer; Rimm, Eric B; Ecsedy, Ethan; Unger, Robert H; Fall, Katja; Finn, Stephen; Jensen, Majken K; Rider, Jennifer R; Kraft, Peter

2016-01-01

Objective To determine the inherited factors associated with the ability to smell asparagus metabolites in urine. Design Genome wide association study. Setting Nurses’ Health Study and Health Professionals Follow-up Study cohorts. Participants 6909 men and women of European-American descent with available genetic data from genome wide association studies. Main outcome measure Participants were characterized as asparagus smellers if they strongly agreed with the prompt “after eating asparagus, you notice a strong characteristic odor in your urine,” and anosmic if otherwise. We calculated per-allele estimates of asparagus anosmia for about nine million single nucleotide polymorphisms using logistic regression. P values <5×10-8 were considered as genome wide significant. Results 58.0% of men (n=1449/2500) and 61.5% of women (n=2712/4409) had anosmia. 871 single nucleotide polymorphisms reached genome wide significance for asparagus anosmia, all in a region on chromosome 1 (1q44: 248139851-248595299) containing multiple genes in the olfactory receptor 2 (OR2) family. Conditional analyses revealed three independent markers associated with asparagus anosmia: rs13373863, rs71538191, and rs6689553. Conclusion A large proportion of people have asparagus anosmia. Genetic variation near multiple olfactory receptor genes is associated with the ability of an individual to smell the metabolites of asparagus in urine. Future replication studies are necessary before considering targeted therapies to help anosmic people discover what they are missing. PMID:27965198

Latitude is significantly associated with the prevalence of multiple sclerosis: a meta-analysis.

PubMed

Simpson, Steve; Blizzard, Leigh; Otahal, Petr; Van der Mei, Ingrid; Taylor, Bruce

2011-10-01

There is a striking latitudinal gradient in multiple sclerosis (MS) prevalence, but exceptions in Mediterranean Europe and northern Scandinavia, and some systematic reviews, have suggested that the gradient may be an artefact. The authors sought to evaluate the association between MS prevalence and latitude by meta-regression. Studies were sourced from online databases, reference mining and author referral. Prevalence estimates were age-standardised to the 2009 European population. Analyses were carried out by means of random-effects meta-regression, weighted with the inverse of within-study variance. The authors included 650 prevalence estimates from 321 peer-reviewed studies; 239 were age-standardised, and 159 provided sex-specific data. The authors found a significant positive association (change in prevalence per degree-latitude) between age-standardised prevalence (1.04, p<0.001) and latitude that diminished at high latitudes. Adjustment for prevalence year strengthened the association with latitude (2.60, p<0.001). An inverse gradient in the Italian region reversed on adjustment for MS-associated HLA-DRB1 allele distributions. Adjustment for HLA-DRB1 allele frequencies did not appreciably alter the gradient in Europe. Adjustment for some potential sources of bias did not affect the observed associations. This, the most comprehensive review of MS prevalence to date, has confirmed a statistically significant positive association between MS prevalence and latitude globally. Exceptions to the gradient in the Italian region and northern Scandinavia are likely a result of genetic and behavioural-cultural variations. The persistence of a positive gradient in Europe after adjustment for HLA-DRB1 allele frequencies strongly supports a role for environmental factors which vary with latitude, the most prominent candidates being ultraviolet radiation (UVR)/vitamin D.

Recruitment of Additional Corticospinal Pathways in the Human Brain with State-Dependent Paired Associative Stimulation.

PubMed

Kraus, Dominic; Naros, Georgios; Guggenberger, Robert; Leão, Maria Teresa; Ziemann, Ulf; Gharabaghi, Alireza

2018-02-07

Standard brain stimulation protocols modify human motor cortex excitability by modulating the gain of the activated corticospinal pathways. However, the restoration of motor function following lesions of the corticospinal tract requires also the recruitment of additional neurons to increase the net corticospinal output. For this purpose, we investigated a novel protocol based on brain state-dependent paired associative stimulation.Motor imagery (MI)-related electroencephalography was recorded in healthy males and females for brain state-dependent control of both cortical and peripheral stimulation in a brain-machine interface environment. State-dependency was investigated with concurrent, delayed, and independent stimulation relative to the MI task. Specifically, sensorimotor event-related desynchronization (ERD) in the β-band (16-22 Hz) triggered peripheral stimulation through passive hand opening by a robotic orthosis and transcranial magnetic stimulation to the respective cortical motor representation, either synchronously or subsequently. These MI-related paradigms were compared with paired cortical and peripheral input applied independent of the brain state. Cortical stimulation resulted in a significant increase in corticospinal excitability only when applied brain state-dependently and synchronously to peripheral input. These gains were resistant to a depotentiation task, revealed a nonlinear evolution of plasticity, and were mediated via the recruitment of additional corticospinal neurons rather than via synchronization of neuronal firing. Recruitment of additional corticospinal pathways may be achieved when cortical and peripheral inputs are applied concurrently, and during β-ERD. These findings resemble a gating mechanism and are potentially important for developing closed-loop brain stimulation for the treatment of hand paralysis following lesions of the corticospinal tract. SIGNIFICANCE STATEMENT The activity state of the motor system influences the

Effects of feed additives on ileal mucosa-associated microbiota composition of broiler chickens.

PubMed

Ruiz, R; Peinado, M J; Aranda-Olmedo, I; Abecia, L; Suárez-Pereira, E; Ortiz Mellet, C; García Fernández, J M; Rubio, L A

2015-07-01

The effects of dietary supplementation with 2 recently developed feed additives on the composition of the mucosa-associated microbiota of the ileum were studied in growing broiler chickens. A total of 48 male 1-d-old broiler chickens of the Cobb 500 strain were distributed in 4 treatments with 2 replicates of 6 birds each. The 2 additives tested were a di-d-fructose dianhydride–enriched caramel (FC) and the garlic derivative propyl propane thiosulfonate (PTS-O). Dietary treatments were a control (commercial diet with no additive), INU (20 g inulin/kg diet), CAR (20 g FC/kg diet), and GAR (90 mgPTS-O/kg diet). As a result of this study, inulin supplementation resulted in lower (P < 0.05) and FC feeding resulted in higher (P < 0.05) Blautia coccoides/Eubacterium rectale log10 number of copies respect to controls. Higher (P < 0.05) bifidobacteria log10 number of copies with respect to the controls was determined in the ileal mucosa of birds fed the PTS-O–supplemented diet. Denaturing gradient gel electrophoresis and PCR analysis on Bifidobacterium spp. revealed the presence of Bifidobacterium longum, Bifidobacterium pseudolongum, and Bifidobacterium pseudocatenulatum in samples from chickens fed the control and the PTS-O–supplemented diet. Bifidobacterium longum was exclusively found in poultry fed the control diet, whereas B. pseudocatenulatum was found only in poultry fed the PTS-O–supplemented diet. This study showed that both PTS-O and FC were able to modulate the composition of the ileal mucosa-associated microbiota of growing broiler chickens. Finally, in addition to B. pseudolongum, the presence of B. longum and B. pseudocatenulatum, species not previously described in intestinal samples of broilers, was also demonstrated.

[Malassezia yeasts and their significance in dermatology].

PubMed

Hort, W; Nilles, M; Mayser, P

2006-07-01

Yeasts of the genus Malassezia belong to the normal microflora of the human skin. In addition they are known to cause a variety of skin diseases; the most frequent of which is pityriasis versicolor. Malassezia yeasts are also thought to be associated with seborrheic dermatitis, dandruff and Malassezia folliculitis. Recently the significance of Malassezia yeasts as a trigger factor for atopic dermatitis of the head and neck region has been pointed out. The role of the Malassezia yeasts in these different diseases has been controversial in the past and remains an issue because of difficulties in isolation, culture and differentiation of the organism. Thanks to molecular techniques, 10 species can actually be differentiated. The article presents the different Malassezia-associated diseases, their clinical picture, diagnosis and appropriate therapy. In addition the speciation of Malassezia is reviewed.

Additional risk factors for infection by multidrug-resistant pathogens in healthcare-associated infection: a large cohort study.

PubMed

Cardoso, Teresa; Ribeiro, Orquídea; Aragão, Irene César; Costa-Pereira, Altamiro; Sarmento, António Eugénio

2012-12-26

There is a lack of consensus regarding the definition of risk factors for healthcare-associated infection (HCAI). The purpose of this study was to identify additional risk factors for HCAI, which are not included in the current definition of HCAI, associated with infection by multidrug-resistant (MDR) pathogens, in all hospitalized infected patients from the community. This 1-year prospective cohort study included all patients with infection admitted to a large, tertiary care, university hospital. Risk factors not included in the HCAI definition, and independently associated with MDR pathogen infection, namely MDR Gram-negative (MDR-GN) and ESKAPE microorganisms (vancomycin-resistant Enterococcus faecium, methicillin-resistant Staphylococcus aureus, extended-spectrum beta-lactamase-producing Escherichia coli and Klebsiella species, carbapenem-hydrolyzing Klebsiella pneumonia and MDR Acinetobacter baumannii, Pseudomonas aeruginosa, Enterobacter species), were identified by logistic regression among patients admitted from the community (either with community-acquired or HCAI). There were 1035 patients with infection, 718 from the community. Of these, 439 (61%) had microbiologic documentation; 123 were MDR (28%). Among MDR: 104 (85%) had MDR-GN and 41 (33%) had an ESKAPE infection. Independent risk factors associated with MDR and MDR-GN infection were: age (adjusted odds ratio (OR) = 1.7 and 1.5, p = 0.001 and p = 0.009, respectively), and hospitalization in the previous year (between 4 and 12 months previously) (adjusted OR = 2.0 and 1,7, p = 0.008 and p = 0.048, respectively). Infection by pathogens from the ESKAPE group was independently associated with previous antibiotic therapy (adjusted OR = 7.2, p < 0.001) and a Karnofsky index <70 (adjusted OR = 3.7, p = 0.003). Patients with infection by MDR, MDR-GN and pathogens from the ESKAPE group had significantly higher rates of inadequate antibiotic therapy than those without (46% vs 7%, 44% vs 10%, 61% vs 15

Additional risk factors for infection by multidrug-resistant pathogens in healthcare-associated infection: a large cohort study

PubMed Central

2012-01-01

Background There is a lack of consensus regarding the definition of risk factors for healthcare-associated infection (HCAI). The purpose of this study was to identify additional risk factors for HCAI, which are not included in the current definition of HCAI, associated with infection by multidrug-resistant (MDR) pathogens, in all hospitalized infected patients from the community. Methods This 1-year prospective cohort study included all patients with infection admitted to a large, tertiary care, university hospital. Risk factors not included in the HCAI definition, and independently associated with MDR pathogen infection, namely MDR Gram-negative (MDR-GN) and ESKAPE microorganisms (vancomycin-resistant Enterococcus faecium, methicillin-resistant Staphylococcus aureus, extended-spectrum beta-lactamase-producing Escherichia coli and Klebsiella species, carbapenem-hydrolyzing Klebsiella pneumonia and MDR Acinetobacter baumannii, Pseudomonas aeruginosa, Enterobacter species), were identified by logistic regression among patients admitted from the community (either with community-acquired or HCAI). Results There were 1035 patients with infection, 718 from the community. Of these, 439 (61%) had microbiologic documentation; 123 were MDR (28%). Among MDR: 104 (85%) had MDR-GN and 41 (33%) had an ESKAPE infection. Independent risk factors associated with MDR and MDR-GN infection were: age (adjusted odds ratio (OR) = 1.7 and 1.5, p = 0.001 and p = 0.009, respectively), and hospitalization in the previous year (between 4 and 12 months previously) (adjusted OR = 2.0 and 1,7, p = 0.008 and p = 0.048, respectively). Infection by pathogens from the ESKAPE group was independently associated with previous antibiotic therapy (adjusted OR = 7.2, p < 0.001) and a Karnofsky index <70 (adjusted OR = 3.7, p = 0.003). Patients with infection by MDR, MDR-GN and pathogens from the ESKAPE group had significantly higher rates of inadequate antibiotic therapy than those without (46% vs 7

Factors Significantly Associated With the Increased Prevalence of Carotid Atherosclerosis in a Northeast Chinese Middle-aged and Elderly Population: A Cross-sectional Study.

PubMed

Pan, Xi-Feng; Lai, Ya-Xin; Gu, Jian-Qiu; Wang, Hao-Yu; Liu, Ai-Hua; Shan, Zhong-Yan

2016-04-01

Carotid atherosclerosis is associated with many serious cardiovascular diseases; hence, it is necessary to identify factors related to its occurrence in order to develop preventive and therapeutic strategies. This study was conducted to identify risk factors associated with carotid atherosclerosis among the population residing in Northeast China.This epidemiological survey was conducted in a representative group of relatively healthy community residents. All participants answered questions about their medical histories and underwent physical examination, blood biochemical analysis, and ultrasonography examinations of their necks and abdomens. The prevalence rates of carotid atherosclerosis under different factors and conditions were then analyzed.The results of this study showed that age, gender, and diabetes significantly affected the prevalence of carotid atherosclerosis in this Northeast Chinese population. In addition, gender-based subgroup analysis revealed additional factors correlated with the prevalence of carotid atherosclerosis in men or women, although their correlations were not significant in the overall population. While high serum TC and LDL-C levels were risk factors for carotid atherosclerosis in men, it showed no clear correlation with the prevalence of carotid atherosclerosis in women. In contrast, the prevalence of carotid atherosclerosis in female participants with high serum TG level, hypertension, obesity and nonalcoholic fatty liver disease were higher than that of the control population, a trend not observed in male participants.Older age, male sex, and diabetes were independently associated with increased risk of carotid atherosclerosis in Northeast China. These findings could lead to improved screening for carotid atherosclerosis for better disease management.

Methotrexate for uveitis associated with juvenile idiopathic arthritis: value and requirement for additional anti-inflammatory medication.

PubMed

Heiligenhaus, A; Mingels, A; Heinz, C; Ganser, G

2007-01-01

To study the value of methotrexate (MTX) and the requirement for additional anti-inflammatory drugs for the treatment of severe chronic iridocyclitis associated with juvenile idiopathic arthritis (JIA). Institutional study of 35 consecutive patients with JIA started on MTX as the single systemic immunosuppressive drug for the treatment of associated iridocyclitis. The clinical epidemiologic data, course of visual acuity (VA), development of complications, and the need for additional anti-inflammatory drugs were analyzed. Mean follow-up with MTX treatment was 27.6 months. Uveitic complications were present in 31 patients before MTX treatment. With MTX, quiescence of uveitis was obtained with (n=21) or without (n=4) additional topical steroids. Additional systemic immunosuppressive drugs were required in another 7 patients: cyclosporine A (n=4), azathioprine (n=1), infliximab (n=1), or etanercept (n=1). Three patients had active uveitis at the end of the follow-up period. During MTX therapy, uveitis first developed in the unaffected fellow eyes in 2 patients, and secondary glaucoma or ocular hypertension occurred in 7 patients. The VA deteriorated in 6, improved in 13, and was stable in the remaining eyes. The data suggest that MTX is very effective in controlling inflammation of uveitis in patients with JIA. However, additional topical steroids or systemic immunosuppressive drugs are often required.

Addition of immunosuppressive treatment to hemoperfusion is associated with improved survival after paraquat poisoning: a nationwide study.

PubMed

Wu, Wen-Pyng; Lai, Ming-Nan; Lin, Ching-Heng; Li, Yu-Fen; Lin, Ching-Yuang; Wu, Ming-Ju

2014-01-01

Paraquat poisoning associates very high mortality rate. Early treatment with hemoperfusion is strongly suggested by animal and human studies. Although the survival benefit of additional immunosuppressive treatment (IST) in combination with hemoperfusion is also reported since 1971, the large-scale randomized control trials to confirm the effects of IST is difficult to be executed. Therefore, we designed this nationwide large-scale population-based retrospective cohort study to investigate the outcome of paraquat poisoning with hemoperfusion and the additional effects of IST combined with hemoperfusion. This nationwide retrospective cohort study utilized data retrieved from the National Health Insurance Research Database (NHIRD) of Taiwan. A total of 1811 hospitalized patients with a diagnosis of paraquat poisoning who received hemoperfusion between 1997 and 2009 were enrolled. The mean age of all 1811 study subjects was 47.3 years. 70% was male. The overall survival rate was only 26.4%. Respiratory failure and renal failure were diagnosed in 56.2% and 36% patients. The average frequency of hemoperfusion was twice. IST was added in 42.2% patients. IST significantly increases survival rate (from 24.3% to 29.3%, P<0.001). The combined IST with methylprednisolone, cyclophosphamide and dexamethasone associates with the highest survival rate (48%, P<0.001). Moreover, patients younger than 45 years of age in the IST group had the best survival (41.0% vs. 33.7%, p<0.001). Our results support the use of IST with hemoperfusion for paraquat-poisoned patients. The best survival effect of IST is the combination of methylprednisolone, cyclophosphamide and daily dexamethasone, especially in patients with younger age.

Significant association of full-thickness rotator cuff tears and estrogen-related receptor-β (ESRRB).

PubMed

Teerlink, Craig C; Cannon-Albright, Lisa A; Tashjian, Robert Z

2015-02-01

The precise etiology of rotator cuff disease is unknown, but prior evidence suggests a role for genetic factors. Variants of estrogen-related receptor-β (ESRRB) have been previously associated with rotator cuff disease. The purpose of the present study was to confirm the association between multiple candidate genes, including ESRRB, and rotator cuff disease in an independent set of patients with rotator cuff tear. The Illumina 5M (Illumina Inc, San Diego, CA, USA) single nucleotide polymorphism (SNP) platform was used to genotype 175 patients with rotator cuff tear. Genotypes were used to select a set of 2595 genetically matched Caucasian controls available from the Illumina iControls database. Tests of association were performed with Genome-wide Efficient Mixed Model Association (GEMMA) software at 69 SNPs that fell within 20 kb of 6 candidate genes (DEFB1, DENND2C, ESRRB, FGF3, FGF10, and FGFR1). Tests of association revealed 1 significantly associated SNP occurring in ESRRB (rs17583842; P = 4.4E-4). Another SNP within ESRRB (rs7157192) had a nominal P value of 7.8E-3. FastPHASE software estimated 2 frequent haplotypes among 54 individuals who carried both risk alleles at these 2 SNPs. The first haplotype had a frequency of 13.9% (n = 15) in risk-allele carriers and only 2.2% in controls (odds ratio, 6.9; 95% confidence interval, 3.9-2.2). The second haplotype had a frequency of 12.9% in risk-allele carriers and only 2.7% in controls (odds ratio, 5.3; 95% confidence interval, 3.0-9.5). The significant association and the presence of high-risk haplotypes identified in the ESRRB gene confirm the association of variants in ESRRB and rotator cuff disease. Copyright © 2015 Journal of Shoulder and Elbow Surgery Board of Trustees. All rights reserved.

The cost efficiency of HPV vaccines is significantly underestimated due to omission of conisation-associated prematurity with neonatal mortality and morbidity.

PubMed

Soergel, Philipp; Makowski, Lars; Schippert, Cordula; Staboulidou, Ismini; Hille, Ursula; Hillemanns, Peter

2012-02-01

Cervical intraepithelial neoplasia (CIN) represents the precursor of invasive cervical cancer and is associated with human papillomavirus infection (HPV) against which two vaccines have been approved in the last years. Standard treatments of high-grade CIN are conisation procedures, which are associated with an increased risk of subsequent pregnancy complications like premature delivery and possible subsequent life-long disability. HPV vaccination has therefore the potential to decrease neonatal morbidity and mortality. This has not been taken into account in published cost-effectiveness models. We calculated the possible reduction rate of conisations for different vaccination strategies for Germany. Using this rate, we computed the reduction of conisation-associated preterm deliveries, life-long disability and neonatal death due to prematurity. The number of life-years saved (LYS) and gain in quality-adjusted life-years (QALYs) was estimated. The incremental costs per LYS / additional QALY were calculated. The reduction of conisation procedures was highest in scenario I (vaccination coverage 90% prior to HPV exposition) with about 50%. The costs per LYS or additional QALY were lowest in scenario I, II and III with 45,101 € or 43,505-47,855 € and rose up to 60,544 € or 58,401-64,240 € in scenario V (50% vaccinated prior to sexual activity + additional 20% catch-up at a mean age of 20 y). Regarding the HPV 16 / 18 vaccines as "vaccines against conisation-related neonatal morbidity and mortality" alone, they already have the potential to be cost-effective. This effect adds up to reduction of cervical cancer cases and decreased costs of screening for CIN. Further studies on cost-effectiveness of HPV vaccination should take the significant amount of neonatal morbidity and mortality into account.

Expression and significance of glucose transporter-1, P-glycoprotein, multidrug resistance-associated protein and glutathione S-transferase-π in laryngeal carcinoma.

PubMed

Mao, Zhong-Ping; Zhao, Li-Jun; Zhou, Shui-Hong; Liu, Meng-Qin; Tan, Wei-Feng; Yao, Hong-Tian

2015-02-01

Increasing glucose transporter-1 (GLUT-1) activity is one of the most important ways to increase the cellular influx of glucose. We previously demonstrated that increased GLUT-1 expression was an independent predictor of survival in patients with laryngeal carcinoma. Thus, GLUT-1 may present a novel therapeutic target in laryngeal carcinoma. In this study, the expression of GLUT-1, P-glycoprotein (P-gp), multidrug resistance-associated protein 1 (MRP1) and glutathione S-transferase-π (GST-π) in laryngeal carcinomas was investigated by immunohistochemistry. Additionally, possible correlations between GLUT-1 and P-gp, MRP1 and GST-π and various clinicopathological parameters were analyzed. In this study, 52.9% (18/34), 58.8% (20/34), 20.6% (7/34) and 58.8% (20/34) of the laryngeal carcinomas were positive for GLUT-1, P-gp, MRP1 and GST-π, respectively. The expression of GLUT-1, P-gp, MRP1 and GST-π was higher in laryngeal carcinoma specimens when compared with laryngeal precancerous lesions (P<0.05). Pearson's correlation analysis showed correlations between GLUT-1 and P-gp (r=0.364; P=0.034), GLUT-1 and MRP1 (r=0.359; P=0.037) and P-gp and GST-π (r=0.426; P=0.012). GLUT-1 expression was found to significantly correlate with tumor-node-metastasis classification (P=0.02) and clinical stage (P=0.037). Furthermore, P-gp was found to significantly correlate with clinical stage (P=0.026). Univariate analysis showed that MRP1 expression was significantly associated with poor survival (c 2 =5.16; P=0.023). Multivariate analysis revealed that lymph node metastasis (P=0.009) and MRP1 overexpression (P=0.023) were significant predictors of poor survival. In the present study, the expression of GLUT-1, P-gp, MRP1 and GST-π in laryngeal carcinomas was investigated, as well as the correlations between these proteins. P-gp was found to significantly correlate with clinical stage, while MRP1 overexpression was significantly associated with poor survival.

The Individual, Joint, and Additive Interaction Associations of Aerobic-Based Physical Activity and Muscle Strengthening Activities on Metabolic Syndrome.

PubMed

Dankel, Scott J; Loenneke, Jeremy P; Loprinzi, Paul D

2016-12-01

Previous research has demonstrated that physical activity and muscle strengthening activities are independently and inversely associated with metabolic syndrome. Despite a number of studies examining the individual associations, only a few studies have examined the joint associations, and to our knowledge, no previous studies have examined the potential additive interaction of performing muscle strengthening activities and aerobic-based physical activity and their association with metabolic syndrome. Using data from the 2003 to 2006 National Health and Nutrition Examination Survey (NHANES), we computed three separate multivariable logistic regression models to examine the individual, combined, and additive interaction of meeting guidelines for accelerometer-assessed physical activity and self-reported muscle strengthening activities, and their association with metabolic syndrome. We found that individuals meeting physical activity and muscle strengthening activity guidelines, respectively, were at 61 and 25 % lower odds of having metabolic syndrome. Furthermore, individuals meeting both guidelines had the lowest odds of having metabolic syndrome (70 %), in part due to the additive interaction of performing both modes of exercise. In this national sample, accelerometer-assessed physical activity and muscle strengthening activities were synergistically associated with metabolic syndrome.

Identification of additional risk loci for stroke and small vessel disease: a meta-analysis of genome-wide association studies.

PubMed

2016-06-01

Genetic determinants of stroke, the leading neurological cause of death and disability, are poorly understood and have seldom been explored in the general population. Our aim was to identify additional loci for stroke by doing a meta-analysis of genome-wide association studies. For the discovery sample, we did a genome-wide analysis of common genetic variants associated with incident stroke risk in 18 population-based cohorts comprising 84 961 participants, of whom 4348 had stroke. Stroke diagnosis was ascertained and validated by the study investigators. Mean age at stroke ranged from 45·8 years to 76·4 years, and data collection in the studies took place between 1948 and 2013. We did validation analyses for variants yielding a significant association (at p<5 × 10(-6)) with all-stroke, ischaemic stroke, cardioembolic ischaemic stroke, or non-cardioembolic ischaemic stroke in the largest available cross-sectional studies (70 804 participants, of whom 19 816 had stroke). Summary-level results of discovery and follow-up stages were combined using inverse-variance weighted fixed-effects meta-analysis, and in-silico lookups were done in stroke subtypes. For genome-wide significant findings (at p<5 × 10(-8)), we explored associations with additional cerebrovascular phenotypes and did functional experiments using conditional (inducible) deletion of the probable causal gene in mice. We also studied the expression of orthologs of this probable causal gene and its effects on cerebral vasculature in zebrafish mutants. We replicated seven of eight known loci associated with risk for ischaemic stroke, and identified a novel locus at chromosome 6p25 (rs12204590, near FOXF2) associated with risk of all-stroke (odds ratio [OR] 1·08, 95% CI 1·05-1·12, p=1·48 × 10(-8); minor allele frequency 21%). The rs12204590 stroke risk allele was also associated with increased MRI-defined burden of white matter hyperintensity-a marker of cerebral small vessel disease

Significant association of serum creatinine with HbA1C in impaired glucose tolerant Pakistani subjects

PubMed Central

Farasat, Tasnim; Sharif, Saima; Naz, Shagufta; Fazal, Sabiha

2015-01-01

Objective: The present study was conducted to assess the serum concentration of creatinine and determine its relationship with potential risk factors of diabetes in Impaired Glucose tolerance subjects. Methods: This cross sectional study was conducted on 100 IGT patients who attended Amin Hayat diabetic center in Lahore from January 2011- June 2011. Patients with age group 34-67 years, (both sexes) were included in the study. Different demographic parameters as age, BMI, WHR, B.P, personal history and socioeconomic status were recorded. Oral Glucose Tolerance Test was performed. The biochemical parameters including HbA1c, lipid profile, urea, uric acid, creatinine and bilirubin level were measured by chemistry analyzer. Results: A strong correlation between creatinine and HbA1c was observed. The level of creatinine was also significantly associated with age in IGT subjects. Creatinine is non-significantly correlated with Cholesterol, LDL-Chol and TG while negatively significantly associated with BMI, fasting blood glucose and HDL-Chol. Conclusion: The present study concluded significant association of serum creatinine with HbA1c, BMI and HDL cholesterol. PMID:26430445

Significant association of serum creatinine with HbA1C in impaired glucose tolerant Pakistani subjects.

PubMed

Farasat, Tasnim; Sharif, Saima; Naz, Shagufta; Fazal, Sabiha

2015-01-01

The present study was conducted to assess the serum concentration of creatinine and determine its relationship with potential risk factors of diabetes in Impaired Glucose tolerance subjects. This cross sectional study was conducted on 100 IGT patients who attended Amin Hayat diabetic center in Lahore from January 2011- June 2011. Patients with age group 34-67 years, (both sexes) were included in the study. Different demographic parameters as age, BMI, WHR, B.P, personal history and socioeconomic status were recorded. Oral Glucose Tolerance Test was performed. The biochemical parameters including HbA1c, lipid profile, urea, uric acid, creatinine and bilirubin level were measured by chemistry analyzer. A strong correlation between creatinine and HbA1c was observed. The level of creatinine was also significantly associated with age in IGT subjects. Creatinine is non-significantly correlated with Cholesterol, LDL-Chol and TG while negatively significantly associated with BMI, fasting blood glucose and HDL-Chol. The present study concluded significant association of serum creatinine with HbA1c, BMI and HDL cholesterol.

A Genome-wide Association Study of Dupuytren Disease Reveals 17 Additional Variants Implicated in Fibrosis.

PubMed

Ng, Michael; Thakkar, Dipti; Southam, Lorraine; Werker, Paul; Ophoff, Roel; Becker, Kerstin; Nothnagel, Michael; Franke, Andre; Nürnberg, Peter; Espirito-Santo, Ana Isabel; Izadi, David; Hennies, Hans Christian; Nanchahal, Jagdeep; Zeggini, Eleftheria; Furniss, Dominic

2017-09-07

Individuals with Dupuytren disease (DD) are commonly seen by physicians and surgeons across multiple specialties. It is an increasingly common and disabling fibroproliferative disorder of the palmar fascia, which leads to flexion contractures of the digits, and is associated with other tissue-specific fibroses. DD affects between 5% and 25% of people of European descent and is the most common inherited disease of connective tissue. We undertook the largest GWAS to date in individuals with a surgically validated diagnosis of DD from the UK, with replication in British, Dutch, and German individuals. We validated association at all nine previously described signals and discovered 17 additional variants with p ≤ 5 × 10 -8 . As a proof of principle, we demonstrated correlation of the high-risk genotype at the statistically most strongly associated variant with decreased secretion of the soluble WNT-antagonist SFRP4, in surgical specimen-derived DD myofibroblasts. These results highlight important pathways involved in the pathogenesis of fibrosis, including WNT signaling, extracellular matrix modulation, and inflammation. In addition, many associated loci contain genes that were hitherto unrecognized as playing a role in fibrosis, opening up new avenues of research that may lead to novel treatments for DD and fibrosis more generally. DD represents an ideal human model disease for fibrosis research. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

Clinical analysis and prognostic significance of haemophagocytic lymphohistiocytosis-associated anaplastic large cell lymphoma in children.

PubMed

Pasqualini, Claudia; Minard-Colin, Veronique; Saada, Veronique; Lamant, Laurence; Delsol, Georges; Patte, Catherine; Le Deley, Marie-Cécile; Valteau-Couanet, Dominique; Brugières, Laurence

2014-04-01

Haemophagocytic lymphohistiocytosis (HLH) has been rarely described in children treated for an anaplastic large-cell lymphoma (ALCL). We evaluated the incidence, the clinical and histological characteristics and the prognosis of HLH associated-ALCL. The medical, biological, cytological and histological data of patients treated for ALK-positive ALCL in the paediatric department of a single institution between 1975 and 2008 were analysed and assessed for HLH according to diagnosis criteria of the Histiocyte Society. Data concerning a series of 50 consecutive children with ALCL were reviewed. HLH-associated ALCL was observed in 12% of the patients. Lung involvement was significantly more frequent in HLH-associated ALCL patients than in the group without HLH (P = 0·004), as well as central nervous system (CNS) and bone marrow involvement (P = 0·001 and P = 0·007 respectively). The histological subtype in children with HLH-associated ALCL did not differ from that of the group without HLH. There was no significant difference between the two groups in 5-year EFS and OS (P = 0·91 and P > 0·99 respectively). In conclusion, HLH is not rare in paediatric ALCL. Despite a high incidence of visceral, CNS and bone marrow involvement, HLH does not seem to exert a significant impact on outcome in children treated for ALCL. © 2014 John Wiley & Sons Ltd.

Significant oral cancer risk associated with low socioeconomic status.

PubMed

Warnakulasuriya, Saman

2009-01-01

oral cancer were 1.85 (95% CI, 1.60-2.15; N=37 studies) for individuals with low educational attainment versus 1.84 (95% CI, 1.47-2.31; N=14) for those with low occupational social class versus and 2.41 (95% CI, 1.59-3.65; N=5) for people with low incomes. Subgroup analyses showed that low SES was significantly associated with increased oral cancer risk in high- and lower-income countries, across the world, and remained when adjusting for potential behavioural confounders. Oral cancer risk associated with low SES is significant and related to lifestyle risk factors. These results provide evidence to steer

Associating cooking additives with sodium hydroxide to pretreat bamboo residues for improving the enzymatic saccharification and monosaccharides production.

PubMed

Huang, Caoxing; He, Juan; Wang, Yan; Min, Douyong; Yong, Qiang

2015-10-01

Cooking additive pulping technique is used in kraft mill to increase delignification degree and pulp yield. In this work, cooking additives were firstly applied in the sodium hydroxide pretreatment for improving the bioconversion of bamboo residues to monosaccharides. Meanwhile, steam explosion and sulfuric acid pretreatments were also carried out on the sample to compare their impacts on monosaccharides production. Results indicated that associating anthraquinone with sodium hydroxide pretreatment showed the best performance in improving the original carbohydrates recovery, delignification, enzymatic saccharification, and monosaccharides production. After consecutive pretreatment and enzymatic saccharification process, 347.49 g, 307.48 g, 142.93 g, and 87.15 g of monosaccharides were released from 1000 g dry bamboo residues pretreated by sodium hydroxide associating with anthraquinone, sodium hydroxide, steam explosion and sulfuric acid, respectively. The results suggested that associating cooking additive with sodium hydroxide is an effective pretreatment for bamboo residues to enhance enzymatic saccharification for monosaccharides production. Copyright © 2015 Elsevier Ltd. All rights reserved.

HIV-Related Sexual Risk among African American Men Preceding Incarceration: Associations with Support from Significant Others, Family, and Friends.

PubMed

Coatsworth, Ashley M; Scheidell, Joy D; Wohl, David A; Whitehead, Nicole E; Golin, Carol E; Judon-Monk, Selena; Khan, Maria R

2017-02-01

We evaluated the association between social support received from significant others, family, and friends and HIV-related sexual risk behaviors among African American men involved in the criminal justice system. Project DISRUPT is a cohort study among African American men released from prison in North Carolina (N = 189). During the baseline (in-prison) survey, we assessed the amount of support men perceived they had received from significant others, family, and friends. We measured associations between low support from each source (significant others, family, or friends were associated with poverty and homelessness, mental disorders, and substance use. Adjusting for age, poverty, and other sources of support, perceiving low support from significant others was strongly associated with multiple partnerships (fully adjusted odds ratio (OR) 2.64, 95% confidence interval (CI) 1.29-5.42). Low significant other support also was strongly associated with sex trade involvement when adjusting for age and poverty status (adjusted OR 3.51, 95% CI 1.25-9.85) but further adjustment for low family and friend support weakened the association (fully adjusted OR 2.81, 95% CI 0.92-8.55). Significant other support was not associated with other sex risk outcomes including concurrent partnerships, anal sex, or sex with an STI/HIV-infected partner. Low family support was associated with multiple partnerships in analyses adjusting for age and poverty (adjusted OR 1.98, 95% CI 1.05-3.76) but the association weakened and was no longer significant after adjusting for other sources of support (fully adjusted OR 1.40, 95% CI 0.65-3.00); family support was not correlated with other risk behaviors. Friend support was not significantly associated with sex risk outcomes. Indicators of overall support from any source were not associated with sex risk outcomes. Helping inmates

Whole-genome scan reveals significant non-additive effects for sire conception rate in Holstein cattle.

PubMed

Nicolini, Paula; Amorín, Rocío; Han, Yi; Peñagaricano, Francisco

2018-02-27

Service sire has a considerable impact on reproductive success in dairy cattle. Most gene mapping studies for bull fertility have focused on additive effects, while non-additive effects have been largely ignored. The main goal of this study was to assess the relevance of non-additive effects on Sire Conception Rate (SCR) in Holstein dairy cattle. The analysis included 7.5 k Holstein bulls with both SCR records and 57.8 k single nucleotide polymorphism (SNP) markers spanning the entire genome. The importance of non-additive effects was evaluated using an efficient two-step mixed model-based approach. Four genomic regions located on chromosomes BTA8, BTA9, BTA13 and BTA17 showed marked dominance and/or recessive effects. Most of these regions harbor genes, such as ADAM28, DNAJA1, TBC1D20, SPO11, PIWIL3 and TMEM119, that are directly implicated in testis development, male germ line maintenance, and sperm maturation. This study provides further evidence for the relevance of non-additive effects in fitness-related traits, such as male fertility. In addition, these findings may point out new strategies for improving service sire fertility in dairy cattle via marker-assisted selection.

A simulations approach for meta-analysis of genetic association studies based on additive genetic model.

PubMed

John, Majnu; Lencz, Todd; Malhotra, Anil K; Correll, Christoph U; Zhang, Jian-Ping

2018-06-01

Meta-analysis of genetic association studies is being increasingly used to assess phenotypic differences between genotype groups. When the underlying genetic model is assumed to be dominant or recessive, assessing the phenotype differences based on summary statistics, reported for individual studies in a meta-analysis, is a valid strategy. However, when the genetic model is additive, a similar strategy based on summary statistics will lead to biased results. This fact about the additive model is one of the things that we establish in this paper, using simulations. The main goal of this paper is to present an alternate strategy for the additive model based on simulating data for the individual studies. We show that the alternate strategy is far superior to the strategy based on summary statistics.

Addition of Immunosuppressive Treatment to Hemoperfusion Is Associated with Improved Survival after Paraquat Poisoning: A Nationwide Study

PubMed Central

Wu, Wen-Pyng; Lai, Ming-Nan; Lin, Ching-Heng; Li, Yu-Fen

2014-01-01

Paraquat poisoning associates very high mortality rate. Early treatment with hemoperfusion is strongly suggested by animal and human studies. Although the survival benefit of additional immunosuppressive treatment (IST) in combination with hemoperfusion is also reported since 1971, the large-scale randomized control trials to confirm the effects of IST is difficult to be executed. Therefore, we designed this nationwide large-scale population-based retrospective cohort study to investigate the outcome of paraquat poisoning with hemoperfusion and the additional effects of IST combined with hemoperfusion. This nationwide retrospective cohort study utilized data retrieved from the National Health Insurance Research Database (NHIRD) of Taiwan. A total of 1811 hospitalized patients with a diagnosis of paraquat poisoning who received hemoperfusion between 1997 and 2009 were enrolled. The mean age of all 1811 study subjects was 47.3 years. 70% was male. The overall survival rate was only 26.4%. Respiratory failure and renal failure were diagnosed in 56.2% and 36% patients. The average frequency of hemoperfusion was twice. IST was added in 42.2% patients. IST significantly increases survival rate (from 24.3% to 29.3%, P<0.001). The combined IST with methylprednisolone, cyclophosphamide and dexamethasone associates with the highest survival rate (48%, P<0.001). Moreover, patients younger than 45 years of age in the IST group had the best survival (41.0% vs. 33.7%, p<0.001). Our results support the use of IST with hemoperfusion for paraquat-poisoned patients. The best survival effect of IST is the combination of methylprednisolone, cyclophosphamide and daily dexamethasone, especially in patients with younger age. PMID:24475310

Pattern of intake of food additives associated with hyperactivity in Irish children and teenagers.

PubMed

Connolly, A; Hearty, A; Nugent, A; McKevitt, A; Boylan, E; Flynn, A; Gibney, M J

2010-04-01

A double-blind randomized intervention study has previously shown that a significant relationship exists between the consumption of various mixes of seven target additives by children and the onset of hyperactive behaviour. The present study set out to ascertain the pattern of intake of two mixes (A and B) of these seven target additives in Irish children and teenagers using the Irish national food consumption databases for children (n = 594) and teenagers (n = 441) and the National Food Ingredient Database. The majority of additive-containing foods consumed by both the children and teenagers contained one of the target additives. No food consumed by either the children or teenagers contained all seven of the target food additives. For each additive intake, estimates for every individual were made assuming that the additive was present at the maximum legal permitted level in those foods identified as containing it. For both groups, mean intakes of the food additives among consumers only were far below the doses used in the previous study on hyperactivity. Intakes at the 97.5th percentile of all food colours fell below the doses used in Mix B, while intakes for four of the six food colours were also below the doses used in Mix A. However, in the case of the preservative sodium benzoate, it exceeded the previously used dose in both children and teenagers. No child or teenager achieved the overall intakes used in the study linking food additives with hyperactivity.

Breast cancer-associated metastasis is significantly increased in a model of autoimmune arthritis

PubMed Central

Das Roy, Lopamudra; Pathangey, Latha B; Tinder, Teresa L; Schettini, Jorge L; Gruber, Helen E; Mukherjee, Pinku

2009-01-01

Introduction Sites of chronic inflammation are often associated with the establishment and growth of various malignancies including breast cancer. A common inflammatory condition in humans is autoimmune arthritis (AA) that causes inflammation and deformity of the joints. Other systemic effects associated with arthritis include increased cellular infiltration and inflammation of the lungs. Several studies have reported statistically significant risk ratios between AA and breast cancer. Despite this knowledge, available for a decade, it has never been questioned if the site of chronic inflammation linked to AA creates a milieu that attracts tumor cells to home and grow in the inflamed bones and lungs which are frequent sites of breast cancer metastasis. Methods To determine if chronic inflammation induced by autoimmune arthritis contributes to increased breast cancer-associated metastasis, we generated mammary gland tumors in SKG mice that were genetically prone to develop AA. Two breast cancer cell lines, one highly metastatic (4T1) and the other non-metastatic (TUBO) were used to generate the tumors in the mammary fat pad. Lung and bone metastasis and the associated inflammatory milieu were evaluated in the arthritic versus the non-arthritic mice. Results We report a three-fold increase in lung metastasis and a significant increase in the incidence of bone metastasis in the pro-arthritic and arthritic mice compared to non-arthritic control mice. We also report that the metastatic breast cancer cells augment the severity of arthritis resulting in a vicious cycle that increases both bone destruction and metastasis. Enhanced neutrophilic and granulocytic infiltration in lungs and bone of the pro-arthritic and arthritic mice and subsequent increase in circulating levels of proinflammatory cytokines, such as macrophage colony stimulating factor (M-CSF), interleukin-17 (IL-17), interleukin-6 (IL-6), vascular endothelial growth factor (VEGF), and tumor necrosis factor

Breast-cancer-associated metastasis is significantly increased in a model of autoimmune arthritis.

PubMed

Das Roy, Lopamudra; Pathangey, Latha B; Tinder, Teresa L; Schettini, Jorge L; Gruber, Helen E; Mukherjee, Pinku

2009-01-01

Sites of chronic inflammation are often associated with the establishment and growth of various malignancies including breast cancer. A common inflammatory condition in humans is autoimmune arthritis (AA) that causes inflammation and deformity of the joints. Other systemic effects associated with arthritis include increased cellular infiltration and inflammation of the lungs. Several studies have reported statistically significant risk ratios between AA and breast cancer. Despite this knowledge, available for a decade, it has never been questioned if the site of chronic inflammation linked to AA creates a milieu that attracts tumor cells to home and grow in the inflamed bones and lungs which are frequent sites of breast cancer metastasis. To determine if chronic inflammation induced by autoimmune arthritis contributes to increased breast cancer-associated metastasis, we generated mammary gland tumors in SKG mice that were genetically prone to develop AA. Two breast cancer cell lines, one highly metastatic (4T1) and the other non-metastatic (TUBO) were used to generate the tumors in the mammary fat pad. Lung and bone metastasis and the associated inflammatory milieu were evaluated in the arthritic versus the non-arthritic mice. We report a three-fold increase in lung metastasis and a significant increase in the incidence of bone metastasis in the pro-arthritic and arthritic mice compared to non-arthritic control mice. We also report that the metastatic breast cancer cells augment the severity of arthritis resulting in a vicious cycle that increases both bone destruction and metastasis. Enhanced neutrophilic and granulocytic infiltration in lungs and bone of the pro-arthritic and arthritic mice and subsequent increase in circulating levels of proinflammatory cytokines, such as macrophage colony stimulating factor (M-CSF), interleukin-17 (IL-17), interleukin-6 (IL-6), vascular endothelial growth factor (VEGF), and tumor necrosis factor-alpha (TNF-alpha) may contribute

Foot structure is significantly associated to subtalar joint kinetics and mechanical energetics.

PubMed

Maharaj, Jayishni N; Cresswell, Andrew G; Lichtwark, Glen A

2017-10-01

Foot structure has been implicated as a risk factor of numerous overuse injuries, however, the mechanism linking foot structure and the development of soft-tissue overuse injuries are not well understood. The aim of this study was to identify factors that could predict foot function during walking. A total of eleven variables (including measures of foot structure, anthropometry and spatiotemporal gait characteristics) were investigated for their predictive ability on identifying kinematic, kinetic and energetic components of the foot. Three-dimensional motion capture and force data were collected at preferred walking speed on an instrumented treadmill. Mechanical measures were subsequently assessed using a custom multi-segment foot model in Opensim. Factors with significant univariate associations were entered into multiple linear regression models to identify a group of factors independently associated with the mechanical measures. Although no model could be created for any of the kinematic measures analysed, approximately 46% and 37% of the variance in the kinetic and energetic measures were associated with three or two factors respectively. Arch-height ratio, foot length and step width were associated with peak subtalar joint (STJ) moment, while greater STJ negative work was correlated to a low arch-height ratio and greater foot mobility. The models presented in this study suggest that the soft-tissue structures of a flat-arched, mobile foot are at a greater risk of injury as they have greater requirements to absorb energy and generate larger forces. However, as these associations are only moderate, other measures may also have an influence. Copyright © 2017. Published by Elsevier B.V.

Expression of Oct-4 is significantly associated with the development and prognosis of colorectal cancer

PubMed Central

ZHOU, HUAN; HU, YU; WANG, WEIPENG; MAO, YONG; ZHU, JINGJIE; ZHOU, BIN; SUN, JING; ZHANG, XUEGUANG

2015-01-01

Octamer-binding transcription factor 4 (Oct-4), is an essential transcription factor, which is required for pluripotency and self-renewal in embryonic stem cells and germ cells. It is also involved in maintaining cancer stem-like properties in certain types of tumor, and is an important biomarker for cancer stem cells. The present study investigated whether Oct-4 expression was associated with colorectal cancer (CRC). In order to achieve this, primary CRC tissues, matched non-tumor tissues and benign polyp tissues, representing different stages of carcinogenesis, were obtained, and Oct-4 expression was analyzed using reverse transcription-quantitative polymerase chain reaction, flow cytometry analysis and immunohistochemistry. Furthermore, the medical records of patients with CRC were reviewed, and clinicopathological analysis was performed in order to assess the association between Oct-4 expression and certain clinicopathological parameters. It was shown that the transcription and translation of Oct-4 increased in a stepwise manner, from non-tumor to benign polyp tissues, and from benign polyps to CRC tissues. Oct-4 expression in CRC was significantly correlated with histological grade (P=0.007), lymph node metastasis (P=0.027), distant metastasis (P=0.017) and TNM stage (P=0.041). Kaplan-Meier survival curve analysis demonstrated that Oct-4+ cases had a shorter median survival time (37.0 months) compared with Oct-4− cases (76.0 months; P=0.001). These results indicated that aberrant expression of Oct-4 may be involved in the development of CRC. Thus, Oct-4 may be a biomarker for the prediction, diagnosis or assessment of prognosis in CRC, in addition to a potential target for the treatment of this disease. PMID:26622555

Microbial biosurfactants as additives for food industries.

PubMed

Campos, Jenyffer Medeiros; Stamford, Tânia Lúcia Montenegro; Sarubbo, Leonie Asfora; de Luna, Juliana Moura; Rufino, Raquel Diniz; Banat, Ibrahim M

2013-01-01

Microbial biosurfactants with high ability to reduce surface and interfacial surface tension and conferring important properties such as emulsification, detergency, solubilization, lubrication and phase dispersion have a wide range of potential applications in many industries. Significant interest in these compounds has been demonstrated by environmental, bioremediation, oil, petroleum, food, beverage, cosmetic and pharmaceutical industries attracted by their low toxicity, biodegradability and sustainable production technologies. Despite having significant potentials associated with emulsion formation, stabilization, antiadhesive and antimicrobial activities, significantly less output and applications have been reported in food industry. This has been exacerbated by uneconomical or uncompetitive costing issues for their production when compared to plant or chemical counterparts. In this review, biosurfactants properties, present uses and potential future applications as food additives acting as thickening, emulsifying, dispersing or stabilising agents in addition to the use of sustainable economic processes utilising agro-industrial wastes as alternative substrates for their production are discussed. © 2013 American Institute of Chemical Engineers.

Association between micronucleus frequency and cervical intraepithelial neoplasia grade in Thinprep cytological test and its significance.

PubMed

Shi, Yong-Hua; Wang, Bo-Wei; Tuokan, Talaf; Li, Qiao-Zhi; Zhang, Ya-Jing

2015-01-01

A micronucleus is an additional small nucleus formed due to chromosomes or chromosomal fragments fail to be incorporated into the nucleus during cell division. In this study, we assessed the utility of micronucleus counting as a screening tool in cervical precancerous lesions in Thinprep cytological test smears under oil immersion. High risk HPV was also detected by hybrid capture-2 in Thinprep cytological test smears. Our results showed that micronucleus counting was significantly higher in high-grade squamous intraepithelial lesion (HSIL) and invasive carcinoma cases compared to low-grade squamous intraepithelial lesion (LSIL) and non-neoplastic cases. Receiver operating characteristic (ROC) curve analysis revealed that micronucleus counting possessed a high degree of sensitivity and specificity for identifying HSIL and invasive carcinoma. Cut-off of 7.5 for MN counting gave a sensitivity of 89.6% and a specificity of 66.7% (P = 0.024 and AUC = 0.892) for detecting HSIL and invasive carcinoma lesions. Multiple linear regression analysis showed that only HSIL and invasive cancer lesions not age, duration of marital life and number of pregnancy are significantly associated with MN counting. The positive rate of high risk HPV was distinctly higher in LSIL, HSIL and invasive cancer than that in non-neoplstic categories. In conclusions, MN evaluation may be viewed as an effective biomarker for cervical cancer screening. The combination of MN count with HPV DNA detection and TCT may serve as an effective means to screen precancerous cervical lesions in most developing nations.

Significant Figures in Measurements with Uncertainty: A Working Criterion

NASA Astrophysics Data System (ADS)

Vilchis, Abraham

2017-03-01

Generally speaking, students have difficulty reporting out measurements and estimates of quantities used in the laboratory, and with handling the significant figures associated with them. When required to make calculation involving quantities with different numbers of significant figures, they have difficulty in assigning the corresponding digits to the final result. When in addition, the quantities have uncertainty, the operations entailed pose an even greater challenge. The article advocates for some working rules for students (and teachers) in an effort to combat this problem.

Mechanical and Electrical Properties of a Polyimide Film Significantly Enhanced by the Addition of Single-Wall Carbon Nanotubes

NASA Technical Reports Server (NTRS)

Meador, Michael A.

2005-01-01

Single-wall carbon nanotubes have been shown to possess a combination of outstanding mechanical, electrical, and thermal properties. The use of carbon nanotubes as an additive to improve the mechanical properties of polymers and/or enhance their thermal and electrical conductivity has been a topic of intense interest. Nanotube-modified polymeric materials could find a variety of applications in NASA missions including large-area antennas, solar arrays, and solar sails; radiation shielding materials for vehicles, habitats, and extravehicular activity suits; and multifunctional materials for vehicle structures and habitats. Use of these revolutionary materials could reduce vehicle weight significantly and improve vehicle performance and capabilities.

Efficient computation of significance levels for multiple associations in large studies of correlated data, including genomewide association studies.

PubMed

Dudbridge, Frank; Koeleman, Bobby P C

2004-09-01

Large exploratory studies, including candidate-gene-association testing, genomewide linkage-disequilibrium scans, and array-expression experiments, are becoming increasingly common. A serious problem for such studies is that statistical power is compromised by the need to control the false-positive rate for a large family of tests. Because multiple true associations are anticipated, methods have been proposed that combine evidence from the most significant tests, as a more powerful alternative to individually adjusted tests. The practical application of these methods is currently limited by a reliance on permutation testing to account for the correlated nature of single-nucleotide polymorphism (SNP)-association data. On a genomewide scale, this is both very time-consuming and impractical for repeated explorations with standard marker panels. Here, we alleviate these problems by fitting analytic distributions to the empirical distribution of combined evidence. We fit extreme-value distributions for fixed lengths of combined evidence and a beta distribution for the most significant length. An initial phase of permutation sampling is required to fit these distributions, but it can be completed more quickly than a simple permutation test and need be done only once for each panel of tests, after which the fitted parameters give a reusable calibration of the panel. Our approach is also a more efficient alternative to a standard permutation test. We demonstrate the accuracy of our approach and compare its efficiency with that of permutation tests on genomewide SNP data released by the International HapMap Consortium. The estimation of analytic distributions for combined evidence will allow these powerful methods to be applied more widely in large exploratory studies.

Variables Associated with Grade R English Additional Language Acquisition in Multilingual Rural Mpumalanga Schools

ERIC Educational Resources Information Center

Moodley, P.; Kritzinger, A.; Vinck, B.

2016-01-01

In a previous study Moodley, Kritzinger and Vinck (2014) found that formal English Additional Language (EAL) instruction contributed significantly better to listening and speaking skills in Grade R learners, than did a play-based approach. The finding in multilingual rural Mpumalanga schools was in agreement with numerous studies elsewhere.…

Molecular Analysis and Clinical Significance of Lactobacillus spp. Recovered from Clinical Specimens Presumptively Associated with Disease

PubMed Central

Martinez, Raquel M.; Hulten, Kristina G.; Bui, Uyen

2014-01-01

Lactobacillus spp. are part of the normal human flora and are generally assumed to be nonpathogenic. We determined the genotypic identification of >100 Lactobacillus isolates from clinical specimens in the context of presumed pathogenic potential (e.g., recovered as the single/predominant isolate from a sterile site or at ≥105 CFU/ml from urine). This study assessed the clinical significance and the frequency of occurrence of each Lactobacillus sp. We identified 16 species of Lactobacillus by 16S rRNA gene sequence analysis, 10 of which could not be associated with disease. While Lactobacillus rhamnosus, Lactobacillus gasseri, and Lactobacillus paracasei were associated with infections, L. gasseri was also a common colonizing/contaminating species. Lactobacillus casei, Lactobacillus johnsonii, and Lactobacillus delbrueckii were associated with at least one infection. Species commonly used in probiotic products (e.g., L. rhamnosus and L. casei) were identical, by 16S rRNA gene sequencing, to our isolates associated with disease. Human isolates of Lactobacillus spp. have differing site associations and levels of clinical significance. Knowing the niche and pathogenic potential of each Lactobacillus sp. can be of importance to both clinical microbiology and the food and probiotic supplement industry. PMID:24131686

Hypoalbuminemia Is Significantly Associated with Increased Clearance Time of High Dose Methotrexate in Patients Being Treated for Lymphoma or Leukemia

PubMed Central

Reiss, Samantha; Buie, Larry; Adel, Nelly; Goldman, Debra A.; Devlin, Sean M.; Douer, Dan

2017-01-01

As a weak acid, methotrexate (MTX) is bound to serum albumin and has variable protein binding. The purpose of this study was to assess serum albumin’s relationship with MTX pharmacokinetics by comparing MTX clearance and toxicities between patients with normal serum albumin to those with hypoalbuminemia. This single-center retrospective study included adult patients with leukemia or lymphoma who received their first MTX at a dose ≥ 1 gram/m2. Hypoalbuminemia was defined as serum albumin ≤ 3.4 g/dL. MTX clearance was defined as the first documented time the MTX level ≤ 0.05 micromolar. Fisher’s Exact tests and Wilcoxon Rank Sum tests were used to examine differences in toxicities and Cox proportional hazards regression was used to assess relationship with time to clearance. Of 523 patients identified, 167 patients were evaluable. One hundred thirty five patients had normal serum albumin and 32 had hypoalbuminemia. Hypoalbuminemia was associated with a higher proportion of patients experiencing edema, ascites or pleural effusions (34% vs. 12% p=0.006) and the concomitant use of nephrotoxic agents (41% vs. 20% p=0.021). Hypoalbuminemia was associated with a significantly longer time to methotrexate clearance (median: 96 hours vs 72 hour p=0.004). In addition, patients with hypoalbuminemia had a higher proportion of hyperbilirubinemia and significantly longer hospitalization (median 14 days vs. 5 days p<0.001). In conclusion, hypoalbuminemia was associated with increased time to MTX clearance and increase length of hospitalization. High dose MTX is safe to administer in patients with low albumin levels, with appropriate leucovorin rescue and good supportive care. PMID:27542957

Is risk associated with drinking water in Australia of significant concern to justify mandatory regulation?

PubMed

McKay, J; Moeller, A

2001-10-01

Presently in Australia there are no mandatory drinking water standards. Here we argue that the risk associated with drinking water in Australia is of a dimension discernible to warrant mandatory regulations. The catchments that supply the major metropolitan areas of Sydney and Adelaide, and the groundwater for the city of Perth have been seriously compromised by the encroachment of development and activities. Melbourne in the past has generally relied on a closed catchment reservoir system; however, population growth in the near future will sequester the full online operation of additional reservoirs, which have multiple land use catchments. In addition to the current landscape circumstances, the management of a water system in itself proposes significant issues of risk. Two critical assumptions that are unique to a mass medium substance like water and dramatically alter the appraisal of risk are: (1) very large numbers of people are potentially exposed, and (2) small changes in contaminant levels may have adverse population outcomes. It is also known that water reticulation systems frequently suffer from contamination problems caused solely by the distribution system, and optimal management of these facilities would best be served by statutory protected transparency and dedicated water quality programs. In 1979, an Australian parliamentary committee stated that an "uncontaminated water supply is" a "basic requirement for the obtainment of good health"; however, recent surveys of Australian water systems show many are not meeting basic water quality criteria, and many communities are not receiving regular monitoring or testing as required by government authorized Australian drinking water guidelines. Exacerbating this situation is the lack of reporting and statutory endorsed standardized procedures to ensure information is properly and promptly recorded and that data are centralized for maximum benefit. The evaluation of risk associated with drinking water in

Significant association of RNF213 p.R4810K, a moyamoya susceptibility variant, with coronary artery disease.

PubMed

Morimoto, Takaaki; Mineharu, Yohei; Ono, Koh; Nakatochi, Masahiro; Ichihara, Sahoko; Kabata, Risako; Takagi, Yasushi; Cao, Yang; Zhao, Lanying; Kobayashi, Hatasu; Harada, Kouji H; Takenaka, Katsunobu; Funaki, Takeshi; Yokota, Mitsuhiro; Matsubara, Tatsuaki; Yamamoto, Ken; Izawa, Hideo; Kimura, Takeshi; Miyamoto, Susumu; Koizumi, Akio

2017-01-01

The genetic architecture of coronary artery disease has not been fully elucidated, especially in Asian countries. Moyamoya disease is a progressive cerebrovascular disease that is reported to be complicated by coronary artery disease. Because most Japanese patients with moyamoya disease carry the p.R4810K variant of the ring finger 213 gene (RNF213), this may also be a risk factor for coronary artery disease; however, this possibility has never been tested. We genotyped the RNF213 p.R4810K variant in 956 coronary artery disease patients and 716 controls and tested the association between p.R4810K and coronary artery disease. We also validated the association in an independent population of 311 coronary artery disease patients and 494 controls. In the replication study, the p.R4810K genotypes were imputed from genome-wide genotyping data based on the 1000 Genomes Project. We used multivariate logistic regression analyses to adjust for well-known risk factors such as dyslipidemia and smoking habits. In the primary study population, the frequency of the minor variant allele was significantly higher in patients with coronary artery disease than in controls (2.04% vs. 0.98%), with an odds ratio of 2.11 (p = 0.017). Under a dominant model, after adjustment for risk factors, the association remained significant, with an odds ratio of 2.90 (95% confidence interval: 1.37-6.61; p = 0.005). In the replication study, the association was significant after adjustment for age and sex (odds ratio = 4.99; 95% confidence interval: 1.16-21.53; p = 0.031), although it did not reach statistical significance when further adjusted for risk factors (odds ratio = 3.82; 95% confidence interval: 0.87-16.77; p = 0.076). The RNF213 p.R4810K variant appears to be significantly associated with coronary artery disease in the Japanese population.

Factors associated with significant liver fibrosis assessed using transient elastography in general population

PubMed Central

You, Seng Chan; Kim, Kwang Joon; Kim, Seung Up; Kim, Beom Kyung; Park, Jun Yong; Kim, Do Young; Ahn, Sang Hoon; Lee, Won Jae; Han, Kwang-Hyub

2015-01-01

AIM: To investigate the prevalence of significant liver fibrosis assessed using transient elastography (TE) and its predictors in asymptomatic general population. METHODS: A total of 159 subjects without chronic viral hepatitis who underwent comprehensive medical health check-up between January 2012 and July 2012 were prospectively recruited. Significant liver fibrosis was defined as liver stiffness value > 7.0 kPa. RESULTS: The mean age and body mass index (BMI) of the study population (men 54.7%) was 56.0 years and 24.3 kg/m2. Among the study subjects, 11 (6.9%) showed significant liver fibrosis. On univariate analysis, BMI, alanine aminotransferase (ALT), homeostasis model assessment of insulin resistance, carotid intimal media thickness (IMT), number of calcified plaques on carotid ultrasound, and visceral fat area on computed tomography were significantly higher in subjects with significant liver fibrosis than in those without (all P < 0.05). However, on multivariate analysis, BMI [odds ratio (OR) =1.487; P = 0.045], ALT (OR = 1.078; P = 0.014), carotid IMT (OR = 3.244; P = 0.027), and the number of calcified carotid plaques (OR = 1.787; P = 0.031) were independent predictors of significant liver fibrosis. CONCLUSION: The prevalence of significant liver fibrosis assessed using TE was 6.9% in apparently healthy subjects. High BMI, high ALT, thicker carotid IMT, and higher numbers of calcified carotid plaques were independently associated with the presence of significant liver fibrosis. PMID:25632188

Atrial fibrillation and acute myocardial infarction without significant coronary stenoses associated with subclinical hyperthyroidism and erythrocytosis.

PubMed

Patanè, Salvatore; Marte, Filippo

2010-11-05

Subclinical hyperthyroidism is an increasingly recognized entity that is defined as a normal serum free thyroxine and free triiodothyronine levels with a thyroid-stimulating hormone level suppressed below the normal range and usually undetectable. It has been reported that sub-clinical hyperthyroidism is not associated with CHD or mortality from cardiovascular causes but is sufficient to induce arrhythmias including atrial fibrillation and atrial flutter. Moreover increased factor X activity in patients with subclinical hyperthyroidism represents a potential hypercoagulable state. It has been also reported an acute myocardial infarction with normal coronary arteries associated with iatrogenic hyperthyroidism and with a myocardial bridge too. It has been also reported an acute myocardial infarction without significant coronary stenoses associated with subclinical hyperthyroidism. Furthermore it has been reported that at highly increased hematocrit levels patients may experience hyperviscosity symptoms. We present a case of atrial fibrillation and acute myocardial infarction without significant coronary stenoses associated with subclinical hyperthyroidism and erythrocytosis. Also this case focuses attention on the importance of a correct evaluation of subclinical hyperthyroidism. Copyright © 2008 Elsevier Ireland Ltd. All rights reserved.

Upregulation of endothelial nitric oxide synthase (eNOS) and its upstream regulators in Opisthorchis viverrini associated cholangiocarcinoma and its clinical significance.

PubMed

Suksawat, Manida; Techasen, Anchalee; Namwat, Nisana; Yongvanit, Puangrat; Khuntikeo, Narong; Titapun, Attapon; Koonmee, Supinda; Loilome, Watcharin

2017-08-01

Endothelial nitric oxide synthase (eNOS) is an isoform of the enzyme nitric oxide synthase (NOS) which is constitutively expressed in endothelial cells and plays important roles in vasodilation. We previously reported the importance of eNOS activation in cholangiocarcinoma (CCA) tissues and cell lines. The present study aims to investigate the relative abundance of eNOS and phosphorylated eNOS (P-eNOS) and their upstream regulators VEGFR3, VEGFC, EphA3 and ephrin-A1, in the Opisthorchis viverrini (Ov)/N-nitrosodimethylamine (NDMA)-induced hamster CCA model and in human CCA by semiquantitative immunohistochemical analysis of the relevant tissues. Results from the hamster model suggested an increase in eNOS and P-eNOS and upstream regulators during CCA genesis. In human CCA, high immunohistochemical staining intensity of all investigated proteins was associated with the presence of metastasis. A pairwise analysis of the staining data for eNOS and its upstream regulators showed that a concurrent increase in eNOS/VEGFR3, eNOS/ephrin-A1, eNOS/VEGFC and eNOS/EphA3 was significantly associated with metastasis. An increase in eNOS/VEGFR3, eNOS/ephrin-A1 was also associated with non-papillary type CCA. Additionally, an increase in eNOS and P-eNOS was significantly correlated with a high micro-vessel level (P=0.04). Our results indicate that the development of CCA involves upregulation of eNOS and P-eNOS and their regulators. This may drive angiogenesis and metastasis in CCA. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Significant reduction of central line-associated bloodstream infection rates in a tertiary neonatal unit.

PubMed

Rallis, Dimitrios; Karagianni, Paraskevi; Papakotoula, Ifigeneia; Nikolaidis, Nikolaos; Tsakalidis, Christos

2016-04-01

To evaluate the effectiveness of a quality initiative in reducing central line-associated bloodstream infections (CLABSIs) in our neonatal intensive care unit, we designed a prospective study (January 2012-September 2013) estimating CLABSI incidence before and after our implementation. CLABSI rates were significantly decreased after our intervention, from 12 cases per 1,000 central vascular catheter (CVC) days during the preinterventional period to 3.4 cases per 1,000 CVC days during the postinterventional period (P = .004). Copyright © 2016 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved.

Significant association of APOA5 and APOC3 gene polymorphisms with meat quality traits in Kele pigs.

PubMed

Hui, Y T; Yang, Y Q; Liu, R Y; Zhang, Y Y; Xiang, C J; Liu, Z Z; Ding, Y H; Zhang, Y L; Wang, B R

2013-09-13

Apolipoprotein A5 (APOA5) and C3 (APOC3) genes are involved in the PPAR lipid metabolism pathway and thus associated with elevated triglyceride levels. However, whether APOA5 and APOC3 genetic polymorphisms affect intramuscular fat deposition and other meat quality traits remains unknown in pigs. One hundred and seventy-one Kele pigs were sampled to investigate genetic variants in the APOA5 and APOC3 genes and their association with seven pork quality traits. We identified 5 single nucleotide polymorphisms (SNPs) in the promoter region of the APOA5 gene and 17 SNPs in the APOC3 gene. Linkage disequilibrium analysis revealed 5 complete linkage disequilibria among these 22 SNPs. We found that 10 SNPs were significantly correlated with meat quality traits, including the mutation A5/-769 in the APOA5 gene, which was significantly associated with cooked weight percentage, and 9 SNPs in the APOC3 gene that were significantly associated with drip loss rate, meat color value of longissimus dorsi muscle and shear force. Therefore, these SNP markers will be useful for marker-assisted selection for improved pork quality.

77 FR 26314 - National Environmental Policy Act: Implementing Procedures; Addition to Categorical Exclusions...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-05-03

... leasing and funding for single- family homesites on Indian land, including associated improvements and...) reducing the resources spent analyzing proposals which generally do not have potentially significant... reviews of actions associated with single-family homes by preparing EAs; the addition of a categorical...

The Growth and Protein Expression of Inflammatory Bowel Disease-Associated Campylobacter concisus Is Affected by the Derivatives of the Food Additive Fumaric Acid.

PubMed

Ma, Rena; Liu, Fang; Yap, Soe F; Lee, Hoyul; Leong, Rupert W; Riordan, Stephen M; Grimm, Michael C; Zhang, Li

2018-01-01

Inflammatory bowel diseases (IBD) are chronic inflammatory conditions of the gastrointestinal tract with multifactorial etiology. Both dietary factors and the microbe Campylobacter concisus have been found to be associated with the condition. The current study examined the effects of sodium fumarate, a neutralized product of the food additives fumaric acid and monosodium fumarate when in the intestinal environment, on the growth of C. concisus to determine the effects of these food additives on IBD-associated bacterial species. Through culture methods and quantification, it was found that neutralized fumaric acid, neutralized monosodium fumarate, and sodium fumarate increased the growth of C. concisus , with the greatest increase in growth at a concentration of 0.4%. Further examination of 50 C. concisus strains on media with added sodium fumarate showed that greatest growth was also achieved at a concentration of 0.4%. At a concentration of 2% sodium fumarate, all strains examined displayed less growth in comparison with those cultured on media without sodium fumarate. Using mass spectrometry, multiple C. concisus proteins showed significant differential expression when cultured on media with and without 0.4% sodium fumarate. The findings presented suggest that patients with IBD should consider avoiding excessive consumption of foods with fumaric acid or its sodium salts, and that the addition of 0.4% sodium fumarate alone to media may assist in the isolation of C. concisus from clinical samples.

The CLU gene rs11136000 variant is significantly associated with Alzheimer's disease in Caucasian and Asian populations.

PubMed

Liu, Guiyou; Wang, Haiyang; Liu, Jiafeng; Li, Jingbo; Li, Hali; Ma, Guoda; Jiang, Yongshuai; Chen, Zugen; Zhao, Bin; Li, Keshen

2014-03-01

Large-scale genomewide association studies have reported that the CLU rs11136000 polymorphism is significantly associated with Alzheimer's disease (AD) in people of Caucasian ancestry. Recently, this association was investigated in Asian populations (Chinese, Japanese, and Korean). However, these studies reported either a weak association or no association between the rs11136000 polymorphism and AD. We believe that this discrepancy may be caused by the relatively small sample size of the previous studies and the genetic heterogeneity of the rs11136000 polymorphism in AD among different populations. For this study, we searched the PubMed and AlzGene databases. We selected 18 independent studies (6 studies of Asian populations and 12 of populations of Caucasian ancestry) that evaluated the association between the rs11136000 polymorphism and AD using a case-control experimental design. We evaluated the genetic heterogeneity of the rs11136000 polymorphism in Caucasian and Asian populations. We then investigated the rs11136000 polymorphism by a meta-analysis in Asian populations using allele, dominant, and recessive models. We identified a significant association between rs11136000 and AD with the allele model (P = 2.00 × 10(-4)) and the dominant model (P = 5.00 × 10(-3)). Meanwhile, a similar genetic risk of the rs11136000 polymorphism in AD was observed in Asian and Caucasian populations. Further meta-analysis in pooled Asian and Caucasian populations indicated a more significant association with the allele (P = 8.30 × 10(-24)), dominant (P = 4.46 × 10(-17)), and recessive (P = 3.92 × 10(-12)) models. Collectively, our findings from this meta-analysis indicate that the effect of the CLU rs11136000 polymorphism on AD risk in Asian cohorts (Chinese, Japanese, and Korean) is consistent with the protective effect observed in Caucasian AD cohorts.

Association between micronucleus frequency and cervical intraepithelial neoplasia grade in Thinprep cytological test and its significance

PubMed Central

Shi, Yong-Hua; Wang, Bo-Wei; Tuokan, Talaf; Li, Qiao-Zhi; Zhang, Ya-Jing

2015-01-01

A micronucleus is an additional small nucleus formed due to chromosomes or chromosomal fragments fail to be incorporated into the nucleus during cell division. In this study, we assessed the utility of micronucleus counting as a screening tool in cervical precancerous lesions in Thinprep cytological test smears under oil immersion. High risk HPV was also detected by hybrid capture-2 in Thinprep cytological test smears. Our results showed that micronucleus counting was significantly higher in high-grade squamous intraepithelial lesion (HSIL) and invasive carcinoma cases compared to low-grade squamous intraepithelial lesion (LSIL) and non-neoplastic cases. Receiver operating characteristic (ROC) curve analysis revealed that micronucleus counting possessed a high degree of sensitivity and specificity for identifying HSIL and invasive carcinoma. Cut-off of 7.5 for MN counting gave a sensitivity of 89.6% and a specificity of 66.7% (P = 0.024 and AUC = 0.892) for detecting HSIL and invasive carcinoma lesions. Multiple linear regression analysis showed that only HSIL and invasive cancer lesions not age, duration of marital life and number of pregnancy are significantly associated with MN counting. The positive rate of high risk HPV was distinctly higher in LSIL, HSIL and invasive cancer than that in non-neoplstic categories. In conclusions, MN evaluation may be viewed as an effective biomarker for cervical cancer screening. The combination of MN count with HPV DNA detection and TCT may serve as an effective means to screen precancerous cervical lesions in most developing nations. PMID:26339413

On Interestingness Measures for Mining Statistically Significant and Novel Clinical Associations from EMRs

PubMed Central

Abar, Orhan; Charnigo, Richard J.; Rayapati, Abner

2017-01-01

Association rule mining has received significant attention from both the data mining and machine learning communities. While data mining researchers focus more on designing efficient algorithms to mine rules from large datasets, the learning community has explored applications of rule mining to classification. A major problem with rule mining algorithms is the explosion of rules even for moderate sized datasets making it very difficult for end users to identify both statistically significant and potentially novel rules that could lead to interesting new insights and hypotheses. Researchers have proposed many domain independent interestingness measures using which, one can rank the rules and potentially glean useful rules from the top ranked ones. However, these measures have not been fully explored for rule mining in clinical datasets owing to the relatively large sizes of the datasets often encountered in healthcare and also due to limited access to domain experts for review/analysis. In this paper, using an electronic medical record (EMR) dataset of diagnoses and medications from over three million patient visits to the University of Kentucky medical center and affiliated clinics, we conduct a thorough evaluation of dozens of interestingness measures proposed in data mining literature, including some new composite measures. Using cumulative relevance metrics from information retrieval, we compare these interestingness measures against human judgments obtained from a practicing psychiatrist for association rules involving the depressive disorders class as the consequent. Our results not only surface new interesting associations for depressive disorders but also indicate classes of interestingness measures that weight rule novelty and statistical strength in contrasting ways, offering new insights for end users in identifying interesting rules. PMID:28736771

Prognostic significance of tumor-associated macrophages in endometrial adenocarcinoma.

PubMed

Kübler, Kirsten; Ayub, Tiyasha H; Weber, Sarah K; Zivanovic, Oliver; Abramian, Alina; Keyver-Paik, Mignon-Denise; Mallmann, Michael R; Kaiser, Christina; Serçe, Nuran Bektas; Kuhn, Walther; Rudlowski, Christian

2014-11-01

Endometrial adenocarcinoma is one of the most common gynecologic malignancies worldwide and in stages confined to the uterus considered to have an excellent prognosis. However, in advanced or recurrent cases when surgery fails to achieve disease control other treatment options are less effective. Thus, new therapeutic avenues are needed. To provide the rationale for the use of novel agents that target immune checkpoints 163 type I endometrial cancer samples were immunohistochemically screened for the presence of CD163(+) tumor-associated macrophages and Foxp3(+) regulatory T cells. Further, a D2-40-based evaluation of lymph vessel density and lymphovascular space invasion was carried out. Correlation analysis with clinicopathological parameters was performed; Kaplan-Meier curves were generated; multivariate analysis was undertaken as appropriate. A substantial amount of tumor-associated macrophages and regulatory T cells was detected in all specimens characterizing endometrial cancer as an immunogenic tumor. However, only the increased infiltration of tumor-associated macrophages was proportionally associated with advanced FIGO stages, high tumor grade, increased lymph vessel density, lymphovascular space invasion and lymph node metastasis. Thus, the presence of tumor-associated macrophages indicates aggressive tumor behavior and appeared to be an independent prognostic factor for recurrence-free survival. Our results make future therapeutic approaches that target tumor-associated macrophages reasonable to improve the outcome of women with advanced or recurrent endometrial adenocarcinoma. Copyright © 2014 Elsevier Inc. All rights reserved.

Associations between multimorbidity and additional burden for working-age adults with specific forms of musculoskeletal conditions: a cross-sectional study.

PubMed

Lowe, Dianne B; Taylor, Michael J; Hill, Sophie J

2017-04-04

Multiple health conditions are increasingly a problem for adults with musculoskeletal conditions. However, multimorbidity research has focused primarily on the elderly and those with a limited subset of musculoskeletal disorders. We sought to determine whether associations between multimorbidity and additional burden differ with specific forms of musculoskeletal conditions among working-age adults. Data were sourced from a nationally representative Australian survey. Specific musculoskeletal conditions examined were osteoarthritis; inflammatory arthritis; other forms of arthritis or arthropathies; musculoskeletal conditions not elsewhere specified; gout; back pain; soft tissue disorders; or osteoporosis. Multimorbidity was defined as the additional presence of one or more of the Australian National Health Priority Area conditions. Burden was assessed by self-reported measures of: (i) self-rated health (ii) musculoskeletal-related healthcare and medicines utilisation and, (iii) general healthcare utilisation. Associations between multimorbidity and additional health or healthcare utilisation burden among working-age adults (aged 18 - 64 years of age) with specific musculoskeletal conditions were estimated using logistic regression, adjusting for confounders. Interaction terms were fitted to identify whether there were specific musculoskeletal conditions where multimorbidity was more strongly associated with poorer health or greater healthcare utilisation than in the remaining musculoskeletal group. Among working-age adults, for each of the specified musculoskeletal conditions, multimorbidity was associated with similar, increased likelihood of additional self-rated health burden and certain types of healthcare utilisation. While there were differences in the relationships between multimorbidity and burden for each of the specific musculoskeletal conditions, no one specific musculoskeletal condition appeared to be consistently associated with greater additional

Phthalates and other additives in plastics: human exposure and associated health outcomes

PubMed Central

Meeker, John D.; Sathyanarayana, Sheela; Swan, Shanna H.

2009-01-01

Concern exists over whether additives in plastics to which most people are exposed, such as phthalates, bisphenol A or polybrominated diphenyl ethers, may cause harm to human health by altering endocrine function or through other biological mechanisms. Human data are limited compared with the large body of experimental evidence documenting reproductive or developmental toxicity in relation to these compounds. Here, we discuss the current state of human evidence, as well as future research trends and needs. Because exposure assessment is often a major weakness in epidemiological studies, and in utero exposures to reproductive or developmental toxicants are important, we also provide original data on maternal exposure to phthalates during and after pregnancy (n = 242). Phthalate metabolite concentrations in urine showed weak correlations between pre- and post-natal samples, though the strength of the relationship increased when duration between the two samples decreased. Phthalate metabolite levels also tended to be higher in post-natal samples. In conclusion, there is a great need for more human studies of adverse health effects associated with plastic additives. Recent advances in the measurement of exposure biomarkers hold much promise in improving the epidemiological data, but their utility must be understood to facilitate appropriate study design. PMID:19528058

A Case Control Study Reveals that Polyomaviruria Is Significantly Associated with Interstitial Cystitis and Vesical Ulceration

PubMed Central

Winter, Benjamin J.; O'Connell, Helen E.; Bowden, Scott; Carey, Marcus; Eisen, Damon P.

2015-01-01

Objectives To investigate whether polyomaviruses contribute to interstitial cystitis pathogenesis. Subjects and Methods A prospective study was performed with 50 interstitial cystitis cases compared with 50 age-matched, disease-free controls for the frequency of polyomaviruria. Associations between polyomaviruria and disease characteristics were analysed in cases. Polyomavirus in urine and bladder tissue was detected with species (JC virus vs. BK virus) specific, real-time PCR. Results Case patients were reflective of interstitial cystitis epidemiology with age range from 26–88 years (median 58) and female predominance (41/50 F). There was a significant increase in the frequency of polyomavirus shedding between cases and controls (p<0.02). Polyomavirus shedding, in particular BK viruria, was associated with vesical ulceration, a marker of disease severity, among interstitial cystitis cases after adjustment for age and sex (OR 6.8, 95% CI 1.89–24.4). There was a significant association among cases between the presence of BK viruria and response to intravesical Clorpactin therapy (OR 4.50, 95% CI 1.17–17.4). Conclusion The presence of polyomaviruria was found to be associated with the ulcerative form of interstitial cystitis. Clorpactin, which has anti-DNA virus activity, was more likely to improve symptoms in the presence of BK viruria. These data from this pilot study suggest associations between polyomaviruria and interstitial cystitis warranting further investigation. PMID:26325074

Immunohistochemical expression of galectin-3 is significantly associated with grade, stage and differentiation of endometrial carcinomas.

PubMed

Al-Maghrabi, Jaudah; Abdelrahman, Amer Shafie; Ghabrah, Tawfik; Butt, Nadeem Shafique; Al-Maghrabi, Basim; Khabaz, Mohamad Nidal

2017-04-01

This study describes galectin-3 immunohistochemical phenotype and its association with clinicopathological factors in the carcinoma of endometrium. Seventy one cases of endometrial carcinoma and 30 cases of benign and normal endometrium were employed for the detection of galectin-3 protein using tissue microarrays and immunohistochemistry staining. Thirty nine (55%) cases, including 54.2% of endometrioid adenocarcinomas and 55.5% serous carcinomas, were positively stained for galectin-3. Brown granular expression of this glycoprotein was detected in transformed epithelial cells of 36 cases including 28 cases with membranous and cytoplasmic staining and 8 cases with only cytoplasmic staining; nuclear expression was present in stromal cells of the remaining 3 cases. Twenty-four (80%) control cases showed granular cytoplasmic and membranous expression, and six control cases were negative. Tumor grade, stage and differentiation were significantly associated with galectin-3 immunoreactivity (p-values are 0.043, 0.016, and 0.044 respectively), cases with membranous and cytoplasmic staining is significantly associated with grade I and stage II, while cases with loss of staining are more frequent in grade II, III and poorly differentiated tumors. No significant association of galectin-3 staining was observed with age, diagnosis, recurrence and alive status. The current study supports the tumor suppression role of galectin-3 in endometrial carcinoma. Greater galectin-3 immunostaining has been found in control endometrial tissues compared to endometrial tumors. Loss or decreased galectin-3 immunoexpression gives a sign for poor prognoses in endometrial carcinoma patients. Copyright © 2017 Elsevier GmbH. All rights reserved.

Atypical Squamous Cells of Undetermined Significance: Bethesda Classification and Association with Human Papillomavirus

PubMed Central

Barcelos, Ana Cristina Macêdo; Michelin, Márcia Antoniazi; Adad, Sheila Jorge; Murta, Eddie Fernando Candido

2011-01-01

Introduction. To analyze patients with atypical squamous cells of undetermined significance (ASCUS) through a cytology review and the presence of microbiological agents, with consideration of colposcopy and semiannual tracking. Methods. 103 women with ASCUS were reviewed and reclassified: normal/inflammatory, ASCUS, low-grade squamous intraepithelial lesion (LSIL), or high-grade squamous intraepithelial lesion (HSIL). If ASCUS confirmed, it was subclassified in reactive or neoplastic ASCUS, ASC-US, or ASC-H; and Regione Emilia Romagna Screening Protocol. Patients underwent a colposcopic examination, and test for Candida sp., bacterial vaginosis, Trichomonas vaginalis, and human papillomavirus (HPV) were performed. Results. Upon review, ASCUS was diagnosis in 70/103 (67.9%), being 38 (54.2%) reactive ASCUS and 32 (45.71%) neoplastic ASCUS; 62 (88.5%) ASC-US and 8 (11.41%) ASC-H. ASCUS (Regione Protocol), respectively 1-5: 15 (21.4%), 19 (27.1%), 3 (27.1%), 16 (22.8%), and 1 (1.4%). A higher number of cases of cervical intraepithelial neoplasia (CIN) II/III in the biopsies of patients with ASC-H compared to ASC-US (P = .0021). High-risk HPV test and presence of CIN II/III are more frequent in ASC-H than ASC-US (P = .031). Conclusions. ASC-H is associated with clinically significant disease. High-risk HPV-positive status in the triage for colposcopy of patients with ASC-US is associated with increased of CIN. PMID:21760701

Expression of HIWI in human esophageal squamous cell carcinoma is significantly associated with poorer prognosis

PubMed Central

2009-01-01

Background HIWI, the human homologue of Piwi family, is present in CD34+ hematopoietic stem cells and germ cells, but not in well-differentiated cell populations, indicating that HIWI may play an impotent role in determining or maintaining stemness of these cells. That HIWI expression has been detected in several type tumours may suggest its association with clinical outcome in cancer patients. Methods With the methods of real-time PCR, western blot, immunocytochemistry and immunohistochemistry, the expression of HIWI in three esophageal squamous cancer cell lines KYSE70, KYSE140 and KYSE450 has been characterized. Then, we investigated HIWI expression in a series of 153 esophageal squamous cell carcinomas using immunohistochemistry and explored its association with clinicopathological features. Results The expression of HIWI was observed in tumour cell nuclei or/and cytoplasm in 137 (89.5%) cases, 16 (10.5%) cases were negative in both nuclei and cytoplasm. 86 (56.2%) were strongly positive in cytoplasm, while 49 (32.0%) were strongly positive in nuclei. The expression level of HIWI in cytoplasm of esophageal cancer cells was significantly associated with histological grade (P = 0.011), T stage (P = 0.035), and clinic outcome (P < 0.001), while there was no correlation between the nuclear HIWI expression and clinicopathological features. Conclusion The expression of HIWI in the cytoplasm of esophageal cancer cells is significantly associated with higher histological grade, clinical stage and poorer clinical outcome, indicating its possible involvement in cancer development. PMID:19995427

[Clinical significance of drug resistance-associated mutations in treatment of hepatitis C with direct-acting antiviral agents].

PubMed

Li, Z; Chen, Z W; Ren, H; Hu, P

2017-03-20

Direct-acting antiviral agents (DAAs) achieve a high sustained virologic response rate in the treatment of chronic hepatitis C virus infection. However, drug resistance-associated mutations play an important role in treatment failure and have attracted more and more attention. This article elaborates on the clinical significance of drug resistance-associated mutations from the aspects of their definition, association with genotype, known drug resistance-associated mutations and their prevalence rates, the impact of drug resistance-associated mutations on treatment naive and treatment-experienced patients, and the role of clinical detection, in order to provide a reference for clinical regimens with DAAs and help to achieve higher sustained virologic response rates.

Preoperative chemoradiotherapy alters the expression and prognostic significance of adhesion molecules in Barrett's-associated adenocarcinoma.

PubMed

Turner, J R; Torres, C M; Wang, H H; Shahsafaei, A; Richards, W G; Sugarbaker, D; Odze, R D

2000-03-01

A variety of prognostic markers have been related to decreased patient survival in patients with epithelial malignancies. These include expression of the homotypic adhesion molecule E-cadherin (ECAD) and the hyaluronic acid receptor CD44. Expression of ECAD and CD44 was evaluated in Barrett's-associated adenocarcinoma (BAd) from 67 patients. Expression was determined by immunoperoxidase staining and graded semiquantitatively based on the proportion of positively stained cells. These data were then correlated with clinical and pathological parameters, including the presence or absence of chemoradiotherapy (chemrad) and patient survival. There were 56 men and 11 women (mean age, 62 years). Thirty-nine (58%) patients received preoperative chemrad. ECAD expression was detected in all (100%) tumors. The ECAD staining grade did not correlate with other pathological features of the tumors. However, ECAD staining was significantly increased in BAd of patients who received chemrad (P = .003), in comparison with those who did not, and in individual patients when prechemrad biopsies and postchemrad resection specimens were compared (P = .04). In terms of prognosis, increased ECAD expression was associated with shortened patient survival only in BAd patients who had received chemrad (univariate analysis of chemrad patients with stage I and II BAd, P = .02). ECAD expression was not significantly associated with survival in BAd patients who did not receive chemrad. CD44 expression was detected in 88% of cases. CD44 expression did not correlate with any of the pathological features of the tumors or with chemrad status. Increased expression of CD44 was significantly associated with shortened patient survival in chemrad patients only (univariate analysis P = .03, multivariate analysis P = .04), although a strong trend was observed when all patients were analyzed regardless of chemrad status (P = .07). The results of this study indicate that chemrad alters the expression of ECAD in

Meta-analysis identifies 29 additional ulcerative colitis risk loci, increasing the number of confirmed associations to 47.

PubMed

Anderson, Carl A; Boucher, Gabrielle; Lees, Charlie W; Franke, Andre; D'Amato, Mauro; Taylor, Kent D; Lee, James C; Goyette, Philippe; Imielinski, Marcin; Latiano, Anna; Lagacé, Caroline; Scott, Regan; Amininejad, Leila; Bumpstead, Suzannah; Baidoo, Leonard; Baldassano, Robert N; Barclay, Murray; Bayless, Theodore M; Brand, Stephan; Büning, Carsten; Colombel, Jean-Frédéric; Denson, Lee A; De Vos, Martine; Dubinsky, Marla; Edwards, Cathryn; Ellinghaus, David; Fehrmann, Rudolf S N; Floyd, James A B; Florin, Timothy; Franchimont, Denis; Franke, Lude; Georges, Michel; Glas, Jürgen; Glazer, Nicole L; Guthery, Stephen L; Haritunians, Talin; Hayward, Nicholas K; Hugot, Jean-Pierre; Jobin, Gilles; Laukens, Debby; Lawrance, Ian; Lémann, Marc; Levine, Arie; Libioulle, Cecile; Louis, Edouard; McGovern, Dermot P; Milla, Monica; Montgomery, Grant W; Morley, Katherine I; Mowat, Craig; Ng, Aylwin; Newman, William; Ophoff, Roel A; Papi, Laura; Palmieri, Orazio; Peyrin-Biroulet, Laurent; Panés, Julián; Phillips, Anne; Prescott, Natalie J; Proctor, Deborah D; Roberts, Rebecca; Russell, Richard; Rutgeerts, Paul; Sanderson, Jeremy; Sans, Miquel; Schumm, Philip; Seibold, Frank; Sharma, Yashoda; Simms, Lisa A; Seielstad, Mark; Steinhart, A Hillary; Targan, Stephan R; van den Berg, Leonard H; Vatn, Morten; Verspaget, Hein; Walters, Thomas; Wijmenga, Cisca; Wilson, David C; Westra, Harm-Jan; Xavier, Ramnik J; Zhao, Zhen Z; Ponsioen, Cyriel Y; Andersen, Vibeke; Torkvist, Leif; Gazouli, Maria; Anagnou, Nicholas P; Karlsen, Tom H; Kupcinskas, Limas; Sventoraityte, Jurgita; Mansfield, John C; Kugathasan, Subra; Silverberg, Mark S; Halfvarson, Jonas; Rotter, Jerome I; Mathew, Christopher G; Griffiths, Anne M; Gearry, Richard; Ahmad, Tariq; Brant, Steven R; Chamaillard, Mathias; Satsangi, Jack; Cho, Judy H; Schreiber, Stefan; Daly, Mark J; Barrett, Jeffrey C; Parkes, Miles; Annese, Vito; Hakonarson, Hakon; Radford-Smith, Graham; Duerr, Richard H; Vermeire, Séverine; Weersma, Rinse K; Rioux, John D

2011-03-01

Genome-wide association studies and candidate gene studies in ulcerative colitis have identified 18 susceptibility loci. We conducted a meta-analysis of six ulcerative colitis genome-wide association study datasets, comprising 6,687 cases and 19,718 controls, and followed up the top association signals in 9,628 cases and 12,917 controls. We identified 29 additional risk loci (P < 5 × 10(-8)), increasing the number of ulcerative colitis-associated loci to 47. After annotating associated regions using GRAIL, expression quantitative trait loci data and correlations with non-synonymous SNPs, we identified many candidate genes that provide potentially important insights into disease pathogenesis, including IL1R2, IL8RA-IL8RB, IL7R, IL12B, DAP, PRDM1, JAK2, IRF5, GNA12 and LSP1. The total number of confirmed inflammatory bowel disease risk loci is now 99, including a minimum of 28 shared association signals between Crohn's disease and ulcerative colitis.

Food Additives and Hyperkinesis

ERIC Educational Resources Information Center

Wender, Ester H.

1977-01-01

The hypothesis that food additives are causally associated with hyperkinesis and learning disabilities in children is reviewed, and available data are summarized. Available from: American Medical Association 535 North Dearborn Street Chicago, Illinois 60610. (JG)

Hierarchical additive modeling of nonlinear association with spatial correlations--an application to relate alcohol outlet density and neighborhood assault rates.

PubMed

Yu, Qingzhao; Li, Bin; Scribner, Richard Allen

2009-06-30

Previous studies have suggested a link between alcohol outlets and assaults. In this paper, we explore the effects of alcohol availability on assaults at the census tract level over time. In addition, we use a natural experiment to check whether a sudden loss of alcohol outlets is associated with deeper decreasing in assault violence. Several features of the data raise statistical challenges: (1) the association between covariates (for example, the alcohol outlet density of each census tract) and the assault rates may be complex and therefore cannot be described using a linear model without covariates transformation, (2) the covariates may be highly correlated with each other, (3) there are a number of observations that have missing inputs, and (4) there is spatial association in assault rates at the census tract level. We propose a hierarchical additive model, where the nonlinear correlations and the complex interaction effects are modeled using the multiple additive regression trees and the residual spatial association in the assault rates that cannot be explained in the model are smoothed using a conditional autoregressive (CAR) method. We develop a two-stage algorithm that connects the nonparametric trees with CAR to look for important covariates associated with the assault rates, while taking into account the spatial association of assault rates in adjacent census tracts. The proposed method is applied to the Los Angeles assault data (1990-1999). To assess the efficiency of the method, the results are compared with those obtained from a hierarchical linear model. Copyright (c) 2009 John Wiley & Sons, Ltd.

Significant Locus and Metabolic Genetic Correlations Revealed in Genome-Wide Association Study of Anorexia Nervosa.

PubMed

Duncan, Laramie; Yilmaz, Zeynep; Gaspar, Helena; Walters, Raymond; Goldstein, Jackie; Anttila, Verneri; Bulik-Sullivan, Brendan; Ripke, Stephan; Thornton, Laura; Hinney, Anke; Daly, Mark; Sullivan, Patrick F; Zeggini, Eleftheria; Breen, Gerome; Bulik, Cynthia M

2017-09-01

The authors conducted a genome-wide association study of anorexia nervosa and calculated genetic correlations with a series of psychiatric, educational, and metabolic phenotypes. Following uniform quality control and imputation procedures using the 1000 Genomes Project (phase 3) in 12 case-control cohorts comprising 3,495 anorexia nervosa cases and 10,982 controls, the authors performed standard association analysis followed by a meta-analysis across cohorts. Linkage disequilibrium score regression was used to calculate genome-wide common variant heritability (single-nucleotide polymorphism [SNP]-based heritability [h 2 SNP ]), partitioned heritability, and genetic correlations (r g ) between anorexia nervosa and 159 other phenotypes. Results were obtained for 10,641,224 SNPs and insertion-deletion variants with minor allele frequencies >1% and imputation quality scores >0.6. The h 2 SNP of anorexia nervosa was 0.20 (SE=0.02), suggesting that a substantial fraction of the twin-based heritability arises from common genetic variation. The authors identified one genome-wide significant locus on chromosome 12 (rs4622308) in a region harboring a previously reported type 1 diabetes and autoimmune disorder locus. Significant positive genetic correlations were observed between anorexia nervosa and schizophrenia, neuroticism, educational attainment, and high-density lipoprotein cholesterol, and significant negative genetic correlations were observed between anorexia nervosa and body mass index, insulin, glucose, and lipid phenotypes. Anorexia nervosa is a complex heritable phenotype for which this study has uncovered the first genome-wide significant locus. Anorexia nervosa also has large and significant genetic correlations with both psychiatric phenotypes and metabolic traits. The study results encourage a reconceptualization of this frequently lethal disorder as one with both psychiatric and metabolic etiology.

Risks associated with endotoxins in feed additives produced by fermentation.

PubMed

Wallace, R John; Gropp, Jürgen; Dierick, Noël; Costa, Lucio G; Martelli, Giovanna; Brantom, Paul G; Bampidis, Vasileios; Renshaw, Derek W; Leng, Lubomir

2016-01-15

Increasingly, feed additives for livestock, such as amino acids and vitamins, are being produced by Gram-negative bacteria, particularly Escherichia coli. The potential therefore exists for animals, consumers and workers to be exposed to possibly harmful amounts of endotoxin from these products. The aim of this review was to assess the extent of the risk from endotoxins in feed additives and to calculate how such risk can be assessed from the properties of the additive. Livestock are frequently exposed to a relatively high content of endotoxin in the diet: no additional hazard to livestock would be anticipated if the endotoxin concentration of the feed additive falls in the same range as feedstuffs. Consumer exposure will be unaffected by the consumption of food derived from animals receiving endotoxin-containing feed, because the small concentrations of endotoxin absorbed do not accumulate in edible tissues. In contrast, workers processing a dusty additive may be exposed to hazardous amounts of endotoxin even if the endotoxin concentration of the product is low. A calculation method is proposed to compare the potential risk to the worker, based on the dusting potential, the endotoxin concentration and technical guidance of the European Food Safety Authority, with national exposure limits.

Dissection of additive, dominance, and imprinting effects for production and reproduction traits in Holstein cattle.

PubMed

Jiang, Jicai; Shen, Botong; O'Connell, Jeffrey R; VanRaden, Paul M; Cole, John B; Ma, Li

2017-05-30

Although genome-wide association and genomic selection studies have primarily focused on additive effects, dominance and imprinting effects play an important role in mammalian biology and development. The degree to which these non-additive genetic effects contribute to phenotypic variation and whether QTL acting in a non-additive manner can be detected in genetic association studies remain controversial. To empirically answer these questions, we analyzed a large cattle dataset that consisted of 42,701 genotyped Holstein cows with genotyped parents and phenotypic records for eight production and reproduction traits. SNP genotypes were phased in pedigree to determine the parent-of-origin of alleles, and a three-component GREML was applied to obtain variance decomposition for additive, dominance, and imprinting effects. The results showed a significant non-zero contribution from dominance to production traits but not to reproduction traits. Imprinting effects significantly contributed to both production and reproduction traits. Interestingly, imprinting effects contributed more to reproduction traits than to production traits. Using GWAS and imputation-based fine-mapping analyses, we identified and validated a dominance association signal with milk yield near RUNX2, a candidate gene that has been associated with milk production in mice. When adding non-additive effects into the prediction models, however, we observed little or no increase in prediction accuracy for the eight traits analyzed. Collectively, our results suggested that non-additive effects contributed a non-negligible amount (more for reproduction traits) to the total genetic variance of complex traits in cattle, and detection of QTLs with non-additive effect is possible in GWAS using a large dataset.

Gadolinium deposition in the brain: association with various GBCAs using a generalized additive model.

PubMed

Bae, Sohi; Lee, Ho-Joon; Han, Kyunghwa; Park, Yae-Won; Choi, Yoon Seong; Ahn, Sung Soo; Kim, Jinna; Lee, Seung-Koo

2017-08-01

To determine the relationship between the number of administrations of various gadolinium-based contrast agents (GBCAs) and increased T1 signal intensity in the globus pallidus (GP) and dentate nucleus (DN). This retrospective study included 122 patients who underwent double-dose GBCA-enhanced magnetic resonance imaging. Two radiologists calculated GP-to-thalamus (TH) signal intensity ratio, DN-to-pons signal intensity ratio and relative change (R change ) between the baseline and final examinations. Interobserver agreement was evaluated. The relationships between R change and several factors, including number of each GBCA administrations, were analysed using a generalized additive model. Six patients (4.9%) received linear GBCAs (mean 20.8 number of administration; range 15-30), 44 patients (36.1%) received macrocyclic GBCAs (mean 26.1; range 14-51) and 72 patients (59.0%) received both types of GBCAs (mean 31.5; range 12-65). Interobserver agreement was almost perfect (0.99; 95% CI: 0.99-0.99). R change (DN:pons) was associated with gadodiamide (p = 0.006) and gadopentetate dimeglumine (p < 0.001), but not with other GBCAs. R change (GP:TH) was not associated with GBCA administration. Previous administration of linear agents gadoiamide and gadopentetate dimeglumine is associated with increased T1 signal intensity in the DN, whereas macrocyclic GBCAs do not show an association. • Certain linear GBCAs are associated with T1 signal change in the dentate nucleus. • The signal change is related to the administration number of certain linear GBCAs. • Difference in signal change may reflect differences in stability of agents.

Clostridium difficile: A healthcare-associated infection of unknown significance in adults in sub-Saharan Africa.

PubMed

Keeley, Alexander J; Beeching, Nicholas J; Stott, Katharine E; Roberts, Paul; Watson, Alastair J; Beadsworth, Michael Bj

2016-06-01

Clostridium difficile infection (CDI) causes a high burden of disease in high-resource healthcare systems, with significant morbidity, mortality, and financial implications. CDI is a healthcare-associated infection for which the primary risk factor is antibiotic usage, and it is the leading cause of bacterial diarrhoea in HIV-infected patients in the United States. Little is known about the disease burden of CDI in sub-Saharan Africa, where HIV and healthcare-associated infections are more prevalent and antibiotic usage is less restricted. This article reviews published literature on CDI in sub-Saharan Africa, highlighting areas for future research. English language publications since 1995 were identified from online databases (PubMed, Medline, Google Scholar, and SCOPUS), using combinations of keywords "C. difficile" , "Africa", and "HIV". Ten relevant studies were identified. There was considerable variation in the methodologies used to assess for carriage of toxigenic C. difficile and its associations. Eight studies reported carriage of toxigenic C. difficile . Three (of three) studies found an association with antibiotic usage. One (of four) studies showed an association with HIV infection. One study showed no association with degree of immunosuppression in HIV. Two (of three) studies showed an association between carriage of toxigenic C. difficile and diarrhoeal illness. While the carriage of toxigenic C. difficile is well described in sub-Saharan Africa, the impact of CDI in the region remains poorly understood and warrants further research.

Patient Outcomes in Association With Significant Other Responses to Chronic Fatigue Syndrome: A Systematic Review of the Literature

PubMed Central

Band, Rebecca; Wearden, Alison; Barrowclough, Christine

2015-01-01

Social processes have been suggested as important in the maintenance of chronic fatigue syndrome (also known as myalgic encephalomyelitis; CFS/ME), but the specific role of close interpersonal relationships remains unclear. We reviewed 14 articles investigating significant other responses to close others with CFS/ME and the relationships between these responses and patient outcomes. Significant other beliefs attributing patient responsibility for the onset and ongoing symptoms of CFS/ME were associated with increased patient distress. Increased symptom severity, disability, and distress were also associated with both solicitous and negative significant other responses. Specific aspects of dyadic relationship quality, including high Expressed Emotion, were identified as important. We propose extending current theoretical models of CFS/ME to include two potential perpetuating interpersonal processes; the evidence reviewed suggests that the development of significant other–focused interventions may also be beneficial. PMID:26617440

Shape of the BMI-mortality association by cause of death, using generalized additive models: NHIS 1986-2006.

PubMed

Zajacova, Anna; Burgard, Sarah A

2012-03-01

Numerous studies have examined the association between body mass index (BMI) and mortality. The precise shape of their association, however, has not been established. We use nonparametric methods to determine the relationship between BMI and mortality. Data from the National Health Interview Survey-Linked Mortality Files 1986-2006 for adults aged 50 to 80 are analyzed using a Poisson approach to survival modeling within the generalized additive model (GAM) framework. The BMI-mortality association is more V shaped than U shaped, with the odds of dying rising steeply from the lowest risk point at BMIs of 23 to 26. The association varies considerably by time since interview and cause of death. For instance, the association has an inverted J shape for respiratory causes but is monotonically increasing for diabetes deaths. Our findings have implications for interpreting results from BMI-mortality studies and suggest caution in translating the findings into public health messages.

Additive Manufacturing Infrared Inspection

NASA Technical Reports Server (NTRS)

Gaddy, Darrell

2014-01-01

Additive manufacturing is a rapid prototyping technology that allows parts to be built in a series of thin layers from plastic, ceramics, and metallics. Metallic additive manufacturing is an emerging form of rapid prototyping that allows complex structures to be built using various metallic powders. Significant time and cost savings have also been observed using the metallic additive manufacturing compared with traditional techniques. Development of the metallic additive manufacturing technology has advanced significantly over the last decade, although many of the techniques to inspect parts made from these processes have not advanced significantly or have limitations. Several external geometry inspection techniques exist such as Coordinate Measurement Machines (CMM), Laser Scanners, Structured Light Scanning Systems, or even traditional calipers and gages. All of the aforementioned techniques are limited to external geometry and contours or must use a contact probe to inspect limited internal dimensions. This presentation will document the development of a process for real-time dimensional inspection technique and digital quality record of the additive manufacturing process using Infrared camera imaging and processing techniques.

Significant association between rare IPO11-HTR1A variants and attention deficit hyperactivity disorder in Caucasians

PubMed Central

Zuo, Lingjun; Saba, Laura; Lin, Xiandong; Tan, Yunlong; Wang, Kesheng; Krystal, John H.; Tabakoff, Boris; Luo, Xingguang

2016-01-01

Objective We comprehensively examined the rare variants in the IPO11-HTR1A region to explore their roles in neuropsychiatric disorders. Method Five hundred seventy-three to 1,181 rare SNPs in subjects of European descent and 1,234-2,529 SNPs in subjects of African descent (0 < minor allele frequency (MAF) < 0.05) were analyzed in a total of 49,268 subjects in 21 independent cohorts with 11 different neuropsychiatric disorders. Associations between rare variant constellations and diseases and associations between individual rare variants and diseases were tested. RNA expression changes of this region were also explored. Results We identified a rare variant constellation across the entire IPO11-HTR1A region that was associated with attention deficit hyperactivity disorder (ADHD) in Caucasians (T5: p=7.9×10−31; Fp: p=1.3×10−32), but not with any other disorder examined; association signals mainly came from IPO11 (T5: p=3.6×10−10; Fp: p=3.2×10−10) and the intergenic region between IPO11 and HTR1A (T5: p=4.1×10−30; Fp: p=5.4×10−32). One association between ADHD and an intergenic rare variant, i.e., rs10042956, exhibited region- and cohort-wide significance (p=5.2×10−6) and survived correction for false discovery rate (q=0.006). Cis-eQTL analysis showed that, 29 among the 41 SNPs within or around IPO11 had replicable significant regulatory effects on IPO11 exon expression (1.5×10−17≤p<0.002) in human brain or peripheral blood mononuclear cell tissues. Conclusion We concluded that IPO11-HTR1A was a significant risk gene region for ADHD in Caucasians. PMID:26079129

Additional Value of Transluminal Attenuation Gradient in CT Angiography to Predict Hemodynamic Significance of Coronary Artery Stenosis

PubMed Central

Stuijfzand, Wynand J.; Danad, Ibrahim; Raijmakers, Pieter G.; Marcu, C. Bogdan; Heymans, Martijn W.; van Kuijk, Cornelis C.; van Rossum, Albert C.; Nieman, Koen; Min, James K.; Leipsic, Jonathon; van Royen, Niels; Knaapen, Paul

2015-01-01

OBJECTIVES The current study evaluates the incremental value of transluminal attenuation gradient (TAG), TAG with corrected contrast opacification (CCO), and TAG with exclusion of calcified coronary segments (ExC) over coronary computed tomography angiogram (CTA) alone using fractional flow reserve (FFR) as the gold standard. BACKGROUND TAG is defined as the contrast opacification gradient along the length of a coronary artery on a coronary CTA. Preliminary data suggest that TAG provides additional functional information. Interpretation of TAG is hampered by multiple heartbeat acquisition algorithms and coronary calcifications. Two correction models have been proposed based on either dephasing of contrast delivery by relating coronary density to corresponding descending aortic opacification (TAG-CCO) or excluding calcified coronary segments (TAG-ExC). METHODS Eighty-five patients with intermediate probability of coronary artery disease were prospectively included. All patients underwent step-and-shoot 256-slice coronary CTA. TAG, TAG-CCO, and TAG-ExC analyses were performed followed by invasive coronary angiography in conjunction with FFR measurements of all major coronary branches. RESULTS Thirty-four patients (40%) were diagnosed with hemodynamically-significant coronary artery disease (i.e., FFR ≤0.80). On a per-vessel basis (n = 253), 59 lesions (23%) were graded as hemodynamically significant, and the diagnostic accuracy of coronary CTA (diameter stenosis ≥50%) was 95%, 75%, 98%, and 54% for sensitivity, specificity, negative predictive value, and positive predictive value, respectively. TAG and TAG-ExC did not discriminate between vessels with or without hemodynamically significant lesions (−13.5 ± 17.1 HU [Hounsfield units] × 10 mm−1 vs. −11.6 ± 13.3 HU × 10 mm−1, p = 0.36; and 13.1 ± 15.9 HU × 10 mm−1 vs. −11.4 ± 11.7 HU × 10 mm−1, p = 0.77, respectively). TAG-CCO was lower in vessels with a hemodynamically-significant lesion (−0

Prognostic significance of microsatellite instability‑associated pathways and genes in gastric cancer.

PubMed

Hang, Xiaosheng; Li, Dapeng; Wang, Jianping; Wang, Ge

2018-07-01

The aim of the present study was to reveal the potential molecular mechanisms of microsatellite instability (MSI) on the prognosis of gastric cancer (GC). The investigation was performed based on an RNAseq expression profiling dataset downloaded from The Cancer Genome Atlas, including 64 high‑level MSI (MSI‑H) GC samples, 44 low‑level MSI (MSI‑L) GC samples and 187 stable microsatellite (MSI‑S) GC samples. Differentially expressed genes (DEGs) were identified between the MSI‑H, MSI‑L and MSI‑S samples. Pathway enrichment analysis was performed for the identified DEGs and the pathway deviation scores of the significant enrichment pathways were calculated. A Multi‑Layer Perceptron (MLP) classifier, based on the different pathways associated with the MSI statuses was constructed for predicting the outcome of patients with GC, which was validated in another independent dataset. A total of 190 DEGs were selected between the MSI‑H, MSI‑L and MSI‑S samples. The MLP classifier was established based on the deviation scores of 10 significant pathways, among which antigen processing and presentation, and inflammatory bowel disease pathways were significantly enriched with HLA‑DRB5, HLA‑DMA, HLA‑DQA1 and HLA‑DRA; the measles, toxoplasmosis and herpes simplex infection pathways were significantly enriched with Janus kinase 2 (JAK2), caspase‑8 (CASP8) and Fas. The classifier performed well on an independent validation set with 100 GC samples. Taken together, the results indicated that MSI status may affect GC prognosis, partly through the antigen processing and presentation, inflammatory bowel disease, measles, toxoplasmosis and herpes simplex infection pathways. HLA‑DRB5, HLA‑DMA, HLA‑DQA1, HLA‑DRA, JAK2, CASP8 and Fas may be predictive factors for prognosis in GC.

Associations Between PET Textural Features and GLUT1 Expression, and the Prognostic Significance of Textural Features in Lung Adenocarcinoma.

PubMed

Koh, Young Wha; Park, Seong Yong; Hyun, Seung Hyup; Lee, Su Jin

2018-02-01

We evaluated the association between positron emission tomography (PET) textural features and glucose transporter 1 (GLUT1) expression level and further investigated the prognostic significance of textural features in lung adenocarcinoma. We evaluated 105 adenocarcinoma patients. We extracted texture-based PET parameters of primary tumors. Conventional PET parameters were also measured. The relationships between PET parameters and GLUT1 expression levels were evaluated. The association between PET parameters and overall survival (OS) was assessed using Cox's proportional hazard regression models. In terms of PET textural features, tumors expressing high levels of GLUT1 exhibited significantly lower coarseness, contrast, complexity, and strength, but significantly higher busyness. On univariate analysis, the metabolic tumor volume, total lesion glycolysis, contrast, busyness, complexity, and strength were significant predictors of OS. Multivariate analysis showed that lower complexity (HR=2.017, 95%CI=1.032-3.942, p=0.040) was independently associated with poorer survival. PET textural features may aid risk stratification in lung adenocarcinoma patients. Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Significance of genome-wide association studies in molecular anthropology.

PubMed

Gupta, Vipin; Khadgawat, Rajesh; Sachdeva, Mohinder Pal

2009-12-01

The successful advent of a genome-wide approach in association studies raises the hopes of human geneticists for solving a genetic maze of complex traits especially the disorders. This approach, which is replete with the application of cutting-edge technology and supported by big science projects (like Human Genome Project; and even more importantly the International HapMap Project) and various important databases (SNP database, CNV database, etc.), has had unprecedented success in rapidly uncovering many of the genetic determinants of complex disorders. The magnitude of this approach in the genetics of classical anthropological variables like height, skin color, eye color, and other genome diversity projects has certainly expanded the horizons of molecular anthropology. Therefore, in this article we have proposed a genome-wide association approach in molecular anthropological studies by providing lessons from the exemplary study of the Wellcome Trust Case Control Consortium. We have also highlighted the importance and uniqueness of Indian population groups in facilitating the design and finding optimum solutions for other genome-wide association-related challenges.

Posttraumatic stress disorder, alone or additively with early life adversity, is associated with obesity and cardiometabolic risk.

PubMed

Farr, O M; Ko, B-J; Joung, K E; Zaichenko, L; Usher, N; Tsoukas, M; Thakkar, B; Davis, C R; Crowell, J A; Mantzoros, C S

2015-05-01

There is some evidence that posttraumatic stress disorder (PTSD) and early life adversity may influence metabolic outcomes such as obesity, diabetes, and cardiovascular disease. However, whether and how these interact is not clear. We analyzed data from a cross-sectional and longitudinal study to determine how PTSD severity influences obesity, insulin sensitivity, and key measures and biomarkers of cardiovascular risk. We then looked at how PTSD and early life adversity may interact to impact these same outcomes. PTSD severity is associated with increasing risk of obesity, diabetes, and cardiovascular disease, with higher symptoms correlating with higher values of BMI, leptin, fibrinogen, and blood pressure, and lower values of insulin sensitivity. PTSD and early life adversity have an additive effect on these metabolic outcomes. The longitudinal study confirmed findings from the cross sectional study and showed that fat mass, leptin, CRP, sICAM-1, and sTNFRII were significantly increased with higher PTSD severity during a 2.5 year follow-up period. Individuals with early life adversity and PTSD are at high risk and should be monitored carefully for obesity, insulin resistance, and cardiometabolic risk. Copyright © 2015 Elsevier B.V. All rights reserved.

Dapagliflozin significantly reduced liver fat accumulation associated with a decrease in abdominal subcutaneous fat in patients with inadequately controlled type 2 diabetes mellitus.

PubMed

Kurinami, Noboru; Sugiyama, Seigo; Yoshida, Akira; Hieshima, Kunio; Miyamoto, Fumio; Kajiwara, Keizo; Jinnouch, Katsunori; Jinnouchi, Tomio; Jinnouchi, Hideaki

2018-05-31

We examined dapagliflozin-induced changes in liver fat accumulation. We prospectively recruited Japanese patients with inadequately controlled type 2 diabetes mellitus (T2DM) [hemoglobin A1c (HbA1c) >7.0%]. Dapagliflozin (5 mg/day) or non-sodium glucose cotransporter 2 inhibitors (SGLT2i) was added to the patients' treatment regimen for 6 months. Changes in liver fat accumulation were assessed by the liver-to-spleen (L/S) attenuation ratio using abdominal computed tomography (CT). This study enrolled 55 Japanese T2DM patients. The L/S ratio significantly increased in the dapagliflozin group compared with the non-SGLT2i group. Abdominal subcutaneous fat area (SFA), visceral fat area, total fat area assessed by abdominal CT, aspartate aminotransferase, alanine aminotransferase (ALT), and γ-glutamyl transpeptidase decreased significantly only in the dapagliflozin group. Changes in the L/S ratio showed a significant negative relationship with changes in abdominal SFA, ALT, and non-esterified fatty acid. In sub-group analyses of non-insulin users, hepatic insulin extraction was assessed by the plasma C-peptide-to-insulin ratio, which was significantly increased in the dapagliflozin group but not in the non-SGLT2i group. In patients with inadequately controlled T2DM, additional dapagliflozin-treatment significantly reduced the liver fat accumulation associated with a decrease in abdominal SFA. Copyright © 2018 Elsevier B.V. All rights reserved.

Acute myocardial infarction without significant coronary stenoses associated with endogenous subclinical hyperthyroidism.

PubMed

Patanè, Salvatore; Marte, Filippo; Sturiale, Mauro

2012-04-05

Subclinical hyperthyroidism is an increasingly recognized entity that is defined as a normal serum free thyroxine and free triiodothyronine levels with a thyroid-stimulating hormone level suppressed below the normal range and usually undetectable. It has been reported that subclinical hyperthyroidism is not associated with coronary heart disease or mortality from cardiovascular causes but it is sufficient to induce arrhythmias including atrial fibrillation and atrial flutter. Nowadays, there is growing interest regarding endogenous sublinical hyperthyroidism and the cardiovascular system. We present a case of acute myocardial infarction without significant coronary stenoses in a 75-year-old Italian woman with endogenous subclinical hyperthyroidism. Also this case focuses attention on the importance of a correct evaluation of endogenous subclinical hyperthyroidism. Copyright © 2009 Elsevier Ireland Ltd. All rights reserved.

Genome-wide association study identifies TF as a significant modifier gene of iron metabolism in HFE hemochromatosis.

PubMed

de Tayrac, Marie; Roth, Marie-Paule; Jouanolle, Anne-Marie; Coppin, Hélène; le Gac, Gérald; Piperno, Alberto; Férec, Claude; Pelucchi, Sara; Scotet, Virginie; Bardou-Jacquet, Edouard; Ropert, Martine; Bouvet, Régis; Génin, Emmanuelle; Mosser, Jean; Deugnier, Yves

2015-03-01

Hereditary hemochromatosis (HH) is the most common form of genetic iron loading disease. It is mainly related to the homozygous C282Y/C282Y mutation in the HFE gene that is, however, a necessary but not a sufficient condition to develop clinical and even biochemical HH. This suggests that modifier genes are likely involved in the expressivity of the disease. Our aim was to identify such modifier genes. We performed a genome-wide association study (GWAS) using DNA collected from 474 unrelated C282Y homozygotes. Associations were examined for both quantitative iron burden indices and clinical outcomes with 534,213 single nucleotide polymorphisms (SNP) genotypes, with replication analyses in an independent sample of 748 C282Y homozygotes from four different European centres. One SNP met genome-wide statistical significance for association with transferrin concentration (rs3811647, GWAS p value of 7×10(-9) and replication p value of 5×10(-13)). This SNP, located within intron 11 of the TF gene, had a pleiotropic effect on serum iron (GWAS p value of 4.9×10(-6) and replication p value of 3.2×10(-6)). Both serum transferrin and iron levels were associated with serum ferritin levels, amount of iron removed and global clinical stage (p<0.01). Serum iron levels were also associated with fibrosis stage (p<0.0001). This GWAS, the largest one performed so far in unselected HFE-associated HH (HFE-HH) patients, identified the rs3811647 polymorphism in the TF gene as the only SNP significantly associated with iron metabolism through serum transferrin and iron levels. Because these two outcomes were clearly associated with the biochemical and clinical expression of the disease, an indirect link between the rs3811647 polymorphism and the phenotypic presentation of HFE-HH is likely. Copyright © 2014 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Socioeconomic status is significantly associated with the dietary intakes of folate and depression scales in Japanese workers (J-HOPE Study).

PubMed

Miyaki, Koichi; Song, Yixuan; Taneichi, Setsuko; Tsutsumi, Akizumi; Hashimoto, Hideki; Kawakami, Norito; Takahashi, Masaya; Shimazu, Akihito; Inoue, Akiomi; Kurioka, Sumiko; Shimbo, Takuro

2013-02-18

The association of socioeconomic status (SES) with nutrient intake attracts public attention worldwide. In the current study, we examined the associations of SES with dietary intake of folate and health outcomes in general Japanese workers. This Japanese occupational cohort consisted off 2266 workers. SES was assessed by a self-administered questionnaire. Intakes of all nutrients were assessed with a validated, brief and self-administered diet history questionnaire (BDHQ). The degree of depressive symptoms was measured by the validated Japanese version of the K6 scale. Multiple linear regression and stratified analysis were used to evaluate the associations of intake with the confounding factors. Path analysis was conducted to describe the impacts of intake on health outcomes. Education levels and household incomes were significantly associated with intake of folate and depression scales (p < 0.05). After adjusting for age, sex and total energy intake, years of education significantly affect the folate intake (β = 0.117, p < 0.001). The structural equation model (SEM) shows that the indirect effect of folate intake is statistically significant and strong (p < 0.05, 56% of direct effect) in the pathway of education level to depression scale. Our study shows both education and income are significantly associated with depression scales in Japanese workers, and the effort to increase the folate intake may alleviate the harms of social disparities on mental health.

A whole genome association study to detect additive and dominant single nucleotide polymorphisms for growth and carcass traits in Korean native cattle, Hanwoo.

PubMed

Li, Yi; Gao, Yuxuan; Kim, You-Sam; Iqbal, Asif; Kim, Jong-Joo

2017-01-01

A whole genome association study was conducted to identify single nucleotide polymorphisms (SNPs) with additive and dominant effects for growth and carcass traits in Korean native cattle, Hanwoo. The data set comprised 61 sires and their 486 Hanwoo steers that were born between spring of 2005 and fall of 2007. The steers were genotyped with the 35,968 SNPs that were embedded in the Illumina bovine SNP 50K beadchip and six growth and carcass quality traits were measured for the steers. A series of lack-of-fit tests between the models was applied to classify gene expression pattern as additive or dominant. A total of 18 (0), 15 (3), 12 (8), 15 (18), 11 (7), and 21 (1) SNPs were detected at the 5% chromosome (genome) - wise level for weaning weight (WWT), yearling weight (YWT), carcass weight (CWT), backfat thickness (BFT), longissimus dorsi muscle area (LMA) and marbling score, respectively. Among the significant 129 SNPs, 56 SNPs had additive effects, 20 SNPs dominance effects, and 53 SNPs both additive and dominance effects, suggesting that dominance inheritance mode be considered in genetic improvement for growth and carcass quality in Hanwoo. The significant SNPs were located at 33 quantitative trait locus (QTL) regions on 18 Bos Taurus chromosomes (i.e. BTA 3, 4, 5, 6, 7, 9, 11, 12, 13, 14, 16, 17, 18, 20, 23, 26, 28, and 29) were detected. There is strong evidence that BTA14 is the key chromosome affecting CWT. Also, BTA20 is the key chromosome for almost all traits measured (WWT, YWT, LMA). The application of various additive and dominance SNP models enabled better characterization of SNP inheritance mode for growth and carcass quality traits in Hanwoo, and many of the detected SNPs or QTL had dominance effects, suggesting that dominance be considered for the whole-genome SNPs data and implementation of successive molecular breeding schemes in Hanwoo.

Frequencies of polymorphisms associated with BSE resistance differ significantly between Bos taurus, Bos indicus, and composite cattle

PubMed Central

Brunelle, Brian W; Greenlee, Justin J; Seabury, Christopher M; Brown, Charles E; Nicholson, Eric M

2008-01-01

Background Transmissible spongiform encephalopathies (TSEs) are neurodegenerative diseases that affect several mammalian species. At least three factors related to the host prion protein are known to modulate susceptibility or resistance to a TSE: amino acid sequence, atypical number of octapeptide repeats, and expression level. These factors have been extensively studied in breeds of Bos taurus cattle in relation to classical bovine spongiform encephalopathy (BSE). However, little is currently known about these factors in Bos indicus purebred or B. indicus × B. taurus composite cattle. The goal of our study was to establish the frequency of markers associated with enhanced susceptibility or resistance to classical BSE in B. indicus purebred and composite cattle. Results No novel or TSE-associated PRNP-encoded amino acid polymorphisms were observed for B. indicus purebred and composite cattle, and all had the typical number of octapeptide repeats. However, differences were observed in the frequencies of the 23-bp and 12-bp insertion/deletion (indel) polymorphisms associated with two bovine PRNP transcription regulatory sites. Compared to B. taurus, B. indicus purebred and composite cattle had a significantly lower frequency of 23-bp insertion alleles and homozygous genotypes. Conversely, B. indicus purebred cattle had a significantly higher frequency of 12-bp insertion alleles and homozygous genotypes in relation to both B. taurus and composite cattle. The origin of these disparities can be attributed to a significantly different haplotype structure within each species. Conclusion The frequencies of the 23-bp and 12-bp indels were significantly different between B. indicus and B. taurus cattle. No other known or potential risk factors were detected for the B. indicus purebred and composite cattle. To date, no consensus exists regarding which bovine PRNP indel region is more influential with respect to classical BSE. Should one particular indel region and

Development of Assays for Detecting Significant Prostate Cancer Based on Molecular Alterations Associated with Cancer in Non-Neoplastic Prostate Tissue

DTIC Science & Technology

2016-12-01

Award Number: W81XWH-11-1-0744 TITLE: Development of Assays for Detecting Significant Prostate Cancer Based on Molecular Alterations Associated...Significant Prostate Cancer Based on Molecular Alterations Associated with Cancer in Non- Neoplastic Prostate Tissue 5b. GRANT NUMBER 10623678 5c...Public Release; Distribution Unlimited 13. SUPPLEMENTARY NOTES 14. ABSTRACT The goal of this project was to develop molecular models to

A Genome Wide Association Study Identifies Common Variants Associated with Lipid Levels in the Chinese Population

PubMed Central

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

Clinicopathological and prognostic significance of metastasis-associated in colon cancer-1 (MACC1) overexpression in colorectal cancer: a meta-analysis

PubMed Central

Zhao, Yang; Dai, Cong; Wang, Meng; Kang, Huafeng; Lin, Shuai; Yang, Pengtao; Liu, Xinghan; Liu, Kang; Xu, Peng; Zheng, Yi; Li, Shanli; Dai, Zhijun

2016-01-01

Metastasis-associated in colon cancer-1 (MACC1) has been reported to be overexpressed in diverse human malignancies, and the increasing amount of evidences suggest that its overexpression is associated with the development and progression of many human tumors. However, the prognostic and clinicopathological value of MACC1 in colorectal cancer remains inconclusive. Therefore, we conducted this meta-analysis to investigate the effect of MACC1 overexpression on clinicopathological features and survival outcomes in colorectal cancer. PubMed, CNKI, and Wanfang databases were searched for relevant articles published update to December 2015. Correlation of MACC1 expression level with overall survival (OS), disease-free survival (DFS), and clinicopathological features were analyzed. In this meta-analysis, fifteen studies with a total of 2,161 colorectal cancer patients were included. Our results showed that MACC1 overexpression was significantly associated with poorer OS and DFS. Moreover, MACC1 overexpression was significantly associated with gender, localization, TNM stage, T stage, and N stage. Together, our meta-analysis showed that MACC1 overexpression was significantly associated with poor survival rates, regional invasion and lymph-node metastasis. MACC1 expression level can serve as a novel prognostic factor in colorectal cancer patients. PMID:27542234

Self-reported interpersonal problems and impact messages as perceived by significant others are differentially associated with the process and outcome of depression therapy.

PubMed

Altenstein-Yamanaka, David; Zimmermann, Johannes; Krieger, Tobias; Dörig, Nadja; Grosse Holtforth, Martin

2017-07-01

Interpersonal factors play a major role in causing and maintaining depression. This study sought to investigate how patients' self-perceived interpersonal problems and impact messages as perceived by significant others are interrelated, change over therapy, and differentially predict process and outcome in psychotherapy of depression. For the present study, we used data from 144 outpatients suffering from major depression that were treated within a psychotherapy study. Interpersonal variables were assessed pre- and posttherapy with the self-report Inventory of Interpersonal Problems-Circumplex Scale (IIP-32; Thomas, Brähler, & Strauss, 2011) and with the informant-based Impact Message Inventory (Caspar, Berger, Fingerle, & Werner, 2016). Patients' levels on the dimensions of Agency and Communion were calculated from both measures; their levels on Interpersonal Distress were measured with the IIP. Depressive and general symptomatology was assessed at pre-, post-, and at 3-month follow-up; patient-reported process measures were assessed during therapy. The Agency scores of IIP and IMI correlated moderately, but the Communion scores did not. IIP Communion was positively associated with the quality of the early therapeutic alliance and with the average level of cognitive-emotional processing during therapy. Whereas IIP Communion and IMI Agency increased over therapy, IIP Distress decreased. A pre-post-decrease in IIP Distress was positively associated with pre-postsymptomatic change over and above the other interpersonal variables, but pre-post-increase in IMI Agency was positively associated with symptomatic improvement from post- to 3-month follow-up. These findings suggest that significant others seem to provide important additional information about the patients' interpersonal style. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

An evaluation of the significance of transfers of debris: criteria for association and exclusion.

PubMed

Cwiklik, C

1999-11-01

Several criteria are proposed for making decisions about comparing sets of debris involving the transfer of non-component particles and fibers--those produced from something other than the item itself--using a model based upon rudimentary set theory. Decisions about the significance of an association or an exclusion based upon trace evidence require an evaluation of debris in its context; reference points for such evaluation are presented. Samples of debris from the sites relevant to the event under investigation must be available, as well as debris standards from the usual environments of the people involved, and must be adequate to permit a determination of normal versus foreign debris. Criteria are proposed for establishing contact based upon corresponding sets of particles and fibers, for excluding contact in the absence of corresponding particles or fibers, and for refraining from making either an association or an exclusion. Conditions for reaching qualified conclusions or other types of associations when these criteria are only partially met are also discussed; conclusions may sometimes be reached if potential sources for debris particles and fibers can be found. Decisions about the strength of an association or an exclusion based upon comparisons of non-component debris particles and fibers can be made by reference to the criteria for reaching a conclusion. The criteria can be tested via Bayes' Theorem. The analysis itself is based primarily upon light microscopy, although other methods may be used as well. Case examples are presented.

Communicating Hydrocephalus Associated with Small- to Medium-Sized Vestibular Schwannomas: Clinical Significance of the Tumor Apparent Diffusion Coefficient Map.

PubMed

Taniguchi, Masaaki; Nakai, Tomoaki; Kohta, Masaaki; Kimura, Hidehito; Kohmura, Eiji

2016-10-01

The etiology of hydrocephalus associated with the small- to medium-sized vestibular schwannomas is still controversial. We investigated tumor-specific factors related to the association of hydrocephalus with small- to medium-sized vestibular schwannomas. Among the 77 patients with vestibular schwannoma smaller than 30 mm, 9 patients demonstrated associated communicating hydrocephalus. Patient medical records, radiologic data, and histopathologic specimens were reviewed retrospectively. The age of the patients, and size, mean apparent diffusion coefficient (ADC) value, and histologic features of the tumors were compared with those of patients without hydrocephalus. The symptoms related to hydrocephalus improved in all patients after tumor removal. Both the mean size and ADC values exhibited a statistically significant difference between the tumors with and without hydrocephalus (P < 0.01). The size and ADC value of the tumor were significantly related to the association with hydrocephalus. The increased tumor ADC value was considered to be the result of degenerative change and suggested the involvement of protein sloughing in the etiology of the associated hydrocephalus. Copyright © 2016 Elsevier Inc. All rights reserved.

The Addition of Postoperative Chemotherapy is Associated with Improved Survival in Patients with Pancreatic Cancer Treated with Preoperative Therapy.

PubMed

Roland, Christina L; Katz, Matthew H G; Tzeng, Ching-Wei D; Lin, Heather; Varadhachary, Gauri R; Shroff, Rachna; Javle, Milind; Fogelman, David; Wolff, Robert A; Vauthey, Jean N; Crane, Christopher H; Lee, Jeffrey E; Fleming, Jason B

2015-12-01

Preoperative/neoadjuvant therapy (NT) is increasingly utilized for the treatment of pancreatic ductal adenocarcinoma (PDAC). However, little data exist regarding information on the use of additional postoperative therapy following NT. The lymph node ratio (LNR) is a prognostic marker of oncologic outcomes after NT and resection. In this study, we evaluated the effectiveness of postoperative therapy following NT, stratified by LNR. A prospective tumor registry database was queried to identify patients with PDAC who underwent resection following NT from 1990 to 2008. Clinicopathologic factors were compared to identify associations with overall survival (OS) and time to recurrence (TTR) based on postoperative chemotherapy status. Thirty-six (14 %) of the 263 patients received additional postoperative therapy. No differences were observed in the pathologic characteristics between patients who received postoperative chemotherapy and those who did not. The median LNR was 0.12 for patients with N + disease. Following NT, the administration of postoperative therapy was associated with improved median OS (72 vs. 33 months; p = 0.008) for patients with an LNR < 0.15. There was no association between postoperative chemotherapy and OS for patients with LNR ≥ 0.15. Multivariate analysis demonstrated that the administration of postoperative systemic therapy in patients with a low LNR was associated with a reduced risk of death (hazard ratio 0.49; p = 0.02). Postoperative chemotherapy after NT in patients with low LNR is associated with improved oncologic outcomes.

CNTNAP2 Is Significantly Associated With Speech Sound Disorder in the Chinese Han Population.

PubMed

Zhao, Yun-Jing; Wang, Yue-Ping; Yang, Wen-Zhu; Sun, Hong-Wei; Ma, Hong-Wei; Zhao, Ya-Ru

2015-11-01

Speech sound disorder is the most common communication disorder. Some investigations support the possibility that the CNTNAP2 gene might be involved in the pathogenesis of speech-related diseases. To investigate single-nucleotide polymorphisms in the CNTNAP2 gene, 300 unrelated speech sound disorder patients and 200 normal controls were included in the study. Five single-nucleotide polymorphisms were amplified and directly sequenced. Significant differences were found in the genotype (P = .0003) and allele (P = .0056) frequencies of rs2538976 between patients and controls. The excess frequency of the A allele in the patient group remained significant after Bonferroni correction (P = .0280). A significant haplotype association with rs2710102T/+rs17236239A/+2538976A/+2710117A (P = 4.10e-006) was identified. A neighboring single-nucleotide polymorphism, rs10608123, was found in complete linkage disequilibrium with rs2538976, and the genotypes exactly corresponded to each other. The authors propose that these CNTNAP2 variants increase the susceptibility to speech sound disorder. The single-nucleotide polymorphisms rs10608123 and rs2538976 may merge into one single-nucleotide polymorphism. © The Author(s) 2015.

"Compacted" procedures for adults' simple addition: A review and critique of the evidence.

PubMed

Chen, Yalin; Campbell, Jamie I D

2018-04-01

We review recent empirical findings and arguments proffered as evidence that educated adults solve elementary addition problems (3 + 2, 4 + 1) using so-called compacted procedures (e.g., unconscious, automatic counting); a conclusion that could have significant pedagogical implications. We begin with the large-sample experiment reported by Uittenhove, Thevenot and Barrouillet (2016, Cognition, 146, 289-303), which tested 90 adults on the 81 single-digit addition problems from 1 + 1 to 9 + 9. They identified the 12 very-small addition problems with different operands both ≤ 4 (e.g., 4 + 3) as a distinct subgroup of problems solved by unconscious, automatic counting: These items yielded a near-perfectly linear increase in answer response time (RT) yoked to the sum of the operands. Using the data reported in the article, however, we show that there are clear violations of the sum-counting model's predictions among the very-small addition problems, and that there is no real RT boundary associated with addends ≤4. Furthermore, we show that a well-known associative retrieval model of addition facts-the network interference theory (Campbell, 1995)-predicts the results observed for these problems with high precision. We also review the other types of evidence adduced for the compacted procedure theory of simple addition and conclude that these findings are unconvincing in their own right and only distantly consistent with automatic counting. We conclude that the cumulative evidence for fast compacted procedures for adults' simple addition does not justify revision of the long-standing assumption that direct memory retrieval is ultimately the most efficient process of simple addition for nonzero problems, let alone sufficient to recommend significant changes to basic addition pedagogy.

Improvement Rate of Acute Otitis Media Caused by Haemophilus influenzae at 1 Week Is Significantly Associated with Time to Recovery

PubMed Central

Yamazaki, Yoshitaka; Qin, Liang; Okitsu, Naohiro; Yahara, Koji; Irimada, Mihoko; Hirakata, Yoichi; Kaku, Mitsuo; Kobayashi, Toshimitsu; Watanabe, Hiroshi

2013-01-01

Acute otitis media (AOM) is the most common upper respiratory tract infection in childhood. Children with AOM were enrolled at Tohoku Rosai Hospital between July 2006 and June 2011 if their middle ear fluid cultures after tympanocentesis yielded only Haemophilus influenzae. The susceptibilities of the isolates to ampicillin were determined, and microtiter biofilm assays and invasion assays using BEAS-2B cells were performed. The association between these bacterial characteristics and clinical relapses of AOM and treatment failures was evaluated. Seventy-four children (39 boys and 35 girls) with a median age of 1 year (interquartile range [IQR], 0.25 to 2 years) were enrolled. Among 74 H. influenzae isolates, 37 showed intermediate resistance or resistance to ampicillin (MIC, ≥2 μg/ml). In the microtiter biofilm assay, the median optical density at 600 nm (OD600) was 0.68 (IQR, 0.24 to 1.02), and 70 isolates formed biofilms. The median invasion rate was 15% (IQR, 0 to 10%), and 46 isolates invaded BEAS-2B cells. Relapses and treatment failures occurred in 19 and 6 children, respectively. There was no significant difference in the invasion rates between patients with and those without relapses or treatment failures. Also, there was no significant association between biofilm formation and relapse or treatment failure. The improvements in the severity scores after 1 week were significantly associated with the recovery time (P < 0.0001). We did not identify any significant association between relapse or treatment failure and bacterial factors. AOM has a multifactorial etiology, and this may explain why we could not find a significant association. An improvement in the severity score after 1 week of treatment may be a useful predictor of the outcome of AOM. PMID:23966504

Exposure to previous cART is associated with significant liver fibrosis and cirrhosis in human immunodeficiency virus-infected patients.

PubMed

Anadol, Evrim; Lust, Kristina; Boesecke, Christoph; Schwarze-Zander, Carolynne; Mohr, Raphael; Wasmuth, Jan-Christian; Rockstroh, Jürgen Kurt; Trebicka, Jonel

2018-01-01

Combined antiretroviral therapy (cART) has improved survival in HIV-patients. While the first antiretrovirals, which became available in particular D-drugs (especially didanosine and stavudine) and unboosted protease inhibitors, may impair liver function, the modern cART seems to decrease liver fibrosis. This study assessed the influence of exposure to previous antiretrovirals on liver fibrosis in HIV-infected patients. This observational cross-sectional single-center study recruited 333 HIV patients and assessed liver fibrosis using transient elastography (TE). 83% were male with a median age of 45, while 131 were co-infected with viral hepatitis. Overall, 18% had significant fibrosis and 7.5% had cirrhosis. 11% of HIV mono-infected patients had significant fibrosis and 2% had cirrhosis. HCV infection (OR:5.3), history of exposure to didanosine (OR:2.7) and HIV load below 40copies/mL (OR:0.5) were independently associated with significant fibrosis, while HCV (OR:5.8), exposure to didanosine (OR:2.9) and azidothymidine (OR:2.8) were independently associated with cirrhosis. Interestingly, in HIV mono-infected patients, a HIV-load below 40copies/mL (OR:0.4) was independently associated with significant fibrosis, and didanosine (OR:20.8) with cirrhosis. In conclusion, history of exposure to didanosine and azidothymidine continues to have an impact on the presence of liver cirrhosis in HIV patients. However, HCV co-infection and ongoing HIV-replication have the strongest effect on development of significant fibrosis in these patients.

Localization of aPKC lambda/iota and its interacting protein, Lgl2, is significantly associated with lung adenocarcinoma progression.

PubMed

Imamura, Naoko; Horikoshi, Yosuke; Matsuzaki, Tomohiko; Toriumi, Kentaro; Kitatani, Kanae; Ogura, Go; Masuda, Ryota; Nakamura, Naoya; Takekoshi, Susumu; Iwazaki, Masayuki

2013-12-20

Atypical protein kinase C lambda/iota (aPKC λ/ι) is expressed in several human cancers; however, the correlation between aPKC λ/ι localization and cancer progression in human lung adenocarcinoma (LAC) remains to be clarified. We found that patients with a high level of aPKC λ/ι expression in LAC had significantly shorter overall survival than those with a low level of aPKC λ/ι expression. In addition, localization of aPKC λ/ι in the apical membrane or at the cell-cell contact was associated with both lymphatic invasion and metastasis. The intercellular adhesion molecule, E-cadherin, was decreased in LACs with highly expressed aPKC λ/ι at the invasion site of tumor cells. This result suggested that the expression levels of aPKC λ/ι and E-cadherin reflect the progression of LAC. On double-immunohistochemical analysis, aPKC λ/ι and Lgl2, a protein that interacts with aPKC λ/ι, were co-localized within LACs. Furthermore, we found that Lgl2 bound the aPKC λ/ι-Par6 complex in tumor tissue by immune-cosedimentation analysis. Apical membrane localization of Lgl2 was correlated with lymphatic invasion and lymph node metastasis. These results thus indicate that aPKC λ/ι expression is altered upon the progression of LAC. This is also the first evidence to show aPKC λ/ι overexpression in LAC and demonstrates that aPKC λ/ι localization at the apical membrane or cell-cell contact is associated with lymphatic invasion and metastasis of the tumor.

Association mapping to discover significant marker-trait associations for resistance against fusarium wilt variant 2 in pigeonpea [Cajanus cajan (L.) Millspaugh] using SSR markers.

PubMed

Patil, Prakash G; Dubey, Jyotirmay; Bohra, Abhishek; Mishra, R K; Saabale, P R; Das, Alok; Rathore, Meenal; Singh, N P

2017-08-01

Pigeonpea production is severely constrained by wilt disease caused by Fusarium udum. In the current study, we discover the putative genomic regions that control resistance response to variant 2 of fusarium wilt using association mapping approach. The association panel comprised of 89 diverse pigeonpea genotypes including seven varieties, three landraces and 79 germplasm lines. The panel was screened rigorously for 3 consecutive years (2013-14, 2014-15 and 2015-2016) against variant 2 in a wilt-sick field. A total of 65 pigeonpea specific hypervariable SSR markers (HASSRs) were screened representing seven linkage groups and 29 scaffolds of the pigeonpea genome. A total of 181 alleles were detected, with average values of gene diversity and polymorphism information content (PIC) of 0.55 and 0.47, respectively. Further analysis using model based (STRUCTURE) and distance based (clustering) approaches separated the entire pigeonpea collection into two distinct subgroups (K = 2). The marker trait associations (MTAs) were established based on three-year wilt incidence data and SSR dataset using a unified mixed linear model. Consequently, six SSR markers were identified, which were significantly associated with wilt resistance and explained up to 6% phenotypic variance (PV) across the years. Among these SSRs, HASSR18 was found to be the most stable and significant, accounting for 5-6% PV across the years. To the best of our knowledge, this is the first report of identification of favourable alleles for resistance to variant 2 of Fusarium udum in pigeonpea using association mapping. The SSR markers identified here will greatly facilitate marker assisted resistance breeding against fusarium wilt in pigeonpea.

High expression of P-cadherin is significantly associated with poor prognosis in patients with non-small-cell lung cancer.

PubMed

Imai, Sachiko; Kobayashi, Masashi; Takasaki, Chihiro; Ishibashi, Hironori; Okubo, Kenichi

2018-04-01

Placental (P)-cadherin expression is associated with malignant phenotype of cancer cell. The loss of E-cadherin has been thought to play a key role in tumor progression in several cancers. In this study, we aimed to clarify the role of P-cadherin expression in non-small-cell lung cancer (NSCLC). NSCLC patients (n = 172) were enrolled in this study; among them, 107 harbored adenocarcinomas, and 65 had squamous cell carcinomas. We examined P-cadherin and E-cadherin expression by immunohistochemical analysis and assessed the associations between each cadherin expression and both cadherin expression patterns with clinicopathological factors and prognosis. To investigate the pathway to acquire tumor progression associated with P-cadherin and E-cadherin, we examined p120 catenin localization by immunohistochemical analysis. High P-cadherin expression was significantly associated with lymphatic metastasis, pathological stage, and Ki-67 proliferation index (P < .05, respectively). Low E-cadherin expression was significantly associated with maximum standardized uptake value, lymphatic metastasis, and pathological stage (P < .05, respectively). The cytoplasmic p120 catenin localization was associated with the low E-cadherin and high P-cadherin expression group (P < .001). High P-cadherin expression was associated with shorter disease-free survival (P = .044) and shorter overall survival (OS; P = .044). The low E-cadherin and high P-cadherin expression group was associated with shorter OS (P = .024). High P-cadherin expression was associated with tumor progression and poor patient survival in NSCLC. In these patients, the low E-cadherin expression might be associated with tumor progression involving cytoplasmic p120 catenin. Copyright © 2018 Elsevier B.V. All rights reserved.

Involvement of the PRKCB1 gene in autistic disorder: significant genetic association and reduced neocortical gene expression.

PubMed

Lintas, C; Sacco, R; Garbett, K; Mirnics, K; Militerni, R; Bravaccio, C; Curatolo, P; Manzi, B; Schneider, C; Melmed, R; Elia, M; Pascucci, T; Puglisi-Allegra, S; Reichelt, K-L; Persico, A M

2009-07-01

Protein kinase C enzymes play an important role in signal transduction, regulation of gene expression and control of cell division and differentiation. The fsI and betaII isoenzymes result from the alternative splicing of the PKCbeta gene (PRKCB1), previously found to be associated with autism. We performed a family-based association study in 229 simplex and 5 multiplex families, and a postmortem study of PRKCB1 gene expression in temporocortical gray matter (BA41/42) of 11 autistic patients and controls. PRKCB1 gene haplotypes are significantly associated with autism (P<0.05) and have the autistic endophenotype of enhanced oligopeptiduria (P<0.05). Temporocortical PRKCB1 gene expression was reduced on average by 35 and 31% for the PRKCB1-1 and PRKCB1-2 isoforms (P<0.01 and <0.05, respectively) according to qPCR. Protein amounts measured for the PKCbetaII isoform were similarly decreased by 35% (P=0.05). Decreased gene expression characterized patients carrying the 'normal' PRKCB1 alleles, whereas patients homozygous for the autism-associated alleles displayed mRNA levels comparable to those of controls. Whole genome expression analysis unveiled a partial disruption in the coordinated expression of PKCbeta-driven genes, including several cytokines. These results confirm the association between autism and PRKCB1 gene variants, point toward PKCbeta roles in altered epithelial permeability, demonstrate a significant downregulation of brain PRKCB1 gene expression in autism and suggest that it could represent a compensatory adjustment aimed at limiting an ongoing dysreactive immune process. Altogether, these data underscore potential PKCbeta roles in autism pathogenesis and spur interest in the identification and functional characterization of PRKCB1 gene variants conferring autism vulnerability.

Genome-Wide Significant Association between Alcohol Dependence and a Variant in the ADH Gene Cluster

PubMed Central

Frank, Josef; Cichon, Sven; Treutlein, Jens; Ridinger, Monika; Mattheisen, Manuel; Hoffmann, Per; Herms, Stefan; Wodarz, Norbert; Soyka, Michael; Zill, Peter; Maier, Wolfgang; Mössner, Rainald; Gaebel, Wolfgang; Dahmen, Norbert; Scherbaum, Norbert; Schmäl, Christine; Steffens, Michael; Lucae, Susanne; Ising, Marcus; Müller-Myhsok, Bertram; Nöthen, Markus M; Mann, Karl; Kiefer, Falk; Rietschel, Marcella

2011-01-01

Alcohol dependence (AD) is an important contributory factor to the global burden of disease. The etiology of AD involves both environmental and genetic factors, and the disorder has a heritability of around 50%. The aim of the present study was to identify susceptibility genes for AD by performing a genome-wide association study (GWAS). The sample comprised 1,333 male in-patients with severe DSM-IV AD and 2,168 controls. These included 487 patients and 1,358 controls from a previous GWAS study by our group. All individuals were of German descent. Single marker tests and a polygenic score based analysis to assess the combined contribution of multiple markers with small effects were performed. The SNP rs1789891, which is located between the ADH1B and ADH1C genes, achieved genome-wide significance (p=1.27E–8; OR=1.46). Other markers from this region were also associated with AD, and conditional analyses indicated that these made a partially independent contribution. The SNP rs1789891 is in complete linkage disequilibrium with the functional Arg272Gln variant (p=1.24E–7, OR=1.31) of the ADH1C gene, which has been reported to modify the rate of ethanol oxidation to acetaldehyde in vitro. A polygenic score based approach produced a significant result (p=9.66E–9). This is the first GWAS of AD to provide genome-wide significant support for the role of the ADH gene cluster and to suggest a polygenic component to the etiology of AD. The latter result suggests that many more AD susceptibility genes still await identification. PMID:22004471

Polymorphisms in the TLR4 and TLR5 gene are significantly associated with inflammatory bowel disease in German shepherd dogs.

PubMed

Kathrani, Aarti; House, Arthur; Catchpole, Brian; Murphy, Angela; German, Alex; Werling, Dirk; Allenspach, Karin

2010-12-23

Inflammatory bowel disease (IBD) is considered to be the most common cause of vomiting and diarrhoea in dogs, and the German shepherd dog (GSD) is particularly susceptible. The exact aetiology of IBD is unknown, however associations have been identified between specific single-nucleotide polymorphisms (SNPs) in Toll-like receptors (TLRs) and human IBD. However, to date, no genetic studies have been undertaken in canine IBD. The aim of this study was to investigate whether polymorphisms in canine TLR 2, 4 and 5 genes are associated with IBD in GSDs. Mutational analysis of TLR2, TLR4 and TLR5 was performed in 10 unrelated GSDs with IBD. Four non-synonymous SNPs (T23C, G1039A, A1571T and G1807A) were identified in the TLR4 gene, and three non-synonymous SNPs (G22A, C100T and T1844C) were identified in the TLR5 gene. The non-synonymous SNPs identified in TLR4 and TLR5 were evaluated further in a case-control study using a SNaPSHOT multiplex reaction. Sequencing information from 55 unrelated GSDs with IBD were compared to a control group consisting of 61 unrelated GSDs. The G22A SNP in TLR5 was significantly associated with IBD in GSDs, whereas the remaining two SNPs were found to be significantly protective for IBD. Furthermore, the two SNPs in TLR4 (A1571T and G1807A) were in complete linkage disequilibrium, and were also significantly associated with IBD. The TLR5 risk haplotype (ACC) without the two associated TLR4 SNP alleles was significantly associated with IBD, however the presence of the two TLR4 SNP risk alleles without the TLR5 risk haplotype was not statistically associated with IBD. Our study suggests that the three TLR5 SNPs and two TLR4 SNPs; A1571T and G1807A could play a role in the pathogenesis of IBD in GSDs. Further studies are required to confirm the functional importance of these polymorphisms in the pathogenesis of this disease.

Minimizing Significant Figure Fuzziness.

ERIC Educational Resources Information Center

Fields, Lawrence D.; Hawkes, Stephen J.

1986-01-01

Addresses the principles and problems associated with the use of significant figures. Explains uncertainty, the meaning of significant figures, the Simple Rule, the Three Rule, and the 1-5 Rule. Also provides examples of the Rules. (ML)

Prevalence of Malaria, Dengue, and Chikungunya Significantly Associated with Mosquito Breeding Sites

PubMed Central

Islam, Mohammad Nazrul; ZulKifle, Mohammad; Sherwani, Arish Mohammad Khan; Ghosh, Susanta Kumar; Tiwari, Satyanarayan

2011-01-01

Objectives: To observe the prevalence of malaria, dengue, and chikungunya and their association with mosquito breeding sites. Methods: The study was observational and analytical. A total of 162 houses and 670 subjects were observed during the study period. One hundred forty-two febrile patients were eligible for the study. After obtaining informed consent from all febrile patients, 140 blood samples were collected to diagnose malaria, dengue, and chikungunya. Larval samples were collected by the standard protocol that follows. Correlation of data was performed by Pearson correlation test. Results: Forty-seven blood samples were found positive: 33 for chikungunya, 3 for dengue, and 11 for malaria. Fifty-one out of 224 larval samples were found positive. Out of the 51 positive samples, 37 were positive for Aedes, 12 were positive for Anopheles, and two were positive for Culex larvae. Interpretation and Conclusion: Mosquito-borne fevers, especially malaria, dengue, and chikungunya, have shown a significant relationship with mosquito breeding sites. PMID:23610486

Marker-Based Estimates Reveal Significant Non-additive Effects in Clonally Propagated Cassava (Manihot esculenta): Implications for the Prediction of Total Genetic Value and the Selection of Varieties.

PubMed

Wolfe, Marnin D; Kulakow, Peter; Rabbi, Ismail Y; Jannink, Jean-Luc

2016-08-31

In clonally propagated crops, non-additive genetic effects can be effectively exploited by the identification of superior genetic individuals as varieties. Cassava (Manihot esculenta Crantz) is a clonally propagated staple food crop that feeds hundreds of millions. We quantified the amount and nature of non-additive genetic variation for three key traits in a breeding population of cassava from sub-Saharan Africa using additive and non-additive genome-wide marker-based relationship matrices. We then assessed the accuracy of genomic prediction for total (additive plus non-additive) genetic value. We confirmed previous findings based on diallel populations, that non-additive genetic variation is significant for key cassava traits. Specifically, we found that dominance is particularly important for root yield and epistasis contributes strongly to variation in CMD resistance. Further, we showed that total genetic value predicted observed phenotypes more accurately than additive only models for root yield but not for dry matter content, which is mostly additive or for CMD resistance, which has high narrow-sense heritability. We address the implication of these results for cassava breeding and put our work in the context of previous results in cassava, and other plant and animal species. Copyright © 2016 Author et al.

Significance of lymph node capsular invasion in esophageal squamous cell carcinoma.

PubMed

Sakai, Makoto; Suzuki, Shigemasa; Sano, Akihiko; Tanaka, Naritaka; Inose, Takanori; Sohda, Makoto; Nakajima, Masanobu; Miyazaki, Tatsuya; Kuwano, Hiroyuki

2012-06-01

Extranodal invasion (ENI) has been reported to be associated with a poor prognosis in several malignancies. However, previous studies have included perinodal fat tissue tumor deposits in their definitions of ENI. To investigate the precise nature of ENI in esophageal squamous cell carcinoma (ESCC), we excluded these tumor deposits from our definition of ENI and defined tumor cell invasion through the lymph node capsule and into the perinodal tissues as lymph node capsular invasion (LNCI). The aim of the current study was to elucidate the significance of LNCI in ESCC. We investigated the associations between LNCI and other clinicopathologic features in 139 surgically resected ESCC. We also investigated the prognostic significance of LNCI in ESCC. LNCI was detected in 35 (25.2%) of 139 patients. The overall survival rate of the ESCC patients with LNCI was significantly lower than that of the ESCC patients with lymph node metastasis who were negative for LNCI. The survival difference between the patients with 1–3 lymph node metastases without LNCI and those with no lymph node metastasis was not significant. LNCI was significantly associated with distant organ recurrence. LNCI was also found to be an independent predictor of overall survival in addition to the number of lymph node metastases. LNCI in ESCC patients is an indicator of distant organ recurrence and a worse prognosis. LNCI could be used as a candidate marker for designing more precise staging and therapeutic strategies for ESCC.

The Leu72Met polymorphism of the ghrelin gene is significantly associated with binge eating disorder.

PubMed

Monteleone, Palmiero; Tortorella, Alfonso; Castaldo, Eloisa; Di Filippo, Carmela; Maj, Mario

2007-02-01

The pathophysiological mechanisms underlying binge eating disorder are poorly understood. Evidence exists for the fact that abnormalities in peptides involved in the regulation of appetite, including ghrelin, may play a role in binge eating behavior. Genes involved in the ghrelin physiology may therefore contribute to the biological vulnerability to binge eating disorder. We examined whether two polymorphisms of the ghrelin gene, the G152A (Arg51Gln) and C214A (Leu72Met), were associated with binge eating disorder. Ninety obese or nonobese women with binge eating disorder and 119 normal weight women were genotyped at the ghrelin gene. Statistical analyses showed that the Leu72Met ghrelin gene variant was significantly more frequent in binge eating disorder patients (chi2=5.940; d.f.=1, P=0.01) and was associated with a moderate, but significant risk to develop binge eating disorder (odds ratio=2.725, 95% confidence interval: 1.168-6.350). Although these data should be regarded as preliminary because of the small sample size, they suggest that the Leu72Met ghrelin gene variant may contribute to the genetic susceptibility to binge eating disorder.

HOMA-IR is associated with significant angiographic coronary artery disease in non-diabetic, non-obese individuals: a cross-sectional study.

PubMed

Mossmann, Márcio; Wainstein, Marco V; Gonçalves, Sandro C; Wainstein, Rodrigo V; Gravina, Gabriela L; Sangalli, Marlei; Veadrigo, Francine; Matte, Roselene; Reich, Rejane; Costa, Fernanda G; Bertoluci, Marcello C

2015-01-01

Insulin resistance is a major component of metabolic syndrome, type 2 Diabetes Mellitus (T2DM) and coronary artery disease (CAD). Although important in T2DM, its role as a predictor of CAD in non-diabetic patients is less studied. In the present study, we aimed to evaluate the association of HOMA-IR with significant CAD, determined by coronary angiography in non-obese, non-T2DM patients. We also evaluate the association between 3 oral glucose tolerance test (OGTT) based insulin sensitivity indexes (Matsuda, STUMVOLL-ISI and OGIS) and CAD. We conducted a cross-sectional study with 54 non-obese, non-diabetic individuals referred for coronary angiography due to suspected CAD. CAD was classified as the "anatomic burden score" corresponding to any stenosis equal or larger than 50 % in diameter on the coronary distribution. Patients without lesions were included in No-CAD group. Patients with at least 1 lesion were included in the CAD group. A 75 g oral glucose tolerance test (OGTT) with measurements of plasma glucose and serum insulin at 0, 30, 60, 90 and 120 min was obtained to calculate insulin sensitivity parameters. HOMA-IR results were ranked and patients were also categorized into insulin resistant (IR) or non-insulin resistant (NIR) if they were respectively above or below the 75th percentile (HOMA-IR > 4.21). The insulin sensitivity tests results were also divided into IR and NIR, respectively below and above each 25th percentile. Chi square was used to study association. Poisson Regression Model was used to compare prevalence ratios between categorized CAD and IR groups. Fifty-four patients were included in the study. There were 26 patients (48 %) with significant CAD. The presence of clinically significant CAD was significant associated with HOMA-IR above p75 (Chi square 4.103, p = 0.0428) and 71 % of patients with HOMA-IR above p75 had significant CAD. Subjects with CAD had increased prevalence ratio of HOMA-IR above p75 compared to subjects without

Rectal hyposensitivity and functional anorectal outlet obstruction are common entities in patients with functional constipation but are not significantly associated

PubMed Central

Lee, Tae Hee; Hong, Su Jin; Jeon, Seong Ran; Kwon, Soon Ha; Kim, Wan Jung; Kim, Hyun Gun; Cho, Won Young; Cho, Joo Young; Kim, Jin-Oh; Lee, Ji Sung

2013-01-01

Background/Aims The causes of functional anorectal outlet obstruction (outlet obstruction) include functional defecation disorder (FDD), rectocele, and rectal intussusception (RI). It is unclear whether outlet obstruction is associated with rectal hyposensitivity (RH) in patients with functional constipation (FC). The aim of this study was to determine the association between RH and outlet obstruction in patients with FC. Methods This was a retrospective study using a prospectively collected constipation database, and the population comprised 107 patients with FC (100 females; median age, 49 years). We performed anorectal manometry, defecography, rectal barostat, and at least two tests (balloon expulsion test, electromyography, or colon transit time study). RH was defined as one or more sensory threshold pressures raised beyond the normal range on rectal barostat. We investigated the association between the presence of RH and an outlet obstruction such as large rectocele (> 2 cm in size), RI, or FDD. Results Forty patients (37.4%) had RH. No significant difference was observed in RH between patients with small and large rectoceles (22 [44.9%] vs. 18 [31%], respectively; p = 0.140). No significant difference was observed in RH between the non-RI and RI groups (36 [36.7%] vs. 4 [30.8%], respectively; p = 0.599). Furthermore, no significant difference in RH was observed between the non-FDD and FDD groups (19 [35.8%] vs. 21 [38.9%], respectively; p = 0.745). Conclusions RH and outlet obstruction are common entities but appear not to be significantly associated. PMID:23345997

Rectal hyposensitivity and functional anorectal outlet obstruction are common entities in patients with functional constipation but are not significantly associated.

PubMed

Lee, Tae Hee; Lee, Joon Seong; Hong, Su Jin; Jeon, Seong Ran; Kwon, Soon Ha; Kim, Wan Jung; Kim, Hyun Gun; Cho, Won Young; Cho, Joo Young; Kim, Jin-Oh; Lee, Ji Sung

2013-01-01

The causes of functional anorectal outlet obstruction (outlet obstruction) include functional defecation disorder (FDD), rectocele, and rectal intussusception (RI). It is unclear whether outlet obstruction is associated with rectal hyposensitivity (RH) in patients with functional constipation (FC). The aim of this study was to determine the association between RH and outlet obstruction in patients with FC. This was a retrospective study using a prospectively collected constipation database, and the population comprised 107 patients with FC (100 females; median age, 49 years). We performed anorectal manometry, defecography, rectal barostat, and at least two tests (balloon expulsion test, electromyography, or colon transit time study). RH was defined as one or more sensory threshold pressures raised beyond the normal range on rectal barostat. We investigated the association between the presence of RH and an outlet obstruction such as large rectocele (> 2 cm in size), RI, or FDD. Forty patients (37.4%) had RH. No significant difference was observed in RH between patients with small and large rectoceles (22 [44.9%] vs. 18 [31%], respectively; p = 0.140). No significant difference was observed in RH between the non-RI and RI groups (36 [36.7%] vs. 4 [30.8%], respectively; p = 0.599). Furthermore, no significant difference in RH was observed between the non-FDD and FDD groups (19 [35.8%] vs. 21 [38.9%], respectively; p = 0.745). RH and outlet obstruction are common entities but appear not to be significantly associated.

Food addiction: its prevalence and significant association with obesity in the general population.

PubMed

Pedram, Pardis; Wadden, Danny; Amini, Peyvand; Gulliver, Wayne; Randell, Edward; Cahill, Farrell; Vasdev, Sudesh; Goodridge, Alan; Carter, Jacqueline C; Zhai, Guangju; Ji, Yunqi; Sun, Guang

2013-01-01

'Food addiction' shares a similar neurobiological and behavioral framework with substance addiction. However whether, and to what degree, 'food addiction' contributes to obesity in the general population is unknown. to assess 1) the prevalence of 'food addiction' in the Newfoundland population; 2) if clinical symptom counts of 'food addiction' were significantly correlated with the body composition measurements; 3) if food addicts were significantly more obese than controls, and 4) if macronutrient intakes are associated with 'food addiction'. A total of 652 adults (415 women, 237 men) recruited from the general population participated in this study. Obesity was evaluated by Body Mass Index (BMI) and Body Fat percentage measured by dual-energy X-ray absorptiometry. 'Food addiction' was assessed using the Yale Food Addiction Scale and macronutrient intake was determined from the Willet Food Frequency Questionnaire. The prevalence of 'food addiction' was 5.4% (6.7% in females and 3.0% in males) and increased with obesity status. The clinical symptom counts of 'food addiction' were positively correlated with all body composition measurements across the entire sample (p<0.001). Obesity measurements were significantly higher in food addicts than controls; Food addicts were 11.7 (kg) heavier, 4.6 BMI units higher, and had 8.2% more body fat and 8.5% more trunk fat. Furthermore, food addicts consumed more calories from fat and protein compared with controls. Our results demonstrated that 'food addiction' contributes to severity of obesity and body composition measurements from normal weight to obese individuals in the general population with higher rate in women as compared to men.

The significance of virulence factors in Helicobacter pylori.

PubMed

Shiota, Seiji; Suzuki, Rumiko; Yamaoka, Yoshio

2013-07-01

Helicobacter pylori (H. pylori) infection is linked to various gastroduodenal diseases; however, only a small fraction of these patients develop associated diseases. Despite the high prevalence of H. pylori infection in Africa and South Asia, the incidence of gastric cancer in these areas is much lower than those in other countries. The incidence of gastric cancer tends to decrease from north to south in East Asia. Such geographical differences in the pathology can be explained, at least in part, by the presence of different types of H. pylori virulence factors in addition to host and environmental factors. Virulence factors of H. pylori, such as CagA, VacA, DupA, IceA, OipA and BabA, have been demonstrated to be the predictors of severe clinical outcomes. Interestingly, a meta-analysis showed that CagA seropositivity was associated with gastric cancer compared with gastritis, even in East Asian countries where almost the strains possess cagA. Another meta-analysis also confirmed the significance of vacA, dupA and iceA. However, it is possible that additional important pathogenic genes may exist because H. pylori consists of approximately 1600 genes. Despite the advances in our understanding of the development of H. pylori infection-related diseases, further work is required to clarify the roles of H. pylori virulence factors. © 2013 The Authors. Journal of Digestive Diseases © 2013 Wiley Publishing Asia Pty Ltd and Chinese Medical Association Shanghai Branch, Chinese Society of Gastroenterology, Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine.

Seizure-associated aphasia has good lateralizing but poor localizing significance.

PubMed

Loesch, Anna Mira; Steger, Hannah; Losher, Claudia; Hartl, Elisabeth; Rémi, Jan; Vollmar, Christian; Noachtar, Soheyl

2017-09-01

To investigate the occurrence of ictal and postictal aphasia in different focal epilepsy syndromes. We retrospectively analyzed the video-electroencephalographic monitoring data of 1,118 patients with focal epilepsy for seizure-associated aphasia (SAA). Statistical analysis included chi-square analysis and Fisher's exact test. We identified 102 of 1,118 patients (9.1%) in whom ictal or postictal aphasia (SAA) was part of their recorded seizures (n = 59 of 102; 57.8%) or who reported aphasia by history (n = 43; 42.2% only reported aphasia by history). Postictal aphasia was present in 18 patients (30.5%). Six of the 59 patients had both ictal and postictal aphasia (10.2%). SAA occurred either with left hemisphere seizure onset or with seizures spreading from the right to the left hemisphere. SAA was most common in patients with parieto-occipital epilepsy (10.9%; five of 46 patients), followed by patients with temporal (6.7%; 28 of 420 patients), focal (not further localized; 4.8%; 22 of 462 patients), and frontal epilepsy (2.1%; four of 190 patients; p = 0.04). SAA was more common in parieto-occipital epilepsy than in frontal epilepsy (p = 0.02). In contrast, there was no significant difference in SAA between temporal and parieto-occipital epilepsy (p = 0.36). SAA has a high lateralizing but limited localizing value, as it often reflects spread of epileptic activity into speech-harboring brain regions. Wiley Periodicals, Inc. © 2017 International League Against Epilepsy.

[Infiltration of tumor associated macrophages in multiple myeloma and its clinical significance].

PubMed

Gui, Q L; Wang, Y S; Huang, S; Wan, Y; Wang, H P; Zhu, Z G; Li, M M; Zhu, H Y; Tao, Q S; Shen, Y Y; Zhang, Q; Qin, H

2018-02-14

Objective: To investigate the clinical significance of tumor associated macrophages (TAM) in multiple myeloma (MM) and the relationship with angiogenesis and immunosuppression. Methods: Seventy cases of MM patients diagnosed from August 2015 to June 2017 were enrolled in the study as experimental group, 20 cases of benign hematological diseases (13 with iron deficiency anemia and 7 with megaloblastic anemia) patients as control group. Immunohistochemical method was used to detect the expression of CD163, CD34 and VEGF in bone marrow samples, and flow cytometry was used to detect the proportion of regulatory T cell (Treg cells), ELISA was used to detect the level of IL-10, and the clinical features were analyzed. Results: ①Among the 70 patients, there were 31 males and 39 females with a median age of 65 (50~78) years old. TAM infiltration density, microvascular density (MVD), VEGF expression level, Treg ratio and IL-10 level in bone marrow samples of 70 MM patients were significantly higher than those of benign hematological diseases ( P <0.05). ②In the MM group, the above indexes of the patients with disease stabilized (15 cases) were lower than those of the newly diagnosed group (35 cases) and the relapse refractory group (20 cases) ( P <0.05), those of relapse refractory group were higher than those of newly diagnosed group ( P >0.05). ③Of the 35 newly diagnosed MM patients, 27 completed 4 courses of treatment. In the effective group (15 cases), the TAM infiltration density after treatment was significantly lower than that before treatment, the difference was statistically significant[(20.20±7.66) vs (28.87±11.97), t =2.362, P =0.025]; while in the ineffective group of 12 cases, the difference of the TAM infiltration density before and after treatment was not statistically significant[(42.00±13.76) vs (48.25±13.59), t =1.119, P =0.275]. ④TAM infiltration density in the effective group after bortezomib treatment (21 cases) were lower than those in the

Bacterial markers of periodontal diseases and their practical significance in dentistry.

PubMed

Chukhlovin, A B; Solovyova, A M; Matelo, S K; Kobiyasova, I V; Morosova, E B; Hokhlacheva, A V; Teplyakov, B G; Syssoev, K A; Konstantinova, V E; Matelo, L N; Totolian, Areg A

2007-10-01

The incidence and prevalence of Actinobacillus actinomycetemcomitans, Porphyronmonas gingivalis, and Tannerella forsythensis in specimens of subgingival dental deposit were evaluated in 495 residents of St. Petersburg aged 6-82 years. The microorganisms were detected by gene-specific PCR of 16S rDNA. In accordance with age-specific increase in the incidence of gingival diseases, the percentage of samples containing T. forsythensis and P. gingivalis was significantly higher in adult and elderly patients in comparison with adolescents. The presence of T. forsythensis significantly correlated with the presence of gingivitis and dental deposit. In addition, the incidence of T. forsythensis was significantly higher in tobacco smokers. These results attest to a relationship between T. forsythensis infection and more frequent periodontal diseases associated with aging and tobacco smoking.

Bubble-chip analysis of human origin distributions demonstrates on a genomic scale significant clustering into zones and significant association with transcription

PubMed Central

Mesner, Larry D.; Valsakumar, Veena; Karnani, Neerja; Dutta, Anindya; Hamlin, Joyce L.; Bekiranov, Stefan

2011-01-01

We have used a novel bubble-trapping procedure to construct nearly pure and comprehensive human origin libraries from early S- and log-phase HeLa cells, and from log-phase GM06990, a karyotypically normal lymphoblastoid cell line. When hybridized to ENCODE tiling arrays, these libraries illuminated 15.3%, 16.4%, and 21.8% of the genome in the ENCODE regions, respectively. Approximately half of the origin fragments cluster into zones, and their signals are generally higher than those of isolated fragments. Interestingly, initiation events are distributed about equally between genic and intergenic template sequences. While only 13.2% and 14.0% of genes within the ENCODE regions are actually transcribed in HeLa and GM06990 cells, 54.5% and 25.6% of zonal origin fragments overlap transcribed genes, most with activating chromatin marks in their promoters. Our data suggest that cell synchronization activates a significant number of inchoate origins. In addition, HeLa and GM06990 cells activate remarkably different origin populations. Finally, there is only moderate concordance between the log-phase HeLa bubble map and published maps of small nascent strands for this cell line. PMID:21173031

Socioeconomic status is significantly associated with dietary salt intakes and blood pressure in Japanese workers (J-HOPE Study).

PubMed

Miyaki, Koichi; Song, Yixuan; Taneichi, Setsuko; Tsutsumi, Akizumi; Hashimoto, Hideki; Kawakami, Norito; Takahashi, Masaya; Shimazu, Akihito; Inoue, Akiomi; Kurioka, Sumiko; Shimbo, Takuro

2013-03-11

The association of socioeconomic status (SES) with nutrients intakes attracts public attention worldwide. In the current study, we examined the associations of SES with dietary salt intake and health outcomes in general Japanese workers (2,266) who participated in this Japanese occupational cohort. SES was assessed by a self-administered questionnaire. Dietary intakes were assessed with a validated, brief, self-administered diet history questionnaire (BDHQ). Multiple linear regression and stratified analysis were used to evaluate the associations of salt intake with the confounding factors. Education levels and household incomes were significantly associated with salt intake, as well as blood pressures (P < 0.05). After adjusting for age, sex and total energy intake, both years of education and household income significantly affect the salt intake (for education, β = -0.031, P = 0.040; for household income, β = -0.046, P = 0.003). SES factors also affect the risk of hypertension, those subjects with higher levels of education or income had lower risk to become hypertensive (ORs for education was 0.904, P < 0.001; ORs for income was 0.956, P = 0.032). Our results show that SES is an independent determinant of salt intake and blood pressure, in order to lower the risk of hypertension, the efforts to narrow the social status gaps should be considered by the health policy-makers.

Strongyloides stercoralis is associated with significant morbidity in rural Cambodia, including stunting in children

PubMed Central

Forrer, Armelle; Khieu, Virak; Schär, Fabian; Hattendorf, Jan; Marti, Hanspeter; Neumayr, Andreas; Char, Meng Chuor; Hatz, Christoph; Muth, Sinuon

2017-01-01

Background Strongyloides stercoralis is a soil-transmitted nematode that can replicate within its host, leading to long-lasting and potentially fatal infections. It is ubiquitous and highly prevalent in Cambodia. The extent of morbidity associated with S. stercoralis infection is difficult to assess due to the broad spectrum of symptoms and, thus, remains uncertain. Methodology/Principal findings Clinical signs were compared among S. stercoralis infected vs. non-infected participants in a cross-sectional survey conducted in 2012 in eight villages of Northern Cambodia, and before and after treatment with a single oral dose of ivermectin (200μg/kg BW) among participants harboring S. stercoralis. Growth retardation among schoolchildren and adolescents was assessed using height-for-age and thinness using body mass index-for-age. S. stercoralis prevalence was 31.1% among 2,744 participants. Urticaria (55% vs. 47%, OR: 1.4, 95% CI: 1.1–1.6) and itching (52% vs. 48%, OR: 1.2, 95% CI: 1.0–1.4) were more frequently reported by infected participants. Gastrointestinal, dermatological, and respiratory symptoms were less prevalent in 103 mono-infected participants after treatment. Urticaria (66% vs. 11%, OR: 0.03, 95% CI: 0.01–0.1) and abdominal pain (81 vs. 27%, OR: 0.07, 95% CI: 0.02–0.2) mostly resolved by treatment. S. stercoralis infection was associated with stunting, with 2.5-fold higher odds in case of heavy infection. Conclusions/Significance The morbidity associated with S. stercoralis confirmed the importance of gastrointestinal and dermatological symptoms unrelated to parasite load, and long-term chronic effects when associated with malnutrition. The combination of high prevalence and morbidity calls for the integration of S. stercoralis into ongoing STH control measures in Cambodia. PMID:29059195

Density of surgeons is significantly associated with reduced risk of deaths from motor vehicle crashes in US counties.

PubMed

Chang, David C; Eastman, Brent; Talamini, Mark A; Osen, Hayley B; Tran Cao, Hop S; Coimbra, Raul

2011-05-01

The concept of surgery and public health has been introduced in recent years, highlighting the impact of surgeons on improving public health outcomes, a relationship that has traditionally been ascribed to general practitioners. The purpose of this study is to quantify the effect of surgeon availability on deaths from motor vehicle crashes (MVC). Retrospective analysis of the Area Resource File from 2006 was performed. The primary outcome variable was the three-year (2001-2003) average in MVC deaths per 1 million population for each county. The primary independent variable was the density of surgeons per 1 million population in year 2003. Multiple linear regression analysis was performed, adjusting for density of general practitioners, urbanicity of the county, and socioeconomic status of the county. A total of 3,225 counties were analyzed. The median number of MVC deaths per million population was 226 (IQR 158-320). The median number of surgeon per million population was 55 (IQR 0-105), while the median number of general practitioners per million population was 424 (IQR 274-620). On unadjusted analysis, each increase of one surgeon per million population was associated with 0.38 fewer MVC deaths per million population (p < 0.001). On multivariate analysis, each increase of one surgeon per million population was significantly associated with 0.16 fewer MVC deaths per million population (p < 0.001). Rural location, persistent poverty, and low educational level were all associated with significant increases in MVC deaths. Higher density of surgeons is associated with significant reduction in deaths from MVCs. This highlights the need for 1) consideration of surgery as primary care and 2) development of inclusive surgical systems designed to provide care commensurate with patients' degree of injury. Copyright © 2011 American College of Surgeons. Published by Elsevier Inc. All rights reserved.

Polymorphisms in the Tlr4 and Tlr5 Gene Are Significantly Associated with Inflammatory Bowel Disease in German Shepherd Dogs

PubMed Central

Kathrani, Aarti; House, Arthur; Catchpole, Brian; Murphy, Angela; German, Alex; Werling, Dirk; Allenspach, Karin

2010-01-01

Inflammatory bowel disease (IBD) is considered to be the most common cause of vomiting and diarrhoea in dogs, and the German shepherd dog (GSD) is particularly susceptible. The exact aetiology of IBD is unknown, however associations have been identified between specific single-nucleotide polymorphisms (SNPs) in Toll-like receptors (TLRs) and human IBD. However, to date, no genetic studies have been undertaken in canine IBD. The aim of this study was to investigate whether polymorphisms in canine TLR 2, 4 and 5 genes are associated with IBD in GSDs. Mutational analysis of TLR2, TLR4 and TLR5 was performed in 10 unrelated GSDs with IBD. Four non-synonymous SNPs (T23C, G1039A, A1571T and G1807A) were identified in the TLR4 gene, and three non-synonymous SNPs (G22A, C100T and T1844C) were identified in the TLR5 gene. The non-synonymous SNPs identified in TLR4 and TLR5 were evaluated further in a case-control study using a SNaPSHOT multiplex reaction. Sequencing information from 55 unrelated GSDs with IBD were compared to a control group consisting of 61 unrelated GSDs. The G22A SNP in TLR5 was significantly associated with IBD in GSDs, whereas the remaining two SNPs were found to be significantly protective for IBD. Furthermore, the two SNPs in TLR4 (A1571T and G1807A) were in complete linkage disequilibrium, and were also significantly associated with IBD. The TLR5 risk haplotype (ACC) without the two associated TLR4 SNP alleles was significantly associated with IBD, however the presence of the two TLR4 SNP risk alleles without the TLR5 risk haplotype was not statistically associated with IBD. Our study suggests that the three TLR5 SNPs and two TLR4 SNPs; A1571T and G1807A could play a role in the pathogenesis of IBD in GSDs. Further studies are required to confirm the functional importance of these polymorphisms in the pathogenesis of this disease. PMID:21203467

Validation of markers with non-additive effects on milk yield and fertility in Holstein and Jersey cows.

PubMed

Aliloo, Hassan; Pryce, Jennie E; González-Recio, Oscar; Cocks, Benjamin G; Hayes, Ben J

2015-07-22

It has been suggested that traits with low heritability, such as fertility, may have proportionately more genetic variation arising from non-additive effects than traits with higher heritability, such as milk yield. Here, we performed a large genome scan with 408,255 single nucleotide polymorphism (SNP) markers to identify chromosomal regions associated with additive, dominance and epistatic (pairwise additive × additive) variability in milk yield and a measure of fertility, calving interval, using records from a population of 7,055 Holstein cows. The results were subsequently validated in an independent set of 3,795 Jerseys. We identified genomic regions with validated additive effects on milk yield on Bos taurus autosomes (BTA) 5, 14 and 20, whereas SNPs with suggestive additive effects on fertility were observed on BTA 5, 9, 11, 18, 22, 27, 29 and the X chromosome. We also confirmed genome regions with suggestive dominance effects for milk yield (BTA 2, 3, 5, 26 and 27) and for fertility (BTA 1, 2, 3, 7, 23, 25 and 28). A number of significant epistatic effects for milk yield on BTA 14 were found across breeds. However on close inspection, these were likely to be associated with the mutation in the diacylglycerol O-acyltransferase 1 (DGAT1) gene, given that the associations were no longer significant when the additive effect of the DGAT1 mutation was included in the epistatic model. In general, we observed a low statistical power (high false discovery rates and small number of significant SNPs) for non-additive genetic effects compared with additive effects for both traits which could be an artefact of higher dependence on linkage disequilibrium between markers and causative mutations or smaller size of non-additive effects relative to additive effects. The results of our study suggest that individual non-additive effects make a small contribution to the genetic variation of milk yield and fertility. Although we found no individual mutation with large dominance

The significance of virulence factors in Helicobacter pylori

PubMed Central

SHIOTA, Seiji; SUZUKI, Rumiko; YAMAOKA, Yoshio

2013-01-01

Helicobacter pylori (H. pylori) infection is linked to various gastroduodenal diseases; however, only a small fraction of these patients develop associated diseases. Despite the high prevalence of H. pylori infection in Africa and South Asia, the incidence of gastric cancer in these areas is much lower than those in other countries. The incidence of gastric cancer tends to decrease from north to south in East Asia. Such geographic differences in the pathology can be explained, at least in part, by the presence of different types of H. pylori virulence factors in addition to the host and environmental factors. Virulence factors of H. pylori, such as cagA, vacA, dupA, iceA, oipA and babA, have been demonstrated to be predictors of severe clinical outcomes. Interestingly, meta-analysis showed that CagA seropositivity was associated with gastric cancer compared with gastritis even in East Asian countries where almost of the strains possessing cagA. Meta-analysis also confirmed the significance of vacA, dupA and iceA. However, there remains the possibility that additional important pathogenic genes can be existed because H. pylori consists of approximately 1 600 genes. Despite advances in our understanding of the development of H. pylori-related diseases, further work is required to clarify the roles of H. pylori virulence factors. PMID:23452293

An Aggregate Measure of Sleep Health Is Associated With Prevalent and Incident Clinically Significant Depression Symptoms Among Community-Dwelling Older Women.

PubMed

Furihata, Ryuji; Hall, Martica H; Stone, Katie L; Ancoli-Israel, Sonia; Smagula, Stephen F; Cauley, Jane A; Kaneita, Yoshitaka; Uchiyama, Makoto; Buysse, Daniel J

2017-03-01

Sleep can be characterized along multiple dimensions. We investigated whether an aggregate measure of sleep health was associated with prevalent and incident clinically significant depression symptoms in a cohort of older women. Participants were older women (mean age 80.1 years) who completed baseline (n = 6485) and follow-up (n = 3806) visits, approximately 6 years apart, in the Study of Osteoporotic Fractures (SOF). Self-reported sleep over the past 12 months was categorized as "good" or "poor" across 5 dimensions: satisfaction with sleep duration, daytime sleepiness, mid-sleep time, sleep onset latency, and sleep duration. An aggregate measure of sleep health was calculated by summing the number of "poor" dimensions. Clinically significant depression symptoms were defined as a score ≥6 on the Geriatric Depression Scale. Relationships between sleep health and depression symptoms were evaluated with multivariate logistic regression, adjusting for health measures and medications. Individual sleep health dimensions of sleep satisfaction, daytime sleepiness, mid-sleep time, and sleep onset latency were significantly associated with prevalent depression symptoms (odds ratios [OR] = 1.26-2.69). Sleep satisfaction, daytime sleepiness, and sleep onset latency were significantly associated with incident depression symptoms (OR = 1.32-1.79). The number of "poor" sleep health dimensions was associated in a gradient fashion with greater odds of prevalent (OR = 1.62-5.41) and incident (OR = 1.47-3.15) depression symptoms. An aggregate, multidimensional measure of sleep health was associated with both prevalent and incident clinically-significant depression symptoms in a gradient fashion. Future studies are warranted to extend these findings in different populations and with different health outcomes. © Sleep Research Society 2016. Published by Oxford University Press on behalf of the Sleep Research Society. All rights reserved. For permissions, please e-mail journals.permissions@oup.com.

Quantifying the Clinical Significance of Cannabis Withdrawal

PubMed Central

Allsop, David J.; Copeland, Jan; Norberg, Melissa M.; Fu, Shanlin; Molnar, Anna; Lewis, John; Budney, Alan J.

2012-01-01

Background and Aims Questions over the clinical significance of cannabis withdrawal have hindered its inclusion as a discrete cannabis induced psychiatric condition in the Diagnostic and Statistical Manual of Mental Disorders (DSM IV). This study aims to quantify functional impairment to normal daily activities from cannabis withdrawal, and looks at the factors predicting functional impairment. In addition the study tests the influence of functional impairment from cannabis withdrawal on cannabis use during and after an abstinence attempt. Methods and Results A volunteer sample of 49 non-treatment seeking cannabis users who met DSM-IV criteria for dependence provided daily withdrawal-related functional impairment scores during a one-week baseline phase and two weeks of monitored abstinence from cannabis with a one month follow up. Functional impairment from withdrawal symptoms was strongly associated with symptom severity (p = 0.0001). Participants with more severe cannabis dependence before the abstinence attempt reported greater functional impairment from cannabis withdrawal (p = 0.03). Relapse to cannabis use during the abstinence period was associated with greater functional impairment from a subset of withdrawal symptoms in high dependence users. Higher levels of functional impairment during the abstinence attempt predicted higher levels of cannabis use at one month follow up (p = 0.001). Conclusions Cannabis withdrawal is clinically significant because it is associated with functional impairment to normal daily activities, as well as relapse to cannabis use. Sample size in the relapse group was small and the use of a non-treatment seeking population requires findings to be replicated in clinical samples. Tailoring treatments to target withdrawal symptoms contributing to functional impairment during a quit attempt may improve treatment outcomes. PMID:23049760

The relationship between serious injury and blood alcohol concentration (BAC) in fatal motor vehicle accidents: BAC = 0.01% is associated with significantly more dangerous accidents than BAC = 0.00%.

PubMed

Phillips, David P; Brewer, Kimberly M

2011-09-01

To analyze the severity of automotive injuries associated with blood alcohol concentration (BAC) in increments of 0.01%. Epidemiological study using the Fatality Analysis Reporting System. All people in US fatal automotive accidents, 1994-2008 (n = 1 495 667). The ratio of serious: non-serious injuries for drivers, by BAC. Accident severity increases significantly even when the driver is merely 'buzzed', a finding that persists after standardization for various confounding factors. Three mechanisms mediate between buzzed driving and high accident severity: compared to sober drivers, buzzed drivers are significantly more likely to speed, to be improperly seatbelted and to drive the striking vehicle. In addition, there is a strong 'dose-response' relationship for all three factors in relation to accident severity (e.g. the greater the BAC, the greater the average speed of the driver and the greater the severity of the accident). The severity of life-threatening motor vehicle accidents increases significantly at blood alcohol concentrations (BACs) far lower than the current US limit of 0.08%. Lowering the legal limit could save lives, prevent serious injuries and reduce financial and social costs associated with motor vehicle accidents. © 2011 Society for the Study of Addiction. No claim to original US government works.

Type 1 IGF Receptor Localization in Paediatric Gliomas: Significant Association with WHO Grading and Clinical Outcome.

PubMed

Clément, Florencia; Martin, Ayelen; Venara, Marcela; de Luján Calcagno, Maria; Mathó, Cecilia; Maglio, Silvana; Lombardi, Mercedes García; Bergadá, Ignacio; Pennisi, Patricia A

2018-06-01

Nuclear localization of insulin-like growth factor receptor type 1 (IGF-1R) has been described as adverse prognostic factor in some cancers. We studied the expression and localization of IGF-1R in paediatric patients with gliomas, as well as its association with World Health Organization (WHO) grading and survival. We conducted a single cohort, prospective study of paediatric patients with gliomas. Samples were taken at the time of the initial surgery; IGF-1R expression and localization were characterized by immunohistochemistry (IHC), subcellular fractionation and western blotting. Tumours (47/53) showed positive staining for IGF-1R by IHC. IGF-1R nuclear labelling was observed in 10/47 cases. IGF-1R staining was mostly non-nuclear in low-grade tumours, while IGF-1R nuclear labelling was predominant in high-grade gliomas (p = 0.0001). Survival was significantly longer in patients with gliomas having non-nuclear IGF-1R localization than in patients with nuclear IGF-1R tumours (p = 0.016). In gliomas, IGF-1R nuclear localization was significantly associated with both high-grade tumours and increased risk of death. Based on a prospective design, we provide evidence of a potential usefulness of intracellular localization of IGF-1R as prognostic factor in paediatric patients with gliomas.

Bleeding complications in dengue are not associated with significant changes in the modulators of the endothelial barrier.

PubMed

Orsi, Fernanda Andrade; Angerami, Rodrigo Nogueira; Mazetto, Bruna Moraes; Quaino, Susan Kelly Picoli; De Paula, Erich Vinícius; Annichino-Bizzachi, Joyce Maria

2014-06-11

Bleeding complications in dengue may occur irrespective of the presence of plasma leakage. We compared plasma levels of modulators of the endothelial barrier among three dengue groups: bleedings without plasma leakage, dengue hemorrhagic fever, and non-complicated dengue. The aim was to evaluate whether the presence of subtle alterations in microvascular permeability could be detected in bleeding patients. Plasma levels of VEGF-A and its soluble receptors were not associated with the occurrence of bleeding in patients without plasma leakage. These results provide additional rationale for considering bleeding as a complication independent of endothelial barrier breakdown, as proposed by the 2009 WHO classification.

The ecological significance of biofilm formation by plant-associated bacteria.

PubMed

Morris, Cindy E; Monier, Jean-Michel

2003-01-01

Bacteria associated with plants have been observed frequently to form assemblages referred to as aggregates, microcolonies, symplasmata, or biofilms on leaves and on root surfaces and within intercellular spaces of plant tissues. In a wide range of habitats, biofilms are purported to be microniches of conditions markedly different from those of the ambient environment and drive microbial cells to effect functions not possible alone or outside of biofilms. This review constructs a portrait of how biofilms associated with leaves, roots and within intercellular spaces influence the ecology of the bacteria they harbor and the relationship of bacteria with plants. We also consider how biofilms may enhance airborne dissemination, ubiquity and diversification of plant-associated bacteria and may influence strategies for biological control of plant disease and for assuring food safety. Trapped by a nexus, coordinates uncertain Ever expanding or contracting Cannibalistic and scavenging sorties Excavations through signs of past alliances Consensus signals sound revelry Then time warped by viscosity Genomes showing codependence A virtual microbial beach party With no curfew and no time-out A few estranged cells seeking exit options, Looking for another menagerie. David Sands, Montana State University, Bozeman, February 2003

Nitrite addition to acidified sludge significantly improves digestibility, toxic metal removal, dewaterability and pathogen reduction

NASA Astrophysics Data System (ADS)

Du, Fangzhou; Keller, Jürg; Yuan, Zhiguo; Batstone, Damien J.; Freguia, Stefano; Pikaar, Ilje

2016-12-01

Sludge management is a major issue for water utilities globally. Poor digestibility and dewaterability are the main factors determining the cost for sludge management, whereas pathogen and toxic metal concentrations limit beneficial reuse. In this study, the effects of low level nitrite addition to acidified sludge to simultaneously enhance digestibility, toxic metal removal, dewaterability and pathogen reduction were investigated. Waste activated sludge (WAS) from a full-scale waste water treatment plant was treated at pH 2 with 10 mg NO2--N/L for 5 h. Biochemical methane potential tests showed an increase in the methane production of 28%, corresponding to an improvement from 247 ± 8 L CH4/kg VS to 317 ± 1 L CH4/kg VS. The enhanced removal of toxic metals further increased the methane production by another 18% to 360 ± 6 L CH4/kg VS (a total increase of 46%). The solids content of dewatered sludge increased from 14.6 ± 1.4% in the control to 18.2 ± 0.8%. A 4-log reduction for both total coliforms and E. coli was achieved. Overall, this study highlights the potential of acidification with low level nitrite addition as an effective and simple method achieving multiple improvements in terms of sludge management.

Nitrite addition to acidified sludge significantly improves digestibility, toxic metal removal, dewaterability and pathogen reduction

PubMed Central

Du, Fangzhou; Keller, Jürg; Yuan, Zhiguo; Batstone, Damien J.; Freguia, Stefano; Pikaar, Ilje

2016-01-01

Sludge management is a major issue for water utilities globally. Poor digestibility and dewaterability are the main factors determining the cost for sludge management, whereas pathogen and toxic metal concentrations limit beneficial reuse. In this study, the effects of low level nitrite addition to acidified sludge to simultaneously enhance digestibility, toxic metal removal, dewaterability and pathogen reduction were investigated. Waste activated sludge (WAS) from a full-scale waste water treatment plant was treated at pH 2 with 10 mg NO2−-N/L for 5 h. Biochemical methane potential tests showed an increase in the methane production of 28%, corresponding to an improvement from 247 ± 8 L CH4/kg VS to 317 ± 1 L CH4/kg VS. The enhanced removal of toxic metals further increased the methane production by another 18% to 360 ± 6 L CH4/kg VS (a total increase of 46%). The solids content of dewatered sludge increased from 14.6 ± 1.4% in the control to 18.2 ± 0.8%. A 4-log reduction for both total coliforms and E. coli was achieved. Overall, this study highlights the potential of acidification with low level nitrite addition as an effective and simple method achieving multiple improvements in terms of sludge management. PMID:28004811

Changes in intestinal tight junction permeability associated with industrial food additives explain the rising incidence of autoimmune disease.

PubMed

Lerner, Aaron; Matthias, Torsten

2015-06-01

The incidence of autoimmune diseases is increasing along with the expansion of industrial food processing and food additive consumption. The intestinal epithelial barrier, with its intercellular tight junction, controls the equilibrium between tolerance and immunity to non-self-antigens. As a result, particular attention is being placed on the role of tight junction dysfunction in the pathogenesis of AD. Tight junction leakage is enhanced by many luminal components, commonly used industrial food additives being some of them. Glucose, salt, emulsifiers, organic solvents, gluten, microbial transglutaminase, and nanoparticles are extensively and increasingly used by the food industry, claim the manufacturers, to improve the qualities of food. However, all of the aforementioned additives increase intestinal permeability by breaching the integrity of tight junction paracellular transfer. In fact, tight junction dysfunction is common in multiple autoimmune diseases and the central part played by the tight junction in autoimmune diseases pathogenesis is extensively described. It is hypothesized that commonly used industrial food additives abrogate human epithelial barrier function, thus, increasing intestinal permeability through the opened tight junction, resulting in entry of foreign immunogenic antigens and activation of the autoimmune cascade. Future research on food additives exposure-intestinal permeability-autoimmunity interplay will enhance our knowledge of the common mechanisms associated with autoimmune progression. Copyright © 2015. Published by Elsevier B.V.

Visceral adiposity is significantly associated with type 2 diabetes in middle-aged and elderly Chinese women: A cross-sectional study.

PubMed

Lv, Xiaofei; Zhou, Weiwei; Sun, Jichao; Lin, Ruhai; Ding, Lin; Xu, Min; Xu, Yu; Zhao, Zhiyun; Chen, Yuhong; Bi, Yufang; Lu, Jieli; Wang, Weiqing; Ning, Guang

2017-10-01

Previous studies suggest that visceral fat is associated with type 2 diabetes (T2D) independent of body mass index (BMI). However, epidemiological data about the relationship between visceral fat and T2D are rare in Chinese. The aim of the present study was to investigate whether visceral fat area (VFA) is associated with T2D beyond and above BMI in the Chinese population. The present community-based cross-sectional study was conducted in 2013 on 4126 individuals (2545 women, 1581 men) aged ≥ 40 years, with T2D diagnosed according to 1999 World Health Organization criteria. The VFA was measured by a fat area analyzer using bioelectrical impedance analysis. Participants were categorized into normal weight and overweight/obese groups according to BMI. Within each group, compared with women with below-median VFA, women with above-median VFA had a significantly increased risk of diabetes (odds ratio [OR] 1.88, 95% confidence interval [CI] 1.31-2.69 in the normal weight group; OR 2.10, 95% CI 1.54-2.85 in the overweight/obese group), whereas among men the corresponding associations were not significant in either group. Among women, after multivariable adjustment including BMI, each one standard deviation increase in VFA was significantly associated with a 45% higher risk of having T2D (OR 1.45, 95% CI 1.26-1.67), whereas among men BMI, not VFA, was independently associated with T2D (OR 1.18, 95% CI 1.02-1.37). Visceral fat was independently associated with T2D in women regardless of obesity status, whereas in men BMI may have a more important effect on T2D than visceral fat. © 2016 Ruijin Hospital, Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd.

Prognostic significance of membrane-associated mucins 1 and 4 in gastric adenocarcinoma.

PubMed

Hwang, Ilseon; Kang, Yu Na; Kim, Jin Young; DO, Young Rok; Song, Hong Suk; Park, Keon Uk

2012-08-01

Aberrant expression of mucins is likely associated with cancer biology as alterations in the expression and/or glycosylation patterns of various mucins have been noted. Expression of the mucin family in gastric cancers has been reported in numerous studies, but the results are conflicting. Therefore, we investigated the potential use of mucin (MUC)1 and 4 as prognostic markers in gastric cancer according to histological subtype. Three-hundred and sixty-five gastric adenocarcinoma patients who underwent surgical resection were selected for this study. Among the 365 gastric cancer samples tested here, 34% consisted of early gastric cancer and 66% were advanced. In terms of location, 68.7% of the cohort had intestinal-type cancer and 30.7% had diffuse-type. We constructed tissue microarrays with formalin-fixed paraffin-embedded blocks of gastric cancer and these micro-arrays were evaluated for phenotypic expression of MUC1/4 using monoclonal antibodies. Two-hundred and ninety-two patients (92.7%) were positive for MUC1 and 216 (60.5%) were positive for MUC4. MUC1 expression was not correlated with any other clinicopathological variables such as age, gender, depth of invasion, lymph node metastasis, Lauren classification or recurrence. However, loss of MUC4 expression was significantly correlated with recurrence (p=0.033). MUC4 expression was also significantly correlated with better disease-free survival (p=0.049) and particularly in the intestinal-type (p=0.018). Our present findings demonstrated that loss of MUC4 expression can be used as a prognostic marker in gastric cancer. Loss of MUC4 expression is a prognostic indicator of increased recurrence and poor disease-free survival in patients with gastric cancer.

Significance of bacteria associated with invertebrates in drinking water distribution networks.

PubMed

Wolmarans, E; du Preez, H H; de Wet, C M E; Venter, S N

2005-01-01

The implication of invertebrates found in drinking water distribution networks to public health is of concern to water utilities. Previous studies have shown that the bacteria associated with the invertebrates could be potentially pathogenic to humans. This study investigated the level and identity of bacteria commonly associated with invertebrates collected from the drinking water treatment systems as well as from the main pipelines leaving the treatment works. On all sampling occasions bacteria were isolated from the invertebrate samples collected. The highest bacterial counts were observed for the samples taken before filtration as was expected. There were, however, indications that optimal removal of invertebrates from water did not always occur. During the investigation, 116 colonies were sampled for further identification. The isolates represent several bacterial genera and species that are pathogenic or opportunistic pathogens of humans. Diarrhoea, meningitis, septicaemia and skin infections are among the diseases associated with these organisms. The estimated number of bacteria that could be associated with a single invertebrate (as based on average invertebrate numbers) could range from 10 to 4000 bacteria per organism. It can, therefore, be concluded that bacteria associated with invertebrates might under the worst case scenario pose a potential health risk to water users. In the light of the above findings it is clear that invertebrates in drinking water should be controlled at levels as low as technically and economically feasible.

Tuberculosis after kidney transplantation is associated with significantly impaired allograft function.

PubMed

Costa, Silvana Daher; de Sandes-Freitas, Tainá Veras; Jacinto, Camilla Neves; Martiniano, Lorena Vasconcelos Mesquita; Amaral, Yago Sucupira; Paes, Fernando José Villar Nogueira; Sales, Maria Luiza de Mattos Brito Oliveira; Esmeraldo, Ronaldo de Matos; Daher, Elizabeth de Francesco

2017-10-01

This study aimed to evaluate renal function before, during, and after the course of tuberculosis (TB) disease in kidney transplant recipients, and assess the risk factors for non-recovery of baseline renal function. We performed a retrospective, single-center cohort study, including all patients with confirmed or presumed TB diagnosis after kidney transplant (n=34, 2.1%). Renal function was assessed by serum creatinine (Cr) and glomerular filtration rate (GFR) adjusted for deaths and graft losses. A significant increase was seen in serum Cr during TB disease and treatment: 1.5 mg/dL at baseline (Cr base ), 1.7 mg/dL at diagnosis (P<.001 vs. Cr base ), and 2.4 mg/dL during the peak (P<.001 vs. Cr base ). According to acute kidney injury (AKI) Kidney Disease: Improving Global Outcomes (KDIGO) classification, 29 (85%) patients had AKI: 16 stage 1, 2 stage 2, and 11 stage 3. Three months after the end of the TB treatment, five patients (14.7%) had lost their graft and two others (5.9%) had died. The GFR was lower than the baseline (42.4 mL/min vs 51.6 mL/min, P=.007). In the univariate analysis, peak Cr (odds ratio [OR] 1.276, 95% confidence interval [CI] 0.955-1.705, P=.100), AKI KDIGO stages 2 or 3 (OR 4.958, 95% CI 1.062-23.157, P=.042), severe disease (OR 5.700, 95% CI 1.147-28.330, P=.033), and acute rejection (AR) episodes after TB diagnosis (OR 3.937, 95% CI 0.551-28.116, P=.172) were associated with non-recovery of baseline renal function. No variable was identified in the multivariable model. Post-transplantation TB was associated with a high incidence of AKI, and complete recovery of baseline renal function was not achieved after treatment. The severity of TB disease, AKI, and AR episodes that occurred after TB diagnosis are potential causes for this outcome. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Pediatric cochlear implants: additional disabilities prevalence, risk factors, and effect on language outcomes.

PubMed

Birman, Catherine S; Elliott, Elizabeth J; Gibson, William P R

2012-10-01

To determine the prevalence of additional disabilities in a pediatric cochlear population, to identify medical and radiologic conditions associated with additional disabilities, and to identify the effect of additional disabilities on speech perception and language at 12 months postoperatively. Retrospective case review. Tertiary referral center and cochlear implant program. Records were reviewed for children 0 to 16 years old inclusive, who had cochlear implant-related operations over a 12-month period. Diagnostic and rehabilitative. Additional disabilities prevalence; medical history and radiologic abnormalities; and the effect on Categories of Auditory Performance (CAP) score at 12 months postoperatively. Eighty-eight children having 96 operations were identified. The overall prevalence of additional disabilities (including developmental delay, cerebral palsy, visual impairment, autism and attention deficit disorder) was 33%. The main conditions associated with additional disabilities were syndromes and chromosomal abnormalities (87%), jaundice (86%), prematurity (62%), cytomegalovirus (60%), and inner ear abnormalities including cochlea nerve hypoplasia or aplasia (75%) and semicircular canal anomalies (56%). At 12 months postoperatively, almost all (96%) of the children without additional disabilities had a CAP score of 5 or greater (speech), compared with 52% of children with additional disabilities. Children with developmental delay had a median CAP score of 4, at 12 months compared with 6 for those without developmental delay. Additional disabilities are prevalent in approximately a third of pediatric cochlear implant patients. Additional disabilities significantly affect the outcomes of cochlear implants.

Gluten-free dough-making of specialty breads: Significance of blended starches, flours and additives on dough behaviour.

PubMed

Collar, Concha; Conte, Paola; Fadda, Costantino; Piga, Antonio

2015-10-01

The capability of different gluten-free (GF) basic formulations made of flour (rice, amaranth and chickpea) and starch (corn and cassava) blends, to make machinable and viscoelastic GF-doughs in absence/presence of single hydrocolloids (guar gum, locust bean and psyllium fibre), proteins (milk and egg white) and surfactants (neutral, anionic and vegetable oil) have been investigated. Macroscopic (high deformation) and macromolecular (small deformation) mechanical, viscometric (gelatinization, pasting, gelling) and thermal (gelatinization, melting, retrogradation) approaches were performed on the different matrices in order to (a) identify similarities and differences in GF-doughs in terms of a small number of rheological and thermal analytical parameters according to the formulations and (b) to assess single and interactive effects of basic ingredients and additives on GF-dough performance to achieve GF-flat breads. Larger values for the static and dynamic mechanical characteristics and higher viscometric profiles during both cooking and cooling corresponded to doughs formulated with guar gum and Psyllium fibre added to rice flour/starch and rice flour/corn starch/chickpea flour, while surfactant- and protein-formulated GF-doughs added to rice flour/starch/amaranth flour based GF-doughs exhibited intermediate and lower values for the mechanical parameters and poorer viscometric profiles. In addition, additive-free formulations exhibited higher values for the temperature of both gelatinization and retrogradation and lower enthalpies for the thermal transitions. Single addition of 10% of either chickpea flour or amaranth flour to rice flour/starch blends provided a large GF-dough hardening effect in presence of corn starch and an intermediate effect in presence of cassava starch (chickpea), and an intermediate reinforcement of GF-dough regardless the source of starch (amaranth). At macromolecular level, both chickpea and amaranth flours, singly added, determined

Extended storage and glucose exhaustion are associated with apoptotic changes in platelets stored in additive solution.

PubMed

Johnson, Lacey; Schubert, Peter; Tan, Shereen; Devine, Dana V; Marks, Denese C

2016-02-01

The storage of platelets (PLTs) in additive solution (AS) may facilitate improved PLT quality and possibly extension of the PLT shelf life. A minimum amount of plasma is required when PLTs are stored in AS, as a source of glucose. The aim of this study was to assess the effect of reducing the plasma carryover to 20% on PLT quality when stored in SSP+ for an extended period. Using a pool-and-split design, buffy coat-derived PLTs were stored in either 30% plasma/SSP+ or 20% plasma/SSP+. In vitro analyses were carried out to Day 10. Metabolites and markers of PLT activation and apoptosis were measured using a blood gas analyzer and flow cytometry. PLT apoptotic protein expression was investigated by Western blotting. Glucose exhaustion occurred in the 20% plasma group between Day 7 and Day 10. The surface expression of P-selectin and PAC-1 was comparable on Day 10 in both groups, suggesting that the PLTs were not activated. However, the exposure of phosphatidylserine and the number of phosphatidylserine-positive microparticles were significantly higher in the 20% group on Day 10. The expression of the proapoptotic proteins Bak, Bax, and cleaved caspase-3 were higher in the 20% plasma group by Day 7 of storage, compared to the 30% plasma group. Exhaustion of glucose was associated with a proapoptotic phenotype. Results such as these should be considered before extending the PLT shelf life beyond 7 days, particularly when stored in ASs lacking glucose with low plasma carryover. © 2015 AABB.

Association of gene polymorphism of the fat mass and obesity associated gene with metabolic syndrome: a retrospective cohort study in Japanese workers.

PubMed

Kawajiri, Tomoka; Osaki, Yoneatsu; Kishimoto, Takuji

2012-06-01

To investigate whether gene polymorphism of the fat mass and obesity associated gene (FTO) is associated with metabolic syndrome (MS), we used two MS criteria, the National Cholesterol Education Program-Adult Treatment panel III (NCEP-ATPIII) definition in 2003 and the Japanese definition in 2005. Subjects were respectively 859 and 865 Japanese workers at a company in Shimane Prefecture, Japan. They were non-MS individuals in 1998 and had regular health checkups between 1998 and 2006. The Cox proportional hazard regression was used to predict MS. Three SNPs in the FTO, rs9939609, rs1121980 and rs1558902, were genotyped by the TaqMan PCR assay and a retrospective study was performed. The three SNPs in the FTO were significantly associated with body mass index, and rs1121980 and rs1558902 were associated with fasting plasma glucose. MS defined by the NCEP-ATPIII definition was significantly associated with additive and dominant models of rs9939609 and rs1121980, and the dominant model of rs1558902, even after adjusting for confounding factors such as age, sex and lifestyle. MS defined by the Japanese definition was significantly associated with the additive model of rs1121980 and additive and dominant models of rs1558902 in multivariate analysis. These results suggested that FTO gene polymorphisms, rs9939609, rs1121980 and rs1558902, were associated with an increased risk of MS among Japanese workers.

Lifestyle factors are significantly associated with the locomotive syndrome: a cross-sectional study.

PubMed

Akahane, Manabu; Yoshihara, Shingo; Maeyashiki, Akie; Tanaka, Yasuhito; Imamura, Tomoaki

2017-10-18

The Japanese Orthopedic Association first proposed the concept of "locomotive syndrome" in 2007. It refers to circumstances in which elderly people need nursing care services or are at high risk of requiring such services within a short time. Recently, the public health burden of providing nursing care for elderly individuals has increased. Therefore, locomotive syndrome, and the means of preventing it, are a major public health focus in Japan. The purpose of this study was to investigate the relationships of lifestyle factors, such as smoking, alcohol consumption, sleep duration, and dental health, with locomotive syndrome. We conducted a cross-sectional study using an internet panel survey. The participants comprised 747 individuals aged 30-90 years. Factors related to demographics (age, sex), general health (number of teeth, presence of periodontal disease), and lifestyle (smoking, alcohol consumption, sleep duration) were assessed. We also used the 25-question Geriatric Locomotive Function Scale to determine whether each participant had locomotive syndrome. Multivariate analysis was conducted using logistic regression to investigate the independent relationships between locomotive syndrome and lifestyle factors after adjusting for sex and age. A greater proportion of women (17.7%) than men (11.2%) had locomotive syndrome (p < 0.05). Participants aged ≥65 years showed significantly higher percentages (men: 21.4%, women: 75.7%) of locomotive syndrome compared with those aged <65 years (p < 0.05). Logistic regression analysis revealed that older age (≥ 65 years), sex, current smoking status, number of existing teeth, and presence of periodontal disease were associated with locomotive syndrome, whereas sleep duration was not. The frequency of alcohol consumption, except for daily drinking, was also associated with locomotive syndrome. Our study indicates that lifestyle factors, such as smoking and number of existing teeth, may partly affect the

Socio-emotionally Significant Experience and Children’s Processing of Irrelevant Auditory Stimuli

PubMed Central

Schermerhorn, Alice C.; Bates, John E.; Puce, Aina; Molfese, Dennis L.

2017-01-01

Theory and research indicate considerable influence of socio-emotionally significant experiences on children’s functioning and adaptation. In the current study, we examined neurophysiological correlates of children’s allocation of information processing resources to socio-emotionally significant events, specifically, simulated marital interactions. We presented 9- to 11-year-old children (n = 24; 11 females) with 15 videos of interactions between two actors posing as a married couple. Task-irrelevant brief auditory probes were presented during the videos, and event-related potentials (ERPs) elicited to the auditory probes were measured. As hypothesized, exposure to higher levels of interparental conflict was associated with smaller P1, P2, and N2 ERPs to the probes. This finding is consistent with the idea that children who had been exposed to more interparental conflict attended more to the videos and diverted fewer cognitive resources to processing the probes, thereby producing smaller ERPs to the probes. In addition, smaller N2s were associated with more child behavior problems, suggesting that allocating fewer processing resources to the probes was associated with more problem behavior. Results are discussed in terms of implications of socio-emotionally significant experiences for children’s processing of interpersonal interactions. PMID:27993611

A Genome-Wide Association Study Identifies Multiple Regions Associated with Head Size in Catfish

PubMed Central

Geng, Xin; Liu, Shikai; Yao, Jun; Bao, Lisui; Zhang, Jiaren; Li, Chao; Wang, Ruijia; Sha, Jin; Zeng, Peng; Zhi, Degui; Liu, Zhanjiang

2016-01-01

Skull morphology is fundamental to evolution and the biological adaptation of species to their environments. With aquaculture fish species, head size is also important for economic reasons because it has a direct impact on fillet yield. However, little is known about the underlying genetic basis of head size. Catfish is the primary aquaculture species in the United States. In this study, we performed a genome-wide association study using the catfish 250K SNP array with backcross hybrid catfish to map the QTL for head size (head length, head width, and head depth). One significantly associated region on linkage group (LG) 7 was identified for head length. In addition, LGs 7, 9, and 16 contain suggestively associated regions for head length. For head width, significantly associated regions were found on LG9, and additional suggestively associated regions were identified on LGs 5 and 7. No region was found associated with head depth. Head size genetic loci were mapped in catfish to genomic regions with candidate genes involved in bone development. Comparative analysis indicated that homologs of several candidate genes are also involved in skull morphology in various other species ranging from amphibian to mammalian species, suggesting possible evolutionary conservation of those genes in the control of skull morphologies. PMID:27558670

Cyclin D1 is significantly associated with stage of tumor and predicts poor survival in endometrial carcinoma patients.

PubMed

Khabaz, Mohamad Nidal; Abdelrahman, Amer Shafie; Butt, Nadeem Shafique; Al-Maghrabi, Basim; Al-Maghrabi, Jaudah

2017-10-01

Cyclin D1 overexpression has been described to have oncogenic role and association with diagnosis, prognosis and survival in various tumors. This study will describe the immunohistochemical phenotype of cyclin D1, and investigate the correlation between these patterns of expression and clinicopathological parameters of endometrial carcinomas, to conclude the clinical relevance of cyclin D1 expression in the evolution of endometrial neoplasms. This study employed 101 endometrial tissue samples which include 71 endometrial carcinomas and thirty normal and benign endometrium cases. All these tissue samples were used in the assembly of tissue microarrays which have been utilized afterward in immunohistochemistry staining to detect cyclin D1 expression. Forty (56.3%) cases of endometrial carcinomas showed brown nuclear expression of cyclin D1 including 36 (61%) cases of endometrioid carcinomas, and 3 (33.3%) cases of serous carcinomas. Twenty three (76.6%) cases of control group demonstrated nuclear expression. High score cyclin D1 immunohistochemical staining has been significantly linked with patient age (P=0.0001). Large proportion of high score cyclin D1 immunohistochemical staining was observed in females who are <40years of age while high proportions of negative staining were observed in older age groups. Histologic type of tissue was also significantly related to cyclin D1 immunohistochemical staining (P-value=0.0001), high staining is more common in normal proliferative and secretory endometrium while serous carcinoma is more prevalent with negative staining. Stage of tumor was significantly associated with cyclin D1 immunohistochemical staining (P-value=0.029), proportion of stage III and IV are higher in negative cyclin D1 immunostaining. Significantly higher proportion of high score cyclin D1 immunostaining is observed in controls while higher proportion of negative cyclin D1 immunostaining is observed among carcinoma cases (P-value=0.0001). No significant

Jointly determining significance levels of primary and replication studies by controlling the false discovery rate in two-stage genome-wide association studies.

PubMed

Jiang, Wei; Yu, Weichuan

2017-01-01

In genome-wide association studies, we normally discover associations between genetic variants and diseases/traits in primary studies, and validate the findings in replication studies. We consider the associations identified in both primary and replication studies as true findings. An important question under this two-stage setting is how to determine significance levels in both studies. In traditional methods, significance levels of the primary and replication studies are determined separately. We argue that the separate determination strategy reduces the power in the overall two-stage study. Therefore, we propose a novel method to determine significance levels jointly. Our method is a reanalysis method that needs summary statistics from both studies. We find the most powerful significance levels when controlling the false discovery rate in the two-stage study. To enjoy the power improvement from the joint determination method, we need to select single nucleotide polymorphisms for replication at a less stringent significance level. This is a common practice in studies designed for discovery purpose. We suggest this practice is also suitable in studies with validation purpose in order to identify more true findings. Simulation experiments show that our method can provide more power than traditional methods and that the false discovery rate is well-controlled. Empirical experiments on datasets of five diseases/traits demonstrate that our method can help identify more associations. The R-package is available at: http://bioinformatics.ust.hk/RFdr.html .

High malnutrition rate in Venezuelan Yanomami compared to Warao Amerindians and Creoles: significant associations with intestinal parasites and anemia.

PubMed

Verhagen, Lilly M; Incani, Renzo N; Franco, Carolina R; Ugarte, Alejandra; Cadenas, Yeneska; Sierra Ruiz, Carmen I; Hermans, Peter W M; Hoek, Denise; Campos Ponce, Maiza; de Waard, Jacobus H; Pinelli, Elena

2013-01-01

Children in rural areas experience the interrelated problems of poor growth, anemia and parasitic infections. We investigated the prevalence of and associations between intestinal helminth and protozoan infections, malnutrition and anemia in school-age Venezuelan children. This cross-sectional study was conducted in 390 children aged 4-16 years from three rural areas of Venezuela: the Amazon Region, Orinoco Delta and Carabobo State. Stool samples were collected for direct parasitic examinations. Anthropometric indicators of chronic (height-for-age Z score) and acute (weight-for-height and Body Mass Index (BMI)-for-age Z score in respectively children under 5 years of age and children aged 5 years and above) malnutrition were calculated. Multivariate linear and logistic regression models were built to determine factors associated with nutritional status and polyparasitism. Hookworm and Strongyloides stercoralis prevalences were highest in children from the Amazon rainforest (respectively 72% and 18%) while children from the Orinoco Delta and Carabobo State showed higher rates of Ascaris lumbricoides (respectively 28% and 37%) and Trichuris trichiura (40% in both regions). The prevalence of Giardia lamblia infection was not significantly different between regions (average: 18%). Anemia prevalence was highest in the Amazon Region (24%). Hemoglobin levels were significantly decreased in children with a hookworm infection. Malnutrition was present in respectively 84%, 30% and 13% of children from the Amazon Region, Orinoco Delta and Carabobo State. In multivariate analysis including all regions, G. lamblia and helminth infections were significantly and negatively associated with respectively height-for-age and weight-for-height/BMI-for-age Z scores. Furthermore, hemoglobin levels were positively associated with the height-for-age Z score (0.11, 95% CI 0.02 - 0.20). In rural populations in Venezuela helminthiasis and giardiasis were associated with acute and chronic

Evaluation of non-additive genetic variation in feed-related traits of broiler chickens.

PubMed

Li, Y; Hawken, R; Sapp, R; George, A; Lehnert, S A; Henshall, J M; Reverter, A

2017-03-01

Genome-wide association mapping and genomic predictions of phenotype of individuals in livestock are predominately based on the detection and estimation of additive genetic effects. Non-additive genetic effects are largely ignored. Studies in animals, plants, and humans to assess the impact of non-additive genetic effects in genetic analyses have led to differing conclusions. In this paper, we examined the consequences of including non-additive genetic effects in genome-wide association mapping and genomic prediction of total genetic values in a commercial population of 5,658 broiler chickens genotyped for 45,176 single nucleotide polymorphism (SNP) markers. We employed mixed-model equations and restricted maximum likelihood to analyze 7 feed related traits (TRT1 - TRT7). Dominance variance accounted for a significant proportion of the total genetic variance in all 7 traits, ranging from 29.5% for TRT1 to 58.4% for TRT7. Using a 5-fold cross-validation schema, we found that in spite of the large dominance component, including the estimated dominance effects in the prediction of total genetic values did not improve the accuracy of the predictions for any of the phenotypes. We offer some possible explanations for this counter-intuitive result including the possible confounding of dominance deviations with common environmental effects such as hatch, different directional effects of SNP additive and dominance variations, and the gene-gene interactions' failure to contribute to the level of variance. © 2016 Poultry Science Association Inc.

Tort reform is associated with significant increases in Texas physicians relative to the Texas population.

PubMed

Stewart, Ronald M; West, Molly; Schirmer, Richard; Sirinek, Kenneth R

2013-01-01

Texas implemented comprehensive tort reform in 2003. We hypothesized that tort reform was followed by a significant increase of physicians practicing in Texas. To test this hypothesis, we compared the rate of physician growth prior to and following tort reform, and the number of licensed physicians and physicians per 100,000. Comparing before and after tort reform, the rate of increase in Texas physicians per 100,000 population increased significantly (p < 0.01). From 2002 to 2012, the Texas population increased 21 %. The number of actively practicing Texas physicians increased by 15,611 a 44 % increase (46 % metro areas vs. 9 % non-metro areas), an increase of 30 physicians per 100,000 population (p < 0.01). Non-metropolitan Texas had a net increase of 215 physicians; however, there was no change in the number of physicians per 100,000. Examining the data by trauma service areas (TSAs), 20 of 22 TSAs had an increase in both number of physicians and physicians per capita, five greater than 50 %. The post-tort reform period in Texas was associated with a significantly increased growth rate of physicians relative to the Texas population. Tort reform, as implemented in Texas, provides a needed framework for improving access to health care.

Disease duration and Medsger's severity score are associated with significant liver fibrosis in patients with systemic sclerosis.

PubMed

Lee, Sang-Won; Kim, Beom Kyung; Park, Jun Yong; Kim, Do Young; Ahn, Sang Hoon; Song, Jason Jungsik; Park, Yong-Beom; Lee, Soo-Kon; Han, Kwang-Hyub; Kim, Seung Up

2015-01-01

We investigated the prevalence and predictors of significant liver fibrosis in patients with systemic sclerosis (SSc) who had no evidences of liver diseases due to viral infection, drug, and heavy alcohol consumption. A total of 44 SSc patients were recruited. In addition to the clinical and laboratory data, the 2013 College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) classification criteria score, modified Rodnan skin score (mRSS), and Medsger's severity score (MSS) were analysed. Liver stiffness (LS) was measured using transient elastography to assess the degree of liver fibrosis and 7.4 kPa was adopted as the cut-off value for significant liver fibrosis. The median age of patients (38 women) was 54 years and the median disease duration was 41.0 months. The median LS value was 4.6 kPa. The median mRSS and MSS were 7.0 and 5.0, respectively. Six (13.6%) patients had significant liver fibrosis. Disease duration (standardised β=0.375, p=0.018) and MSS (standardised β=0.398, p=0.047) significantly correlated with LS values. In multivariate analysis, disease duration≥63 months (odds ratio (OR) 19.166, 95% confidence interval 1.090, 336.962, p=0.043) and MSS≥7 (OR 19.796, 95% confidence interval 1.439, 272.252, p=0.026) independently predicted the presence of significant liver fibrosis. The prevalence of significant liver fibrosis was relatively high (13.6%) and its independent predictors were disease duration and MSS.

Diverse Genome-wide Association Studies Associate the IL12/IL23 Pathway with Crohn Disease

PubMed Central

Wang, Kai; Zhang, Haitao; Kugathasan, Subra; Annese, Vito; Bradfield, Jonathan P.; Russell, Richard K.; Sleiman, Patrick M.A.; Imielinski, Marcin; Glessner, Joseph; Hou, Cuiping; Wilson, David C.; Walters, Thomas; Kim, Cecilia; Frackelton, Edward C.; Lionetti, Paolo; Barabino, Arrigo; Van Limbergen, Johan; Guthery, Stephen; Denson, Lee; Piccoli, David; Li, Mingyao; Dubinsky, Marla; Silverberg, Mark; Griffiths, Anne; Grant, Struan F.A.; Satsangi, Jack; Baldassano, Robert; Hakonarson, Hakon

2009-01-01

Previous genome-wide association (GWA) studies typically focus on single-locus analysis, which may not have the power to detect the majority of genuinely associated loci. Here, we applied pathway analysis using Affymetrix SNP genotype data from the Wellcome Trust Case Control Consortium (WTCCC) and uncovered significant association between Crohn Disease (CD) and the IL12/IL23 pathway, harboring 20 genes (p = 8 × 10−5). Interestingly, the pathway contains multiple genes (IL12B and JAK2) or homologs of genes (STAT3 and CCR6) that were recently identified as genuine susceptibility genes only through meta-analysis of several GWA studies. In addition, the pathway contains other susceptibility genes for CD, including IL18R1, JUN, IL12RB1, and TYK2, which do not reach genome-wide significance by single-marker association tests. The observed pathway-specific association signal was subsequently replicated in three additional GWA studies of European and African American ancestry generated on the Illumina HumanHap550 platform. Our study suggests that examination beyond individual SNP hits, by focusing on genetic networks and pathways, is important to unleashing the true power of GWA studies. PMID:19249008

Food Additives Permitted for Direct Addition to Food for Human Consumption; Folic Acid. Final rule.

PubMed

2016-04-15

The Food and Drug Administration (FDA or we) is amending the food additive regulations to provide for the safe use of folic acid in corn masa flour. We are taking this action in response to a food additive petition filed jointly by Gruma Corporation, Spina Bifida Association, March of Dimes Foundation, American Academy of Pediatrics, Royal DSM N.V., and National Council of La Raza.

Rib fractures and their association With solid organ injury: higher rib fractures have greater significance for solid organ injury screening.

PubMed

Rostas, Jack W; Lively, Timothy B; Brevard, Sidney B; Simmons, Jon D; Frotan, Mohammad A; Gonzalez, Richard P

2017-04-01

The purpose of this study was to identify patients with rib injuries who were at risk for solid organ injury. A retrospective chart review was performed of all blunt trauma patients with rib fractures during the period from July 2007 to July 2012. Data were analyzed for association of rib fractures and solid organ injury. In all, 1,103 rib fracture patients were identified; 142 patients had liver injuries with 109 (77%) associated right rib fractures. Right-sided rib fractures with highest sensitivity for liver injury were middle rib segment (5 to 8) and lower segment (9 to 12) with liver injury sensitivities of 68% and 43%, respectively (P < .001); 151 patients had spleen injuries with 119 (79%) associated left rib fractures. Left middle segment rib fractures and lower segment rib fractures had sensitivities of 80% and 63% for splenic injury, respectively (P < .003). Rib fractures higher in the thoracic cage have significant association with solid organ injury. Using rib fractures from middle plus lower segments as indication for abdominal screening will significantly improve rib fracture sensitivity for identification of solid organ injury. Copyright © 2016 Elsevier Inc. All rights reserved.

The presence of advanced lesions and associating risk factors for advanced cervical carcinoma in patients with atypical sguamous cells of undetermined significance.

PubMed

Sun, L L; Chen, W; Fan, Y Y; Wang, M L; Wang, L N

2015-01-01

To characterize histopathological status, high-risk human papillomavirus (hr-HPV) infection status, and associated risk factors in patients with atypical squamous cells of undetermined significance (ASCUS). Cervical biopsies obtained from 130 ASCUS patients were subjected to histopathological examination and hr-HPV testing. Associations between advanced lesions and hr-HPV load or age were analyzed, and the confounding factors for high-grade cervical lesions were identified. Cervical biopsies from ASCUS patients had a wide range of pathological states, ranging from normal to invasive cervical carcinoma. High-risk HPV infection was significantly associated with advanced cervical lesions in ASCUS patients; hr-HPV infection and the number of gestations were risk factors for developing advanced cervical disease. A significant portion of ASCUS patients harbor advanced cervical lesions. The number of gestations and hr-HPV infection can increase the risk of developing advanced cervical lesions in ASCUS patients.

Significant inverse association of equol-producer status with coronary artery calcification but not dietary isoflavones in healthy Japanese men.

PubMed

Ahuja, Vasudha; Miura, Katsuyuki; Vishnu, Abhishek; Fujiyoshi, Akira; Evans, Rhobert; Zaid, Maryam; Miyagawa, Naoko; Hisamatsu, Takashi; Kadota, Aya; Okamura, Tomonori; Ueshima, Hirotsugu; Sekikawa, Akira

2017-01-01

Equol, a metabolite of the dietary isoflavone daidzein, is produced by the action of gut bacteria in some individuals who are termed as equol-producers. It is proposed to have stronger atheroprotective properties than dietary isoflavones. We examined a cross-sectional association of dietary isoflavones and equol-producer status with coronary artery calcification (CAC), a biomarker of coronary atherosclerosis, among men in Japan. A population-based sample of 272 Japanese men aged 40-49 years recruited from 2004 to 2007 was examined for serum isoflavones, serum equol, CAC and other factors. Equol-producers were classified as individuals having a serum level of equol >83 nm. The presence of CAC was defined as a coronary Ca score ≥10 Agatston units. The associations of dietary isoflavones and equol-producers with CAC were analysed using multiple logistic regression. The median of dietary isoflavones, equol and CAC were 512·7 (interquartile range (IQR) 194·1, 1170·0), 9·1 (IQR 0·10, 33·1) and 0·0 (IQR 0·0, 1·0) nm, respectively. Prevalence of CAC and equol-producers was 9·6 and 16·0 %, respectively. Dietary isoflavones were not significantly associated with CAC. After multivariable adjustment, the OR for the presence of CAC in equol-producers compared with equol non-producers was 0·10 (95 % CI 0·01, 0·90, P<0·04). Equol-producers had significantly lower CAC than equol non-producers, but there was no significant association between dietary isoflavones and CAC, suggesting that equol may be a key factor for atheroprotective properties of isoflavones in Japanese men. This finding must be confirmed in larger studies or clinical trials of equol that is now available as a dietary supplement.

Relationship and significance of gait deviations associated with limb length discrepancy: A systematic review.

PubMed

Khamis, Sam; Carmeli, Eli

2017-09-01

Controversy still exists as to the clinical significance of leg length discrepancy (LLD) in spite of the fact that further evidence has been emerging regarding the relationship between several clinical conditions and LLD. The objectives of our study were to review the available research with regard to LLD as a cause of clinically significant gait deviations, to determine if there is a relationship between the magnitude of LLD and the presence of gait deviations and to identify the most common gait deviations associated with LLD. In line with the PRISMA guidelines, a literature search was carried out throughout the Medline, CINAHL and EMBASE databases. Twelve articles met the predetermined inclusion criteria and were included in the review. Quality assessment using the Methodological Index for Non-Randomized Studies (MINORS) scale was completed for all included studies. Two main methodologies were found in 4 studies evaluating gait asymmetry in patients or healthy participants with anatomic LLD and 8 studies evaluating gait deviations while simulating LLD by employing artificial lifts of 1-5cm on healthy subjects. A significant relationship was found between anatomic LLD and gait deviation. Evidence suggests that gait deviations may occur with discrepancies of >1cm, with greater impact seen as the discrepancy increases. Compensatory strategies were found to occur in both the shorter and longer limb, throughout the lower limb. As the discrepancy increases, more compensatory strategies occur. Sagittal plane deviations seem to be the most effective deviations, although, frontal plane compensations also occur in the pelvis, hip and foot. Copyright © 2017 Elsevier B.V. All rights reserved.

Finding missing heritability in less significant Loci and allelic heterogeneity: genetic variation in human height.

PubMed

Zhang, Ge; Karns, Rebekah; Sun, Guangyun; Indugula, Subba Rao; Cheng, Hong; Havas-Augustin, Dubravka; Novokmet, Natalija; Durakovic, Zijad; Missoni, Sasa; Chakraborty, Ranajit; Rudan, Pavao; Deka, Ranjan

2012-01-01

Genome-wide association studies (GWAS) have identified many common variants associated with complex traits in human populations. Thus far, most reported variants have relatively small effects and explain only a small proportion of phenotypic variance, leading to the issues of 'missing' heritability and its explanation. Using height as an example, we examined two possible sources of missing heritability: first, variants with smaller effects whose associations with height failed to reach genome-wide significance and second, allelic heterogeneity due to the effects of multiple variants at a single locus. Using a novel analytical approach we examined allelic heterogeneity of height-associated loci selected from SNPs of different significance levels based on the summary data of the GIANT (stage 1) studies. In a sample of 1,304 individuals collected from an island population of the Adriatic coast of Croatia, we assessed the extent of height variance explained by incorporating the effects of less significant height loci and multiple effective SNPs at the same loci. Our results indicate that approximately half of the 118 loci that achieved stringent genome-wide significance (p-value<5×10(-8)) showed evidence of allelic heterogeneity. Additionally, including less significant loci (i.e., p-value<5×10(-4)) and accounting for effects of allelic heterogeneity substantially improved the variance explained in height.

Significant Beneficial Association of High Dietary Selenium Intake with Reduced Body Fat in the CODING Study

PubMed Central

Wang, Yongbo; Gao, Xiang; Pedram, Pardis; Shahidi, Mariam; Du, Jianling; Yi, Yanqing; Gulliver, Wayne; Zhang, Hongwei; Sun, Guang

2016-01-01

Selenium (Se) is a trace element which plays an important role in adipocyte hypertrophy and adipogenesis. Some studies suggest that variations in serum Se may be associated with obesity. However, there are few studies examining the relationship between dietary Se and obesity, and findings are inconsistent. We aimed to investigate the association between dietary Se intake and a panel of obesity measurements with systematic control of major confounding factors. A total of 3214 subjects participated in the study. Dietary Se intake was determined from the Willett food frequency questionnaire. Body composition was measured using dual-energy X-ray absorptiometry. Obese men and women had the lowest dietary Se intake, being 24% to 31% lower than corresponding normal weight men and women, classified by both BMI and body fat percentage. Moreover, subjects with the highest dietary Se intake had the lowest BMI, waist circumference, and trunk, android, gynoid and total body fat percentages, with a clear dose-dependent inverse relationship observed in both gender groups. Furthermore, significant negative associations discovered between dietary Se intake and obesity measurements were independent of age, total dietary calorie intake, physical activity, smoking, alcohol, medication, and menopausal status. Dietary Se intake alone may account for 9%–27% of the observed variations in body fat percentage. The findings from this study strongly suggest that high dietary Se intake is associated with a beneficial body composition profile. PMID:26742059

Stromal p16 expression is significantly increased in endometrial carcinoma

PubMed Central

Yoon, Nara; Kim, Ji-Ye; Kim, Hyun-Soo

2017-01-01

p16 is a negative regulator of cell proliferation and is considered a tumor suppressor protein. Alterations in p16 protein expression are associated with tumor development and progression. However, the p16 expression status in the peritumoral stroma has not been investigated in the endometrium. Therefore, we evaluated stromal p16 expression in different types of endometrial lesions using immunohistochemistry. Differences in the p16 expression status according to the degree of malignancy and histological type were analyzed. This study included 62, 26, and 36 cases of benign, precancerous, and malignant endometrial lesions, respectively. Most benign lesions showed negative or weak expression, whereas precancerous lesions showed a variable degree of staining proportion and intensity. Atypical hyperplasia/endometrial intraepithelial neoplasia (AH/EIN) and serous endometrial intraepithelial carcinoma (SEIC) had significantly higher stromal p16 expression levels than benign lesions. Endometrioid carcinoma (EC), serous carcinoma (SC), and carcinosarcoma showed significantly elevated stromal p16 expression levels compared with benign and precancerous lesions. In addition, there were significant differences in stromal p16 expression between AH/EIN and SEIC and between EC and SC. In contrast, differences in stromal p16 expression among nonpathological endometrium, atrophic endometrium, endometrial polyp, and hyperplasia without atypia were not statistically significant. Our observations suggest that stromal p16 expression is involved in the development and progression of endometrial carcinoma, and raise the possibility that p16 overexpression in the peritumoral stroma is associated with aggressive oncogenic behavior of endometrial SC. PMID:27902476

Whole-genome association analysis of pork meat pH revealed three significant regions and several potential genes in Finnish Yorkshire pigs.

PubMed

Verardo, Lucas L; Sevón-Aimonen, Marja-Liisa; Serenius, Timo; Hietakangas, Ville; Uimari, Pekka

2017-02-13

One of the most commonly used quality measurements of pork is pH measured 24 h after slaughter. The most probable mode of inheritance for this trait is oligogenic with several known major genes, such as PRKAG3. In this study, we used whole-genome SNP genotypes of over 700 AI boars; after a quality check, 42,385 SNPs remained for association analysis. All the boars were purebred Finnish Yorkshire. To account for relatedness of the animals, a pedigree-based relationship matrix was used in a mixed linear model to test the effect of SNPs on pH measured from loin. A bioinformatics analysis was performed to identify the most promising genes in the significant regions related to meat quality. Genome-wide association study (GWAS) revealed three significant chromosomal regions: one on chromosome 3 (39.9 Mb-40.1 Mb) and two on chromosome 15 (58.5 Mb-60.5 Mb and 132 Mb-135 Mb including PRKAG3). A conditional analysis with a significant SNP in the PRKAG3 region, MARC0083357, as a covariate in the model retained the significant SNPs on chromosome 3. Even though linkage disequilibrium was relatively high over a long distance between MARC0083357 and other significant SNPs on chromosome 15, some SNPs retained their significance in the conditional analysis, even in the vicinity of PRKAG3. The significant regions harbored several genes, including two genes involved in cyclic AMP (cAMP) signaling: ADCY9 and CREBBP. Based on functional and transcription factor-gene networks, the most promising candidate genes for meat pH are ADCY9, CREBBP, TRAP1, NRG1, PRKAG3, VIL1, TNS1, and IGFBP5, and the key transcription factors related to these genes are HNF4A, PPARG, and Nkx2-5. Based on SNP association, pathway, and transcription factor analysis, we were able to identify several genes with potential to control muscle cell homeostasis and meat quality. The associated SNPs can be used in selection for better pork. We also showed that post-GWAS analysis reveals important information about the

Additional red and reddened stars in Cyg OB2 association

NASA Technical Reports Server (NTRS)

Parthasarathy, M.; Jain, S. K.

1989-01-01

Several new red and reddened stars are detected in the most heavily reddened associations Cyg OB2. About 47 IRAS sources are detected in Cyg OB2. Their flux distributions, and colors, suggest that they are young stellar objects embedded in dust envelopes or disks (some of them may be proto stars) and are most likely members of the Cyg OB2 association. The large values of the flux ratio L sub IR/L sub VIS suggests that the central objects are obscured because of very large extinction.

Clinical significance of miR-146a in gastric cancer cases.

PubMed

Kogo, Ryunosuke; Mimori, Koshi; Tanaka, Fumiaki; Komune, Shizuo; Mori, Masaki

2011-07-01

The profiles of microRNAs change significantly in gastric cancer. MiR-146a is reported to be a tumor suppressor in pancreatic cancer, breast cancer, and prostate cancer. We investigated the clinical significance of miR-146a in gastric cancer, in particular focusing on hypothetical miR-146a target genes, such as epidermal growth factor receptor (EGFR) and interleukin-1 receptor-associated kinase (IRAK1). We examined miR-146a levels in 90 gastric cancer samples by q-real-time (qRT)-PCR and analyzed the association between miR-146a levels and clinicopathologic factors and prognosis. The regulation of EGFR and IRAK1 by miR-146a was examined with miR-146a-transfected gastric cancer cells. Moreover, we analyzed the association between miR-146a levels and the G/C single nucleotide polymorphism (SNP) within pre-miR-146a seed sequences in 76 gastric cancer samples, using direct sequencing of genomic DNA. In 90 clinical samples of gastric cancer, miR-146a levels in cancer tissues were significantly lower than those in the corresponding noncancerous tissue (P < 0.001). Lower levels of miR-146a were associated with lymph node metastasis and venous invasion (P < 0.05). Moreover, a lower level of miR-146a was an independent prognostic factor for overall survival (P = 0.003). Ectopic expression of miR-146a inhibited migration and invasion and downregulated EGFR and IRAK1 expression in gastric cancer cells. In addition, G/C SNP within the pre-miR-146a seed sequence significantly reduced miR-146a levels in the GG genotype compared with the CC genotype. MiR-146a contains an SNP, which is associated with mature miR-146a expression. MiR-146a targeting of EGFR and IRAK1 is an independent prognostic factor in gastric cancer cases.

Septic tank additive impacts on microbial populations.

PubMed

Pradhan, S; Hoover, M T; Clark, G H; Gumpertz, M; Wollum, A G; Cobb, C; Strock, J

2008-01-01

Environmental health specialists, other onsite wastewater professionals, scientists, and homeowners have questioned the effectiveness of septic tank additives. This paper describes an independent, third-party, field scale, research study of the effects of three liquid bacterial septic tank additives and a control (no additive) on septic tank microbial populations. Microbial populations were measured quarterly in a field study for 12 months in 48 full-size, functioning septic tanks. Bacterial populations in the 48 septic tanks were statistically analyzed with a mixed linear model. Additive effects were assessed for three septic tank maintenance levels (low, intermediate, and high). Dunnett's t-test for tank bacteria (alpha = .05) indicated that none of the treatments were significantly different, overall, from the control at the statistical level tested. In addition, the additives had no significant effects on septic tank bacterial populations at any of the septic tank maintenance levels. Additional controlled, field-based research iswarranted, however, to address additional additives and experimental conditions.

Significant Impacts of Increasing Aridity on the Arid Soil Microbiome.

PubMed

Neilson, Julia W; Califf, Katy; Cardona, Cesar; Copeland, Audrey; van Treuren, Will; Josephson, Karen L; Knight, Rob; Gilbert, Jack A; Quade, Jay; Caporaso, J Gregory; Maier, Raina M

2017-01-01

Global deserts occupy one-third of the Earth's surface and contribute significantly to organic carbon storage, a process at risk in dryland ecosystems that are highly vulnerable to climate-driven ecosystem degradation. The forces controlling desert ecosystem degradation rates are poorly understood, particularly with respect to the relevance of the arid-soil microbiome. Here we document correlations between increasing aridity and soil bacterial and archaeal microbiome composition along arid to hyperarid transects traversing the Atacama Desert, Chile. A meta-analysis reveals that Atacama soil microbiomes exhibit a gradient in composition, are distinct from a broad cross-section of nondesert soils, and yet are similar to three deserts from different continents. Community richness and diversity were significantly positively correlated with soil relative humidity (SoilRH). Phylogenetic composition was strongly correlated with SoilRH, temperature, and electrical conductivity. The strongest and most significant correlations between SoilRH and phylum relative abundance were observed for Acidobacteria , Proteobacteria , Planctomycetes , Verrucomicrobia , and Euryarchaeota (Spearman's rank correlation [ r s ] = >0.81; false-discovery rate [ q ] = ≤0.005), characterized by 10- to 300-fold decreases in the relative abundance of each taxon. In addition, network analysis revealed a deterioration in the density of significant associations between taxa along the arid to hyperarid gradient, a pattern that may compromise the resilience of hyperarid communities because they lack properties associated with communities that are more integrated. In summary, results suggest that arid-soil microbiome stability is sensitive to aridity as demonstrated by decreased community connectivity associated with the transition from the arid class to the hyperarid class and the significant correlations observed between soilRH and both diversity and the relative abundances of key microbial phyla

Ubiquitin-like and ubiquitin-associated domain proteins: significance in proteasomal degradation

PubMed Central

Lau, Alan F.

2009-01-01

The ubiquitin–proteasome pathway of protein degradation is one of the major mechanisms that are involved in the maintenance of the proper levels of cellular proteins. The regulation of proteasomal degradation thus ensures proper cell functions. The family of proteins containing ubiquitin-like (UbL) and ubiquitin-associated (UBA) domains has been implicated in proteasomal degradation. UbL–UBA domain containing proteins associate with substrates destined for degradation as well as with subunits of the proteasome, thus regulating the proper turnover of proteins. PMID:19468686

Interim Significant Noncompliance Policy for Clean Water Act Violations Associated with CSOs, SSOs, CAFOs, and Storm Water Point Sources

EPA Pesticide Factsheets

This policy addresses significant noncompliance (SNC) violations associated with combined sewer overflows (CSOs), sanitary sewer overflows (SSOs), concentrated animal feeding operations (CAFOs), and storm water point source discharges covered by the National Pollutant Discharge Elimination System (NPDES) program under the Clean Water Act (CWA).

Sleep duration is significantly associated with carotid artery atherosclerosis incidence in a Japanese population.

PubMed

Abe, Tsueko; Aoki, Toshinari; Yata, Syogo; Okada, Masahiko

2011-08-01

Previous studies have indicated that sleep duration is associated with total mortality in a U-shaped fashion. The purpose of the current study was to examine the relationship between self-reported sleep duration and carotid artery atherosclerosis in a Japanese population. In 2009-2010, a total of 2498 participants (1195 men, 1303 women; age range, 23-92 years) were recruited from members of a Japanese community receiving annual health check-up at a local health center who agreed to participate in the study. Exclusion criteria were as follows: age <40 or ≥85 years; and more than one missing value from either laboratory data or questionnaire responses. A total of 2214 participants were entered into the study. Carotid artery arteriosclerosis was evaluated ultrasonographically and quantified as intima-medial thickness (IMT). The presence of carotid artery atherosclerosis was defined as IMT≥1.2 mm. Sleep durations were compared with IMT measurements after controlling for confounding factors such as age, sex, lipid profile, fasting plasma glucose, hemoglobin A1c, blood pressure, alcohol intake, and smoking habit. Sleep duration ≥7 h correlated significantly with the incidence of IMT≥1.2 m when compared with a sleep duration of 6 h (multivariate-adjusted odds ratio, 1.263; 95% confidence interval, 1.031-1.546, P=0.024). Shorter sleep duration ≤5 h did not correlate significantly with the risk compared with a sleep duration of 6 h. Long sleep duration (≥7 h) correlated significantly with the incidence of carotid artery atherosclerosis compared with a sleep duration of 6 h, but shorter sleep duration did not. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

ACE I/D and MTHFR C677T polymorphisms are significantly associated with type 2 diabetes in Arab ethnicity: a meta-analysis.

PubMed

Al-Rubeaan, Khalid; Siddiqui, Khalid; Saeb, Amr T M; Nazir, Nyla; Al-Naqeb, Dhekra; Al-Qasim, Sara

2013-05-15

In this meta-analysis study, SNPs were investigated for their association with type 2 diabetes (T2D) in both Arab and Caucasian ethnicities. A total of 55 SNPs were analyzed, of which 11 fulfilled the selection criteria, and were used for analysis. It was found that TCF7L2 rs7903146 was significantly associated with a pooled OR of 1.155 (95%C.I.=1.059-1.259), p<0.0001 and I(2)=78.30% among the Arab population, whereas among Caucasians, the pooled OR was 1.45 (95%C.I.=1.386-1.516), p<0.0001 and I(2)=77.20%. KCNJ11 rs5219 was significantly associated in both the populations with a pooled OR of 1.176(1.092-1.268), p<0.0001 and I(2)=32.40% in Caucasians and a pooled OR of 1.28(1.111-1.475), p=0.001 among Arabs. The ACE I/D polymorphism was found to be significantly associated with a pooled OR of 1.992 (95%C.I.=1.774-2.236), p<0.0001 and I(2)=83.20% among the Arab population, whereas among Caucasians, the pooled OR was 1.078 (95%C.I.=0.993-1.17), p=0.073 and I(2)=0%. Similarly, MTHFR C677T polymorphism was also found to be significantly associated among Arabs with a pooled OR of 1.924 (95%C.I.=1.606-2.304), p<0.0001 and I(2)=27.20%, whereas among Caucasians, the pooled OR was 0.986 (95%C.I.=0.868-1.122), p=0.835 and I(2)=0%. Meanwhile PPARG-2 Pro12Ala, CDKN2A/2B rs10811661, IGF2BP2 rs4402960, HHEX rs7923837, CDKAL1 rs7754840, EXT2 rs1113132 and SLC30A8 rs13266634 were found to have no significant association with T2D among Arabs. In conclusion, it seems from this study that both Arabs and Caucasians have different SNPs associated with T2D. Moreover, this study sheds light on the profound necessity for further investigations addressing the question of the genetic components of T2D in Arabs. Copyright © 2013 Elsevier B.V. All rights reserved.

The presence of dupA in Helicobacter pylori is not significantly associated with duodenal ulceration in Belgium, South Africa, China, or North America.

PubMed

Argent, Richard H; Burette, Alain; Miendje Deyi, Véronique Y; Atherton, John C

2007-11-01

A previous study suggested that Helicobacter pylori strains possessing dupA are positively associated with duodenal ulceration and negatively associated with gastric adenocarcinoma. We determined the prevalence of dupA in H. pylori strains recovered from 4 independent populations and found a significant association with gastric cancer but not with duodenal ulceration.

Identification of novel genes significantly affecting growth in catfish through GWAS analysis.

PubMed

Li, Ning; Zhou, Tao; Geng, Xin; Jin, Yulin; Wang, Xiaozhu; Liu, Shikai; Xu, Xiaoyan; Gao, Dongya; Li, Qi; Liu, Zhanjiang

2018-06-01

Growth is the most important economic trait in aquaculture. Improvements in growth-related traits can enhance production, reduce costs and time to produce market-size fish. Catfish is the major aquaculture species in the United States, accounting for 65% of the US finfish production. However, the genes underlying growth traits in catfish were not well studied. Currently, the majority of the US catfish industry uses hybrid catfish derived from channel catfish female mated with blue catfish male. Interestingly, channel catfish and blue catfish exhibit differences in growth-related traits, and therefore the backcross progenies provide an efficient system for QTL analysis. In this study, we conducted a genome-wide association study for catfish body weight using the 250 K SNP array with 556 backcross progenies generated from backcross of male F1 hybrid (female channel catfish × male blue catfish) with female channel catfish. A genomic region of approximately 1 Mb on linkage group 5 was found to be significantly associated with body weight. In addition, four suggestively associated QTL regions were identified on linkage groups 1, 2, 23 and 24. Most candidate genes in the associated regions are known to be involved in muscle growth and bone development, some of which were reported to be associated with obesity in humans and pigs, suggesting that the functions of these genes may be evolutionarily conserved in controlling growth. Additional fine mapping or functional studies should allow identification of the causal genes for fast growth in catfish, and elucidation of molecular mechanisms of regulation of growth in fish.

Genes with mutation significance were highly associated with the clinical pattern of patients with breast cancer.

PubMed

Ding, Wan-Jun; Zeng, Tao; Wang, Li-Jun; Lei, Hong-Bo; Ge, Wei; Wang, Zhi

2017-11-17

In the United States, breast cancer is the second leading cause of cancer death in women. Over the past 20 years, breast cancer incidence and mortality rates increased rapidly in developing regions. We aimed to identify the gene mutation patterns that associated with the clinical patterns, including survival status, histo-pathological classes and so forth, of breast cancer. We retrieved 1098 cases of the clinical information, and level-3 legacy data of mRNA expression level, protein expression data and mutation files from GDC data portal. The genes with mutation significance were obtained. We studied the impacts of mutation types on the expression levels of mRNA and protein. Different statistics methods were used to calculate the correlation between the mutation types and the expression data or histo-clinical measures. There were 24 genes with mutation significance identified. The most mutated genes were selected to study the role of specific mutations played on the patients with breast cancer. One interesting finding was the missense mutations on TP53 were related with high expression levels of mRNA and protein. The missense mutations on TP53 were highly related with the morphology, race, ER status, PR status and HER2 Status, while the truncated mutations were only related with the morphology, ER status and PR status. The missense mutation on PIK3CA was highly associated with the morphology, race, ER status and PR status. The mutants with different mutants and the wild type of the most mutated genes had different impacts on the histo-clinical measures that might help personalized therapy.

High Malnutrition Rate in Venezuelan Yanomami Compared to Warao Amerindians and Creoles: Significant Associations WITH Intestinal Parasites and Anemia

PubMed Central

Verhagen, Lilly M.; Incani, Renzo N.; Franco, Carolina R.; Ugarte, Alejandra; Cadenas, Yeneska; Sierra Ruiz, Carmen I.; Hermans, Peter W. M.; Hoek, Denise; Campos Ponce, Maiza; de Waard, Jacobus H.; Pinelli, Elena

2013-01-01

Background Children in rural areas experience the interrelated problems of poor growth, anemia and parasitic infections. We investigated the prevalence of and associations between intestinal helminth and protozoan infections, malnutrition and anemia in school-age Venezuelan children. Methods This cross-sectional study was conducted in 390 children aged 4-16 years from three rural areas of Venezuela: the Amazon Region, Orinoco Delta and Carabobo State. Stool samples were collected for direct parasitic examinations. Anthropometric indicators of chronic (height-for-age Z score) and acute (weight-for-height and Body Mass Index (BMI)-for-age Z score in respectively children under 5 years of age and children aged 5 years and above) malnutrition were calculated. Multivariate linear and logistic regression models were built to determine factors associated with nutritional status and polyparasitism. Results Hookworm and Strongyloides stercoralis prevalences were highest in children from the Amazon rainforest (respectively 72% and 18%) while children from the Orinoco Delta and Carabobo State showed higher rates of Ascaris lumbricoides (respectively 28% and 37%) and Trichuris trichiura (40% in both regions). The prevalence of Giardia lamblia infection was not significantly different between regions (average: 18%). Anemia prevalence was highest in the Amazon Region (24%). Hemoglobin levels were significantly decreased in children with a hookworm infection. Malnutrition was present in respectively 84%, 30% and 13% of children from the Amazon Region, Orinoco Delta and Carabobo State. In multivariate analysis including all regions, G. lamblia and helminth infections were significantly and negatively associated with respectively height-for-age and weight-for-height/BMI-for-age Z scores. Furthermore, hemoglobin levels were positively associated with the height-for-age Z score (0.11, 95% CI 0.02 - 0.20). Conclusions In rural populations in Venezuela helminthiasis and giardiasis were

Cross-modal pattern of brain activations associated with the processing of self- and significant other's name.

PubMed

Tacikowski, Pawel; Brechmann, André; Nowicka, Anna

2013-09-01

Previous neuroimaging studies have shown that the patterns of brain activity during the processing of personally relevant names (e.g., own name, friend's name, partner's name, etc.) and the names of famous people (e.g., celebrities) are different. However, it is not known how the activity in this network is influenced by the modality of the presented stimuli. In this fMRI study, we investigated the pattern of brain activations during the recognition of aurally and visually presented full names of the subject, a significant other, a famous person and unknown individuals. In both modalities, we found that the processing of self-name and the significant other's name was associated with increased activation in the medial prefrontal cortex (MPFC). Acoustic presentations of these names also activated bilateral inferior frontal gyri (IFG). This pattern of results supports the role of MPFC in the processing of personally relevant information, irrespective of their modality. Copyright © 2012 Wiley Periodicals, Inc., a Wiley company.

Occult pneumothoraces in Chinese patients with significant blunt chest trauma: radiological classification and proposed clinical significance.

PubMed

Lee, Ryan K L; Graham, Colin A; Yeung, Janice H H; Ahuja, Anil T; Rainer, Timothy H

2012-12-01

An occult pneumothorax (OP) is a pneumothorax not seen on a supine chest X-ray (CXR) but detected on abdominal or thoracic computed tomography (CT) scanning. With the increasing use of CT in the management of significantly injured trauma patients, more OPs are being detected. The aim of this study was to classify OPs diagnosed on thoracic CT (TCT) and correlate them with their clinical significance. Retrospective analysis of prospectively collected trauma registry data. Total 36 (N=36) consecutive significantly injured trauma patients admitted through the emergency department (ED) who sustained blunt chest trauma and underwent TCT between 1 January 2007 and 31 December 2008 were included. OP was defined as the identification (by a consultant radiologist) of a pneumothorax on TCT that had not been detected on supine CXR. OPs were classified by laterality (unilateral/bilateral) and location (apical, basal, non apical/basal). The size of pneumothoraces, severity of injury [including number of associated thoracic injuries and injury severity score (ISS)], length of hospital stay and mortality were compared between groups. The need for tube thoracostomy and clinical outcome were also analysed. Patients with bilateral OPs (N=8) had significantly more associated thoracic injuries (median: 2 vs. 1, p=0.01), higher ISS (median: 35 vs. 23, p=0.02) and longer hospital stay (median: 20 days vs. 11 days, p=0.01) than those with a unilateral OP (N=28). Basal OPs (N=7) were significantly larger than apical (N=10) and non-apical/basal Ops (N=11). Basal OPs were associated with significantly more associated thoracic injuries (median: 2 vs. 1, p=0.01), higher ISS (median: 35 vs. 25, p=0.04) and longer hospital stays (median: 23 days vs. 17 days, p=0.02) than apical Ops, which had higher ISS (median: 35 vs. 25, p=0.04) and longer hospital stays (median: 23 days vs. 15 days, p=0.02) than non-apical/basal OPs. Non-apical/basal OPs were associated with more related injuries (median: 2

Cost Per Additional Responder Associated With Ixekizumab and Etanercept in the Treatment of Moderate-to-Severe Psoriasis.

PubMed

Feldman, Steven R; Foster, Shonda A; Zhu, Baojin; Burge, Russel; Al Sawah, Sarah; Goldblum, Orin M

2017-12-01

BACKGROUND: Newer psoriasis treatments can achieve greater levels of efficacy than older systemic therapies; however, current psoriasis costs are substantial. We sought to estimate costs per additional responder associated with ixekizumab and etanercept, versus placebo, using efficacy data from phase 3 clinical trials (UNCOVER-2 and UNCOVER-3). METHODS: In UNCOVER-2/UNCOVER-3, patients received subcutaneous placebo, etanercept 50 mg twice weekly (BIW), or ixekizumab one 80 mg injection every 2 weeks (Q2W) after a 160-mg starting dose. Twelve-week induction-phase Psoriasis Area and Severity Index (PASI) 75, PASI 90, and PASI 100 response rates for ixekizumab, etanercept, and placebo were obtained from pooled data from the overall and United States (US) subgroup intention-to-treat (ITT) populations, and used to calculate numbers needed to treat (NNTs) to achieve one additional PASI 75, PASI 90, or PASI 100 response for ixekizumab Q2W and etanercept BIW versus placebo. Twelve-week drug costs per patient were calculated based on the UNCOVER-2/UNCOVER-3 dosing schedule and wholesale acquisition costs. Mean costs per additional responder for PASI 75, PASI 90, and PASI 100 for each treatment versus placebo were calculated for pooled UN-COVER-2/UNCOVER-3 overall and US subgroup ITT populations. RESULTS: Pooled overall ITT population: costs per additional PASI 75, PASI 90, or PASI 100 responder were US $37,540, US $46,299, or US $80,710 for ixekizumab Q2W and US $57,533, US $120,720, or US $404,695 for etanercept BIW, respectively. US subgroup ITT population: costs per additional PASI 75, PASI 90, or PASI 100 responder were US $38,165, US $49,740, or US $93,536 for ixekizumab Q2W and US $69,580, US $140,881, or US $631,875 for etanercept BIW, respectively. CONCLUSIONS: Twelve-week costs per additional responder were lower for ixekizumab Q2W than for etanercept BIW across all levels of clearance (PASI 75, PASI 90, and PASI 100) in the pooled UNCOVER-2/UNCOVER-3 overall and

A History of Falls is Associated with a Significant Increase in Acute Mortality in Women after Stroke.

PubMed

Foster, Emma J; Barlas, Raphae S; Wood, Adrian D; Bettencourt-Silva, Joao H; Clark, Allan B; Metcalf, Anthony K; Bowles, Kristian M; Potter, John F; Myint, Phyo K

2017-10-01

The risks of falls and fractures increase after stroke. Little is known about the prognostic significance of previous falls and fractures after stroke. This study examined whether having a history of either event is associated with poststroke mortality. We analyzed stroke register data collected prospectively between 2003 and 2015. Eight sex-specific models were analyzed, to which the following variables were incrementally added to examine their potential confounding effects: age, type of stroke, Oxfordshire Community Stroke Project classification, previous comorbidities, frailty as indicated by the prestroke modified Rankin Scale score, and acute illness parameters. Logistic regression was applied to investigate in-hospital and 30-day mortality, and Cox proportional-hazards models were applied to investigate longer-term outcomes of mortality. In total, 10,477 patients with stroke (86.1% ischemic) were included in the analysis. They were aged 77.7±11.9 years (mean±SD), and 52.2% were women. A history of falls was present in 8.6% of the men (n=430) and 20.2% of the women (n=1,105), while 3.8% (n=189) of the men and 12.9% of the women (n=706) had a history of both falls and fractures. Of the outcomes examined, a history of falls alone was associated with increased in-hospital mortality [odds ratio (OR)=1.33, 95% confidence interval (CI)=1.03-1.71] and 30-day mortality (OR=1.34, 95% CI=1.03-1.73) in women in the fully adjusted models. The Cox proportional-hazards models for longer-term outcomes and the history of falls and fractures combined showed no significant results. The history of falls is an important factor for acute stroke mortality in women. A previous history of falls may therefore be an important factor to consider in the short-term stroke prognosis, particularly in women. Copyright © 2017 Korean Neurological Association

Significant association between asthma risk and the GSTM1 and GSTT1 deletion polymorphisms: an updated meta-analysis of case-control studies.

PubMed

Liang, Siqiao; Wei, Xuan; Gong, Chen; Wei, Jinmei; Chen, Zhangrong; Chen, Xiaoli; Wang, Zhibo; Deng, Jingmin

2013-07-01

Polymorphisms in GSTM1 and GSTT1 may be associated with asthma risk, yet several studies and meta-analyses have reported inconclusive results. Therefore, an updated meta-analysis was conducted. Literature searches were performed using the Pubmed, Embase and Web of Science databases until October 2012. Variant 'null' genotype was compared with wild-type 'present' in the pooled data. All statistical analyses were performed using STATA 11.0. A total of 26 case-control studies were suitable for inclusion in the meta-analysis. In the overall population, a significant association was found for both the GSTM1 (odds ratio (OR) = 1.452; 95% confidence interval (CI): 1.192-1.770) and GSTT1 polymorphism (OR = 1.792; 95% CI:1.293-2.483). For subgroup analysis by age, GSTM1 significantly increased risk for both children (OR = 1.368; 95% CI: 1.051-1.781) and adults (OR = 1.859; 95% CI: 1.183-2.921). For GSTT1, a significant association was only found in the adult population (OR = 2.312; 95%CI: 1.204-4.439). Based on subgroup analysis by ethnicity, a significant association for GSTM1 was found in Europe (OR = 1.303; 95% CI: 1.018-1.667), Africa (OR = 2.175; 95%CI: 1.560-3.031) and Latin America (OR = 2.265; 95%CI: 1.375-3.729). For GSTT1, significantly increased risk was found only for Asian (OR = 2.105; 95% CI: 1.101-4.025) and Russian (OR = 2.747; 95% CI: 1.071-7.046) populations. This meta-analysis provides evidence that GSTM1 and GSTT1 polymorphisms may be risk factors for asthma. © 2013 The Authors. Respirology © 2013 Asian Pacific Society of Respirology.

Non-additive genetic variation in growth, carcass and fertility traits of beef cattle.

PubMed

Bolormaa, Sunduimijid; Pryce, Jennie E; Zhang, Yuandan; Reverter, Antonio; Barendse, William; Hayes, Ben J; Goddard, Michael E

2015-04-02

A better understanding of non-additive variance could lead to increased knowledge on the genetic control and physiology of quantitative traits, and to improved prediction of the genetic value and phenotype of individuals. Genome-wide panels of single nucleotide polymorphisms (SNPs) have been mainly used to map additive effects for quantitative traits, but they can also be used to investigate non-additive effects. We estimated dominance and epistatic effects of SNPs on various traits in beef cattle and the variance explained by dominance, and quantified the increase in accuracy of phenotype prediction by including dominance deviations in its estimation. Genotype data (729 068 real or imputed SNPs) and phenotypes on up to 16 traits of 10 191 individuals from Bos taurus, Bos indicus and composite breeds were used. A genome-wide association study was performed by fitting the additive and dominance effects of single SNPs. The dominance variance was estimated by fitting a dominance relationship matrix constructed from the 729 068 SNPs. The accuracy of predicted phenotypic values was evaluated by best linear unbiased prediction using the additive and dominance relationship matrices. Epistatic interactions (additive × additive) were tested between each of the 28 SNPs that are known to have additive effects on multiple traits, and each of the other remaining 729 067 SNPs. The number of significant dominance effects was greater than expected by chance and most of them were in the direction that is presumed to increase fitness and in the opposite direction to inbreeding depression. Estimates of dominance variance explained by SNPs varied widely between traits, but had large standard errors. The median dominance variance across the 16 traits was equal to 5% of the phenotypic variance. Including a dominance deviation in the prediction did not significantly increase its accuracy for any of the phenotypes. The number of additive × additive epistatic effects that were

The additive effects of minoxidil and retinol on human hair growth in vitro.

PubMed

Yoo, Hyeon Gyeong; Chang, In-Young; Pyo, Hyun Keol; Kang, Yong Jung; Lee, Seung Ho; Kwon, Oh Sang; Cho, Kwang Hyun; Eun, Hee Chul; Kim, Kyu Han

2007-01-01

Minoxidil enhances hair growth by prolonging the anagen phase and induces new hair growth in androgenetic alopecia (AGA), whereas retinol significantly improves scalp skin condition and promotes hair growth. We investigated the combined effects of minoxidil and retinol on human hair growth in vitro and on cultured human dermal papilla cells (DPCs) and epidermal keratinocytes (HaCaT). The combination of minoxidil and retinol additively promoted hair growth in hair follicle organ cultures. In addition, minoxidil plus retinol more effectively elevated phosphorylated Erk, phosphorylated Akt levels, and the Bcl-2/Bax ratio than minoxidil alone in DPCs and HaCaT. We found that the significant hair shaft elongation demonstrated after minoxidil plus retinol treatment would depend on the dual kinetics associated with the activations of Erk- and Akt-dependent pathways and the prevention of apoptosis by increasing the Bcl-2/Bax ratio.

Structured Additive Quantile Regression for Assessing the Determinants of Childhood Anemia in Rwanda.

PubMed

Habyarimana, Faustin; Zewotir, Temesgen; Ramroop, Shaun

2017-06-17

Childhood anemia is among the most significant health problems faced by public health departments in developing countries. This study aims at assessing the determinants and possible spatial effects associated with childhood anemia in Rwanda. The 2014/2015 Rwanda Demographic and Health Survey (RDHS) data was used. The analysis was done using the structured spatial additive quantile regression model. The findings of this study revealed that the child's age; the duration of breastfeeding; gender of the child; the nutritional status of the child (whether underweight and/or wasting); whether the child had a fever; had a cough in the two weeks prior to the survey or not; whether the child received vitamin A supplementation in the six weeks before the survey or not; the household wealth index; literacy of the mother; mother's anemia status; mother's age at the birth are all significant factors associated with childhood anemia in Rwanda. Furthermore, significant structured spatial location effects on childhood anemia was found.

Compost Addition Enhanced Hyphal Growth and Sporulation of Arbuscular Mycorrhizal Fungi without Affecting Their Community Composition in the Soil

PubMed Central

Yang, Wei; Gu, Siyu; Xin, Ying; Bello, Ayodeji; Sun, Wenpeng; Xu, Xiuhong

2018-01-01

Arbuscular mycorrhizal (AM) fungi form symbiotic associations with most crop plant species in agricultural ecosystems, and are conspicuously influenced by various agricultural practices. To understand the impact of compost addition on AM fungi, we examined effect of four compost rates (0, 11.25, 22.5, and 45 Mg/ha) on the abundance and community composition of AM fungi in seedling, flowering, and mature stage of soybean in a 1-year compost addition experiment system in Northeast China. Soybean [Glycine max (L.) Merrill] was used as test plant. Moderate (22.5 Mg/ha) and high (45 Mg/ha) levels of compost addition significantly increased AM root colonization and extraradical hyphal (ERH) density compared with control, whereas low (11.5 Mg/ha) level of compost addition did not cause significant increase in AM root colonization and ERH density. AM fungal spore density was significantly enhanced by all the compost rates compared with control. The temporal variations analysis revealed that, AM root colonization in seedling stage was significantly lower than in flowering and mature stage. Although AM fungal operational taxonomic unit richness and community composition was unaffected by compost addition, some abundant AM fungal species showed significantly different response to compost addition. In mature stage, Rhizophagus fasciculatum showed increasing trend along with compost addition gradient, whereas the opposite was observed with Paraglomus sp. In addition, AM fungal community composition exhibited significant temporal variation during growing season. Further analysis indicated that the temporal variation in AM fungal community only occurred in control treatment, but not in low, moderate, and high level of compost addition treatments. Our findings highlighted the significant effects of compost addition on AM growth and sporulation, and emphasized that growth stage is a stronger determinant than 1-year compost addition in shaping AM fungal community in black soil of

Compost Addition Enhanced Hyphal Growth and Sporulation of Arbuscular Mycorrhizal Fungi without Affecting Their Community Composition in the Soil.

PubMed

Yang, Wei; Gu, Siyu; Xin, Ying; Bello, Ayodeji; Sun, Wenpeng; Xu, Xiuhong

2018-01-01

Arbuscular mycorrhizal (AM) fungi form symbiotic associations with most crop plant species in agricultural ecosystems, and are conspicuously influenced by various agricultural practices. To understand the impact of compost addition on AM fungi, we examined effect of four compost rates (0, 11.25, 22.5, and 45 Mg/ha) on the abundance and community composition of AM fungi in seedling, flowering, and mature stage of soybean in a 1-year compost addition experiment system in Northeast China. Soybean [ Glycine max (L.) Merrill] was used as test plant. Moderate (22.5 Mg/ha) and high (45 Mg/ha) levels of compost addition significantly increased AM root colonization and extraradical hyphal (ERH) density compared with control, whereas low (11.5 Mg/ha) level of compost addition did not cause significant increase in AM root colonization and ERH density. AM fungal spore density was significantly enhanced by all the compost rates compared with control. The temporal variations analysis revealed that, AM root colonization in seedling stage was significantly lower than in flowering and mature stage. Although AM fungal operational taxonomic unit richness and community composition was unaffected by compost addition, some abundant AM fungal species showed significantly different response to compost addition. In mature stage, Rhizophagus fasciculatum showed increasing trend along with compost addition gradient, whereas the opposite was observed with Paraglomus sp. In addition, AM fungal community composition exhibited significant temporal variation during growing season. Further analysis indicated that the temporal variation in AM fungal community only occurred in control treatment, but not in low, moderate, and high level of compost addition treatments. Our findings highlighted the significant effects of compost addition on AM growth and sporulation, and emphasized that growth stage is a stronger determinant than 1-year compost addition in shaping AM fungal community in black soil of

Evidence That Environmental and Familial Risks for Psychosis Additively Impact a Multidimensional Subthreshold Psychosis Syndrome.

PubMed

Pries, Lotta-Katrin; Guloksuz, Sinan; Ten Have, Margreet; de Graaf, Ron; van Dorsselaer, Saskia; Gunther, Nicole; Rauschenberg, Christian; Reininghaus, Ulrich; Radhakrishnan, Rajiv; Bak, Maarten; Rutten, Bart P F; van Os, Jim

2018-06-06

The observed link between positive psychotic experiences (PE) and psychosis spectrum disorder (PSD) may be stronger depending on concomitant presence of PE with other dimensions of psychopathology. We examined whether the effect of common risk factors for PSD on PE is additive and whether the impact of risk factors on the occurrence of PE depends on the co-occurrence of other symptom dimensions (affective dysregulation, negative symptoms, and cognitive alteration). Data from the Netherlands Mental Health Survey and Incidence Study 2 were used. Risk factors included childhood adversity, cannabis use, urbanicity, foreign born, hearing impairment, and family history of affective disorders. Logistic regression models were applied to test (1) the additive effect of risk factors (4 levels) on PE and (2) the moderating effects of symptom dimensions on the association between risk factors (present/absent) and PE, using additive interaction, expressed as the interaction contrast ratio. Risk factors were additive: the greater the number of risk factors, the greater the odds of PE. Furthermore, concomitant presence of the other symptom dimensions all increased the impact of risk factors on PE. After controlling for age, sex, and education, only affective dysregulation and negative symptoms remained significant moderators; only affective dysregulation remained a significant moderator if all dimensions were adjusted for each other. Risk factors may not be directly associated with PE but additively give rise to a multidimensional subthreshold state anticipating the multidimensional clinical syndrome. Early motivational and cognitive impairments in the context of PE may be reducible to affective dysregulation.

Diagnostic Significance of Cortical Superficial Siderosis for Alzheimer Disease in Patients with Cognitive Impairment.

PubMed

Inoue, Y; Nakajima, M; Uetani, H; Hirai, T; Ueda, M; Kitajima, M; Utsunomiya, D; Watanabe, M; Hashimoto, M; Ikeda, M; Yamashita, Y; Ando, Y

2016-02-01

Because the diagnostic significance of cortical superficial siderosis for Alzheimer disease and the association between cortical superficial siderosis and the topographic distribution of cerebral microbleeds have been unclear, we investigated the association between cortical superficial siderosis and clinicoradiologic characteristics of patients with cognitive impairment. We studied 347 patients (217 women, 130 men; mean age, 74 ± 9 years) who visited our memory clinic and underwent MR imaging (3T SWI). We analyzed the association between cortical superficial siderosis and the topographic distribution of cerebral microbleeds plus clinical characteristics including types of dementia. We used multivariate logistic regression analysis to determine the diagnostic significance of cortical superficial siderosis for Alzheimer disease. Twelve patients (3.5%) manifested cortical superficial siderosis. They were older (P = .026) and had strictly lobar cerebral microbleeds significantly more often than did patients without cortical superficial siderosis (50.0% versus 19.4%, P = .02); the occurrence of strictly deep and mixed cerebral microbleeds, however, did not differ in the 2 groups. Alzheimer disease was diagnosed in 162 (46.7%) patients. Of these, 8 patients (4.9%) had cortical superficial siderosis. In the multivariate logistic regression analysis for the diagnosis of Alzheimer disease, lacunar infarcts were negatively and independently associated with Alzheimer disease (P = .007). Although cortical superficial siderosis was associated with a strictly lobar cerebral microbleed location, it was not independently associated with Alzheimer disease in a memory clinic setting. Additional studies are required to investigate the temporal changes of these cerebral amyloid angiopathy-related MR imaging findings. © 2016 by American Journal of Neuroradiology.

A pathway-based analysis provides additional support for an immune-related genetic susceptibility to Parkinson's disease

PubMed Central

Holmans, Peter; Moskvina, Valentina; Jones, Lesley; Sharma, Manu; Vedernikov, Alexey; Buchel, Finja; Sadd, Mohamad; Bras, Jose M.; Bettella, Francesco; Nicolaou, Nayia; Simón-Sánchez, Javier; Mittag, Florian; Gibbs, J. Raphael; Schulte, Claudia; Durr, Alexandra; Guerreiro, Rita; Hernandez, Dena; Brice, Alexis; Stefánsson, Hreinn; Majamaa, Kari; Gasser, Thomas; Heutink, Peter; Wood, Nicholas W.; Martinez, Maria; Singleton, Andrew B.; Nalls, Michael A.; Hardy, John; Morris, Huw R.; Williams, Nigel M.; Arepalli, Sampath; Barker, Roger; Barrett, Jeffrey; Ben-Shlomo, Yoav; Berendse, Henk W.; Berg, Daniela; Bhatia, Kailash; de Bie, Rob M.A.; Biffi, Alessandro; Bloem, Bas; Brice, Alexis; Bochdanovits, Zoltan; Bonin, Michael; Bras, Jose M.; Brockmann, Kathrin; Brooks, Janet; Burn, David J.; Charlesworth, Gavin; Chen, Honglei; Chinnery, Patrick F.; Chong, Sean; Clarke, Carl E.; Cookson, Mark R.; Cooper, Jonathan M.; Corvol, Jen-Christophe; Counsell, Carl; Damier, Philippe; Dartigues, Jean Francois; Deloukas, Panagiotis; Deuschl, Günther; Dexter, David T.; van Dijk, Karin D.; Dillman, Allissa; Durif, Frank; Durr, Alexandra; Edkins, Sarah; Evans, Jonathan R.; Foltynie, Thomas; Gao, Jianjun; Gardner, Michelle; Gasser, Thomas; Gibbs, J. Raphael; Goate, Alison; Gray, Emma; Guerreiro, Rita; Gústafsson, Ómar; Hardy, John; Harris, Clare; Hernandez, Dena G.; Heutink, Peter; van Hilten, Jacobus J.; Hofman, Albert; Hollenbeck, Albert; Holmans, Peter; Holton, Janice; Hu, Michele; Huber, Heiko; Hudson, Gavin; Hunt, Sarah E.; Huttenlocher, Johanna; Illig, Thomas; Langford, Cordelia; Lees, Andrew; Lesage, Suzanne; Lichtner, Peter; Limousin, Patricia; Lopez, Grisel; Lorenz, Delia; Martinez, Maria; McNeill, Alisdair; Moorby, Catriona; Moore, Matthew; Morris, Huw; Morrison, Karen E.; Moskvina, Valentina; Mudanohwo, Ese; Nalls, Michael A.; Pearson, Justin; Perlmutter, Joel S.; Pétursson, Hjörvar; Plagnol, Vincent; Pollak, Pierre; Post, Bart; Potter, Simon; Ravina, Bernard; Revesz, Tamas; Riess, Olaf; Rivadeneira, Fernando; Rizzu, Patrizia; Ryten, Mina; Saad, Mohamad; Sawcer, Stephen; Schapira, Anthony; Scheffer, Hans; Sharma, Manu; Shaw, Karen; Sheerin, Una-Marie; Shoulson, Ira; Schulte, Claudia; Sidransky, Ellen; Simón-Sánchez, Javier; Singleton, Andrew B.; Smith, Colin; Stefánsson, Hreinn; Stefánsson, Kári; Steinberg, Stacy; Stockton, Joanna D.; Sveinbjornsdottir, Sigurlaug; Talbot, Kevin; Tanner, Carlie M.; Tashakkori-Ghanbaria, Avazeh; Tison, François; Trabzuni, Daniah; Traynor, Bryan J.; Uitterlinden, André G.; Velseboer, Daan; Vidailhet, Marie; Walker, Robert; van de Warrenburg, Bart; Wickremaratchi, Mirdhu; Williams, Nigel; Williams-Gray, Caroline H.; Winder-Rhodes, Sophie; Wood, Nicholas

2013-01-01

Parkinson's disease (PD) is the second most common neurodegenerative disease affecting 1–2% in people >60 and 3–4% in people >80. Genome-wide association (GWA) studies have now implicated significant evidence for association in at least 18 genomic regions. We have studied a large PD-meta analysis and identified a significant excess of SNPs (P < 1 × 10−16) that are associated with PD but fall short of the genome-wide significance threshold. This result was independent of variants at the 18 previously implicated regions and implies the presence of additional polygenic risk alleles. To understand how these loci increase risk of PD, we applied a pathway-based analysis, testing for biological functions that were significantly enriched for genes containing variants associated with PD. Analysing two independent GWA studies, we identified that both had a significant excess in the number of functional categories enriched for PD-associated genes (minimum P = 0.014 and P = 0.006, respectively). Moreover, 58 categories were significantly enriched for associated genes in both GWA studies (P < 0.001), implicating genes involved in the ‘regulation of leucocyte/lymphocyte activity’ and also ‘cytokine-mediated signalling’ as conferring an increased susceptibility to PD. These results were unaltered by the exclusion of all 178 genes that were present at the 18 genomic regions previously reported to be strongly associated with PD (including the HLA locus). Our findings, therefore, provide independent support to the strong association signal at the HLA locus and imply that the immune-related genetic susceptibility to PD is likely to be more widespread in the genome than previously appreciated. PMID:23223016

7 CFR 1469.4 - Significant resource concerns.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 7 Agriculture 10 2010-01-01 2010-01-01 false Significant resource concerns. 1469.4 Section 1469.4... Provisions § 1469.4 Significant resource concerns. (a) Soil quality and water quality are nationally significant resource concerns for all land uses. (b) For each sign-up, the Chief may determine additional...

Radiotherapy is associated with significant improvement in local and regional control in Merkel cell carcinoma

PubMed Central

2012-01-01

Introduction Merkel cell carcinoma (MCC) is a rare tumour of skin. This study is a retrospective audit of patients with MCC from St Vincent’s and Mater Hospital, Sydney, Australia. The aim of this study was to investigate the influence of radiotherapy (RT) on the local and regional control of MCC lesions and survival of patients with MCC. Method The data bases in anatomical pathology, RT and surgery. We searched for patients having a diagnosis of MCC between 1996 and 2007. Patient, tumour and treatment characteristics were collected and analysed. Univariate survival analysis of categorical variables was conducted with the Kaplan-Meier method together with the Log-Rank test for statistical significance. Continuous variables were assessed using the Cox regression method. Multivariate analysis was performed for significant univariate results. Results Sixty seven patients were found. Sixty two who were stage I-III and were treated with radical intent were analysed. 68% were male. The median age was 74 years. Forty-two cases (68%) were stage I or II, and 20 cases (32%) were stage III. For the subset of 42 stage I and II patients, those that had RT to their primary site had a 2-year local recurrence free survival of 89% compared with 36% for patients not receiving RT (p<0.001). The cumulative 2-year regional recurrence free survival for patients having adjuvant regional RT was 84% compared with 43% for patients not receiving this treatment (p<0.001). Immune status at initial surgery was a significant predictor for OS and MCCSS. In a multivariate analysis combining macroscopic size (mm) and immune status at initial surgery, only immune status remained a significant predictor of overall survival (HR=2.096, 95% CI: 1.002-4.385, p=0.049). Conclusions RT is associated with significant improvement in local and regional control in Merkel cell carcinoma. Immunosuppression is an important factor in overall survival. PMID:23075308

Robust and Comprehensive Analysis of 20 Osteoporosis Candidate Genes by Very High-Density Single-Nucleotide Polymorphism Screen Among 405 White Nuclear Families Identified Significant Association and Gene–Gene Interaction

PubMed Central

Xiong, Dong-Hai; Shen, Hui; Zhao, Lan-Juan; Xiao, Peng; Yang, Tie-Lin; Guo, Yan; Wang, Wei; Guo, Yan-Fang; Liu, Yong-Jun; Recker, Robert R; Deng, Hong-Wen

2007-01-01

Many “novel” osteoporosis candidate genes have been proposed in recent years. To advance our knowledge of their roles in osteoporosis, we screened 20 such genes using a set of high-density SNPs in a large family-based study. Our efforts led to the prioritization of those osteoporosis genes and the detection of gene–gene interactions. Introduction We performed large-scale family-based association analyses of 20 novel osteoporosis candidate genes using 277 single nucleotide polymorphisms (SNPs) for the quantitative trait BMD variation and the qualitative trait osteoporosis (OP) at three clinically important skeletal sites: spine, hip, and ultradistal radius (UD). Materials and Methods One thousand eight hundred seventy-three subjects from 405 white nuclear families were genotyped and analyzed with an average density of one SNP per 4 kb across the 20 genes. We conducted association analyses by SNP- and haplotype-based family-based association test (FBAT) and performed gene–gene interaction analyses using multianalytic approaches such as multifactor-dimensionality reduction (MDR) and conditional logistic regression. Results and Conclusions We detected four genes (DBP, LRP5, CYP17, and RANK) that showed highly suggestive associations (10,000-permutation derived empirical global p ≤ 0.01) with spine BMD/OP; four genes (CYP19, RANK, RANKL, and CYP17) highly suggestive for hip BMD/OP; and four genes (CYP19, BMP2, RANK, and TNFR2) highly suggestive for UD BMD/OP. The associations between BMP2 with UD BMD and those between RANK with OP at the spine, hip, and UD also met the experiment-wide stringent criterion (empirical global p ≤ 0.0007). Sex-stratified analyses further showed that some of the significant associations in the total sample were driven by either male or female subjects. In addition, we identified and validated a two-locus gene–gene interaction model involving GCR and ESR2, for which prior biological evidence exists. Our results suggested the

Rolling Tobacco in Banana Leaves, Newspaper, or Copybook Paper Associated With Significant Reduction in Lung Function in Vanuatu.

PubMed

Weitz, Charles A; Olszowy, Kathryn M; Dancause, Kelsey N; Sun, Cheng; Pomer, Alysa; Silverman, Howard; Lee, G; Tarivonda, Len; Chan, Chim W; Kaneko, Akira; Lum, J K; Garruto, Ralph M

2017-04-01

In addition to the widespread availability of packaged cigarettes, the inhabitants of island nations of the Southwest Pacific frequently smoke commercially available loose tobacco using manufactured rolling papers, as well as locally grown tobacco rolled in manufactured rolling paper or wrapped in leaves, copybook paper, and newspaper. In this study, Vanuatu men who smoked local tobacco rolled in leaves, copybook paper, or newspaper showed significantly lower forced vital capacity (FVC), forced expiratory volume in 1 second (FEV 1 ), and FEV 1 /FVC ratios than men who smoked packaged cigarettes, store-bought tobacco rolled in manufactured rolling paper, or who smoked locally grown tobacco rolled in manufactured rolling papers. The addition of toxins from these unusual tobacco-wrapping media produces lung function deficits similar to the pattern noted among tobacco smokers who also inhale smoke from burning biomass. Thus, public health initiatives should consider including strategies addressing the use of wrapping media among smokers in South Pacific island societies.

Carboniferous volcanic rocks associated with back-arc extension in the western Chinese Tianshan, NW China: Insight from temporal-spatial character, petrogenesis and tectonic significance

NASA Astrophysics Data System (ADS)

Su, Wenbo; Cai, Keda; Sun, Min; Wan, Bo; Wang, Xiangsong; Bao, Zihe; Xiao, Wenjiao

2018-06-01

The Yili-Central Tianshan Block, as a Late Paleozoic major continental silver of the Central Asian Orogenic Belt, holds a massive volume of Carboniferous volcanic rocks, occurring as subparallel magmatic belts. However, the petrogenesis and tectonic implications of these volcanic rocks remain enigmatic. This study compiled isotopic age data for mapping their temporal-spatial character, and conducted petrogenetic study of these magmatic belts, aiming to understand their tectonic implications. Our compiled dataset reveals four magmatic belts in the Yili-Central Tianshan Block, including the Keguqinshan-Tulasu belt and the Awulale belt in the north, and the Wusun Mountain belt and the Haerk-Nalati belt in the south. In addition, our new zircon U-Pb dating results define two significant Early Carboniferous eruptive events (ca. 355-350 Ma and 325 Ma) in the Wusun Mountain belt. Volcanic rocks of the early significant eruptive event (ca. 355-350 Ma) in the Wusun Mountain comprise basalt, trachy-andesite, andesite, dacite and rhyolite, which are similar to the typical rock assemblage of a continental arc. Their positive εNd(t) values (+0.3 to +1.5) and relatively high Th/Yb and Nb/Yb ratios suggest the derivation from a mantle source with additions of slab-derived components. The gabbroic dykes and rhyolites of the late volcanic event (ca. 325 Ma) form a bimodal rock association, and they show alkaline features, with relatively low Th/Yb and Th/Nb ratios, and higher positive εNd(t) values (εNd(t) = +3.3-+5.0). It is interpreted that the gabbroic dykes and rhyolites may have been derived from mantle and juvenile crustal sources, respectively. The isotopic and trace elemental variations with time elapse of the Wusun Mountain magmatic belt show an important clue for strengthening depletion of the magma sources. Considering the distinctive temporal-spatial character of the Carboniferous volcanic rocks, two separate subduction systems in the southern and northern margins of

Two Cases of Generalized Seizures and the Velocardiofacial Syndrome - A Clinically Significant Association?

ERIC Educational Resources Information Center

El Tahir, M. O.; Kerr, M.; Jones, R. G.

2004-01-01

Velocardiofacial syndrome (VCFS) is caused by a micro deletion of chromosome 22q11 and associated with multiple system abnormalities. There is an increasing recognition of associations with psychiatric disorders. Neurological and brain abnormalities have been reported but to date no association with generalized epilepsy has been reported in…

Operating Room Anesthesia Subspecialization Is Not Associated With Significantly Greater Quality of Supervision of Anesthesia Residents and Nurse Anesthetists.

PubMed

Dexter, Franklin; Ledolter, Johannes; Epstein, Richard H; Hindman, Bradley J

2017-04-01

Supervision of anesthesia residents and nurse anesthetists is a major responsibility of faculty anesthesiologists. The quality of their supervision can be assessed quantitatively by the anesthesia residents and nurse anesthetists. Supervision scores are an independent measure of the contribution of the anesthesiologist to patient care. We evaluated the association between quality of supervision and level of specialization of anesthesiologists. We used two 6-month periods, one with no feedback to anesthesiologists of the residents' and nurse anesthetists' evaluations, and the other with feedback. Supervision scores provided by residents and nurse anesthetists were considered separately. Sample sizes among the 4 combinations ranged from n = 51 to n = 62 University of Iowa faculty. For each supervising anesthesiologist and 6-month period, we calculated the proportion of anesthetic cases attributable to each anesthesia Current Procedural Terminology code. The sum of the square of the proportions, a measurement of diversity, is known as the Herfindahl index. The inverse of this index represents the effective number of common procedures. The diversity (degree of specialization) of each faculty anesthesiologist was measured attributing each case to: (1) the anesthesiologist who supervised for the longest total period of time, (2) the anesthesiologist who started the case, or (3) the anesthesiologist who started the case, limited to cases started during "regular hours" (defined as nonholiday Monday to Friday, 07:00 AM to 02:59 PM). Inferential analysis was performed using bivariate-weighted least-squares regression. The point estimates of all 12 slopes were in the direction of greater specialization of practice of the evaluated faculty anesthesiologist being associated with significantly lower supervision scores. Among supervision scores provided by nurse anesthetists, the association was statistically significant for the third of the 6-month periods under the first and

Multi-species data integration and gene ranking enrich significant results in an alcoholism genome-wide association study.

PubMed

Zhao, Zhongming; Guo, An-Yuan; van den Oord, Edwin J C G; Aliev, Fazil; Jia, Peilin; Edenberg, Howard J; Riley, Brien P; Dick, Danielle M; Bettinger, Jill C; Davies, Andrew G; Grotewiel, Michael S; Schuckit, Marc A; Agrawal, Arpana; Kramer, John; Nurnberger, John I; Kendler, Kenneth S; Webb, Bradley T; Miles, Michael F

2012-01-01

A variety of species and experimental designs have been used to study genetic influences on alcohol dependence, ethanol response, and related traits. Integration of these heterogeneous data can be used to produce a ranked target gene list for additional investigation. In this study, we performed a unique multi-species evidence-based data integration using three microarray experiments in mice or humans that generated an initial alcohol dependence (AD) related genes list, human linkage and association results, and gene sets implicated in C. elegans and Drosophila. We then used permutation and false discovery rate (FDR) analyses on the genome-wide association studies (GWAS) dataset from the Collaborative Study on the Genetics of Alcoholism (COGA) to evaluate the ranking results and weighting matrices. We found one weighting score matrix could increase FDR based q-values for a list of 47 genes with a score greater than 2. Our follow up functional enrichment tests revealed these genes were primarily involved in brain responses to ethanol and neural adaptations occurring with alcoholism. These results, along with our experimental validation of specific genes in mice, C. elegans and Drosophila, suggest that a cross-species evidence-based approach is useful to identify candidate genes contributing to alcoholism.

Lack of significant association between spina bifida and the fragile X syndrome

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

Schiano, C.M.; Demb, H.B.; Brown, W.T.

1995-12-04

Folic acid is involved in two common disorders associated with developmental disabilities. Spina bifida is a malformation that may be associated with mental retardation, learning disabilities, and epilepsy. Its incidence can be reduced by the ingestion of folic acid before, and at the time of, conception. The fragile X syndrome is a genetic disorder which is the most common form of inherited mental retardation. This disorder can be diagnosed by the induction of fragile sites on the X chromosome which is cultured in a medium deficient in folic acid. In several studies, folic acid was reported to alleviate some ofmore » the developmental and behavioral manifestations associated in the fragile X syndrome, while in others, it has no effect. 9 refs.« less

Association between the CpG island methylator phenotype and its prognostic significance in primary pulmonary adenocarcinoma.

PubMed

Koh, Young Wha; Chun, Sung-Min; Park, Young-Soo; Song, Joon Seon; Lee, Geon Kook; Khang, Shin Kwang; Jang, Se Jin

2016-08-01

Aberrant methylation of promoter CpG islands is one of the most important inactivation mechanisms for tumor suppressor and tumor-related genes. Previous studies using genome-wide DNA methylation microarray analysis have suggested the existence of a CpG island methylator phenotype (CIMP) in lung adenocarcinomas. Although the biological behavior of these tumors varies according to tumor stage, no large-scale study has examined the CIMP in lung adenocarcinoma patients according to tumor stage. Furthermore, there have been no reported results regarding the clinical significance of each of the six CIMP markers. To examine the CIMP in patients with pulmonary adenocarcinoma after a surgical resection, we performed methylation analysis of six genes (CCNA1, ACAN, GFRA1, EDARADD, MGC45800, and p16 (INK4A)) in 230 pulmonary adenocarcinoma cases using the SEQUENOM MassARRAY platform. Fifty-four patients (28 %, 54/191) were in the CIMP-high (CIMP-H) group associated with high nodal stage (P = 0.007), the presence of micropapillary or solid histology (P = 0.003), and the absence of an epidermal growth factor receptor (EGFR) mutation (P = 0.002). By multivariate analysis, CIMP was an independent prognostic marker for overall survival (OS) and disease-specific survival (P = 0.03 and P = 0.43, respectively). In the stage I subgroups alone, CIMP-H patients had lower OS rates than the CIMP-low (CIMP-L) group (P = 0.041). Of the six CIMP markers, ACAN alone was significantly associated with patient survival. CIMP predicted the risk of progression independently of clinicopathological variables and enables the stratification of pulmonary adenocarcinoma patients, particularly among stage I cases.

Significant association between ERCC2 and MTHR polymorphisms and breast cancer susceptibility in Moroccan population: genotype and haplotype analysis in a case-control study.

PubMed

Hardi, Hanaa; Melki, Rahma; Boughaleb, Zouhour; El Harroudi, Tijani; Aissaoui, Souria; Boukhatem, Noureddine

2018-03-15

Genetic determinants of breast cancer (BC) remained largely unknown in the majority of Moroccan patients. The purpose of this study was to explore the association of ERCC2 and MTHFR polymorphisms with genetic susceptibility to breast cancer in Moroccan population. We genotyped ERCC2 polymorphisms (rs1799793 (G934A) and rs13181 (A2251C)) and MTHFR polymorphisms (rs1801133 (C677T) and rs1801131 (A1298C)) using TaqMan SNP Genotyping Assays. Genotypes were compared in 151 BC cases and 156 population-matched controls. Allelic, genotypic and haplotype associations with the risk and clinicopathological features of BC were assessed using logistic regression analyses. ERCC2-rs1799793-AA genotype was associated with high risk of BC compared to wild type genotype (recessive model: OR: 2.90, 95% CI: 1.34-6.26, p = 0.0069) even after Bonferroni correction (p < 0,0125). MTHFR rs1801133-TT genotype was associated with increased risk of BC (recessive model, OR: 2.49, 95% CI: 1.17-5.29, p = 0.017) but the association turned insignificant after Bonferroni correction. For the rest of SNPs, no statistical associations to BC risk were detected. Significant association with clinical features was detected for MTHFR-rs1801133-TC genotype with early age at diagnosis and familial BC. Following Bonferroni correction, only association with familial BC remained significant. MTHFR-rs1801131-CC genotype was associated with sporadic BC. ERCC2-rs1799793-AA genotype correlated with ER+ and PR+ breast cancer. ERCC2-rs13181-CA genotype was significantly associated large tumors (T ≥ 3) in BC patients. None of these associations passed Bonferroni correction. Haplotype analysis showed that ERCC2 A-C haplotype was significantly associated with increased BC risk (OR: 3.71, 95% CI: 1.7-8.12, p = 0.0002 and p = 0.0008 before and after Bonferroni correction, respectively) and positive expression of ER and PR in BC patients. ERCC2 G-C haplotype was correlated with PR negative and

77 FR 37659 - Procurement List; Proposed Additions

Federal Register 2010, 2011, 2012, 2013, 2014

2012-06-22

... additions to the procurement list. SUMMARY: The Committee is proposing to add products and services to the...- 598-5067 and 1670-01-598-5071 to its Procurement List. The Coverage statement associated with this... connection with the products and services proposed for addition to the Procurement List. Comments on this...

PARTICLE-ASSOCIATED MICROORGANISMS IN STORMWATER RUNOFF

EPA Science Inventory

This research investigated the effects of blending and chemical addition before analysis of the concentration of microorganisms in stormwater runoff to determine whether clumped or particle-associated organisms play a significant role. All organisms, except for Escherichia coli, ...

First High-Density Linkage Map and Single Nucleotide Polymorphisms Significantly Associated With Traits of Economic Importance in Yellowtail Kingfish Seriola lalandi.

PubMed

Nguyen, Nguyen H; Rastas, Pasi M A; Premachandra, H K A; Knibb, Wayne

2018-01-01

The genetic resources available for the commercially important fish species Yellowtail kingfish (YTK) ( Seriola lalandi) are relative sparse. To overcome this, we aimed (1) to develop a linkage map for this species, and (2) to identify markers/variants associated with economically important traits in kingfish (with an emphasis on body weight). Genetic and genomic analyses were conducted using 13,898 single nucleotide polymorphisms (SNPs) generated from a new high-throughput genotyping by sequencing platform, Diversity Arrays Technology (DArTseq TM ) in a pedigreed population comprising 752 animals. The linkage analysis enabled to map about 4,000 markers to 24 linkage groups (LGs), with an average density of 3.4 SNPs per cM. The linkage map was integrated into a genome-wide association study (GWAS) and identified six variants/SNPs associated with body weight ( P < 5e -8 ) when a multi-locus mixed model was used. Two out of the six significant markers were mapped to LGs 17 and 23, and collectively they explained 5.8% of the total genetic variance. It is concluded that the newly developed linkage map and the significantly associated markers with body weight provide fundamental information to characterize genetic architecture of growth-related traits in this population of YTK S. lalandi .

Efficacy of feed additives against Campylobacter in live broilers during the entire rearing period.

PubMed

Guyard-Nicodème, M; Keita, A; Quesne, S; Amelot, M; Poezevara, T; Le Berre, B; Sánchez, J; Vesseur, P; Martín, Á; Medel, P; Chemaly, Marianne

2016-02-01

Poultry meat is the major source of human campylobacteriosis, the most frequently reported zoonosis in the EU. The prevalence of Campylobacter colonization in European broiler flocks is 71%. Despite considerable efforts, there is still no effective strategy available to prevent or reduce Campylobacter colonization in broilers. This study tested a wide variety of feed additives to reduce Campylobacter shedding in primary poultry production. Twelve additives containing organic or fatty acids, monoglycerides, plant extracts, prebiotics, or probiotics were tested. For each additive, broilers contaminated with Campylobacter jejuni were fed with an additive free diet (control group) or with a supplemented diet (treated group) and Campylobacter loads compared at three sampling times. No treatment was able to prevent broiler colonization by Campylobacter, and there was a high degree of variation in contamination among the birds. At 14 d of age, eight treatments significantly decreased the colonization level compared to the control group by a maximum of 2 log10 CFU/g. At 35 d of age, three of these treatments still had a significant effect with a maximum reduction of 1.88 log10 CFU/g for a probiotic. At 42 d of age, only one short-chain fatty acid was still significantly efficient with a mean reduction over 2 log10 CFU/g. In addition, a probiotic and a prebiotic-like compound significantly decreased the contamination by a maximum of 3 log10 CFU/g, only at the 42-d sampling period. This study gives promising results regarding the use of feed additives to reduce Campylobacter infection in flocks. Nevertheless, a global approach, combining intervention measures at the different steps of the broiler meat production chain could have a greater impact on the reduction of public health risk. © 2015 Poultry Science Association Inc.

Additive and non-additive genetic components of the jack male life history in Chinook salmon (Oncorhynchus tshawytscha).

PubMed

Forest, Adriana R; Semeniuk, Christina A D; Heath, Daniel D; Pitcher, Trevor E

2016-08-01

Chinook salmon, Oncorhynchus tshawytscha, exhibit alternative reproductive tactics (ARTs) where males exist in two phenotypes: large "hooknose" males and smaller "jacks" that reach sexual maturity after only 1 year in seawater. The mechanisms that determine "jacking rate"-the rate at which males precociously sexually mature-are known to involve both genetics and differential growth rates, where individuals that become jacks exhibit higher growth earlier in life. The additive genetic components have been studied and it is known that jack sires produce significantly more jack offspring than hooknose sires, and vice versa. The current study was the first to investigate both additive and non-additive genetic components underlying jacking through the use of a full-factorial breeding design using all hooknose sires. The effect of dams and sires descendant from a marker-assisted broodstock program that identified "high performance" and "low performance" lines using growth- and survival-related gene markers was also studied. Finally, the relative growth of jack, hooknose, and female offspring was examined. No significant dam, sire, or interaction effects were observed in this study, and the maternal, additive, and non-additive components underlying jacking were small. Differences in jacking rates in this study were determined by dam performance line, where dams that originated from the low performance line produced significantly more jacks. Jack offspring in this study had a significantly larger body size than both hooknose males and females starting 1 year post-fertilization. This study provides novel information regarding the genetic architecture underlying ARTs in Chinook salmon that could have implications for the aquaculture industry, where jacks are not favoured due to their small body size and poor flesh quality.

Low-level maternal exposure to nicotine associates with significant metabolic perturbations in second-trimester amniotic fluid.

PubMed

Fischer, S Taylor; Lili, Loukia N; Li, Shuzhao; Tran, ViLinh T; Stewart, Kim B; Schwartz, Charles E; Jones, Dean P; Sherman, Stephanie L; Fridovich-Keil, Judith L

2017-10-01

Decades of public health research have documented that smoking in pregnancy poses significant health risks to both mother and child. More recent studies have shown that even passive maternal exposure to secondhand smoke associates with negative birth outcomes. However, the mechanisms linking exposure to outcomes have remained obscure. As a first step toward defining the metabolic consequence of low-level nicotine exposure on fetal development, we conducted an untargeted metabolomic analysis of 81 paired samples of maternal serum and amniotic fluid collected from karyotypically normal pregnancies in the second trimester. By comparing the m/z and retention times of our mass spectral features with confirmed standards, we identified cotinine, a nicotine derivative, and used the calculated cotinine concentrations to classify our maternal serum samples into exposure groups using previously defined cut-offs. We found that cotinine levels consistent with low-level maternal exposure to nicotine associated with distinct metabolic perturbations, particularly in amniotic fluid. In fact, the metabolic effects in amniotic fluid of ostensibly low-level exposed mothers showed greater overlap with perturbations previously observed in the sera of adult smokers than did the perturbations observed in the corresponding maternal sera. Dysregulated fetal pathways included aspartate and asparagine metabolism, pyrimidine metabolism, and metabolism of other amino acids. We also observed a strong negative association between level of maternal serum cotinine and acetylated polyamines in the amniotic fluid. Combined, these results confirm that low-level maternal nicotine exposure, indicated by a maternal serum cotinine level of 2-10ng/mL, is associated with striking metabolic consequences in the fetal compartment, and that the affected pathways overlap those perturbed in the sera of adult smokers. Copyright © 2017 Elsevier Ltd. All rights reserved.

Comparative genomics reveals genes significantly associated with woody hosts in the plant pathogen Pseudomonas syringae

PubMed Central

Laue, Bridget E.; Sharp, Paul M.; Green, Sarah

2016-01-01

Summary The diversification of lineages within Pseudomonas syringae has involved a number of adaptive shifts from herbaceous hosts onto various species of tree, resulting in the emergence of highly destructive diseases such as bacterial canker of kiwi and bleeding canker of horse chestnut. This diversification has involved a high level of gene gain and loss, and these processes are likely to play major roles in the adaptation of individual lineages onto their host plants. In order to better understand the evolution of P. syringae onto woody plants, we have generated de novo genome sequences for 26 strains from the P. syringae species complex that are pathogenic on a range of woody species, and have looked for statistically significant associations between gene presence and host type (i.e. woody or herbaceous) across a phylogeny of 64 strains. We have found evidence for a common set of genes associated with strains that are able to colonize woody plants, suggesting that divergent lineages have acquired similarities in genome composition that may form the genetic basis of their adaptation to woody hosts. We also describe in detail the gain, loss and rearrangement of specific loci that may be functionally important in facilitating this adaptive shift. Overall, our analyses allow for a greater understanding of how gene gain and loss may contribute to adaptation in P. syringae. PMID:27145446

Inflammation-associated microsatellite alterations: Mechanisms and significance in the prognosis of patients with colorectal cancer.

PubMed

Koi, Minoru; Tseng-Rogenski, Stephanie S; Carethers, John M

2018-01-15

Microsatellite alterations within genomic DNA frameshift as a result of defective DNA mismatch repair (MMR). About 15% of sporadic colorectal cancers (CRCs) manifest hypermethylation of the DNA MMR gene MLH1 , resulting in mono- and di-nucleotide frameshifts to classify it as microsatellite instability-high (MSI-H) and hypermutated, and due to frameshifts at coding microsatellites generating neo-antigens, produce a robust protective immune response that can be enhanced with immune checkpoint blockade. More commonly, approximately 50% of sporadic non-MSI-H CRCs demonstrate frameshifts at di- and tetra-nucleotide microsatellites to classify it as MSI-low/elevated microsatellite alterations at selected tetranucleotide repeats (EMAST) as a result of functional somatic inactivation of the DNA MMR protein MSH3 via a nuclear-to-cytosolic displacement. The trigger for MSH3 displacement appears to be inflammation and/or oxidative stress, and unlike MSI-H CRC patients, patients with MSI-L/EMAST CRCs show poor prognosis. These inflammatory-associated microsatellite alterations are a consequence of the local tumor microenvironment, and in theory, if the microenvironment is manipulated to lower inflammation, the microsatellite alterations and MSH3 dysfunction should be corrected. Here we describe the mechanisms and significance of inflammatory-associated microsatellite alterations, and propose three areas to deeply explore the consequences and prevention of inflammation's effect upon the DNA MMR system.

Inflammation-associated microsatellite alterations: Mechanisms and significance in the prognosis of patients with colorectal cancer

PubMed Central

Koi, Minoru; Tseng-Rogenski, Stephanie S; Carethers, John M

2018-01-01

Microsatellite alterations within genomic DNA frameshift as a result of defective DNA mismatch repair (MMR). About 15% of sporadic colorectal cancers (CRCs) manifest hypermethylation of the DNA MMR gene MLH1, resulting in mono- and di-nucleotide frameshifts to classify it as microsatellite instability-high (MSI-H) and hypermutated, and due to frameshifts at coding microsatellites generating neo-antigens, produce a robust protective immune response that can be enhanced with immune checkpoint blockade. More commonly, approximately 50% of sporadic non-MSI-H CRCs demonstrate frameshifts at di- and tetra-nucleotide microsatellites to classify it as MSI-low/elevated microsatellite alterations at selected tetranucleotide repeats (EMAST) as a result of functional somatic inactivation of the DNA MMR protein MSH3 via a nuclear-to-cytosolic displacement. The trigger for MSH3 displacement appears to be inflammation and/or oxidative stress, and unlike MSI-H CRC patients, patients with MSI-L/EMAST CRCs show poor prognosis. These inflammatory-associated microsatellite alterations are a consequence of the local tumor microenvironment, and in theory, if the microenvironment is manipulated to lower inflammation, the microsatellite alterations and MSH3 dysfunction should be corrected. Here we describe the mechanisms and significance of inflammatory-associated microsatellite alterations, and propose three areas to deeply explore the consequences and prevention of inflammation’s effect upon the DNA MMR system. PMID:29375743

[Is surgical education associated with additional costs? A controlled economic study on the German DRG System for primary TKA].

PubMed

Göbel, P; Piesche, K; Randau, T; Wimmer, M D; Wirtz, D C; Gravius, S

2013-04-01

Total knee arthroplasty (TKA) is one of the most common procedures in orthopaedic surgery, the cost of surgical training has as yet not been quantified. In a pilot study, we investigated the economic impact of surgical training under DRG system influences, analysing the cost-proceeds structure in surgical training for orthopaedic residents. Consecutive TKAs were performed by the most educated surgeon (Group A) having implanted ≥ 1000 TKAs, another attending (Group B) with ≥ 200 TKAs and a resident (Group C) having assisted in 25 TKAs (n = 30 patients per Group A-C). All patients were embedded in a standardised clinical pathway. By analysing the costs parameters such as numbers of blood transfusions, the operating time and the length of stay in the hospital we investigated the health care-related costs matched to the DRG-based financial refunding. Data were analysed after undergoing a analysis of variance followed by a post-hoc Scheffé procedure. On the one hand the resident generated additional costs of 1111,7 ± 97 € in comparison to the Group A surgeon and 1729,8 ± 152 € compared to the attending Group B (p > 0,05), these were generated by longer stay in hospital, longer operation time and higher need of resources. On the other hand there were significantly higher proceeds of the Group C in comparison to the attending Group B and also to Group A: 474,78 ± 82 € vs. A and 150,54 ± 52 € vs. Group B (p < 0,05). This was generated both by a higher patient clinical level of complexity (PCCL) and increased complication rates resulting in a consecutively augmented profit by grouping these patients to a more lucrative DRG. Overall the deficit per patient treated by the resident is 637 ± 77 € vs. Group A and 1579,3 ± 137 € vs. Group B (p > 0,05). The German DRG matrix results in higher profits accounted to the learning surgeon by increased PCCL relevant status and grouping the case to a more profitable DRG. Hereby, the additional costs are only partly

Mumps Parotitis and Ovarian Cancer: Modern Significance of an Historic Association

DTIC Science & Technology

2009-10-01

ligation or a breast mastitis , found to protect against ovarian cancer, might do so by causing overexpression of the hypoglycosylated form of MUC1...negative plates were incubated overnight and washed three times with PBS before addition of 100 μl of 2.5% bovine serum albumin in PBS. Serially...a breast mastitis which have been shown to protect against ovarian cancer(10), might confer protection because of injury to the tissue causing

The effects of workplace psychosocial factors on whether Japanese dual-earner couples with preschool children have additional children: a prospective study

PubMed Central

EGUCHI, Hisashi; SHIMAZU, Akihito; FUJIWARA, Takeo; IWATA, Noboru; SHIMADA, Kyoko; TAKAHASHI, Masaya; TOKITA, Masahito; WATAI, Izumi; KAWAKAMI, Norito

2016-01-01

This study explored the effect of workplace psychosocial factors (job demand, job control, and workplace social support) on dual-earner couples in Japan having additional children, using a prospective study design. We conducted a 2-year prospective cohort study with 103 dual-earner couples with preschool children in Japan, as part of the Tokyo Work–Family Interface Study II. We used multivariable logistic regression analyses to evaluate the prospective association of job strain (categorized into low-strain job, active job, passive job, and strain job groups) and workplace social support (high and low) with couples having additional children during the follow-up period, adjusting for age, for men and women separately. Men in the active job group (i.e., with high job demands and high job control) had a significantly higher odds ratio (OR) of having additional children during the follow-up period, after controlling for age (OR 9.07, 95% confidence interval: 1.27–64.85). No significant association between any workplace psychosocial factor and having additional children was confirmed among women. Having an active job may have a positive influence on having additional children among men in dual-earner couples. PMID:27760893

The effects of workplace psychosocial factors on whether Japanese dual-earner couples with preschool children have additional children: a prospective study.

PubMed

Eguchi, Hisashi; Shimazu, Akihito; Fujiwara, Takeo; Iwata, Noboru; Shimada, Kyoko; Takahashi, Masaya; Tokita, Masahito; Watai, Izumi; Kawakami, Norito

2016-12-07

This study explored the effect of workplace psychosocial factors (job demand, job control, and workplace social support) on dual-earner couples in Japan having additional children, using a prospective study design. We conducted a 2-year prospective cohort study with 103 dual-earner couples with preschool children in Japan, as part of the Tokyo Work-Family Interface Study II. We used multivariable logistic regression analyses to evaluate the prospective association of job strain (categorized into low-strain job, active job, passive job, and strain job groups) and workplace social support (high and low) with couples having additional children during the follow-up period, adjusting for age, for men and women separately. Men in the active job group (i.e., with high job demands and high job control) had a significantly higher odds ratio (OR) of having additional children during the follow-up period, after controlling for age (OR 9.07, 95% confidence interval: 1.27-64.85). No significant association between any workplace psychosocial factor and having additional children was confirmed among women. Having an active job may have a positive influence on having additional children among men in dual-earner couples.

Significant Change in Marine Plankton Structure and Carbon Production After the Addition of River Water in a Mesocosm Experiment.

PubMed

Fouilland, E; Trottet, A; Alves-de-Souza, C; Bonnet, D; Bouvier, T; Bouvy, M; Boyer, S; Guillou, L; Hatey, E; Jing, H; Leboulanger, C; Le Floc'h, E; Liu, H; Mas, S; Mostajir, B; Nouguier, J; Pecqueur, D; Rochelle-Newall, E; Roques, C; Salles, C; Tournoud, M-G; Vasseur, C; Vidussi, F

2017-08-01

Rivers are known to be major contributors to eutrophication in marine coastal waters, but little is known on the short-term impact of freshwater surges on the structure and functioning of the marine plankton community. The effect of adding river water, reducing the salinity by 15 and 30%, on an autumn plankton community in a Mediterranean coastal lagoon (Thau Lagoon, France) was determined during a 6-day mesocosm experiment. Adding river water brought not only nutrients but also chlorophyceans that did not survive in the brackish mesocosm waters. The addition of water led to initial increases (days 1-2) in bacterial production as well as increases in the abundances of bacterioplankton and picoeukaryotes. After day 3, the increases were more significant for diatoms and dinoflagellates that were already present in the Thau Lagoon water (mainly Pseudo-nitzschia spp. group delicatissima and Prorocentrum triestinum) and other larger organisms (tintinnids, rotifers). At the same time, the abundances of bacterioplankton, cyanobacteria, and picoeukaryote fell, some nutrients (NH 4 + , SiO 4 3- ) returned to pre-input levels, and the plankton structure moved from a trophic food web based on secondary production to the accumulation of primary producers in the mesocosms with added river water. Our results also show that, after freshwater inputs, there is rapid emergence of plankton species that are potentially harmful to living organisms. This suggests that flash flood events may lead to sanitary issues, other than pathogens, in exploited marine areas.

High aryl acylamidase activity associated with cobra venom acetylcholinesterase: biological significance.

PubMed

Rajesh, Ramanna V; Layer, Paul G; Boopathy, Rathanam

2009-01-01

Investigation of the non-classical functions of cholinesterases (ChEs) has been the subject of interest in the past three decades. One of which is aryl acylamidase (AAA) activity associated with ChEs, but characterized in in vitro, as an enzyme, splitting the artificial substrate o-nitroacetanilide with unknown physiological function. In the present study, we have compared levels of AAA activity of AChE from different sources like goat brain, electric eel organ and from venoms of different snakes. Remarkably cobra venom showed the highest AAA activity and also high AAA/AChE ratio. Both serotonergenic and cholinergic inhibitors inhibited the cobra venom AAA activity in a concentration dependent manner, which also underlines the association of AAA with AChE of cobra venom. The study becomes interesting because of i) the cobra venom AChE exists in monomeric globular forms; ii) in Alzheimer's disease too the most abundant forms of cholinesterases are monomeric globular forms, thought to be involved in the pathogenesis of Alzheimer's disease; iii) the effect of Alzheimer's disease drugs on the AAA activity of cobra venom, indicated that AAA activity of cobra venom was more sensitive than AChE and iv) Huperzine and Tacrine showed more pronounced effect on AAA. Thus, this study elucidates the high AAA associated with cobra venom AChE may serve as one of the prominent activity to test the pharmacological effect of AD drugs, as other sources were found to have lower activity.

HbA1c is significantly associated with arterial stiffness but not with carotid atherosclerosis in a community-based population without type 2 diabetes: The Dong-gu study.

PubMed

Lee, Young-Hoon; Shin, Min-Ho; Choi, Jin-Su; Rhee, Jung-Ae; Nam, Hae-Sung; Jeong, Seul-Ki; Park, Kyeong-Soo; Ryu, So-Yeon; Choi, Seong-Woo; Kim, Bok-Hee; Oh, Gyung-Jae; Kweon, Sun-Seog

2016-04-01

We examined the associations between HbA1c levels and various atherosclerotic vascular parameters among adults without diabetes from the general population. A total of 6500 community-dwelling adults, who were free of type 2 diabetes and ≥50 years of age, were included. High-resolution B-mode ultrasound was used to evaluate carotid artery structure, including intima-media thickness (IMT), plaque, and luminal diameter. Brachial-ankle pulse wave velocity (baPWV), which is a useful indicator of systemic arterial stiffness, was determined using an automatic waveform analysis device. No significant associations were observed between HbA1c, carotid IMT, plaque, or luminal diameter in a fully adjusted model. However, the odds ratio (95% confidence interval) for high baPWV (defined as the highest quartile) increased by 1.43 (1.19-1.71) per 1% HbA1c increase after adjusting for conventional risk factors in a multivariate logistic regression analysis. In addition, HbA1c was independently associated with baPWV in a multivariate linear regression analysis. High-normal HbA1c level was independently associated with arterial stiffness, but not with carotid atherosclerotic parameters, in the general population without diabetes. Our results suggest that the functional atherosclerotic process may already be accelerated according to HbA1c level, even at a level below the diagnostic threshold for diabetes. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Need for tissue plasminogen activator for central venous catheter dysfunction is significantly associated with thrombosis in pediatric cancer patients.

PubMed

MacLean, Jessica; MacDonald, Tamara; Digout, Carol; Smith, Nadine; Rigby, Krista; Kulkarni, Ketan

2018-06-01

Central venous catheter (CVC) dysfunction is a common complication among pediatric cancer patients. Tissue plasminogen activator (tPA) is administered to resolve CVC dysfunction. The present study was designed to determine risk factors associated with requirement of tPA for CVC dysfunction and to assess the clinical impact of CVC dysfunction in terms of CVC loss and venous thrombotic events (VTE). Case records of all pediatric patients with cancer from the Maritimes, Canada were reviewed following ethics approval. Data regarding demographics, clinical diagnosis, CVC dysfunction, characteristics of CVCs, and VTE were pooled from multiple data sources. Seven hundred and forty-one patients required ≥1 CVC. 26.3% of patients required tPA for ≥1 episodes of CVC dysfunction. Requirement of one or more doses of tPA for episodes of CVC dysfunction increased the odds of VTE by two times (95% confidence interval, 1.1-3.6). Patients that required ≥1 doses of tPA required significantly more CVCs (2.05 ± 1.29 per individual patient, 55% of the patients needed >1 CVCs) as compared to the remainder (1.52 ± 0.95 per individual patient, 32% needed >1 CVCs) (P = 0.0001). Multivariate analysis revealed age > 10 years, diagnosis of sarcoma, and tunneled line were independently associated with tPA requirement. We determined independent risk factors associated with requirement of tPA for CVC dysfunction. Requirement of tPA for CVC dysfunction was associated with significantly increased risk of VTE and requirement of more CVCs. These observations can assist in identification of patients at increased risk of CVC dysfunction and inform approaches to reduce CVC loss and VTE. © 2018 Wiley Periodicals, Inc.

Mapping quantitative trait loci with additive effects and additive x additive epistatic interactions for biomass yield, grain yield, and straw yield using a doubled haploid population of wheat (Triticum aestivum L.).

PubMed

Li, Z K; Jiang, X L; Peng, T; Shi, C L; Han, S X; Tian, B; Zhu, Z L; Tian, J C

2014-02-28

Biomass yield is one of the most important traits for wheat (Triticum aestivum L.)-breeding programs. Increasing the yield of the aerial parts of wheat varieties will be an integral component of future wheat improvement; however, little is known regarding the genetic control of aerial part yield. A doubled haploid population, comprising 168 lines derived from a cross between two winter wheat cultivars, 'Huapei 3' (HP3) and 'Yumai 57' (YM57), was investigated. Quantitative trait loci (QTL) for total biomass yield, grain yield, and straw yield were determined for additive effects and additive x additive epistatic interactions using the QTLNetwork 2.0 software based on the mixed-linear model. Thirteen QTL were determined to have significant additive effects for the three yield traits, of which six also exhibited epistatic effects. Eleven significant additive x additive interactions were detected, of which seven occurred between QTL showing epistatic effects only, two occurred between QTL showing epistatic effects and additive effects, and two occurred between QTL with additive effects. These QTL explained 1.20 to 10.87% of the total phenotypic variation. The QTL with an allele originating from YM57 on chromosome 4B and another QTL contributed by HP3 alleles on chromosome 4D were simultaneously detected on the same or adjacent chromosome intervals for the three traits in two environments. Most of the repeatedly detected QTL across environments were not significant (P > 0.05). These results have implications for selection strategies in wheat biomass yield and for increasing the yield of the aerial part of wheat.

Endometrial carcinomas with significant mucinous differentiation associated with higher frequency of k-ras mutations: a morphologic and molecular correlation study.

PubMed

Xiong, Jinjun; He, Mai; Jackson, Cynthia; Ou, Joyce J; Sung, C James; Breese, Virgina; Steinhoff, Margaret M; Quddus, M Ruhul; Tejada-Berges, Trevor; Lawrence, W Dwayne

2013-09-01

K-ras gene product in the mitogen-activated protein kinase/extracellular signal-regulated kinase pathway is critical in the development of certain types of malignancies. K-ras mutation-associated pancreatic and ovarian carcinomas often display mucinous differentiation. Previous studies have shown that k-ras mutation is found in 10% to 30% of endometrial carcinomas. We investigated k-ras mutations in several morphologic subtypes of endometrial carcinomas with particular emphasis on various degrees of mucinous differentiation. Genomic DNA was extracted from formalin-fixed paraffin-embedded (FFPE) tissue sections. Polymerase chain reaction amplification for k-ras codons 12 and 13 were performed, followed by sequencing using capillary electrophoresis. The Fisher exact test is used to compare the prevalent difference of k-ras mutation among the groups. P < 0.05 was considered significant. K-ras mutations were detected in 8 (80%) of 10 mucinous carcinomas, 12 (67%) of 18 endometrioid carcinomas (ECs) with significant mucinous differentiation (ECMD), 4 (25%) of 16 ECs, and 1 (9%) of 11 serous carcinomas. The differences were statistically significant between mucinous carcinomas versus EC (P < 0.01) and ECMD versus EC (P < 0.05). The findings suggest that mucinous carcinoma and endometrioid carcinoma with significant mucinous component are more likely to be associated with k-ras mutation. Potential clinical implications of k-ras mutation lies in the management of recurrent or higher-stage endometrial mucinous tumors, which would not be responsive to treatment protocols containing epidermal growth factor receptor inhibitors.

Mutation profiling of 19 candidate genes in acute myeloid leukemia suggests significance of DNMT3A mutations.

PubMed

Shin, Sang-Yong; Lee, Seung-Tae; Kim, Hee-Jin; Cho, Eun Hae; Kim, Jong-Won; Park, Silvia; Jung, Chul Won; Kim, Sun-Hee

2016-08-23

We selected 19 significantly-mutated genes in AMLs, including FLT3, DNMT3A, NPM1, TET2, RUNX1, CEBPA, WT1, IDH1, IDH2, NRAS, ASXL1, SETD2, PTPN11, TP53, KIT, JAK2, KRAS, BRAF and CBL, and performed massively parallel sequencing for 114 patients with acute myeloid leukemias, mainly including those with normal karyotypes (CN-AML). More than 80% of patients had at least one mutation in the genes tested. DNMT3A mutation was significantly associated with adverse outcome in addition to conventional risk stratification such as the European LeukemiaNet (ELN) classification. We observed clinical usefulness of mutation testing on multiple target genes and the association with disease subgroups, clinical features and prognosis in AMLs.

The pathological significance of Notch1 in oral squamous cell carcinoma.

PubMed

Yoshida, Ryoji; Nagata, Masashi; Nakayama, Hideki; Niimori-Kita, Kanako; Hassan, Wael; Tanaka, Takuji; Shinohara, Masanori; Ito, Takaaki

2013-10-01

Notch signaling has been reported to be involved in several types of malignant tumors; however, the role and activation mechanism of Notch signaling in oral squamous cell carcinoma (OSCC) remains poorly characterized. The purpose of this study was to elucidate the pathological significance of Notch signaling and its activation mechanism in the development and progression of OSCC. In this study, we showed that the expression of Notch1 and intracellular Notch domain (NICD) are upregulated in OSCCs. In addition, Notch1 and NICD were found to be characteristically localized at the invasive tumor front. TNF-α, a major inflammatory cytokine, significantly activated Notch signaling in vitro. In a clinicopathological analysis, Notch1 expression correlated with both the T-stage and the clinical stage. Furthermore, loss of Notch1 expression correlated with the inhibition of cell proliferation and TNF-α-dependent invasiveness in an OSCC cell line. In addition, γ-secretase inhibitor (GSI) prevented cell proliferation and TNF-α-dependent invasion of OSCC cells in vitro. These results indicate that altered expression of Notch1 is associated with increased cancer progression and that Notch1 regulates the steps involved in cell metastasis in OSCC. Moreover, inactivating Notch signaling with GSI could therefore be a useful approach for treating patients with OSCC.

Common germline polymorphisms associated with breast cancer-specific survival.

PubMed

Pirie, Ailith; Guo, Qi; Kraft, Peter; Canisius, Sander; Eccles, Diana M; Rahman, Nazneen; Nevanlinna, Heli; Chen, Constance; Khan, Sofia; Tyrer, Jonathan; Bolla, Manjeet K; Wang, Qin; Dennis, Joe; Michailidou, Kyriaki; Lush, Michael; Dunning, Alison M; Shah, Mitul; Czene, Kamila; Darabi, Hatef; Eriksson, Mikael; Lambrechts, Dieter; Weltens, Caroline; Leunen, Karin; van Ongeval, Chantal; Nordestgaard, Børge G; Nielsen, Sune F; Flyger, Henrik; Rudolph, Anja; Seibold, Petra; Flesch-Janys, Dieter; Blomqvist, Carl; Aittomäki, Kristiina; Fagerholm, Rainer; Muranen, Taru A; Olsen, Janet E; Hallberg, Emily; Vachon, Celine; Knight, Julia A; Glendon, Gord; Mulligan, Anna Marie; Broeks, Annegien; Cornelissen, Sten; Haiman, Christopher A; Henderson, Brian E; Schumacher, Frederick; Le Marchand, Loic; Hopper, John L; Tsimiklis, Helen; Apicella, Carmel; Southey, Melissa C; Cross, Simon S; Reed, Malcolm Wr; Giles, Graham G; Milne, Roger L; McLean, Catriona; Winqvist, Robert; Pylkäs, Katri; Jukkola-Vuorinen, Arja; Grip, Mervi; Hooning, Maartje J; Hollestelle, Antoinette; Martens, John Wm; van den Ouweland, Ans Mw; Marme, Federick; Schneeweiss, Andreas; Yang, Rongxi; Burwinkel, Barbara; Figueroa, Jonine; Chanock, Stephen J; Lissowska, Jolanta; Sawyer, Elinor J; Tomlinson, Ian; Kerin, Michael J; Miller, Nicola; Brenner, Hermann; Butterbach, Katja; Holleczek, Bernd; Kataja, Vesa; Kosma, Veli-Matti; Hartikainen, Jaana M; Li, Jingmei; Brand, Judith S; Humphreys, Keith; Devilee, Peter; Tollenaar, Robert Aem; Seynaeve, Caroline; Radice, Paolo; Peterlongo, Paolo; Manoukian, Siranoush; Ficarazzi, Filomena; Beckmann, Matthias W; Hein, Alexander; Ekici, Arif B; Balleine, Rosemary; Phillips, Kelly-Anne; Benitez, Javier; Zamora, M Pilar; Perez, Jose Ignacio Arias; Menéndez, Primitiva; Jakubowska, Anna; Lubinski, Jan; Gronwald, Jacek; Durda, Katarzyna; Hamann, Ute; Kabisch, Maria; Ulmer, Hans Ulrich; Rüdiger, Thomas; Margolin, Sara; Kristensen, Vessela; Nord, Siljie; Evans, D Gareth; Abraham, Jean; Earl, Helena; Poole, Christopher J; Hiller, Louise; Dunn, Janet A; Bowden, Sarah; Yang, Rose; Campa, Daniele; Diver, W Ryan; Gapstur, Susan M; Gaudet, Mia M; Hankinson, Susan; Hoover, Robert N; Hüsing, Anika; Kaaks, Rudolf; Machiela, Mitchell J; Willett, Walter; Barrdahl, Myrto; Canzian, Federico; Chin, Suet-Feung; Caldas, Carlos; Hunter, David J; Lindstrom, Sara; Garcia-Closas, Montserrat; Couch, Fergus J; Chenevix-Trench, Georgia; Mannermaa, Arto; Andrulis, Irene L; Hall, Per; Chang-Claude, Jenny; Easton, Douglas F; Bojesen, Stig E; Cox, Angela; Fasching, Peter A; Pharoah, Paul Dp; Schmidt, Marjanka K

2015-04-22

Previous studies have identified common germline variants nominally associated with breast cancer survival. These associations have not been widely replicated in further studies. The purpose of this study was to evaluate the association of previously reported SNPs with breast cancer-specific survival using data from a pooled analysis of eight breast cancer survival genome-wide association studies (GWAS) from the Breast Cancer Association Consortium. A literature review was conducted of all previously published associations between common germline variants and three survival outcomes: breast cancer-specific survival, overall survival and disease-free survival. All associations that reached the nominal significance level of P value <0.05 were included. Single nucleotide polymorphisms that had been previously reported as nominally associated with at least one survival outcome were evaluated in the pooled analysis of over 37,000 breast cancer cases for association with breast cancer-specific survival. Previous associations were evaluated using a one-sided test based on the reported direction of effect. Fifty-six variants from 45 previous publications were evaluated in the meta-analysis. Fifty-four of these were evaluated in the full set of 37,954 breast cancer cases with 2,900 events and the two additional variants were evaluated in a reduced sample size of 30,000 samples in order to ensure independence from the previously published studies. Five variants reached nominal significance (P <0.05) in the pooled GWAS data compared to 2.8 expected under the null hypothesis. Seven additional variants were associated (P <0.05) with ER-positive disease. Although no variants reached genome-wide significance (P <5 x 10(-8)), these results suggest that there is some evidence of association between candidate common germline variants and breast cancer prognosis. Larger studies from multinational collaborations are necessary to increase the power to detect associations, between

Esomeprazole use is independently associated with significant reduction of BMD: 1-year prospective comparative safety study of four proton pump inhibitors.

PubMed

Bahtiri, Elton; Islami, Hilmi; Hoxha, Rexhep; Qorraj-Bytyqi, Hasime; Rexhepi, Sylejman; Hoti, Kreshnik; Thaçi, Kujtim; Thaçi, Shpetim; Karakulak, Çağla

2016-09-01

Because of the efficacy of proton pump inhibitors (PPIs), their the use is increasing dramatically. The risk of adverse effects of short-term PPI therapy is low, but there are important safety concerns for potential adverse effects of prolonged PPI therapy. Findings from studies assessing the association between PPI use and bone mineral density (BMD) and/or fracture risk are contradictory. The aim of this study was to prospectively assess potential association of PPI treatment with the 12-month change in BMD of the lumbar spine, femur neck, and total hip. The study was performed in 200 PPI users and 50 PPI nonusers. Lumbar spine (L1-L4), femur neck, and total hip BMD were measured by dual-energy X-ray absorptiometry at the baseline and at 12 months. A total of 209 subjects completed the entire 12 months of the study and were included in the final analysis. A Wilcoxon signed-rank test showed that at 12 months PPI use was associated with statistically significant reductions in femur neck and total hip T scores (Z = -2.764, p = 0.005 and Z = -3.281, p = 0.001, respectively). A multiple linear regression analysis showed that only esomeprazole added significantly to the prediction of total lumbar spine and femur neck T scores (p = 0.048 and p = 0.037, respectively). Compared with the baseline, 12 months of PPI treatment resulted in lower femur neck and total hip BMD T scores. Among the four PPIs studied, esomeprazole was independently associated with significant reduction of BMD, whereas omeprazole had no effects on BMD. Considering the widespread use of PPIs, BMD screening should be considered in the case of prolonged PPI use.

Adult acute megakaryoblastic leukemia: rare association with cytopenias of undetermined significance and p210 and p190 BCR–ABL transcripts

PubMed Central

Trifa, Adrian; Selicean, Cristina; Moisoiu, Vlad; Frinc, Ioana; Zdrenghea, Mihnea; Tomuleasa, Ciprian

2017-01-01

Acute megakaryocytic leukemia (M7-AML) is a rare form of acute myeloid leukemia (AML), which is associated with poor prognosis. The case presented in the current report is a statement for the difficult diagnosis and clinical management of M7-AML in the context of a previous hematologic disorder of undetermined significance and associated genetic abnormalities. Probably, following the complete hematologic remission and further with induction chemotherapy plus tyrosine kinase inhibitor therapy, the clinical management of this case will be followed by a allogeneic bone marrow transplantation, the only proven therapy to improve overall survival. PMID:29089774

Significant Scales in Community Structure

NASA Astrophysics Data System (ADS)

Traag, V. A.; Krings, G.; van Dooren, P.

2013-10-01

Many complex networks show signs of modular structure, uncovered by community detection. Although many methods succeed in revealing various partitions, it remains difficult to detect at what scale some partition is significant. This problem shows foremost in multi-resolution methods. We here introduce an efficient method for scanning for resolutions in one such method. Additionally, we introduce the notion of ``significance'' of a partition, based on subgraph probabilities. Significance is independent of the exact method used, so could also be applied in other methods, and can be interpreted as the gain in encoding a graph by making use of a partition. Using significance, we can determine ``good'' resolution parameters, which we demonstrate on benchmark networks. Moreover, optimizing significance itself also shows excellent performance. We demonstrate our method on voting data from the European Parliament. Our analysis suggests the European Parliament has become increasingly ideologically divided and that nationality plays no role.

Acute progressive paraplegia in heroin-associated myelopathy.

PubMed

Mahoney, Kyle W; Romba, Meghan; Gailloud, Philippe; Izbudak, Izlem; Saylor, Deanna

2018-05-01

As the opioid epidemic continues, understanding manifestations of abuse, including heroin-associated myelopathy remains essential. Here we describe a young man with a past medical history significant for polysubstance abuse who developed acute-onset, rapidly progressive myelopathy after resumption of intravenous heroin use. He had significant spinal cord involvement with findings suggestive of heroin-associated myelopathy. The salient features of this case include diffusion imaging of the spine and spinal angiography supporting a possible vasculopathy as the pathophysiologic mechanism underlying heroin-associated myelopathy. Additionally, CSF studies showed the transition from a neutrophilic pleocytosis to a lymphocytic pleocytosis suggesting an inflammatory component. Copyright © 2018 Elsevier Ltd. All rights reserved.

Lack of significant associations with early career performance suggest no link between the DMRT3 "Gait Keeper" mutation and precocity in Coldblooded trotters.

PubMed

Jäderkvist Fegraeus, Kim; Lawrence, Chameli; Petäjistö, Katrine; Johansson, Maria K; Wiklund, Maja; Olsson, Christina; Andersson, Leif; Andersson, Lisa S; Røed, Knut H; Ihler, Carl-Fredrik; Strand, Eric; Lindgren, Gabriella; Velie, Brandon D

2017-01-01

The Swedish-Norwegian Coldblooded trotter (CBT) is a local breed in Sweden and Norway mainly used for harness racing. Previous studies have shown that a mutation from cytosine (C) to adenine (A) in the doublesex and mab-3 related transcription factor 3 (DMRT3) gene has a major impact on harness racing performance of different breeds. An association of the DMRT3 mutation with early career performance has also been suggested. The aim of the current study was to investigate this proposed association in a randomly selected group of CBTs. 769 CBTs (485 raced, 284 unraced) were genotyped for the DMRT3 mutation. The association with racing performance was investigated for 13 performance traits and three different age intervals: 3 years, 3 to 6 years, and 7 to 10 years of age, using the statistical software R. Each performance trait was analyzed for association with DMRT3 using linear models. The results suggest no association of the DMRT3 mutation with precocity (i.e. performance at 3 years of age). Only two traits (race time and number of disqualifications) were significantly different between the genotypes, with AA horses having the fastest times and CC horses having the highest number of disqualifications at 3 years of age. The frequency of the AA genotype was significantly lower in the raced CBT sample compared with the unraced sample and less than 50% of the AA horses participated in a race. For the age intervals 3 to 6 and 7 to 10 years the AA horses also failed to demonstrate significantly better performance than the other genotypes. Although suggested as the most favorable genotype for racing performance in Standardbreds and Finnhorses across all ages, the AA genotype does not appear to be associated with superior performance, early or late, in the racing career of CBTs.

Additional weekend therapy may reduce length of rehabilitation stay after stroke: a meta-analysis of individual patient data.

PubMed

English, Coralie; Shields, Nora; Brusco, Natasha K; Taylor, Nicholas F; Watts, Jennifer J; Peiris, Casey; Bernhardt, Julie; Crotty, Maria; Esterman, Adrian; Segal, Leonie; Hillier, Susan

2016-07-01

Among people receiving inpatient rehabilitation after stroke, does additional weekend physiotherapy and/or occupational therapy reduce the length of rehabilitation hospital stay compared to those who receive a weekday-only service, and does this change after controlling for individual factors? Does additional weekend therapy improve the ability to walk and perform activities of daily living, measured at discharge? Does additional weekend therapy improve health-related quality of life, measured 6 months after discharge from rehabilitation? Which individual, clinical and hospital characteristics are associated with shorter length of rehabilitation hospital stay? This study pooled individual data from two randomised, controlled trials (n=350) using an individual patient data meta-analysis and multivariate regression. People with stroke admitted to inpatient rehabilitation facilities. Additional weekend therapy (physiotherapy and/or occupational therapy) compared to usual care (5 days/week therapy). Length of rehabilitation hospital stay, independence in activities of daily living measured with the Functional Independence Measure, walking speed and health-related quality of life. Participants who received weekend therapy had a shorter length of rehabilitation hospital stay. In the un-adjusted analysis, this was not statistically significant (MD -5.7 days, 95% CI -13.0 to 1.5). Controlling for hospital site, age, walking speed and Functional Independence Measure score on admission, receiving weekend therapy was significantly associated with a shorter length of rehabilitation hospital stay (β=7.5, 95% CI 1.7 to 13.4, p=0.001). There were no significant between-group differences in Functional Independence Measure scores (MD 1.9 points, 95% CI -2.8 to 6.6), walking speed (MD 0.06 m/second, 95% CI -0.15 to 0.04) or health-related quality of life (SMD -0.04, 95% CI -0.26 to 0.19) at discharge. Modest evidence indicates that additional weekend therapy might reduce

MAMP (microbe-associated molecular pattern)-induced changes in plasma membrane-associated proteins.

PubMed

Uhlíková, Hana; Solanský, Martin; Hrdinová, Vendula; Šedo, Ondrej; Kašparovský, Tomáš; Hejátko, Jan; Lochman, Jan

2017-03-01

Plant plasma membrane associated proteins play significant roles in Microbe-Associated Molecular Pattern (MAMP) mediated defence responses including signal transduction, membrane transport or energetic metabolism. To elucidate the dynamics of proteins associated with plasma membrane in response to cryptogein, a well-known MAMP of defence reaction secreted by the oomycete Phytophthora cryptogea, 2D-Blue Native/SDS gel electrophoresis of plasma membrane fractions was employed. This approach revealed 21 up- or down-regulated protein spots of which 15 were successfully identified as proteins related to transport through plasma membrane, vesicle trafficking, and metabolic enzymes including cytosolic NADP-malic enzyme and glutamine synthetase. Observed changes in proteins were also confirmed on transcriptional level by qRT-PCR analysis. In addition, a significantly decreased accumulation of transcripts observed after employment of a mutant variant of cryptogein Leu41Phe, exhibiting a conspicuous defect in induction of resistance, sustains the contribution of identified proteins in cryptogein-triggered cellular responses. Our data provide further evidence for dynamic MAMP-induced changes in plasma membrane associated proteins. Copyright © 2016 Elsevier GmbH. All rights reserved.

Serious fighting-related injuries produce a significant reduction in intelligence.

PubMed

Schwartz, Joseph A; Beaver, Kevin M

2013-10-01

Fighting-related injuries are common among adolescents within the United States, but how such injuries relate to subsequent cognitive functioning remains unclear. In particular, the long-term effect of fighting-related injuries suffered during important developmental periods, such as adolescence, on subsequent cognitive functioning has been overlooked by previous studies. The purpose of this study is to examine the association between sustaining serious fighting-related injuries and changes in verbal intelligence (IQ) over a 5- to 6-year time period. Longitudinal multivariate statistical models were used to analyze data from the National Longitudinal Study of Adolescent Health collected between 1994 and 2002 and analyzed in 2013. Even a single fighting-related injury resulted in a significant reduction in IQ over time even after controlling for age, race, sex, and changes in socioeconomic status (SES) over the study period. Additionally, females experienced a significantly greater reduction in IQ from each fighting-related injury than males. Fighting-related injuries have a significant impact on subsequent cognitive functioning and intelligence. The implications for future policies and research are discussed in more detail. Copyright © 2013 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.

Dissociation between exact and approximate addition in developmental dyslexia.

PubMed

Yang, Xiujie; Meng, Xiangzhi

2016-09-01

Previous research has suggested that number sense and language are involved in number representation and calculation, in which number sense supports approximate arithmetic, and language permits exact enumeration and calculation. Meanwhile, individuals with dyslexia have a core deficit in phonological processing. Based on these findings, we thus hypothesized that children with dyslexia may exhibit exact calculation impairment while doing mental arithmetic. The reaction time and accuracy while doing exact and approximate addition with symbolic Arabic digits and non-symbolic visual arrays of dots were compared between typically developing children and children with dyslexia. Reaction time analyses did not reveal any differences across two groups of children, the accuracies, interestingly, revealed a distinction of approximation and exact addition across two groups of children. Specifically, two groups of children had no differences in approximation. Children with dyslexia, however, had significantly lower accuracy in exact addition in both symbolic and non-symbolic tasks than that of typically developing children. Moreover, linguistic performances were selectively associated with exact calculation across individuals. These results suggested that children with dyslexia have a mental arithmetic deficit specifically in the realm of exact calculation, while their approximation ability is relatively intact. Copyright © 2016 Elsevier Ltd. All rights reserved.

Antiwear Additive Mechanisms in Sliding Contacts

NASA Technical Reports Server (NTRS)

Baldwin, B. A.

1984-01-01

The possible mechanisms associated with wear in a sliding contact and how an oil and antiwear additive can mitigate wear or prevent catastropic seizure of the contacting parts was examined. The various load and temperature regimes are examined and the mechanisms which are predominant under these conditions are determined. The critical mechanism(s) depend on the test parameters, particularly load and temperature, although sliding speed is also a factor. Different ways to improve the efficiency of antiwear additives are suggested.

Mitochondrial DNA content in embryo culture medium is significantly associated with human embryo fragmentation.

PubMed

Stigliani, S; Anserini, P; Venturini, P L; Scaruffi, P

2013-10-01

Is the amount of cell-free DNA released by human embryos into culture medium correlated with embryo morphological features? The mitochondrial DNA (mtDNA) content of culture medium is significantly associated with the fragmentation rate on Days 2 and 3 of embryo development, whether the oocyte came from women ≤ 35 or >35 years old. Cellular fragmentation is often utilized as one of the morphological parameters for embryo quality assessment. The amount of cellular fragments is considered to be an important morphological parameter for embryo implantation potential. It has been hypothesized that fragments are apoptotic bodies or anuclear cytoplasmatic pieces of blastomeres, although no definitive conclusion has been drawn about their pathogenesis. Human fertilized oocytes were individually cultured from Day 1 to Days 2 and 3. A total of 800 samples (166 spent media from Day 2 and 634 from Day 3) were enrolled into the present study. Double-stranded DNA (dsDNA) was quantified in 800 spent embryo culture media by Pico Green dye fluorescence assay. After DNA purification, genomic DNA (gDNA) and mtDNA were profiled by specific quantitative PCR. Statistical analyses defined correlations among DNA contents, embryo morphology and maternal age. Different independent tests confirmed the presence of DNA into embryo culture medium and, for the first time, we demonstrate that both gDNA and mtDNA are detectable in the secretome. The amount of DNA is larger in embryos with bad quality cleavage compared with high-grade embryos, suggesting that the DNA profile of culture medium is an objective marker for embryo quality assessment. In particular, DNA profiles are significantly associated with fragmentation feature (total dsDNA: P = 0.0010; mtDNA; P = 0.0247) and advanced maternal age. It is necessary to establish whether DNA profiling of spent embryo culture medium is a robust onsite test that can improve the prediction of blastulation, implantation and/or pregnancy rate. The

PATTERNS OF CLINICALLY SIGNIFICANT COGNITIVE IMPAIRMENT IN HOARDING DISORDER.

PubMed

Mackin, R Scott; Vigil, Ofilio; Insel, Philip; Kivowitz, Alana; Kupferman, Eve; Hough, Christina M; Fekri, Shiva; Crothers, Ross; Bickford, David; Delucchi, Kevin L; Mathews, Carol A

2016-03-01

The cognitive characteristics of individuals with hoarding disorder (HD) are not well understood. Existing studies are relatively few and somewhat inconsistent but suggest that individuals with HD may have specific dysfunction in the cognitive domains of categorization, speed of information processing, and decision making. However, there have been no studies evaluating the degree to which cognitive dysfunction in these domains reflects clinically significant cognitive impairment (CI). Participants included 78 individuals who met DSM-V criteria for HD and 70 age- and education-matched controls. Cognitive performance on measures of memory, attention, information processing speed, abstract reasoning, visuospatial processing, decision making, and categorization ability was evaluated for each participant. Rates of clinical impairment for each measure were compared, as were age- and education-corrected raw scores for each cognitive test. HD participants showed greater incidence of CI on measures of visual memory, visual detection, and visual categorization relative to controls. Raw-score comparisons between groups showed similar results with HD participants showing lower raw-score performance on each of these measures. In addition, in raw-score comparisons HD participants also demonstrated relative strengths compared to control participants on measures of verbal and visual abstract reasoning. These results suggest that HD is associated with a pattern of clinically significant CI in some visually mediated neurocognitive processes including visual memory, visual detection, and visual categorization. Additionally, these results suggest HD individuals may also exhibit relative strengths, perhaps compensatory, in abstract reasoning in both verbal and visual domains. © 2015 Wiley Periodicals, Inc.

Antiinflammatory and ROS Suppressive Effects of the Addition of Fiber to a High-Fat High-Calorie Meal.

PubMed

Ghanim, Husam; Batra, Manav; Abuaysheh, Sanaa; Green, Kelly; Makdissi, Antoine; Kuhadiya, Nitesh D; Chaudhuri, Ajay; Dandona, Paresh

2017-03-01

Fiber intake is associated with a reduction in the occurrence of cardiovascular events and diabetes. To investigate whether the addition of fiber to a high-fat, high-calorie (HFHC) meal prevents proinflammatory changes induced by the HFHC meal. Ten normal fasting subjects consumed an HFHC meal with or without an additional 30 g of insoluble dietary fiber on 2 separate visits. Blood samples were collected over 5 hours, and mononuclear cells (MNCs) were isolated. Fiber addition to the HFHC meal significantly lowered glucose excursion in the first 90 minutes and increased insulin and C-peptide secretion throughout the 5-hour follow-up period compared with the meal alone. The HFHC meal induced increases in lipopolysaccharide (LPS) concentrations, MNC reactive oxygen species generation, and the expression of interleukin (IL)-1β, tumor necrosis factor α (TNF-α), Toll-like receptor (TLR)-4, and CD14. The addition of fiber prevented an increase in LPS and significantly reduced the increases in ROS generation and the expression of IL-1β, TNF-α, TLR-4, and CD14. In addition, the meal increased Suppressor of cytokine signaling (SOCS)-3 and protein tyrosine phosphatase 1B (PTP-1B) messenger RNA and protein levels, which were inhibited when fiber was added. The addition of fiber to a proinflammatory HFHC meal had beneficial anti-inflammatory and metabolic effects. Thus, the fiber content of the American Heart Association meal may contribute to its noninflammatory nature. If these actions of dietary fiber are sustained following long-term intake, they may contribute to fiber's known benefits in the prevention of insulin resistance, type 2 diabetes, and atherosclerosis. Copyright © 2017 by the Endocrine Society

Filaggrin gene polymorphism associated with Epstein-Barr virus-associated tumors in China.

PubMed

Yang, Yang; Liu, Wen; Zhao, Zhenzhen; Zhang, Yan; Xiao, Hua; Luo, Bing

2017-08-01

Mutations of filaggrin gene (FLG) have been identified as the cause of ichthyosis vulgaris, while recently FLG mutations were found to be associated with gastric cancer. This study aimed to investigate the association of filaggrin polymorphism with Epstein-Barr virus-associated tumors in China. A total of 200 patients with three types of tumors and 117 normal control samples were genotyped at three common FLG mutation loci (rs3126085, K4671X, R501X) by using Sequenom MassARRAY technique. The χ 2 test was used to evaluate the relationship between the mutation and the three kinds of tumors. A two-sided P value of <0.05 was considered statistically significant. The results showed that two single-nucleotide polymorphism (SNP) loci (rs3126085, K4671X) were significantly associated with nasopharyngeal carcinoma in genetic model. In addition, the two SNPs K4671X and rs3126085 were related to Epstein-Barr virus (EBV)-associated gastric carcinoma (EBVaGC) and EBV-negative gastric carcinoma (EBVnGC), respectively. Furthermore, allele distributions in EBVaGC and EBVnGC were verified to be different in both SNP loci.

Supplier Selection Using Weighted Utility Additive Method

NASA Astrophysics Data System (ADS)

Karande, Prasad; Chakraborty, Shankar

2015-10-01

Supplier selection is a multi-criteria decision-making (MCDM) problem which mainly involves evaluating a number of available suppliers according to a set of common criteria for choosing the best one to meet the organizational needs. For any manufacturing or service organization, selecting the right upstream suppliers is a key success factor that will significantly reduce purchasing cost, increase downstream customer satisfaction and improve competitive ability. The past researchers have attempted to solve the supplier selection problem employing different MCDM techniques which involve active participation of the decision makers in the decision-making process. This paper deals with the application of weighted utility additive (WUTA) method for solving supplier selection problems. The WUTA method, an extension of utility additive approach, is based on ordinal regression and consists of building a piece-wise linear additive decision model from a preference structure using linear programming (LP). It adopts preference disaggregation principle and addresses the decision-making activities through operational models which need implicit preferences in the form of a preorder of reference alternatives or a subset of these alternatives present in the process. The preferential preorder provided by the decision maker is used as a restriction of a LP problem, which has its own objective function, minimization of the sum of the errors associated with the ranking of each alternative. Based on a given reference ranking of alternatives, one or more additive utility functions are derived. Using these utility functions, the weighted utilities for individual criterion values are combined into an overall weighted utility for a given alternative. It is observed that WUTA method, having a sound mathematical background, can provide accurate ranking to the candidate suppliers and choose the best one to fulfill the organizational requirements. Two real time examples are illustrated to prove

Pharmacological and Chemical Effects of Cigarette Additives

PubMed Central

Rabinoff, Michael; Caskey, Nicholas; Rissling, Anthony; Park, Candice

2007-01-01

We investigated tobacco industry documents and other sources for evidence of possible pharmacological and chemical effects of tobacco additives. Our findings indicated that more than 100 of 599 documented cigarette additives have pharmacological actions that camouflage the odor of environmental tobacco smoke emitted from cigarettes, enhance or maintain nicotine delivery, could increase the addictiveness of cigarettes, and mask symptoms and illnesses associated with smoking behaviors. Whether such uses were specifically intended for these agents is unknown. Our results provide a clear rationale for regulatory control of tobacco additives. PMID:17666709

Gene copy number variation and its significance in cyanobacterial phylogeny

PubMed Central

2012-01-01

Background In eukaryotes, variation in gene copy numbers is often associated with deleterious effects, but may also have positive effects. For prokaryotes, studies on gene copy number variation are rare. Previous studies have suggested that high numbers of rRNA gene copies can be advantageous in environments with changing resource availability, but further association of gene copies and phenotypic traits are not documented. We used one of the morphologically most diverse prokaryotic phyla to test whether numbers of gene copies are associated with levels of cell differentiation. Results We implemented a search algorithm that identified 44 genes with highly conserved copies across 22 fully sequenced cyanobacterial taxa. For two very basal cyanobacterial species, Gloeobacter violaceus and a thermophilic Synechococcus species, distinct phylogenetic positions previously found were supported by identical protein coding gene copy numbers. Furthermore, we found that increased ribosomal gene copy numbers showed a strong correlation to cyanobacteria capable of terminal cell differentiation. Additionally, we detected extremely low variation of 16S rRNA sequence copies within the cyanobacteria. We compared our results for 16S rRNA to three other eubacterial phyla (Chroroflexi, Spirochaetes and Bacteroidetes). Based on Bayesian phylogenetic inference and the comparisons of genetic distances, we could confirm that cyanobacterial 16S rRNA paralogs and orthologs show significantly stronger conservation than found in other eubacterial phyla. Conclusions A higher number of ribosomal operons could potentially provide an advantage to terminally differentiated cyanobacteria. Furthermore, we suggest that 16S rRNA gene copies in cyanobacteria are homogenized by both concerted evolution and purifying selection. In addition, the small ribosomal subunit in cyanobacteria appears to evolve at extraordinary slow evolutionary rates, an observation that has been made previously for morphological

Exome-wide association analysis reveals novel coding sequence variants associated with lipid traits in Chinese.

PubMed

Tang, Clara S; Zhang, He; Cheung, Chloe Y Y; Xu, Ming; Ho, Jenny C Y; Zhou, Wei; Cherny, Stacey S; Zhang, Yan; Holmen, Oddgeir; Au, Ka-Wing; Yu, Haiyi; Xu, Lin; Jia, Jia; Porsch, Robert M; Sun, Lijie; Xu, Weixian; Zheng, Huiping; Wong, Lai-Yung; Mu, Yiming; Dou, Jingtao; Fong, Carol H Y; Wang, Shuyu; Hong, Xueyu; Dong, Liguang; Liao, Yanhua; Wang, Jiansong; Lam, Levina S M; Su, Xi; Yan, Hua; Yang, Min-Lee; Chen, Jin; Siu, Chung-Wah; Xie, Gaoqiang; Woo, Yu-Cho; Wu, Yangfeng; Tan, Kathryn C B; Hveem, Kristian; Cheung, Bernard M Y; Zöllner, Sebastian; Xu, Aimin; Eugene Chen, Y; Jiang, Chao Qiang; Zhang, Youyi; Lam, Tai-Hing; Ganesh, Santhi K; Huo, Yong; Sham, Pak C; Lam, Karen S L; Willer, Cristen J; Tse, Hung-Fat; Gao, Wei

2015-12-22

Blood lipids are important risk factors for coronary artery disease (CAD). Here we perform an exome-wide association study by genotyping 12,685 Chinese, using a custom Illumina HumanExome BeadChip, to identify additional loci influencing lipid levels. Single-variant association analysis on 65,671 single nucleotide polymorphisms reveals 19 loci associated with lipids at exome-wide significance (P<2.69 × 10(-7)), including three Asian-specific coding variants in known genes (CETP p.Asp459Gly, PCSK9 p.Arg93Cys and LDLR p.Arg257Trp). Furthermore, missense variants at two novel loci-PNPLA3 p.Ile148Met and PKD1L3 p.Thr429Ser-also influence levels of triglycerides and low-density lipoprotein cholesterol, respectively. Another novel gene, TEAD2, is found to be associated with high-density lipoprotein cholesterol through gene-based association analysis. Most of these newly identified coding variants show suggestive association (P<0.05) with CAD. These findings demonstrate that exome-wide genotyping on samples of non-European ancestry can identify additional population-specific possible causal variants, shedding light on novel lipid biology and CAD.

Clinical significance of dental root canal microflora.

PubMed

Gomes, B P; Lilley, J D; Drucker, D B

1996-01-01

Previous work by this group has shown that a significant association exists between pain and the presence of either Prevotella or Peptostreptococcus spp. in dental root canals. The aim of this study was to examine a more extensive series of canals microbiologically, to determine whether any other particular endodontic symptoms or clinical signs showed specific associations with individual bacterial species. Seventy root canals were examined microbiologically and clinical data collected to investigate in detail such associations. Of the canals studied, 37 were associated with pain, 49 with tenderness to percussion, 23 with swelling, six with purulent exudate and 57 presented with wet root canals. Anaerobes were isolated from 70.3% of painful canals and from 29.7% of pain-free canals. Significant associations were found between (a) pain and either Prevotella spp. or peptostreptococci, both with P < 0.01; (b) tenderness to percussion and Prevotella spp. (P < 0.01) or anaerobes (P < 0.05); (c) swelling and Eubacterium spp. (P < 0.01), or with Prevotella spp. or Pstr. micros, both with P < 0.05; (d) purulent exudate and any one of F. necrophorum (P < 0.01), Prev. loescheii, Streptoccoccus constellatus or Bacteroides spp. (each P < 0.05); (e) wet canal and facultative anaerobes (P < 0.01), and any one of the genera of Eubacterium, Peptostreptococcus, Prevotella or Propionibacterium (each P < 0.05). It was concluded that several different endodontic clinical signs and symptoms are significantly associated with specific bacterial species.

Is valve choice a significant determinant of paravalular leak post-transcatheter aortic valve implantation? A systematic review and meta-analysis.

PubMed

O'Sullivan, Katie E; Gough, Aideen; Segurado, Ricardo; Barry, Mitchel; Sugrue, Declan; Hurley, John

2014-05-01

Paravalvular regurgitation (PVR) following transcatheter aortic valve implantation (TAVI) is associated with poor survival. The two main valve delivery systems used to date differ significantly in both structure and deployment technique. The primary objective of this study was to perform a systematic review and meta-analysis of studies identifying PVR in patients post-TAVI using Medtronic CoreValve (MCV) and Edward Sapien (ES) valves in order to identify whether a significant difference exists between valve types. The secondary objective was to identify additional factors predisposing to PVR to provide an overview of the other associated considerations. A systematic review and meta-analysis of the current literature to identify PVR rate in patients with MCV and ES valves was performed. We also sought to examine other factors predisposing to PVR. A total of 5910 patients were identified from 9 studies. PVR rates for MCV and ES were analysed. MCV was associated with a higher PVR rate of 15.75% [95% confidence interval (CI) 12.48-19.32] compared with ES 3.93% [95% CI 1.05-8.38]. We separately reviewed predisposing factors associated with PVR. A formal comparison of the MCV and ES valve leakage rates by mixed-effects meta-regression with a fixed-effect moderator variable for valve type (MCV or ES) suggested a statistically significant difference in leakage rate between the two valve types (P = 0.0002). Unfavourable anatomical and pathological factors as well as valve choice have an impact on rates of PVR. Additionally, certain anatomical features dictate valve choice. A direct comparison of all the predisposing factors at this time is not possible and will require prospective multivariate analysis. There is, however, a significant difference in the PVR rates between valves based on the published observational data available to date. The ES valve associated with a lower incidence of PVR overall; therefore, we conclude that valve choice is indeed a significant

Transcatheter closure of hemodynamic significant patent ductus arteriosus in 32 premature infants by amplatzer ductal occluder additional size-ADOIIAS.

PubMed

Morville, Patrice; Akhavi, Ahmad

2017-10-01

The advent of Amplatzer Duct Occluder II additional Size (ADOIIAS) provided the potential to close hemodynamic significant patent ductus arteriosus (HSPDA) and to analyze the feasibility, safety and efficacy of the device. Treatment of a patent ductus arteriosus (PDA) in very premature neonates is still a dilemma for the neonatalogist who has to consider its significance and has to choose among different treatment options. Because surgical ligation and medical therapy both have their drawbacks, interventional catheterization might provide an alternative means of closing HSPDA. Between September 2013 and June 2015, 32 premature infants with complications related to HSPDA defined by ultrasound (US) underwent transcatheter closure. The procedure was performed in the catheterization laboratory by venous cannulation without angiography. The position of the occluder was directed by X-ray and US. In particular we looked at procedural details, device size selection, complications, and short and mid-term outcomes. Thirty two premature infants, all of whom had clinical complications related to HSPDA, born at gestational ages ranging between 23.6 and 36 weeks (mean ± standard deviation 28 ± 3 weeks) underwent attempted transcatheter PDA closure using the ADOIIAS. Their mean age and weight at the time of procedure was 25 days (range 8-70 days) and 1373 g (range 680-2480 g), respectively. Ten infants weighed ≤1,000g. All ducts were tubular. The mean PDA and device waist diameters were 3.2 ± 0.6mm (range 2.2-4) and 4.4 ± 0.6 mm, respectively, and the mean PDA and device lengths 5.2 ± 2.0 mm (range 2-10) and 3.4 ± 1.3 mm. Median fluoroscopy and procedural times were 11 min (range 3-24) and 28 min (range 10-90), respectively. Complete closure was achieved in all but one patient. There was no device migration. A left pulmonary artery (LPA) obstruction developed in one patient. Five infants died. Four deaths were related to complications of

Associations between lifestyle factors and hand eczema severity: are tobacco smoking, obesity and stress significantly linked to eczema severity?

PubMed

Sørensen, Jennifer A; Fisker, Maja H; Agner, Tove; Clemmensen, Kim K B; Ebbehøj, Niels E

2017-03-01

It has been suggested that lifestyle factors such as smoking, overweight and stress may influence the prevalence and severity of hand eczema. To investigate the association between lifestyle factors and hand eczema severity in a cohort of patients with work-related hand eczema. Individuals with work-related hand eczema notified in the period between June 2012 and November 2013 were included in this questionnaire-based cross-sectional study. Participants responded to a questionnaire including questions on lifestyle factors, as well as a photographic guide for assessment of severity of hand eczema and questions on quality of life. A total of 773 individuals (546 women and 227 men) responded to the questionnaire and were included in the study. A strong association was found between tobacco smoking and hand eczema severity (p = 0.003), whereas no significant association was found for body weight and stress. Other factors linked to severe eczema were male sex and older age (p = 0.04 and p = 0.01, respectively), and wet work (p = 0.08). The data from the present study strongly support an association between smoking and hand eczema severity. However, owing to the cross-sectional design of the study, no conclusion on causation can be drawn. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Eating Habits and Food Additive Intakes Are Associated with Emotional States Based on EEG and HRV in Healthy Korean Children and Adolescents.

PubMed

Kim, Jin Young; Kang, Hye Lim; Kim, Dae-Keun; Kang, Seung Wan; Park, Yoo Kyoung

2017-07-01

Recent study suggests that psychological issues and eating habits are closely related. In this study, we aimed to find the association between eating habits and intakes of artificial sweeteners with emotional states of schoolchildren using quantitatively analyzing objective biosignals. The study was conducted at the National Standard Reference Data Center for Korean EEG as a cross-sectional study. Three hundred eighteen healthy children who have not been diagnosed with neurologic or psychiatric disorders were evaluated (168 girls and 150 boys; mean age of 11.8 ± 3.6 years). Analysis indicators were a dietary intake checklist for children's nutrition-related behavior score (NBS), consisting of 19 items; food frequency questionnaires (FFQs), consisting of 76 items; the Child Depression Inventory (CDI); State-Trait Anxiety Inventory-State (STAI-S); State-Trait Anxiety Inventory-Trait (STAI-T); electroencephalograph (EEG); and heart rate variability (HRV). Higher scores on the CDI, STAI-S, and STAI-T indicate negative emotions, and these scores were significantly decreased from the first to the fourth quartiles. The HRV results showed that the standard deviation of all normal-to-normal (SDNN) intervals was significantly higher in the first quartile than in the fourth quartile (p < 0.05). The intakes of artificial sweeteners and processed foods such as hamburgers correlate with higher theta/beta ratios, and intakes of natural foods such as legumes and fruits correlate with lower theta/beta ratios (p < 0.05). From this result we confirmed a link between overall nutritional behavior, food additive intakes, and emotion in apparently healthy children and adolescents.

Assessment of Tools for Marker-Assisted Selection in a Marine Commercial Species: Significant Association between MSTN-1 Gene Polymorphism and Growth Traits

PubMed Central

Sánchez-Ramos, Irma; Cross, Ismael; Mácha, Jaroslav; Martínez-Rodríguez, Gonzalo; Krylov, Vladimir; Rebordinos, Laureana

2012-01-01

Growth is a priority trait from the point of view of genetic improvement. Molecular markers linked to quantitative trait loci (QTL) have been regarded as useful for marker-assisted selection in complex traits as growth. Polymorphisms have been studied in five candidate genes influencing growth in gilthead seabream (Sparus aurata): the growth hormone (GH), insulin-like growth factor-1 (IGF-1), myostatin (MSTN-1), prolactin (PRL), and somatolactin (SL) genes. Specimens evaluated were from a commercial broodstock comprising 131 breeders (from which 36 males and 44 females contributed to the progeny). In all samples eleven gene fragments, covering more than 13,000 bp, generated by PCR-RFLP, were analyzed; tests were made for significant associations between these markers and growth traits. ANOVA results showed a significant association between MSTN-1 gene polymorphism and growth traits. Pairwise tests revealed several RFLPs in the MSTN-1 gene with significant heterogeneity of genotypes among size groups. PRL and MSTN-1 genes presented linkage disequilibrium. The MSTN-1 gene was mapped in the centromeric region of a medium-size acrocentric chromosome pair. PMID:22666112

Significant rising antibody titres to influenza A are associated with an acute reduction in milk yield in cattle.

PubMed

Crawshaw, Timothy R; Brown, Ian H; Essen, Steve C; Young, Stuart C L

2008-10-01

Sporadic cases of an acute fall in milk production, "milk drop", were investigated in a Holstein Friesian dairy herd in Devon. The investigation was a case control study with two controls per case. Paired blood samples demonstrated that rising antibody titres to human influenza A/England/333/80 (H1N1) and human influenza A/Eng/427/88 (H3N2) were associated with an acute fall in milk production. Rising titres to bovine respiratory syncytial virus (BRSV), bovine virus diarrhoea virus (BVD), infectious bovine rhinotracheitis (IBR) and parainfluenza virus 3 (PI3) were not associated with an acute fall in milk production. Cases with rises in antibody to influenza A had significantly higher respiratory scores and rectal temperatures than their controls. The mean loss of milk production for the cases with rises in antibody to influenza A compared to their controls was 159.9L. This study provides further evidence that influenza A persists in cattle and causes clinical disease.

Selectivity in Genetic Association with Sub-classified Migraine in Women

PubMed Central

Chasman, Daniel I.; Anttila, Verneri; Buring, Julie E.; Ridker, Paul M.; Schürks, Markus; Kurth, Tobias

2014-01-01

Migraine can be sub-classified not only according to presence of migraine aura (MA) or absence of migraine aura (MO), but also by additional features accompanying migraine attacks, e.g. photophobia, phonophobia, nausea, etc. all of which are formally recognized by the International Classification of Headache Disorders. It remains unclear how aura status and the other migraine features may be related to underlying migraine pathophysiology. Recent genome-wide association studies (GWAS) have identified 12 independent loci at which single nucleotide polymorphisms (SNPs) are associated with migraine. Using a likelihood framework, we explored the selective association of these SNPs with migraine, sub-classified according to aura status and the other features in a large population-based cohort of women including 3,003 active migraineurs and 18,108 free of migraine. Five loci met stringent significance for association with migraine, among which four were selective for sub-classified migraine, including rs11172113 (LRP1) for MO. The number of loci associated with migraine increased to 11 at suggestive significance thresholds, including five additional selective associations for MO but none for MA. No two SNPs showed similar patterns of selective association with migraine characteristics. At one extreme, SNPs rs6790925 (near TGFBR2) and rs2274316 (MEF2D) were not associated with migraine overall, MA, or MO but were selective for migraine sub-classified by the presence of one or more of the additional migraine features. In contrast, SNP rs7577262 (TRPM8) was associated with migraine overall and showed little or no selectivity for any of the migraine characteristics. The results emphasize the multivalent nature of migraine pathophysiology and suggest that a complete understanding of the genetic influence on migraine may benefit from analyses that stratify migraine according to both aura status and the additional diagnostic features used for clinical characterization of

Submicroscopic and Asymptomatic Plasmodium Parasitaemia Associated with Significant Risk of Anaemia in Papua, Indonesia

PubMed Central

Handayuni, Irene; Trianty, Leily; Utami, Retno A. S.; Tirta, Yusrifar Kharisma; Kenangalem, Enny; Lampah, Daniel; Kusuma, Andreas; Wirjanata, Grennady; Kho, Steven; Simpson, Julie A.; Auburn, Sarah; Douglas, Nicholas M.; Noviyanti, Rintis; Anstey, Nicholas M.; Poespoprodjo, Jeanne R.; Marfurt, Jutta

2016-01-01

Submicroscopic Plasmodium infections are an important parasite reservoir, but their clinical relevance is poorly defined. A cross-sectional household survey was conducted in southern Papua, Indonesia, using cluster random sampling. Data were recorded using a standardized questionnaire. Blood samples were collected for haemoglobin measurement. Plasmodium parasitaemia was determined by blood film microscopy and PCR. Between April and July 2013, 800 households and 2,830 individuals were surveyed. Peripheral parasitaemia was detected in 37.7% (968/2,567) of individuals, 36.8% (357) of whom were identified by blood film examination. Overall the prevalence of P. falciparum parasitaemia was 15.4% (396/2567) and that of P. vivax 18.3% (471/2567). In parasitaemic individuals, submicroscopic infection was significantly more likely in adults (adjusted odds ratio (AOR): 3.82 [95%CI: 2.49–5.86], p<0.001) compared to children, females (AOR = 1.41 [1.07–1.86], p = 0.013), individuals not sleeping under a bednet (AOR = 1.4 [1.0–1.8], p = 0.035), and being afebrile (AOR = 3.2 [1.49–6.93], p = 0.003). The risk of anaemia (according to WHO guidelines) was 32.8% and significantly increased in those with asymptomatic parasitaemia (AOR 2.9 [95% 2.1–4.0], p = 0.007), and submicroscopic P. falciparum infections (AOR 2.5 [95% 1.7–3.6], p = 0.002). Asymptomatic and submicroscopic infections in this area co-endemic for P. falciparum and P. vivax constitute two thirds of detectable parasitaemia and are associated with a high risk of anaemia. Novel public health strategies are needed to detect and eliminate these parasite reservoirs, for the benefit both of the patient and the community. PMID:27788243

Clinical significance of anismus in encopresis.

PubMed

Catto-Smith, A G; Nolan, T M; Coffey, C M

1998-09-01

Treatments designed to relieve paradoxical contraction of the anal sphincters during defecation (anismus) have had limited success in children with encopresis. This has raised doubts as to the clinical relevance of this diagnosis in childhood as anorectal dysfunction. Our aim was to determine whether, in patients who had treatment-resistant encopresis, the presence of electromyographic anismus was associated with increased faecal retention. Sixty-eight children with soiling (mean age 8.7+/-2.06 years) were assessed by clinical examination, abdominal radiography and then with anorectal manometry. Patients with electromyographic anismus (n=32; 47%) had significantly increased radiographic rectal faecal retention and were significantly less likely to be able to defecate water-filled balloons. There were no significant differences in response to prior therapy, history of primary encopresis, behavioural adjustment or in sociodemographic data. Our results suggest that electromyographic anismus is associated with obstructed defecation and faecal retention.

Tibial Tray Thickness Significantly Increases Medial Tibial Bone Resorption in Cobalt-Chromium Total Knee Arthroplasty Implants.

PubMed

Martin, J Ryan; Watts, Chad D; Levy, Daniel L; Miner, Todd M; Springer, Bryan D; Kim, Raymond H

2017-01-01

Stress shielding is an uncommon complication associated with primary total knee arthroplasty. Patients are frequently identified radiographically with minimal clinical symptoms. Very few studies have evaluated risk factors for postoperative medial tibial bone loss. We hypothesized that thicker cobalt-chromium tibial trays are associated with increased bone loss. We performed a retrospective review of 100 posterior stabilized, fixed-bearing total knee arthroplasty where 50 patients had a 4-mm-thick tibial tray (thick tray cohort) and 50 patients had a 2.7-mm-thick tibial tray (thin tray cohort). A clinical evaluation and a radiographic assessment of medial tibial bone loss were performed on both cohorts at a minimum of 2 years postoperatively. Mean medial tibial bone loss was significantly higher in the thick tray cohort (1.07 vs 0.16 mm; P = .0001). In addition, there were significantly more patients with medial tibial bone loss in the thick tray group compared with the thin tray group (44% vs 10%, P = .0002). Despite these differences, there were no statistically significant differences in range of motion, knee society score, complications, or revision surgeries performed. A thicker cobalt-chromium tray was associated with significantly more medial tibial bone loss. Despite these radiographic findings, we found no discernable differences in clinical outcomes in our patient cohort. Further study and longer follow-up are needed to understand the effects and clinical significance of medial tibial bone loss. Copyright © 2016 Elsevier Inc. All rights reserved.

Leukoaraiosis Significantly Worsens Driving Performance of Ordinary Older Drivers

PubMed Central

Zheng, Rencheng; Fang, Fang; Ohori, Masanori; Nakamura, Hiroki; Kumagai, Yasuhiho; Okada, Hiroshi; Teramura, Kazuhiko; Nakayama, Satoshi; Irimajiri, Akinori; Taoka, Hiroshi; Okada, Satoshi

2014-01-01

Background Leukoaraiosis is defined as extracellular space caused mainly by atherosclerotic or demyelinated changes in the brain tissue and is commonly found in the brains of healthy older people. A significant association between leukoaraiosis and traffic crashes was reported in our previous study; however, the reason for this is still unclear. Method This paper presents a comprehensive evaluation of driving performance in ordinary older drivers with leukoaraiosis. First, the degree of leukoaraiosis was examined in 33 participants, who underwent an actual-vehicle driving examination on a standard driving course, and a driver skill rating was also collected while the driver carried out a paced auditory serial addition test, which is a calculating task given verbally. At the same time, a steering entropy method was used to estimate steering operation performance. Results The experimental results indicated that a normal older driver with leukoaraiosis was readily affected by external disturbances and made more operation errors and steered less smoothly than one without leukoaraiosis during driving; at the same time, their steering skill significantly deteriorated. Conclusions Leukoaraiosis worsens the driving performance of older drivers because of their increased vulnerability to distraction. PMID:25295736

Daily Administration of Short-Acting Liothyronine Is Associated with Significant Triiodothyronine Excursions and Fails to Alter Thyroid-Responsive Parameters.

PubMed

Jonklaas, Jacqueline; Burman, Kenneth D

2016-06-01

Although most studies of levothyroxine-liothyronine combination therapy employ once-daily hormone administration, the kinetics of once-daily liothyronine have been studied infrequently. The aim of this study was to document both the peak and trough serum triiodothyronine (T3) levels that occur with once-daily liothyronine administration, along with changes in thyroid-responsive parameters. Participants with hypothyroidism were studied prospectively at an academic institution. Patients were switched from levothyroxine monotherapy to liothyronine monotherapy with 15 μg liothyronine for two weeks, and then continued liothyronine at doses of 30-45 μg for a further four weeks in an open-label, single-arm study. Weekly trough levels of T3 were documented. In addition, hourly T3 concentrations immediately following liothyronine tablet administration were documented for eight hours during the sixth week of therapy. Serum thyrotropin (TSH) and free thyroxine (fT4) concentrations were documented. Biochemical markers, markers of energy metabolism, anthropometric parameters, well-being, and hyperthyroid symptoms were also assessed. Mean serum TSH levels increased from 1.56 ± 0.81 mIU/L at baseline to 5.90 ± 5.74 mIU/L at two weeks and 3.84 ± 3.66 mIU/L at six weeks. Trough T3 levels decreased from 99.5 ± 22.9 to 91.9 ± 40.2 at two weeks and recovered to 96.1 ± 32.2 at six weeks. The peak T3 concentration after dosing of liothyronine during week 6 was 292.8 ± 152.3 ng/dL. fT4 levels fell once levothyroxine was discontinued and plateaued at 0.44 ng/dL at week 4. The sex hormone binding globulin (SHBG) concentration decreased at week 2 (p = 0.002). Hyperthyroid symptoms and SF36-PCS scores increased significantly at weeks 4-5 of liothyronine therapy (p = 0.04-0.005). Preference for liothyronine therapy increased from 6% to 39% over the study period. Once-daily dosing of liothyronine at doses of 30-45 μg did not return serum

Significantly enhanced production of acarbose in fed-batch fermentation with the addition of S-adenosylmethionine.

PubMed

Sun, Li-Hui; Li, Ming-Gang; Wang, Yuan-Shan; Zheng, Yu-Guo

2012-06-01

Acarbose, a pseudo-oligosaccharide, is widely used clinically in therapies for non-insulin-dependent diabetes. In the present study, S-adenosylmethionine (SAM) was added to selected media in order to investigate its effect on acarbose fermentation by Actinoplanes utahensis ZJB- 08196. Acarbose titer was seen to increase markedly when concentrations of SAM were added over a period of time. The effects of glucose and maltose on the production of acarbose were investigated in both batch and fed-batch fermentation. Optimal acarbose production was observed at relatively low glucose levels and high maltose levels. Based on these results, a further fed-batch experiment was designed so as to enhance the production of acarbose. Fed-batch fermentation was carried out at an initial glucose level of 10 g/l and an initial maltose level of 60 g/l. Then, 12 h post inoculation, 100 micromol/l SAM was added. In addition, 8 g/l of glucose was added every 24 h, and 20 g/l of maltose was added at 96 h. By way of this novel feeding strategy, the maximum titer of acarbose achieved was 6,113 mg/l at 192 h. To our knowledge, the production level of acarbose achieved in this study is the highest ever reported.

The autonomic control and functional significance of the changes in heart rate associated with air breathing in the jeju, Hoplerythrinus unitaeniatus.

PubMed

McKenzie, D J; Campbell, H A; Taylor, E W; Micheli, M; Rantin, F T; Abe, A S

2007-12-01

The jeju is a teleost fish with bimodal respiration that utilizes a modified swim bladder as an air-breathing organ (ABO). Like all air-breathing fish studied to date, jeju exhibit pronounced changes in heart rate (fH) during air-breathing events, and it is believed that these may facilitate oxygen uptake (MO2) from the ABO. The current study employed power spectral analysis (PSA) of fH patterns, coupled with instantaneous respirometry, to investigate the autonomic control of these phenomena and their functional significance for the efficacy of air breathing. The jeju obtained less than 5% of total MO2 (MtO2) from air breathing in normoxia at 26 degrees C, and PSA of beat-to-beat variability in fH revealed a pattern similar to that of unimodal water-breathing fish. In deep aquatic hypoxia (water PO2)=1 kPa) the jeju increased the frequency of air breathing (fAB) tenfold and maintained MtO2 unchanged from normoxia. This was associated with a significant increase in heart rate variability (HRV), each air breath (AB) being preceded by a brief bradycardia and then followed by a brief tachycardia. These fH changes are qualitatively similar to those associated with breathing in unimodal air-breathing vertebrates. Within 20 heartbeats after the AB, however, a beat-to-beat variability in fH typical of water-breathing fish was re-established. Pharmacological blockade revealed that both adrenergic and cholinergic tone increased simultaneously prior to each AB, and then decreased after it. However, modulation of inhibitory cholinergic tone was responsible for the major proportion of HRV, including the precise beat-to-beat modulation of fH around each AB. Pharmacological blockade of all variations in fH associated with air breathing in deep hypoxia did not, however, have a significant effect upon fAB or the regulation of MtO2. Thus, the functional significance of the profound HRV during air breathing remains a mystery.

Lack of significant associations with early career performance suggest no link between the DMRT3 “Gait Keeper” mutation and precocity in Coldblooded trotters

PubMed Central

Lawrence, Chameli; Petäjistö, Katrine; Johansson, Maria K.; Wiklund, Maja; Olsson, Christina; Andersson, Leif; Andersson, Lisa S; Røed, Knut H.; Ihler, Carl-Fredrik; Strand, Eric

2017-01-01

The Swedish-Norwegian Coldblooded trotter (CBT) is a local breed in Sweden and Norway mainly used for harness racing. Previous studies have shown that a mutation from cytosine (C) to adenine (A) in the doublesex and mab-3 related transcription factor 3 (DMRT3) gene has a major impact on harness racing performance of different breeds. An association of the DMRT3 mutation with early career performance has also been suggested. The aim of the current study was to investigate this proposed association in a randomly selected group of CBTs. 769 CBTs (485 raced, 284 unraced) were genotyped for the DMRT3 mutation. The association with racing performance was investigated for 13 performance traits and three different age intervals: 3 years, 3 to 6 years, and 7 to 10 years of age, using the statistical software R. Each performance trait was analyzed for association with DMRT3 using linear models. The results suggest no association of the DMRT3 mutation with precocity (i.e. performance at 3 years of age). Only two traits (race time and number of disqualifications) were significantly different between the genotypes, with AA horses having the fastest times and CC horses having the highest number of disqualifications at 3 years of age. The frequency of the AA genotype was significantly lower in the raced CBT sample compared with the unraced sample and less than 50% of the AA horses participated in a race. For the age intervals 3 to 6 and 7 to 10 years the AA horses also failed to demonstrate significantly better performance than the other genotypes. Although suggested as the most favorable genotype for racing performance in Standardbreds and Finnhorses across all ages, the AA genotype does not appear to be associated with superior performance, early or late, in the racing career of CBTs. PMID:28489879

Sibling Competition & Growth Tradeoffs. Biological vs. Statistical Significance.

PubMed

Kramer, Karen L; Veile, Amanda; Otárola-Castillo, Erik

2016-01-01

Early childhood growth has many downstream effects on future health and reproduction and is an important measure of offspring quality. While a tradeoff between family size and child growth outcomes is theoretically predicted in high-fertility societies, empirical evidence is mixed. This is often attributed to phenotypic variation in parental condition. However, inconsistent study results may also arise because family size confounds the potentially differential effects that older and younger siblings can have on young children's growth. Additionally, inconsistent results might reflect that the biological significance associated with different growth trajectories is poorly understood. This paper addresses these concerns by tracking children's monthly gains in height and weight from weaning to age five in a high fertility Maya community. We predict that: 1) as an aggregate measure family size will not have a major impact on child growth during the post weaning period; 2) competition from young siblings will negatively impact child growth during the post weaning period; 3) however because of their economic value, older siblings will have a negligible effect on young children's growth. Accounting for parental condition, we use linear mixed models to evaluate the effects that family size, younger and older siblings have on children's growth. Congruent with our expectations, it is younger siblings who have the most detrimental effect on children's growth. While we find statistical evidence of a quantity/quality tradeoff effect, the biological significance of these results is negligible in early childhood. Our findings help to resolve why quantity/quality studies have had inconsistent results by showing that sibling competition varies with sibling age composition, not just family size, and that biological significance is distinct from statistical significance.

Basophil activation test with food additives in chronic urticaria patients.

PubMed

Kang, Min-Gyu; Song, Woo-Jung; Park, Han-Ki; Lim, Kyung-Hwan; Kim, Su-Jung; Lee, Suh-Young; Kim, Sae-Hoon; Cho, Sang-Heon; Min, Kyung-Up; Chang, Yoon-Seok

2014-01-01

The role of food additives in chronic urticaria (CU) is still under investigation. In this study, we aimed to explore the association between food additives and CU by using the basophil activation test (BAT). The BAT using 15 common food additives was performed for 15 patients with CU who had a history of recurrent urticarial aggravation following intake of various foods without a definite food-specific IgE. Of the 15 patients studied, two (13.3%) showed positive BAT results for one of the tested food additives. One patient responded to monosodium glutamate, showing 18.7% of CD203c-positive basophils. Another patient showed a positive BAT result to sodium benzoate. Both patients had clinical correlations with the agents, which were partly determined by elimination diets. The present study suggested that at least a small proportion of patients with CU had symptoms associated with food additives. The results may suggest the potential utility of the BAT to identity the role of food additives in CU.

No additive effect of cannabis on cognition in schizophrenia.

PubMed

Power, Brian D; Dragovic, Milan; Badcock, Johanna C; Morgan, Vera A; Castle, David; Jablensky, Assen; Stefanis, Nikos C

2015-10-01

We aimed to examine the association between lifetime cannabis use and estimates of both premorbid and current cognitive function in psychotic disorders in an Australian cohort. In an Australian multicenter cohort, 1237 participants with an established ICD-10 diagnosis of psychotic disorder were categorised according to history of lifetime cannabis use (non-users, n=354; cannabis users, n=221; cannabis dependency, n=662). Groups were analyzed according to available indices of cognitive ability: the National Adult Reading Test - Revised (NART-R) for ability prior to illness onset; and the Digit Symbol Coding Test (DSCT) for current ability. Two-way analysis of variance was conducted without any covariate, followed by a two-way analysis of covariance (using age, age at onset of psychiatric illness, premorbid IQ and the Socio-Economic Index for Areas (SEIFA) rankings). Whilst there appeared to be a significant association between cannabis use and mean DSCT (higher DSCT scores in cannabis using groups) F(2,1080)=9.478, p<0.001, η2=0.017), once covariates were used in the analysis there were no significant differences between groups in mean DSCT scores (F(2,1011)=0.929, p=0.395, η2=0.002). Similarly there were no differences between groups in mean NART scores once, age, age at illness onset and SEIFA rankings were used as covariates (F(2,1032)=1.617, p=0.199, η2=0.003). Confounding variables underpin the association between cannabis use and cognitive function in psychotic disorders. Taken together, it would appear that cannabis use or dependence has no additive effect on cognitive dysfunction in these disorders. Crown Copyright © 2015. Published by Elsevier B.V. All rights reserved.

Affective picture modulation: valence, arousal, attention allocation and motivational significance.

PubMed

Leite, Jorge; Carvalho, Sandra; Galdo-Alvarez, Santiago; Alves, Jorge; Sampaio, Adriana; Gonçalves, Oscar F

2012-03-01

The present study analyses the modulatory effects of affective pictures in the early posterior negativity (EPN), the late positive potential (LPP) and the human startle response on both the peripheral (eye blink EMG) and central neurophysiological levels (Probe P3), during passive affective pictures viewing. The affective pictures categories were balanced in terms of valence (pleasant; unpleasant) and arousal (high; low). The data shows that EPN may be sensitive to specific stimulus characteristics (affective relevant pictures versus neutral pictures) associated with early stages of attentional processing. In later stages, the heightened attentional resource allocation as well as the motivated significance of the affective stimuli was found to elicit enhanced amplitudes of slow wave processes thought to be related to enhanced encoding, namely LPP,. Although pleasant low arousing pictures were effective in engaging the resources involved in the slow wave processes, the highly arousing affective stimuli (pleasant and unpleasant) were found to produce the largest enhancement of the LPP, suggesting that high arousing stimuli may are associated with increased motivational significance. Additionally the response to high arousing stimuli may be suggestive of increased motivational attention, given the heightened attentional allocation, as expressed in the P3 probe, especially for the pleasant pictures. The hedonic valence may then serve as a mediator of the attentional inhibition to the affective priming, potentiating or inhibiting a shift towards defensive activation, as measured by the startle reflex. Copyright © 2011 Elsevier B.V. All rights reserved.

Composite Gypsum Binders with Silica-containing Additives

NASA Astrophysics Data System (ADS)

Chernysheva, N. V.; Lesovik, V. S.; Drebezgova, M. Yu; Shatalova, S. V.; Alaskhanov, A. H.

2018-03-01

New types of fine mineral additives are proposed for designing water-resistant Composite Gypsum Binders (CGB); these additives significantly differ from traditional quartz feed: wastes from wet magnetic separation of Banded Iron Formation (BIF WMS waste), nanodispersed silica powder (NSP), chalk. Possibility of their combined use has been studied as well.

Postural tachycardia syndrome is associated with significant symptoms and functional impairment predominantly affecting young women: a UK perspective

PubMed Central

McDonald, Claire; Koshi, Sharon; Busner, Lorna; Kavi, Lesley; Newton, Julia L

2014-01-01

Objective To examine a large UK cohort of patients with postural tachycardia syndrome (PoTS), to compare demographic characteristics, symptoms and treatment of PoTS at one centre compared to the largest patient group PoTS UK and to verify if their functional limitation is similar to patients with chronic fatigue syndrome (CFS). Design A cross-sectional study assessed the frequency of symptoms and their associated variables. Patients and setting Two PoTS cohorts were: (1) recruited via PoTS UK, (2) diagnosed at Newcastle Hospitals National Health Service (NHS) Foundation Trust 2009–2012. Patients with PoTS were then compared to a matched cohort with CFS. Main outcome measures Patients’ detailed demographics, time to diagnosis, education, disability, medications, comorbidity and precipitants. Symptom assessment tools captured, Fatigue Impact Scale, Epworth Sleepiness Scale, Orthostatic Grading Scale (OGS), Hospital Anxiety and Depression Scale, Health Assessment Questionnaire, Cognitive Failures Questionnaire. Results 136 patients with PoTS participated (84 members of PoTS UK (170 cohort; 50% return) and 52 (87 cohort; 60%) from Newcastle Clinics). The PoTS UK population was significantly younger than the clinic patients, with significantly fewer men (p=0.005). Over 60% had a university or postgraduate degree. Significantly more of the PoTS UK cohort were working, with hours worked being significantly higher (p=0.001). Time to diagnosis was significantly longer in the PoTS UK cohort (p=0.04). Symptom severity was comparable between cohorts. The PoTS total group was compared with a matched CFS cohort; despite comparable levels of fatigue and sleepiness, autonomic symptom burden (OGS) was statistically significantly higher. The most common treatment regime included β-blockers. Overall, 21 treatment combinations were described. Up to 1/3 were taking no treatment. Conclusions Patients with PoTS are predominantly women, young, well educated and have significant and

Non-additive Effects in Genomic Selection

PubMed Central

Varona, Luis; Legarra, Andres; Toro, Miguel A.; Vitezica, Zulma G.

2018-01-01

In the last decade, genomic selection has become a standard in the genetic evaluation of livestock populations. However, most procedures for the implementation of genomic selection only consider the additive effects associated with SNP (Single Nucleotide Polymorphism) markers used to calculate the prediction of the breeding values of candidates for selection. Nevertheless, the availability of estimates of non-additive effects is of interest because: (i) they contribute to an increase in the accuracy of the prediction of breeding values and the genetic response; (ii) they allow the definition of mate allocation procedures between candidates for selection; and (iii) they can be used to enhance non-additive genetic variation through the definition of appropriate crossbreeding or purebred breeding schemes. This study presents a review of methods for the incorporation of non-additive genetic effects into genomic selection procedures and their potential applications in the prediction of future performance, mate allocation, crossbreeding, and purebred selection. The work concludes with a brief outline of some ideas for future lines of that may help the standard inclusion of non-additive effects in genomic selection. PMID:29559995

Non-additive Effects in Genomic Selection.

PubMed

Varona, Luis; Legarra, Andres; Toro, Miguel A; Vitezica, Zulma G

2018-01-01

In the last decade, genomic selection has become a standard in the genetic evaluation of livestock populations. However, most procedures for the implementation of genomic selection only consider the additive effects associated with SNP (Single Nucleotide Polymorphism) markers used to calculate the prediction of the breeding values of candidates for selection. Nevertheless, the availability of estimates of non-additive effects is of interest because: (i) they contribute to an increase in the accuracy of the prediction of breeding values and the genetic response; (ii) they allow the definition of mate allocation procedures between candidates for selection; and (iii) they can be used to enhance non-additive genetic variation through the definition of appropriate crossbreeding or purebred breeding schemes. This study presents a review of methods for the incorporation of non-additive genetic effects into genomic selection procedures and their potential applications in the prediction of future performance, mate allocation, crossbreeding, and purebred selection. The work concludes with a brief outline of some ideas for future lines of that may help the standard inclusion of non-additive effects in genomic selection.

Improvements in floating point addition/subtraction operations

DOEpatents

Farmwald, P.M.

1984-02-24

Apparatus is described for decreasing the latency time associated with floating point addition and subtraction in a computer, using a novel bifurcated, pre-normalization/post-normalization approach that distinguishes between differences of floating point exponents.

Nanoparticle-Reinforced Associative Network Hydrogels

PubMed Central

Agrawal, Sarvesh K.; Sanabria-DeLong, Naomi; Tew, Gregory N.; Bhatia, Surita R.

2009-01-01

ABA triblock copolymers in solvents selective for the midblock are known to form associative micellar gels. We have modified the structure and rheology of ABA triblock copolymer gels comprising poly(lactide)-poly(ethylene oxide)-poly(lactide) (PLA-PEO-PLA) through addition of a clay nanoparticle, laponite. Addition of laponite particles resulted in additional junction points in the gel via adsorption of the PEO corona chains onto the clay surfaces. Rheological measurements showed that this strategy led to a significant enhancement of the gel elastic modulus with small amounts of nanoparticles. Further characterization using SAXS and DLS confirmed that nanoparticles increase the intermicellar attraction and result in aggregation of PLA-PEO-PLA micelles. PMID:18947244

Food additives and preschool children.

PubMed

Martyn, Danika M; McNulty, Breige A; Nugent, Anne P; Gibney, Michael J

2013-02-01

Food additives have been used throughout history to perform specific functions in foods. A comprehensive framework of legislation is in place within Europe to control the use of additives in the food supply and ensure they pose no risk to human health. Further to this, exposure assessments are regularly carried out to monitor population intakes and verify that intakes are not above acceptable levels (acceptable daily intakes). Young children may have a higher dietary exposure to chemicals than adults due to a combination of rapid growth rates and distinct food intake patterns. For this reason, exposure assessments are particularly important in this age group. The paper will review the use of additives and exposure assessment methods and examine factors that affect dietary exposure by young children. One of the most widely investigated unfavourable health effects associated with food additive intake in preschool-aged children are suggested adverse behavioural effects. Research that has examined this relationship has reported a variety of responses, with many noting an increase in hyperactivity as reported by parents but not when assessed using objective examiners. This review has examined the experimental approaches used in such studies and suggests that efforts are needed to standardise objective methods of measuring behaviour in preschool children. Further to this, a more holistic approach to examining food additive intakes by preschool children is advisable, where overall exposure is considered rather than focusing solely on behavioural effects and possibly examining intakes of food additives other than food colours.

Effects of biochar addition on toxic element concentrations in plants: A meta-analysis.

PubMed

Peng, Xin; Deng, Yinger; Peng, Yan; Yue, Kai

2018-03-01

Consuming food contaminated by toxic elements (TEs) could pose a substantial risk to human health. Recently, biochar has been extensively studied as an effective soil ameliorant in situ because of its ability to suppress the phytoavailability of TEs. However, despite the research interest, the effects of biochar applications to soil on different TE concentrations in different plant parts remain unclear. Here, we synthesize 1813 individual observations data collected from 97 articles to evaluate the effects of biochar addition on TE concentrations in plant parts. We found that (1) the experiment type, biochar feedstock and pyrolysis temperature all significantly decreased the TE concentration in plant parts; (2) the responses of Cd and Pb concentrations in edible and indirectly edible plant parts were significantly more sensitive to the effect of biochar than the Zn, Ni, Mn, Cr, Co and Cu concentrations; and (3) the biochar dosage and surface area, significantly influenced certain TE concentrations in plant tissues as determined via correlation analysis. Moreover, the only exception in this study was found for metalloid element (i.e., As) concentrations in plants, which were not significantly influenced by biochar addition. Overall, the effects of biochar on TE concentrations in plant tissues were negative, at least on average, and the central trends suggest that biochar has a considerable ability to mitigate the transfer of TEs to food, thereby reducing the associated health risks. Our results provide an initial quantitative determination of the effects of biochar addition on multifarious TEs in different plant parts as well as an assessment of the ability of biochar to reduce TE concentrations in plants. Copyright © 2017 Elsevier B.V. All rights reserved.

Contributions of Work-Related Stress and Emotional Intelligence to Teacher Engagement: Additive and Interactive Effects.

PubMed

Mérida-López, Sergio; Extremera, Natalio; Rey, Lourdes

2017-09-29

This study examined the additive and interactive effects of role stress and emotional intelligence for predicting engagement among 288 teachers. Emotional intelligence and engagement were positively associated. Role ambiguity and role conflict showed negative associations with vigor and dedication scores. The interaction of role ambiguity and emotional intelligence was significant in explaining engagement dimensions. Similar results were found considering overall teacher engagement. Emotional intelligence boosted engagement when the levels of role ambiguity were higher. Our findings suggest the need for future research examining the impact of job hindrances on the links between emotional intelligence and teachers' occupational well-being indicators. Finally, the implications for emotional intelligence training in education are discussed.

Lack of significant association between type 2 diabetes mellitus with longitudinal change in diurnal salivary cortisol: the multiethnic study of atherosclerosis.

PubMed

Spanakis, Elias K; Wang, Xu; Sánchez, Brisa N; Diez Roux, Ana V; Needham, Belinda L; Wand, Gary S; Seeman, Teresa; Golden, Sherita Hill

2016-07-01

Cross-sectional association has been shown between type 2 diabetes and hypothalamic-pituitary-adrenal (HPA) axis dysregulation; however, the temporality of this association is unknown. Our aim was to determine if type 2 diabetes is associated with longitudinal change in daily cortisol curve features. We hypothesized that the presence of type 2 diabetes may lead to a more blunted and abnormal HPA axis profile over time, suggestive of increased HPA axis dysregulation. This was a longitudinal cohort study, including 580 community-dwelling individuals (mean age 63.7 ± 9.1 years; 52.8 % women) with (n = 90) and without (n = 490) type 2 diabetes who attended two MultiEthnic Study of Atherosclerosis Stress ancillary study exams separated by 6 years. Outcome measures that were collected were wake-up and bedtime cortisol, cortisol awakening response (CAR), total area under the curve (AUC), and early, late, and overall decline slopes. In univariate analyses, wake-up and AUC increased over 6 years more in persons with as compared to those without type 2 diabetes (11 vs. 7 % increase for wake-up and 17 vs. 11 % for AUC). The early decline slope became flatter over time with a greater flattening observed in diabetic compared to non-diabetic individuals (23 vs. 9 % flatter); however, the change was only statistically significant for wake-up cortisol (p-value: 0.03). Over time, while CAR was reduced more, late decline and overall decline became flatter, and bedtime cortisol increased less in those with as compared to those without type 2 diabetes, none of these changes were statistically significant in adjusted models. We did not identify any statistically significant change in cortisol curve features over 6 years by type 2 diabetes status.

Lack of significant association between type 2 diabetes mellitus with longitudinal change in diurnal salivary cortisol: the multiethnic study of atherosclerosis

PubMed Central

Spanakis, Elias K.; Wang, Xu; Sánchez, Brisa N.; Diez Roux, Ana V.; Needham, Belinda L.; Wand, Gary S.; Seeman, Teresa; Golden, Sherita Hill

2016-01-01

Cross-sectional association has been shown between type 2 diabetes and hypothalamic–pituitary–adrenal (HPA) axis dysregulation; however, the temporality of this association is unknown. Our aim was to determine if type 2 diabetes is associated with longitudinal change in daily cortisol curve features. We hypothesized that the presence of type 2 diabetes may lead to a more blunted and abnormal HPA axis profile over time, suggestive of increased HPA axis dysregulation. This was a longitudinal cohort study, including 580 community-dwelling individuals (mean age 63.7 ± 9.1 years; 52.8 % women) with (n = 90) and without (n = 490) type 2 diabetes who attended two MultiEthnic Study of Atherosclerosis Stress ancillary study exams separated by 6 years. Outcome measures that were collected were wake-up and bedtime cortisol, cortisol awakening response (CAR), total area under the curve (AUC), and early, late, and overall decline slopes. In univariate analyses, wake-up and AUC increased over 6 years more in persons with as compared to those without type 2 diabetes (11 vs. 7 % increase for wake-up and 17 vs. 11 % for AUC). The early decline slope became flatter over time with a greater flattening observed in diabetic compared to non-diabetic individuals (23 vs. 9 % flatter); however, the change was only statistically significant for wake-up cortisol (p-value: 0.03). Over time, while CAR was reduced more, late decline and overall decline became flatter, and bedtime cortisol increased less in those with as compared to those without type 2 diabetes, none of these changes were statistically significant in adjusted models. We did not identify any statistically significant change in cortisol curve features over 6 years by type 2 diabetes status. PMID:26895003

A Study to Determine if Addition of Palatal Petechiae to Centor Criteria Adds More Significance to Clinical Diagnosis of Acute Strep Pharyngitis in Children.

PubMed

Nibhanipudi, Kumara V

2016-01-01

Objective. A study to determine if addition of palatal petechiae to Centor criteria adds more value for clinical diagnosis of acute strep pharyngitis in children. Hypothesis. In children, Centor Criteria does not cover all the symptoms and signs of acute strep pharyngitis. We hypothesize that addition of palatal petechiae to Centor Criteria will increase the possibility of clinical diagnosis of group A streptococcal pharyngitis in children. Methods. One hundred patients with a complaint of sore throat were enrolled in the study. All the patients were examined clinically using the Centor Criteria. They were also examined for other signs and symptoms like petechial lesions over the palate, abdominal pain, and skin rash. All the patients were given rapid strep tests, and throat cultures were sent. No antibiotics were given until culture results were obtained. Results. The sample size was 100 patients. All 100 had fever, sore throat, and erythema of tonsils. Twenty of the 100 patients had tonsillar exudates, 85/100 had tender anterior cervical lymph nodes, and 86/100 had no cough. In total, 9 out of the 100 patients had positive throat cultures. We observed that petechiae over the palate, a very significant sign, is not included in the Centor Criteria. Palatal petechiae were present in 8 out of the 100 patients. Six out of these 8 with palatal petechiae had positive throat culture for strep (75%). Only 7 out of 20 with exudates had positive strep culture. Sixteen out of the 100 patients had rapid strep test positive. Those 84/100 who had negative rapid strep also had negative throat culture. Statistics. We used Fisher's exact test, comparing throat culture positive and negative versus presence of exudates and palatal hemorrhages with positive and negative throat cultures and the resultant P value <.0001. Conclusion. Our study concludes that addition of petechiae over the palate to Centor Criteria will increase the possibility of diagnosing acute group A streptococcal

Increasing hepatitis B viral load is associated with risk of significant liver fibrosis in HBeAg-negative but not HBeAg-positive chronic hepatitis B.

PubMed

Croagh, Catherine M N; Bell, Sally J; Slavin, John; Kong, Yu X G; Chen, Robert Y; Locarnini, Stephen; Desmond, Paul V

2010-09-01

To evaluate the association between demographical features, serum ALT and HBV DNA and the prevalence of significant fibrosis and inflammation on liver biopsy in patients with chronic hepatitis B. In this cross-sectional study of patients on St Vincent's Hospital HBV database, patients were classified into three groups on the basis of HBeAg status and HBV DNA level and the prevalence of significant (F2/3/4) fibrosis and (A2/3) inflammation in each group was established. Patients were also divided into HBeAg-positive and -negative groups and examined for the prevalence of significant fibrosis/inflammation in the strata of HBV DNA and ALT. Predictors of significant fibrosis and inflammation in HBeAg-positive and -negative patients were examined by logistic regression. Three hundred and ninety four patients (HBeAg positive=198; HBeAg negative=196) with liver biopsy were identified. Fifty-eight percent of HBeAg-negative patients with HBV DNA >25,000 IU/ml had F2/3/4 fibrosis. HBV DNA and F2/3/4 were positively correlated in HBeAg-negative patients [odds ratio (OR) 1.42, P=0.001] but inversely correlated in HBeAg-positive patients (OR 0.71, P=0.03). HBV DNA was an independent predictor of significant fibrosis in HBeAg negative (P=0.03) but not HBeAg-positive patients. In HBeAg-positive patients, age was the only predictor of significant fibrosis (P=0.001) and ALT the only predictor of significant inflammation (P=0.003). In the whole cohort there was a close positive association between inflammation and fibrosis. Increasing levels of HBV DNA are associated with increasing prevalence of significant fibrosis only in patients with HBeAg-negative CHB.

Clinical significance of NGAL and KIM-1 for acute kidney injury in patients with scrub typhus.

PubMed

Sun, In O; Shin, Sung Hye; Cho, A Young; Yoon, Hyun Ju; Chang, Mi Yok; Lee, Kwang Young

2017-01-01

The aim of this study is to investigate the clinical significance of neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule-1 (KIM-1) for acute kidney injury (AKI) in patients with scrub typhus. From 2014 to 2015, 145 patients were diagnosed with scrub typhus. Of these, we enrolled 138 patients who were followed up until renal recovery or for at least 3 months. We measured serum and urine NGAL and KIM-1 levels and evaluated prognostic factors affecting scrub typhus-associated AKI. Of the 138 patients, 25 had scrub typhus-associated AKI. The incidence of AKI was 18.1%; of which 11.6%, 4.3%, and 2.2% were classified as risk, injury, and failure, respectively, according to RIFLE criteria. Compared with patients in the non-AKI group, patients in the AKI group were older and showed higher total leukocyte counts and hypoalbuminemia or one or more comorbidities such as hypertension (72% vs 33%, p<0.01), diabetes (40% vs 14%, p<0.01), or chronic kidney disease (32% vs 1%, p<0.01). In addition, serum NGAL values (404± 269 vs 116± 78 ng/mL, P<0.001), KIM-1 values (0.80± 0.52 vs 0.33± 0.68 ng/mL, P<0.001), urine NGAL/creatinine values (371± 672 vs 27± 39 ng/mg, P<0.001) and urine KIM-1/creatinine values (4.04± 2.43 vs 2.38± 1.89 ng/mg, P<0.001) were higher in the AKI group than in the non-AKI group. By multivariate logistic regression, serum NGAL and the presence of chronic kidney disease were significant predictors of AKI. Serum NGAL might be an additive predictor for scrub typhus-associated AKI.

Cleaning and Cleanliness Measurement of Additive Manufactured Parts

NASA Technical Reports Server (NTRS)

Mitchell, Mark A.; Edwards, Kevin; Fox, Eric; Boothe, Richard

2017-01-01

Additive Manufacturing processes allow for the manufacture of complex three dimensional components that otherwise could not be manufactured. Post treatment processes require the removal of any remnant bulk powder that may become entrapped within small cavities and channels within a component. This project focuses on several gross cleaning methods and the verification metrics associated with additive manufactured parts for oxygen propulsion usage.

Addition of omega-3 fatty acid and coenzyme Q10 to statin therapy in patients with combined dyslipidemia.

PubMed

Tóth, Štefan; Šajty, Matej; Pekárová, Tímea; Mughees, Adil; Štefanič, Peter; Katz, Matan; Spišáková, Katarína; Pella, Jozef; Pella, Daniel

2017-07-26

Statins represent a group of drugs that are currently indicated in the primary and secondary prevention of cardiovascular events. Their administration can be associated with side effects and the insufficient reduction of triacylglyceride (TAG) levels. This study aimed to assess the effect of the triple combination of statins with omega-3 fatty acids and coenzyme Q10 (CoQ10) on parameters associated with atherogenesis and statin side effects. In this pilot randomized double-blind trial, 105 subjects who met the criteria of combined dislipidemia and elevated TAG levels were randomly divided into three groups. In the control group, unaltered statin therapy was indicated. In the second and third groups, omega-3 PUFA 2.52 g/day (Zennix fa Pleuran) and omega-3 PUFA 2.52 g+CoQ10 200 mg/day (Pharma Nord ApS) were added, res//. At the end of the 3-month period (±1 week), all patients were evaluated. Significant reduction of hepatic enzymes activity, systolic blood preasure, inflammatory markers and TAG levels were detected in both groups in comparison to the control group. Activity of SOD and GPx increased significantly after additive therapy. Coenzyme Q10 addition significantly reduced most of the abovementioned parameters (systolic blood preasure, total cholesterol, LDL, hsCRP, IL-6, SOD) in comparison with the statin+omega-3 PUFA group. The intensity of statin adverse effects were significantly reduced in the group with the addition of CoQ10. The results of this pilot study suggest the possible beneficial effects of triple combination on the lipid and non-lipid parameters related to atherogenesis and side effects of statin treatment.

Additives

NASA Technical Reports Server (NTRS)

Smalheer, C. V.

1973-01-01

The chemistry of lubricant additives is discussed to show what the additives are chemically and what functions they perform in the lubrication of various kinds of equipment. Current theories regarding the mode of action of lubricant additives are presented. The additive groups discussed include the following: (1) detergents and dispersants, (2) corrosion inhibitors, (3) antioxidants, (4) viscosity index improvers, (5) pour point depressants, and (6) antifouling agents.

Genome-wide association study of Alzheimer's disease.

PubMed

Kamboh, M I; Demirci, F Y; Wang, X; Minster, R L; Carrasquillo, M M; Pankratz, V S; Younkin, S G; Saykin, A J; Jun, G; Baldwin, C; Logue, M W; Buros, J; Farrer, L; Pericak-Vance, M A; Haines, J L; Sweet, R A; Ganguli, M; Feingold, E; Dekosky, S T; Lopez, O L; Barmada, M M

2012-05-15

In addition to apolipoprotein E (APOE), recent large genome-wide association studies (GWASs) have identified nine other genes/loci (CR1, BIN1, CLU, PICALM, MS4A4/MS4A6E, CD2AP, CD33, EPHA1 and ABCA7) for late-onset Alzheimer's disease (LOAD). However, the genetic effect attributable to known loci is about 50%, indicating that additional risk genes for LOAD remain to be identified. In this study, we have used a new GWAS data set from the University of Pittsburgh (1291 cases and 938 controls) to examine in detail the recently implicated nine new regions with Alzheimer's disease (AD) risk, and also performed a meta-analysis utilizing the top 1% GWAS single-nucleotide polymorphisms (SNPs) with P<0.01 along with four independent data sets (2727 cases and 3336 controls) for these SNPs in an effort to identify new AD loci. The new GWAS data were generated on the Illumina Omni1-Quad chip and imputed at ~2.5 million markers. As expected, several markers in the APOE regions showed genome-wide significant associations in the Pittsburg sample. While we observed nominal significant associations (P<0.05) either within or adjacent to five genes (PICALM, BIN1, ABCA7, MS4A4/MS4A6E and EPHA1), significant signals were observed 69-180 kb outside of the remaining four genes (CD33, CLU, CD2AP and CR1). Meta-analysis on the top 1% SNPs revealed a suggestive novel association in the PPP1R3B gene (top SNP rs3848140 with P = 3.05E-07). The association of this SNP with AD risk was consistent in all five samples with a meta-analysis odds ratio of 2.43. This is a potential candidate gene for AD as this is expressed in the brain and is involved in lipid metabolism. These findings need to be confirmed in additional samples.

Genome-wide association study of Alzheimer's disease

PubMed Central

Kamboh, M I; Demirci, F Y; Wang, X; Minster, R L; Carrasquillo, M M; Pankratz, V S; Younkin, S G; Saykin, A J; Jun, G; Baldwin, C; Logue, M W; Buros, J; Farrer, L; Pericak-Vance, M A; Haines, J L; Sweet, R A; Ganguli, M; Feingold, E; DeKosky, S T; Lopez, O L; Barmada, M M

2012-01-01

In addition to apolipoprotein E (APOE), recent large genome-wide association studies (GWASs) have identified nine other genes/loci (CR1, BIN1, CLU, PICALM, MS4A4/MS4A6E, CD2AP, CD33, EPHA1 and ABCA7) for late-onset Alzheimer's disease (LOAD). However, the genetic effect attributable to known loci is about 50%, indicating that additional risk genes for LOAD remain to be identified. In this study, we have used a new GWAS data set from the University of Pittsburgh (1291 cases and 938 controls) to examine in detail the recently implicated nine new regions with Alzheimer's disease (AD) risk, and also performed a meta-analysis utilizing the top 1% GWAS single-nucleotide polymorphisms (SNPs) with P<0.01 along with four independent data sets (2727 cases and 3336 controls) for these SNPs in an effort to identify new AD loci. The new GWAS data were generated on the Illumina Omni1-Quad chip and imputed at ∼2.5 million markers. As expected, several markers in the APOE regions showed genome-wide significant associations in the Pittsburg sample. While we observed nominal significant associations (P<0.05) either within or adjacent to five genes (PICALM, BIN1, ABCA7, MS4A4/MS4A6E and EPHA1), significant signals were observed 69–180 kb outside of the remaining four genes (CD33, CLU, CD2AP and CR1). Meta-analysis on the top 1% SNPs revealed a suggestive novel association in the PPP1R3B gene (top SNP rs3848140 with P=3.05E–07). The association of this SNP with AD risk was consistent in all five samples with a meta-analysis odds ratio of 2.43. This is a potential candidate gene for AD as this is expressed in the brain and is involved in lipid metabolism. These findings need to be confirmed in additional samples. PMID:22832961

Prognostic Significance of Anti-Aminoacyl-tRNA Synthetase Antibodies in Polymyositis/Dermatomyositis-Associated Interstitial Lung Disease: A Retrospective Case Control Study

PubMed Central

Hozumi, Hironao; Enomoto, Noriyuki; Kono, Masato; Fujisawa, Tomoyuki; Inui, Naoki; Nakamura, Yutaro; Sumikawa, Hiromitsu; Johkoh, Takeshi; Nakashima, Ran; Imura, Yoshitaka; Mimori, Tsuneyo; Suda, Takafumi

2015-01-01

Background In polymyositis/dermatomyositis (PM/DM), anti-aminoacyl-tRNA synthetase (ARS) antibodies are closely associated with interstitial lung disease (ILD), a frequent pulmonary complication. However, the clinical significance of anti-ARS antibodies is not well established. Objective We aimed to evaluate the clinical significance of anti-ARS antibodies in PM/DM-ILD patients. Methods Forty-eight consecutive PM/DM-ILD patients were studied retrospectively. Anti-ARS antibodies were screened by ELISA and confirmed by RNA immunoprecipitation test. Medical records, high-resolution computed tomography images, and surgical lung biopsy specimens were compared between ARS-positive (ARS group) and ARS-negative patients (non-ARS group). Results Anti-ARS antibodies were detected in 23 of 48 patients (48%). Radiologically, nonspecific interstitial pneumonia (NSIP) pattern was observed more frequently in the ARS group than in the non-ARS group (73.9% vs. 40%, P = 0.02). Pathologically, NSIP was the most frequent in both groups. Ten-year survival rate was also significantly higher in the ARS group than in the non-ARS group (91.6% vs. 58.7%, P = 0.02). Univariate Cox hazards analysis revealed that the presence of anti-ARS antibodies was associated with better prognosis (HR = 0.34, 95% CI 0.08–0.80; P = 0.01). Conclusions The presence of anti-ARS antibodies is a possible prognostic marker in patients with PM/DM-ILD. PMID:25789468

Serum Vitamin D Is Significantly Inversely Associated with Disease Severity in Caucasian Adults with Obstructive Sleep Apnea Syndrome

PubMed Central

Kerley, Conor P.; Hutchinson, Katrina; Bolger, Kenneth; McGowan, Aisling; Faul, John; Cormican, Liam

2016-01-01

Study Objectives: To evaluate vitamin D (25(OH)D) levels in obstructive sleep apnea syndrome (OSAS) and possible relationships to OSAS severity, sleepiness, lung function, nocturnal heart rate (HR), and body composition. We also aimed to compare the 25(OH)D status of a subset of OSAS patients compared to controls matched for important determinants of both OSAS and vitamin D deficiency (VDD). Methods: This was a cross-sectional study conducted at an urban, clinical sleep medicine outpatient center. We recruited newly diagnosed, Caucasian adults who had recently undergone nocturnal polysomnography. We compared body mass index (BMI), body composition (bioelectrical impedance analysis), neck circumference, sleepiness (Epworth Sleepiness Scale), lung function, and vitamin D status (serum 25-hydrpoxyvitamin D (25(OH)D) across OSAS severity categories and non-OSAS subjects. Next, using a case-control design, we compared measures of serum 25(OH)D from OSAS cases to non-OSAS controls who were matched for age, gender, skin pigmentation, sleepiness, season, and BMI. Results: 106 adults (77 male; median age = 54.5; median BMI = 34.3 kg/m2) resident in Dublin, Ireland (latitude 53°N) were recruited and categorized as non-OSAS or mild/moderate/severe OSAS. 98% of OSAS cases had insufficient 25(OH)D (< 75 nmol/L), including 72% with VDD (< 50 nmol/L). 25(OH)D levels decreased with OSAS severity (P = 0.003). 25(OH)D was inversely correlated with BMI, percent body fat, AHI, and nocturnal HR. Subsequent multivariate regression analysis revealed that 25(OH)D was independently associated with both AHI (P = 0.016) and nocturnal HR (P = 0.0419). Our separate case-control study revealed that 25(OH)D was significantly lower in OSAS cases than matched, non-OSAS subjects (P = 0.001). Conclusions: We observed widespread vitamin D deficiency and insufficiency in a Caucasian, OSAS population. There were significant, independent, inverse relationships between 25(OH)D and AHI as well as

Chromosomal DNA damage measured using the cytokinesis-block micronucleus cytome assay is significantly associated with cognitive impairment in South Australians.

PubMed

Lee, Sau Lai; Thomas, Philip; Hecker, Jane; Faunt, Jeffrey; Fenech, Michael

2015-01-01

Loss of genome integrity may be associated with increased risk for neurodegenerative disease. The aim of this study was to investigate whether mild cognitive impairment (MCI) or Alzheimer's disease (AD) individuals have increased DNA damage relative to age- and gender- matched controls using the cytokinesis-block micronucleus cytome (CBMN-Cyt) assay. DNA damage was measured as micronuclei (MN), nucleoplasmic bridges (NPB), and nuclear buds (NBUD) in binucleated cells. The assay was performed on blood samples from 80 participants consisting of (i) MCI cases (N = 20) and age- and gender- matched controls (N = 20), and (ii) AD cases (N = 20) and age- and gender- matched controls (N = 20). There was a significant increase in MCI NBUD frequency (P = 0.006) relative to controls, which was also observed in male (P = 0.03) and female (P = 0.04) subgroups. For AD cases, there were no significant differences in assay biomarkers relative to controls. There was a significant negative correlation between Mini Mental State Examination (MMSE) and (i) MN in all controls, (R = -0.3, P = 0.04), and AD cases (R = -0.4, P = 0.03), (ii) NPB in all controls, (R = -0.4, P = 0.006) and AD cases (R = -0.5, P = 0.01), and (iii) NBUD in MCI cases (R = -0.5, P = 0.007) and AD cases (R = -0.7, P = 0.0002). The results suggest that an increase in lymphocyte CBMN-Cyt DNA damage biomarkers may be associated with cognitive decline. © 2014 Wiley Periodicals, Inc.

Prognostic and clinicopathological significance of CCAT2 in Chinese patients with various tumors.

PubMed

Tian, Guang-Wei; Li, Nan; Xin, Yan

2017-07-24

Colon cancer-associated transcript 2 (CCAT2) as a long noncoding RNA (lncRNA) is overexpressed and plays a significant prognostic role in patients with tumors. The present study aimed to comprehensively evaluate the clinical value of CCAT2 in the Chinese population, as a potential prognostic marker in multiple cancers. A systematic search of eligible studies was conducted in the PubMed, Web of Science, Cochrane Library, Wanfang and the China National Knowledge Infrastructure databases as of March 31, 2017. Approximately 1,711 tumor patients from 16 eligible studies were selected. Analyses of the pooled data were performed, and the odds ratio (OR) or hazard ratio (HR) and the 95% confidence interval (95% CI) were calculated and summarized to evaluate the strength of this association using a fixed- or random-effects model. Overall analyses showed that increased CCAT2 expression was associated with a higher risk of lymph node metastasis (LNM), an increased potential for distant metastasis (DM) and higher clinical stage (p<0.001 for LNM, p = 0.001 for DM, p<0.001 for clinical stage). HR and the 95% CI for overall survival (OS) were assessed to pool the effect size using a fixed-effects model. A significant association was observed between increased CCAT2 expression and poor OS (pooled HR = 1.91, 95% CI, 1.63-2.22, p<0.001). These results indicate that CCAT2 is a biomarker to predict tumor progression and a potential prognostic marker in multiple cancers. Additional well-designed clinical studies are needed to validate these findings.

The effect of rework content addition on the microstructure and viscoelastic properties of processed cheese.

PubMed

Černíková, Michaela; Nebesářová, Jana; Salek, Richardos Nikolaos; Popková, Romana; Buňka, František

2018-04-01

The aim of this work was to add various amounts of rework (0.0 to 20.0% wt/wt) to processed cheeses with a dry matter content of 36% (wt/wt) and fat with a dry matter content of 45% (wt/wt). The effect of the rework addition on the viscoelastic properties and microstructure of the processed cheeses was observed. The addition of rework (in this case, to processed cheese with a spreadable consistency) in the amounts of 2.5, 5.0, and 10.0% (wt/wt) increased the firmness of the processed cheese. With the further addition of rework, the consistency of the processed cheeses no longer differed significantly. The conclusions obtained by the measurement of viscoelastic properties were supported by cryo-scanning electron microscopy, where fat droplets in samples with added rework of over 10.0% (wt/wt) were smaller than fat droplets in processed cheeses with lower additions of rework. Copyright © 2018 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Oil-soluble hairy nanoparticles as lubricant additives

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

Zhao, Bin

Oil-soluble polymer brush-grafted nanoparticles (hairy NPs) were synthesized by surface-initiated atom transfer radical polymerization of lauryl methacrylate from initiator-functionalized silica nanoparticles and used as an additive for polyalphaolefin (PAO) for friction and wear reduction. Addition of 1 wt% hairy nanoparticles into PAO led to significant friction and wear reduction compared with PAO base oil.

Association analysis of bitter receptor genes in five isolated populations identifies a significant correlation between TAS2R43 variants and coffee liking.

PubMed

Pirastu, Nicola; Kooyman, Maarten; Traglia, Michela; Robino, Antonietta; Willems, Sara M; Pistis, Giorgio; d'Adamo, Pio; Amin, Najaf; d'Eustacchio, Angela; Navarini, Luciano; Sala, Cinzia; Karssen, Lennart C; van Duijn, Cornelia; Toniolo, Daniela; Gasparini, Paolo

2014-01-01

Coffee, one of the most popular beverages in the world, contains many different physiologically active compounds with a potential impact on people's health. Despite the recent attention given to the genetic basis of its consumption, very little has been done in understanding genes influencing coffee preference among different individuals. Given its markedly bitter taste, we decided to verify if bitter receptor genes (TAS2Rs) variants affect coffee liking. In this light, 4066 people from different parts of Europe and Central Asia filled in a field questionnaire on coffee liking. They have been consequently recruited and included in the study. Eighty-eight SNPs covering the 25 TAS2R genes were selected from the available imputed ones and used to run association analysis for coffee liking. A significant association was detected with three SNP: one synonymous and two functional variants (W35S and H212R) on the TAS2R43 gene. Both variants have been shown to greatly reduce in vitro protein activity. Surprisingly the wild type allele, which corresponds to the functional form of the protein, is associated to higher liking of coffee. Since the hTAS2R43 receptor is sensible to caffeine, we verified if the detected variants produced differences in caffeine bitter perception on a subsample of people coming from the FVG cohort. We found a significant association between differences in caffeine perception and the H212R variant but not with the W35S, which suggests that the effect of the TAS2R43 gene on coffee liking is mediated by caffeine and in particular by the H212R variant. No other significant association was found with other TAS2R genes. In conclusion, the present study opens new perspectives in the understanding of coffee liking. Further studies are needed to clarify the role of the TAS2R43 gene in coffee hedonics and to identify which other genes and pathways are involved in its genetics.

Association Analysis of Bitter Receptor Genes in Five Isolated Populations Identifies a Significant Correlation between TAS2R43 Variants and Coffee Liking

PubMed Central

Pirastu, Nicola; Kooyman, Maarten; Traglia, Michela; Robino, Antonietta; Willems, Sara M.; Pistis, Giorgio; d’Adamo, Pio; Amin, Najaf; d’Eustacchio, Angela; Navarini, Luciano; Sala, Cinzia; Karssen, Lennart C.; van Duijn, Cornelia; Toniolo, Daniela; Gasparini, Paolo

2014-01-01

Coffee, one of the most popular beverages in the world, contains many different physiologically active compounds with a potential impact on people’s health. Despite the recent attention given to the genetic basis of its consumption, very little has been done in understanding genes influencing coffee preference among different individuals. Given its markedly bitter taste, we decided to verify if bitter receptor genes (TAS2Rs) variants affect coffee liking. In this light, 4066 people from different parts of Europe and Central Asia filled in a field questionnaire on coffee liking. They have been consequently recruited and included in the study. Eighty-eight SNPs covering the 25 TAS2R genes were selected from the available imputed ones and used to run association analysis for coffee liking. A significant association was detected with three SNP: one synonymous and two functional variants (W35S and H212R) on the TAS2R43 gene. Both variants have been shown to greatly reduce in vitro protein activity. Surprisingly the wild type allele, which corresponds to the functional form of the protein, is associated to higher liking of coffee. Since the hTAS2R43 receptor is sensible to caffeine, we verified if the detected variants produced differences in caffeine bitter perception on a subsample of people coming from the FVG cohort. We found a significant association between differences in caffeine perception and the H212R variant but not with the W35S, which suggests that the effect of the TAS2R43 gene on coffee liking is mediated by caffeine and in particular by the H212R variant. No other significant association was found with other TAS2R genes. In conclusion, the present study opens new perspectives in the understanding of coffee liking. Further studies are needed to clarify the role of the TAS2R43 gene in coffee hedonics and to identify which other genes and pathways are involved in its genetics. PMID:24647340

Suicide and Additional Homicides Associated with Intimate Partner Homicide: North Carolina 2004-2013.

PubMed

Smucker, Sierra; Kerber, Rose E; Cook, Philip J

2018-06-01

Intimate partner homicide (IPH) is a critical public health and safety issue in the USA. In this study, we determine the prevalence and correlates of perpetrator suicide and additional homicides following intimate partner homicide (IPH) in a large, diverse state with high quality data. We extract IPHs from the North Carolina Violent Death Reporting System for 2004-2013 and identify suicides and other homicides that were part of the same incidents. We analyze the likelihood (in odds ration form) of perpetrator suicide and additional homicides using logistic regression analysis. Almost all IPH-suicide cases were by men with guns (86.6%). Almost one-half of IPHs committed by men with guns ended with suicide. Male-perpetrated IPH incidents averaged 1.58 deaths if a gun was used, and 1.14 deaths otherwise. It is well-known that gun access increases the chance that a violent domestic relationship will end in death. The current findings demonstrate that gun IPH is often coupled with additional killings. As suicidal batterers will not be deterred from IPH by threat of punishment, the results underline the importance of preemption by limiting batterers' access to guns.

Basophil Activation Test with Food Additives in Chronic Urticaria Patients

PubMed Central

Kang, Min-Gyu; Song, Woo-Jung; Park, Han-Ki; Lim, Kyung-Hwan; Kim, Su-Jung; Lee, Suh-Young; Kim, Sae-Hoon; Cho, Sang-Heon; Min, Kyung-Up

2014-01-01

The role of food additives in chronic urticaria (CU) is still under investigation. In this study, we aimed to explore the association between food additives and CU by using the basophil activation test (BAT). The BAT using 15 common food additives was performed for 15 patients with CU who had a history of recurrent urticarial aggravation following intake of various foods without a definite food-specific IgE. Of the 15 patients studied, two (13.3%) showed positive BAT results for one of the tested food additives. One patient responded to monosodium glutamate, showing 18.7% of CD203c-positive basophils. Another patient showed a positive BAT result to sodium benzoate. Both patients had clinical correlations with the agents, which were partly determined by elimination diets. The present study suggested that at least a small proportion of patients with CU had symptoms associated with food additives. The results may suggest the potential utility of the BAT to identity the role of food additives in CU. PMID:24527415

Diesel fuel detergent additive performance and assessment

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

Vincent, M.W.; Papachristos, M.J.; Williams, D.

Diesel fuel detergent additives are increasingly linked with high quality automotive diesel fuels. Both in Europe and in the USA, field problems associated with fuel injector coking or fouling have been experienced. In Europe indirect injection (IDI) light duty engines used in passenger cars were affected, while in the USA, a direct injection (DI) engine in heavy duty truck applications experienced field problems. In both cases, a fuel additive detergent performance test has evolved using an engine linked with the original field problem, although engine design modifications employed by the manufacturers have ensured improved operation in service. Increasing awareness ofmore » the potential for injector nozzle coking to cause deterioration in engine performance is coupled with a need to meet ever more stringent exhaust emissions legislation. These two requirements indicate that the use of detergency additives will continue to be associated with high quality diesel fuels. The paper examines detergency performance evaluated in a range of IDI and DI engines and correlates performance in the two most widely recognised test engines, namely the Peugeot 1.9 litre IDI, and Cummins L10 DI engines. 17 refs., 18 figs., 5 tabs.« less

Assessing Dependency using Self-report and Indirect Measures: Examining the Significance of Discrepancies

PubMed Central

Cogswell, Alex; Alloy, Lauren B.; Karpinski, Andrew; Grant, David

2011-01-01

The present study addressed convergence between self-report and indirect approaches to assessing dependency. The study was moderately successful in validating an implicit measure, which was found to be reliable, orthogonal to two self-report instruments, and predictive of external criteria. This study also examined discrepancies between scores on self-report and implicit measures, and has implications for their significance. The possibility that discrepancies themselves are pathological was not supported, although discrepancies were associated with particular personality profiles. Finally, this study offered additional evidence for the relation between dependency and depressive symptomatology, and identified implicit dependency as contributing unique variance in predicting past major depression. PMID:20552505

Assessing dependency using self-report and indirect measures: examining the significance of discrepancies.

PubMed

Cogswell, Alex; Alloy, Lauren B; Karpinski, Andrew; Grant, David A

2010-07-01

The present study addressed convergence between self-report and indirect approaches to assessing dependency. We were moderately successful in validating an implicit measure, which was found to be reliable, orthogonal to 2 self-report instruments, and predictive of external criteria. This study also examined discrepancies between scores on self-report and implicit measures, and has implications for their significance. The possibility that discrepancies themselves are pathological was not supported, although discrepancies were associated with particular personality profiles. Finally, this study offered additional evidence for the relation between dependency and depressive symptomatology and identified implicit dependency as contributing unique variance in predicting past major depression.

Sibling Competition & Growth Tradeoffs. Biological vs. Statistical Significance

PubMed Central

Kramer, Karen L.; Veile, Amanda; Otárola-Castillo, Erik

2016-01-01

Early childhood growth has many downstream effects on future health and reproduction and is an important measure of offspring quality. While a tradeoff between family size and child growth outcomes is theoretically predicted in high-fertility societies, empirical evidence is mixed. This is often attributed to phenotypic variation in parental condition. However, inconsistent study results may also arise because family size confounds the potentially differential effects that older and younger siblings can have on young children’s growth. Additionally, inconsistent results might reflect that the biological significance associated with different growth trajectories is poorly understood. This paper addresses these concerns by tracking children’s monthly gains in height and weight from weaning to age five in a high fertility Maya community. We predict that: 1) as an aggregate measure family size will not have a major impact on child growth during the post weaning period; 2) competition from young siblings will negatively impact child growth during the post weaning period; 3) however because of their economic value, older siblings will have a negligible effect on young children’s growth. Accounting for parental condition, we use linear mixed models to evaluate the effects that family size, younger and older siblings have on children’s growth. Congruent with our expectations, it is younger siblings who have the most detrimental effect on children’s growth. While we find statistical evidence of a quantity/quality tradeoff effect, the biological significance of these results is negligible in early childhood. Our findings help to resolve why quantity/quality studies have had inconsistent results by showing that sibling competition varies with sibling age composition, not just family size, and that biological significance is distinct from statistical significance. PMID:26938742

Genome-Wide Association Study of Intelligence: Additive Effects of Novel Brain Expressed Genes

ERIC Educational Resources Information Center

Loo, Sandra K.; Shtir, Corina; Doyle, Alysa E.; Mick, Eric; McGough, James J.; McCracken, James; Biederman, Joseph; Smalley, Susan L.; Cantor, Rita M.; Faraone, Stephen V.; Nelson, Stanley F.

2012-01-01

Objective: The purpose of the present study was to identify common genetic variants that are associated with human intelligence or general cognitive ability. Method: We performed a genome-wide association analysis with a dense set of 1 million single-nucleotide polymorphisms (SNPs) and quantitative intelligence scores within an ancestrally…

Daily Administration of Short-Acting Liothyronine Is Associated with Significant Triiodothyronine Excursions and Fails to Alter Thyroid-Responsive Parameters

PubMed Central

Burman, Kenneth D.

2016-01-01

Background: Although most studies of levothyroxine–liothyronine combination therapy employ once-daily hormone administration, the kinetics of once-daily liothyronine have been studied infrequently. The aim of this study was to document both the peak and trough serum triiodothyronine (T3) levels that occur with once-daily liothyronine administration, along with changes in thyroid-responsive parameters. Methods: Participants with hypothyroidism were studied prospectively at an academic institution. Patients were switched from levothyroxine monotherapy to liothyronine monotherapy with 15 μg liothyronine for two weeks, and then continued liothyronine at doses of 30–45 μg for a further four weeks in an open-label, single-arm study. Weekly trough levels of T3 were documented. In addition, hourly T3 concentrations immediately following liothyronine tablet administration were documented for eight hours during the sixth week of therapy. Serum thyrotropin (TSH) and free thyroxine (fT4) concentrations were documented. Biochemical markers, markers of energy metabolism, anthropometric parameters, well-being, and hyperthyroid symptoms were also assessed. Results: Mean serum TSH levels increased from 1.56 ± 0.81 mIU/L at baseline to 5.90 ± 5.74 mIU/L at two weeks and 3.84 ± 3.66 mIU/L at six weeks. Trough T3 levels decreased from 99.5 ± 22.9 to 91.9 ± 40.2 at two weeks and recovered to 96.1 ± 32.2 at six weeks. The peak T3 concentration after dosing of liothyronine during week 6 was 292.8 ± 152.3 ng/dL. fT4 levels fell once levothyroxine was discontinued and plateaued at 0.44 ng/dL at week 4. The sex hormone binding globulin (SHBG) concentration decreased at week 2 (p = 0.002). Hyperthyroid symptoms and SF36-PCS scores increased significantly at weeks 4–5 of liothyronine therapy (p = 0.04–0.005). Preference for liothyronine therapy increased from 6% to 39% over the study period. Conclusions: Once-daily dosing of

Significance of HER2 and C-MYC oncogene amplifications in breast cancer in atomic bomb survivors: associations with radiation exposure and histologic grade.

PubMed

Miura, Shiro; Nakashima, Masahiro; Ito, Masahiro; Kondo, Hisayoshi; Meirmanov, Serik; Hayashi, Tomayoshi; Soda, Midori; Matsuo, Takeshi; Sekine, Ichiro

2008-05-15

It has been postulated that radiation induces breast cancers in atomic bomb (A-bomb) survivors. Oncogene amplification is an important mechanism during breast carcinogenesis and also serves as an indicator of genomic instability (GIN). The objective of this study was to clarify the association of oncogene amplification in breast cancer in A-bomb survivors with radiation exposure. In total, 593 breast cancers were identified in A-bomb survivors from 1968 to 1999, and the association between breast cancer incidence and A-bomb radiation exposure was evaluated. Invasive ductal cancers from 67 survivors and 30 nonsurvivors were analyzed for amplification of the HER2 and C-MYC genes by fluorescence in situ hybridization, and expression levels of hormone receptors were analyzed by immunostaining. The incidence rate increased significantly as exposure distance decreased from the hypocenter (hazard ratio per 1-km decrement, 1.47; 95% confidence interval [95% CI], 1.30-1.66). The incidence of HER2 and C-MYC amplification was increased significantly in the order of the control group, the distal group (P = .0238), and the proximal group (P = .0128). Multivariate analyses revealed that distance was a risk factor for the coamplification of C-MYC and HER2 in breast cancer in survivors (odds ratio per 1-km increment, 0.17; 95% CI, 0.01-0.63). The histologic grade of breast cancers became significantly higher in the order of the control group, the distal group, and the proximal group and was associated with oncogene amplifications. The current results suggested that A-bomb radiation may affect the development of oncogene amplification by inducing GIN and may be associated with a higher histologic grade in breast cancer among A-bomb survivors. (c) 2008 American Cancer Society.

Expression of thymidylate synthase (TS) and its prognostic significance in patients with cutaneous angiosarcoma.

PubMed

Shimizu, A; Kaira, K; Okubo, Y; Utsumi, D; Bolag, A; Yasuda, M; Takahashi, K; Ishikawa, O

2017-01-01

Cutaneous angiosarcoma (CA) is extremely rare, and little is known about the biological significance of possible biomarkers for chemotherapeutic agents. Thymidylate synthase (TS) is an attractive target for cancer treatment in various human neoplasms. It remains unclear whether the expression of TS is associated with the clinicopathological features of CA patients. The aim of this study was to elucidate the relationship between TS expression and the clinicopathological significance in CA patients. Fifty-one patients with CA were included in this study. TS expression and Ki-67 labeling index were examined using immunohistochemical analysis. TS was positively expressed in 39% (20/51) of CA patients. No statistically significant prognostic factor was identified as a predictor of overall survival (OS) for all patients by univariate analysis, whereas a significant prognostic variable for progression free survival (PFS) was found to be the clinical stage. In addition, both univariate and multivariate analyses confirmed that positive expression of TS was a significant predictor of worse PFS in CA patients of clinical stage 1. Positive TS expression in CA was identified as a significant predictor of worse outcome in patients of clinical stage 1.

Additive Effects of Cointoxicants in Single-Opioid Induced Deaths

PubMed Central

Sorg, Marcella H.; Long, D. Leann; Abate, Marie A.; Kaplan, James A.; Kraner, James C.; Greenwald, Margaret S.; Andrew, Thomas A.; Shapiro, Steven L.; Wren, Jamie A.

2017-01-01

A forensic drug database (FDD) was used to capture comprehensive data from all drug-related deaths in West Virginia, with deaths also included from the northern New England states of Maine, Vermont, and New Hampshire. All four states serve predominantly rural populations under two million and all have similar state medical examiner systems that employ statewide uniform death certification policies and practices. This study focused on 1482 single opioid deaths (fentanyl, hydrocodone, methadone, and oxycodone) in the FDD from 2007–2011. We modeled relationships between the opioid concentrations and the presence or absence of the following commonly occurring non-opioid cointoxicants: benzodiazepines (alprazolam and diazepam), alcohol, tricyclic antidepressants, selective serotonin reuptake inhibitors, and diphenhydramine. Additional covariates of state, age, body mass index, and sex were included. Results showed that the presence of alcohol, benzodiazepines, and antidepressants were each associated with statistically significant lower concentrations of some but not all of the opioids studied, which may obscure the interpretation of postmortem toxicology results alone. Fentanyl concentrations appeared to be the least associated with the presence or absence of the variables studied, and cointoxicant alcohol appeared to be associated with lower concentrations in opioid concentrations than were most of the other factors in the model studied. These findings underscore the importance of documenting all potential cointoxicants in opioid-related deaths. PMID:29399239

Additive Biotech-Chances, challenges, and recent applications of additive manufacturing technologies in biotechnology.

PubMed

Krujatz, Felix; Lode, Anja; Seidel, Julia; Bley, Thomas; Gelinsky, Michael; Steingroewer, Juliane

2017-10-25

The diversity and complexity of biotechnological applications are constantly increasing, with ever expanding ranges of production hosts, cultivation conditions and measurement tasks. Consequently, many analytical and cultivation systems for biotechnology and bioprocess engineering, such as microfluidic devices or bioreactors, are tailor-made to precisely satisfy the requirements of specific measurements or cultivation tasks. Additive manufacturing (AM) technologies offer the possibility of fabricating tailor-made 3D laboratory equipment directly from CAD designs with previously inaccessible levels of freedom in terms of structural complexity. This review discusses the historical background of these technologies, their most promising current implementations and the associated workflows, fabrication processes and material specifications, together with some of the major challenges associated with using AM in biotechnology/bioprocess engineering. To illustrate the great potential of AM, selected examples in microfluidic devices, 3D-bioprinting/biofabrication and bioprocess engineering are highlighted. Copyright © 2017 Elsevier B.V. All rights reserved.

Revealing Significant Relations between Chemical/Biological Features and Activity: Associative Classification Mining for Drug Discovery

ERIC Educational Resources Information Center

Yu, Pulan

2012-01-01

Classification, clustering and association mining are major tasks of data mining and have been widely used for knowledge discovery. Associative classification mining, the combination of both association rule mining and classification, has emerged as an indispensable way to support decision making and scientific research. In particular, it offers a…

Significant association between IL10-1082/-819 and TNF-308 haplotypes and the susceptibility to cervical carcinogenesis in women infected by Human papillomavirus.

PubMed

Chagas, Bárbara Simas; Lima, Rita de Cássia Pereira de; Paiva Júnior, Sérgio de Sá Leitão; Silva, Ruany Cristyne de Oliveira; Cordeiro, Marcelo Nazário; Silva Neto, Jacinto da Costa; Batista, Marcus Vinicius de Aragão; Silva, Anna Jéssica Duarte; Gurgel, Ana Pavla Almeida Diniz; Freitas, Antonio Carlos de

2018-06-20

Human papillomavirus (HPV) is responsible for high-grade cervical lesions and cervical cancer. The inflammation plays a key role in cervical cancer progression. In this context, studies propose an association between TNFα and IL10 SNPs and susceptibility to HPV infection. The present work aimed to investigate the possible association between IL10 and TNFα promoter polymorphisms and HPV infection in the cervical carcinogenesis risk in women from Brazil. A total of 654 samples was evaluated in this study. HPV detection was performed by PCR and HPV genotyping was performed by PCR and sequencing of positive MY09/11 PCR product. Genotyping of IL10 SNPs (rs1800871 and rs1800896) was performed by High Resolution Melt analysis. Genotyping of TNFα SNP (rs1800629) was performed by fluorogenic allele-specific probes. The distribution of TNF-308 (rs1800629) allelic (p = 0.03) and genotype (p = 0.03) frequencies and HPV-58 infection has showed a statistically significant difference between case and control groups for the assessed TNFα polymorphism. When it comes to TNFα (rs1800629) allelic and genotypic distribution and HPVs 18 and 31 infections, no statistically significant differences between case and control groups were observed for the studied TNFα polymorphism. The allelic and genotypic distribution of IL10-819 (rs1800871) and IL10-1082 (rs1800896) and HPV infection (HPVs 58, 18 and 31) has showed no statistically significant differences between case and control groups for the assessed IL10 polymorphisms. Furthermore, it was observed that haplotypes were associated with an increased cervical cancer risk in HPVs 16, 18 and 58-positive women. It was observed that women carrying the GTA and ATG haplotypes had 3.85 and 17.99-fold, respectively, increased cervical cancer susceptibility when infected by HPV-58. In women infected with HPV-16 and HPV-18, statistically significant results in women carrying the GTA and ATA haplotypes was observed. They had a 2.32 and 3

Do reading additions improve reading in pre-presbyopes with low vision?

PubMed

Alabdulkader, Balsam; Leat, Susan

2012-09-01

This study compared three different methods of determining a reading addition and the possible improvement on reading performance in children and young adults with low vision. Twenty-eight participants with low vision, aged 8 to 32 years, took part in the study. Reading additions were determined with (a) a modified Nott dynamic retinoscopy, (b) a subjective method, and (c) an age-based formula. Reading performance was assessed with MNREAD-style reading charts at 12.5 cm, with and without each reading addition in random order. Outcome measures were reading speed, critical print size, MNREAD threshold, and the area under the reading speed curve. For the whole group, there was no significant improvement in reading performance with any of the additions. When participants with normal accommodation at 12.5 cm were excluded, the area under the reading speed curve was significantly greater with all reading additions compared with no addition (p = 0.031, 0.028, and 0.028, respectively). Also, the reading acuity threshold was significantly better with all reading additions compared with no addition (p = 0.014, 0.030, and 0.036, respectively). Distance and near visual acuity, age, and contrast sensitivity did not predict improvement with a reading addition. All, but one, of the participants who showed a significant improvement in reading with an addition had reduced accommodation. A reading addition may improve reading performance for young people with low vision and should be considered as part of a low vision assessment, particularly when accommodation is reduced.

PERSONAL AND ENVIRONMENTAL RISK FACTORS SIGNIFICANTLY ASSOCIATED WITH ELEVATED BLOOD LEAD LEVELS IN RURAL THAI CHILDREN.

PubMed

Swaddiwudhipong, Witaya; Kavinum, Suporn; Papwijitsil, Ratchadaporn; Tontiwattanasap, Worawit; Khunyotying, Wanlee; Umpan, Jiraporn; BoonthuM, Ratchaneekorn; Kaewnate, Yingyot; Boonmee, Sasis; Thongchub, Winai; Rodsung, Thassanee

2014-11-01

A community-based study was conducted to determine personal risk factors and environmental sources of lead exposure for elevated blood lead levels (≥ 10 µg/dl, EBLLs) among rural children living at the Thailand-Myanmar border in Tak Province, northwestern Thailand. Six hundred ninety-five children aged 1-14 years old were screened for BLLs. Environmental specimens for lead measurements included samples of water from the streams, taps, and household containers, house floor dust, and foods. Possible lead release from the cooking ware was determined using the leaching method with acetic acid. The overall prevalence of EBLLs was 47.1% and the geometric mean level of blood lead was 9.16 µg/dl. Personal risk factors significantly associated with EBLLs included being male, younger age, anemia, and low weight-for-age. Significant environmental risk factors were exposure to a lead-acid battery of solar energy system and use of a non-certified metal cooking pot. Some families whose children had high BLLs reported production of lead bullets from the used batteries at home. About one-third of the house dust samples taken near batteries contained lead content above the recommended value, compared with none of those taken from other areas and from the houses with no batteries. The metal pots were safe for cooking rice but might be unsafe for acidic food preparation. Both nutritional intervention and lead exposure prevention programs are essential to reduce EBLLs in this population.

FoxP2 is significantly associated with schizophrenia and major depression in the Chinese Han population.

PubMed

Li, Tao; Zeng, Zhen; Zhao, Qian; Wang, Ti; Huang, Ke; Li, Junyan; Li, You; Liu, Jie; Wei, Zhiyun; Wang, Yang; Feng, Guoyin; He, Lin; Shi, Yongyong

2013-03-01

The FoxP2 gene, located on 7q31, encodes a transcription factor. It was first discovered through investigations of a large multigenerational family (the KE family) with a rare severe speech and language disorder (Fisher et al., Nat. Genet. 1998;18:168; Lai et al., Nature 2001;413:519). Subsequent studies gave powerful and convincing functional evidence to the connection between FoxP2 and language disorder ( Vernes et al. 2006 ; Groszer et al., Curr Biol 2008;18:354; Vernes et al., New Engl J Med 359(22):2337). Language disorder is commonly considered as a core symptom of schizophrenia and some other mental diseases; thus, we decided to investigate whether the FoxP2 gene played a significant role in schizophrenia, major depression or bipolar disorder in a sample set recruited from the Chinese Han population. In this study, we focused on 12 SNPs in the FoxP2 gene and carried out case-control studies in 1135 schizophrenia patients, 1135 unrelated major depression patients, 1135 unrelated bipolar disorder patients and 1135 unrelated normal controls recruited from the Chinese Han population. We found rs10447760 was significantly associated with schizophrenia (allelic P = 0.00069) and major depression (allelic P = 0.0011). Our study indicated that the rare variant rs10447760 in FoxP2 may play an important role in schizophrenia and major depression in the Chinese Han population.

Prevalence and Clinical Significance of Night Eating Syndrome in University Students

PubMed Central

Runfola, Cristin D.; Allison, Kelly C.; Hardy, Kristina K.; Lock, James; Peebles, Rebecka

2014-01-01

Purpose Most studies of night eating syndrome (NES) fail to control for binge eating, despite moderate overlap between the two conditions. Establishing the independent clinical significance of NES is imperative for it to be considered worthy of clinical attention. We compared students with and without NES on eating disorder symptomatology, quality of life, and mental health, while exploring the role of binge eating in associations. Methods Students (N=1636) ages 18 to 26 (M=20.9) recruited from ten U.S. universities completed an online survey including the Night Eating Questionnaire (NEQ), Eating Disorder Examination-Questionnaire (EDE-Q), Project Eating Among Teens, and the Health-Related Quality of Life-4. NES was diagnosed according to endorsement of proposed diagnostic criteria on the NEQ. Groups (NES vs. non-NES) were compared on all dependent variables and stratified by binge eating status in secondary analyses. Results The prevalence of NES in our sample was 4.2%; it was 2.9% after excluding those with binge eating. Body mass index did not differ between groups, but students with NES were significantly more likely to have histories of underweight and anorexia nervosa. In students with NES, EDE-Q scores were significantly higher; purging, laxative use, and compulsive exercise were more frequent; quality of life was reduced; and histories of depression, attention-deficit/hyperactivity disorder, and self-injury were more common. Binge eating did not account for all of these differences; the presence of it and NES was associated with additive risk for psychopathology on some items. Conclusions NES may be a distinct clinical entity from other DSM-5 eating disorders. PMID:24485551

Serum Vitamin D Is Significantly Inversely Associated with Disease Severity in Caucasian Adults with Obstructive Sleep Apnea Syndrome.

PubMed

Kerley, Conor P; Hutchinson, Katrina; Bolger, Kenneth; McGowan, Aisling; Faul, John; Cormican, Liam

2016-02-01

To evaluate vitamin D (25(OH)D) levels in obstructive sleep apnea syndrome (OSAS) and possible relationships to OSAS severity, sleepiness, lung function, nocturnal heart rate (HR), and body composition. We also aimed to compare the 25(OH)D status of a subset of OSAS patients compared to controls matched for important determinants of both OSAS and vitamin D deficiency (VDD). This was a cross-sectional study conducted at an urban, clinical sleep medicine outpatient center. We recruited newly diagnosed, Caucasian adults who had recently undergone nocturnal polysomnography. We compared body mass index (BMI), body composition (bioelectrical impedance analysis), neck circumference, sleepiness (Epworth Sleepiness Scale), lung function, and vitamin D status (serum 25-hydrpoxyvitamin D (25(OH)D) across OSAS severity categories and non-OSAS subjects. Next, using a case-control design, we compared measures of serum 25(OH)D from OSAS cases to non-OSAS controls who were matched for age, gender, skin pigmentation, sleepiness, season, and BMI. 106 adults (77 male; median age = 54.5; median BMI = 34.3 kg/m(2)) resident in Dublin, Ireland (latitude 53°N) were recruited and categorized as non-OSAS or mild/moderate/severe OSAS. 98% of OSAS cases had insufficient 25(OH)D (< 75 nmol/L), including 72% with VDD (< 50 nmol/L). 25(OH)D levels decreased with OSAS severity (P = 0.003). 25(OH)D was inversely correlated with BMI, percent body fat, AHI, and nocturnal HR. Subsequent multivariate regression analysis revealed that 25(OH)D was independently associated with both AHI (P = 0.016) and nocturnal HR (P = 0.0419). Our separate case-control study revealed that 25(OH)D was significantly lower in OSAS cases than matched, non-OSAS subjects (P = 0.001). We observed widespread vitamin D deficiency and insufficiency in a Caucasian, OSAS population. There were significant, independent, inverse relationships between 25(OH)D and AHI as well as nocturnal HR, a known cardiovascular risk factor

Estimation of additive forces and moments for supersonic inlets

NASA Technical Reports Server (NTRS)

Perkins, Stanley C., Jr.; Dillenius, Marnix F. E.

1991-01-01

A technique for estimating the additive forces and moments associated with supersonic, external compression inlets as a function of mass flow ratio has been developed. The technique makes use of a low order supersonic paneling method for calculating minimum additive forces at maximum mass flow conditions. A linear relationship between the minimum additive forces and the maximum values for fully blocked flow is employed to obtain the additive forces at a specified mass flow ratio. The method is applicable to two-dimensional inlets at zero or nonzero angle of attack, and to axisymmetric inlets at zero angle of attack. Comparisons with limited available additive drag data indicate fair to good agreement.

Additive manufacture (3d printing) of plasma diagnostic components and assemblies for fusion experiments

NASA Astrophysics Data System (ADS)

Sieck, Paul; Woodruff, Simon; Stuber, James; Romero-Talamas, Carlos; Rivera, William; You, Setthivoine; Card, Alexander

2015-11-01

Additive manufacturing (or 3D printing) is now becoming sufficiently accurate with a large range of materials for use in printing sensors needed universally in fusion energy research. Decreasing production cost and significantly lowering design time of energy subsystems would realize significant cost reduction for standard diagnostics commonly obtained through research grants. There is now a well-established set of plasma diagnostics, but these expensive since they are often highly complex and require customization, sometimes pace the project. Additive manufacturing (3D printing) is developing rapidly, including open source designs. Basic components can be printed for (in some cases) less than 1/100th costs of conventional manufacturing. We have examined the impact that AM can have on plasma diagnostic cost by taking 15 separate diagnostics through an engineering design using Conventional Manufacturing (CM) techniques to determine costs of components and labor costs associated with getting the diagnostic to work as intended. With that information in hand, we set about optimizing the design to exploit the benefits of AM. Work performed under DOE Contract DE-SC0011858.

Stress-altered synaptic plasticity and DAMP signaling in the hippocampus-PFC axis; elucidating the significance of IGF-1/IGF-1R/CaMKIIα expression in neural changes associated with a prolonged exposure therapy.

PubMed

Ogundele, Olalekan M; Ebenezer, Philip J; Lee, Charles C; Francis, Joseph

2017-06-14

Traumatic stress patients showed significant improvement in behavior after a prolonged exposure to an unrelated stimulus. This treatment method attempts to promote extinction of the fear memory associated with the initial traumatic experience. However, the subsequent prolonged exposure to such stimulus creates an additional layer of neural stress. Although the mechanism remains unclear, prolonged exposure therapy (PET) likely involves changes in synaptic plasticity, neurotransmitter function and inflammation; especially in parts of the brain concerned with the formation and retrieval of fear memory (Hippocampus and Prefrontal Cortex: PFC). Since certain synaptic proteins are also involved in danger-associated molecular pattern signaling (DAMP), we identified the significance of IGF-1/IGF-1R/CaMKIIα expression as a potential link between the concurrent progression of synaptic and inflammatory changes in stress. Thus, a comparison between IGF-1/IGF-1R/CaMKIIα, synaptic and DAMP proteins in stress and PET may highlight the significance of PET on synaptic morphology and neuronal inflammatory response. In behaviorally characterized Sprague-Dawley rats, there was a significant decline in neural IGF-1 (p<0.001), hippocampal (p<0.001) and cortical (p<0.05) IGF-1R expression. These animals showed a significant loss of presynaptic markers (synaptophysin; p<0.001), and changes in neurotransmitters (VGLUT2, Tyrosine hydroxylase, GABA, ChAT). Furthermore, naïve stressed rats recorded a significant decrease in post-synaptic marker (PSD-95; p<0.01) and synaptic regulator (CaMKIIα; p<0.001). As part of the synaptic response to a decrease in brain CaMKIIα, small ion conductance channel (KCa2.2) was upregulated in the brain of naïve stressed rats (p<0.01). After a PET, an increase in IGF-1 (p<0.05) and IGF-1R was recorded in the Stress-PET group (p<0.001). As such, hippocampal (p<0.001), but not cortical (ns) synaptophysin expression increased in Stress-PET. Although PSD-95

Urinary Collagen Fragments Are Significantly Altered in Diabetes: A Link to Pathophysiology

PubMed Central

Argilés, Àngel; Cerna, Marie; Delles, Christian; Dominiczak, Anna F.; Gayrard, Nathalie; Iphöfer, Alexander; Jänsch, Lothar; Jerums, George; Medek, Karel; Mischak, Harald; Navis, Gerjan J.; Roob, Johannes M.; Rossing, Kasper; Rossing, Peter; Rychlík, Ivan; Schiffer, Eric; Schmieder, Roland E.; Wascher, Thomas C.; Winklhofer-Roob, Brigitte M.; Zimmerli, Lukas U.; Zürbig, Petra; Snell-Bergeon, Janet K.

2010-01-01

Background The pathogenesis of diabetes mellitus (DM) is variable, comprising different inflammatory and immune responses. Proteome analysis holds the promise of delivering insight into the pathophysiological changes associated with diabetes. Recently, we identified and validated urinary proteomics biomarkers for diabetes. Based on these initial findings, we aimed to further validate urinary proteomics biomarkers specific for diabetes in general, and particularity associated with either type 1 (T1D) or type 2 diabetes (T2D). Methodology/Principal Findings Therefore, the low-molecular-weight urinary proteome of 902 subjects from 10 different centers, 315 controls and 587 patients with T1D (n = 299) or T2D (n = 288), was analyzed using capillary-electrophoresis mass-spectrometry. The 261 urinary biomarkers (100 were sequenced) previously discovered in 205 subjects were validated in an additional 697 subjects to distinguish DM subjects (n = 382) from control subjects (n = 315) with 94% (95% CI: 92–95) accuracy in this study. To identify biomarkers that differentiate T1D from T2D, a subset of normoalbuminuric patients with T1D (n = 68) and T2D (n = 42) was employed, enabling identification of 131 biomarker candidates (40 were sequenced) differentially regulated between T1D and T2D. These biomarkers distinguished T1D from T2D in an independent validation set of normoalbuminuric patients (n = 108) with 88% (95% CI: 81–94%) accuracy, and in patients with impaired renal function (n = 369) with 85% (95% CI: 81–88%) accuracy. Specific collagen fragments were associated with diabetes and type of diabetes indicating changes in collagen turnover and extracellular matrix as one hallmark of the molecular pathophysiology of diabetes. Additional biomarkers including inflammatory processes and pro-thrombotic alterations were observed. Conclusions/Significance These findings, based on the largest proteomic study performed to date on subjects with

Contributions of Work-Related Stress and Emotional Intelligence to Teacher Engagement: Additive and Interactive Effects

PubMed Central

2017-01-01

This study examined the additive and interactive effects of role stress and emotional intelligence for predicting engagement among 288 teachers. Emotional intelligence and engagement were positively associated. Role ambiguity and role conflict showed negative associations with vigor and dedication scores. The interaction of role ambiguity and emotional intelligence was significant in explaining engagement dimensions. Similar results were found considering overall teacher engagement. Emotional intelligence boosted engagement when the levels of role ambiguity were higher. Our findings suggest the need for future research examining the impact of job hindrances on the links between emotional intelligence and teachers’ occupational well-being indicators. Finally, the implications for emotional intelligence training in education are discussed. PMID:28961218

Expression of cytoskeleton regulatory protein Mena in human hepatocellular carcinoma and its prognostic significance.

PubMed

Hu, Kunpeng; Wang, Jiani; Yao, Zhicheng; Liu, Bo; Lin, Yuan; Liu, Lei; Xu, Lihua

2014-05-01

The molecular mechanisms of the development and progression of hepatocellular carcinoma (HCC) are poorly understood. The main objective of this study was to analyze the expression of Enabled [mammalian Ena (Mena)] protein and its clinical significance in human HCC. The Mena expression was examined at mRNA and protein levels by real-time quantitative polymerase chain reaction and Western blotting analysis in ten paired HCC tissues and the adjacent normal tissues. The expression of Mena protein in 81 specimens of HCC tissues was determined by immunohistochemistry. Associations of Mena expression with the clinicopathological features were analyzed, and prognosis of HCC patients was evaluated. The result shows the expression of Mena mRNA and protein was higher in HCC than in the adjacent normal tissues in ten paired samples. Mena was mainly accumulated in the cytoplasm of tumor cells and over-expressed in 40.74% (33/81) patients by immunohistochemical staining. Over-expression of Mena was significantly associated with poor cellular differentiation (P = 0.025), advanced tumor stage (P = 0.003) and worse disease-free survival (DFS, P < 0.001). In addition, Mena is an independent prognostic factor for DFS in multivariate analysis (HR 2.309, 95% CI 1.104-4.828; P = 0.026). Mena is up-regulated in HCC and associated with tumor differentiation and clinical stage. Mena may be an independent prognostic marker for DFS of HCC patients.

Risk factors and clinical indicators for the development of biliary strictures post liver transplant: Significance of bilirubin

PubMed Central

Forrest, Elizabeth Ann; Reiling, Janske; Lipka, Geraldine; Fawcett, Jonathan

2017-01-01

AIM To identify risk factors associated with the formation of biliary strictures post liver transplantation over a period of 10-year in Queensland. METHODS Data on liver donors and recipients in Queensland between 2005 and 2014 was obtained from an electronic patient data system. In addition, intra-operative and post-operative characteristics were collected and a logistical regression analysis was performed to evaluate their association with the development of biliary strictures. RESULTS Of 296 liver transplants performed, 285 (96.3%) were from brain dead donors. Biliary strictures developed in 45 (15.2%) recipients. Anastomotic stricture formation (n = 25, 48.1%) was the commonest complication, with 14 (58.3%) of these occurred within 6-mo of transplant. A percutaneous approach or endoscopic retrograde cholangiography was used to treat 17 (37.8%) patients with biliary strictures. Biliary reconstruction was initially or ultimately required in 22 (48.9%) patients. In recipients developing biliary strictures, bilirubin was significantly increased within the first post-operative week (Day 7 total bilirubin 74 μmol/L vs 49 μmol/L, P = 0.012). In both univariate and multivariate regression analysis, Day 7 total bilirubin > 55 μmol/L was associated with the development of biliary stricture formation. In addition, hepatic artery thrombosis and primary sclerosing cholangitis were identified as independent risk factors. CONCLUSION In addition to known risk factors, bilirubin levels in the early post-operative period could be used as a clinical indicator for biliary stricture formation. PMID:29312864

Amino-Acid Network Clique Analysis of Protein Mutation Non-Additive Effects: A Case Study of Lysozme.

PubMed

Ming, Dengming; Chen, Rui; Huang, He

2018-05-10

Optimizing amino-acid mutations in enzyme design has been a very challenging task in modern bio-industrial applications. It is well known that many successful designs often hinge on extensive correlations among mutations at different sites within the enzyme, however, the underpinning mechanism for these correlations is far from clear. Here, we present a topology-based model to quantitively characterize non-additive effects between mutations. The method is based on the molecular dynamic simulations and the amino-acid network clique analysis. It examines if the two mutation sites of a double-site mutation fall into to a 3-clique structure, and associates such topological property of mutational site spatial distribution with mutation additivity features. We analyzed 13 dual mutations of T4 phage lysozyme and found that the clique-based model successfully distinguishes highly correlated or non-additive double-site mutations from those additive ones whose component mutations have less correlation. We also applied the model to protein Eglin c whose structural topology is significantly different from that of T4 phage lysozyme, and found that the model can, to some extension, still identify non-additive mutations from additive ones. Our calculations showed that mutation non-additive effects may heavily depend on a structural topology relationship between mutation sites, which can be quantitatively determined using amino-acid network k -cliques. We also showed that double-site mutation correlations can be significantly altered by exerting a third mutation, indicating that more detailed physicochemical interactions should be considered along with the network clique-based model for better understanding of this elusive mutation-correlation principle.

Hand eczema and occupational contact allergies in healthcare workers with a focus on rubber additives.

PubMed

Hamnerius, Nils; Svedman, Cecilia; Bergendorff, Ola; Björk, Jonas; Bruze, Magnus; Engfeldt, Malin; Pontén, Ann

2018-06-20

Hand eczema (HE) in healthcare workers (HCWs) is common. Besides wet work, healthcare work also implies exposure to contact allergens. To assess HE and contact allergy related to occupational exposures in HCWs. In a cross-sectional study, 311 HCWs with HE within the preceding 12 months and a control group of 114 HCWs without HE were investigated with the baseline series and a special patch test series based on substances found in the gloves, soaps, alcoholic hand disinfectants and hand creams provided at the hospitals. Contact allergy to rubber additives was significantly more common in HCWs with HE (6%) than in HCWs without HE (1%, P = .02). The corresponding percentages for fragrances were 11% and 3%, respectively (P = .004). Occupational HE was found in 193 of 311 (62%) HCWs. Of these, 22 of 193 (11%) had occupational allergic contact dermatitis, including 17 with glove-related rubber contact allergy. Contact allergy to diphenylguanidine was as common as contact allergy to thiurams. Occupational contact allergy to rubber additives was significantly associated with sick-leave related to HE. Contact allergy to rubber additives in medical gloves is the most common cause of occupational allergic contact dermatitis in HCWs. Aimed patch testing with relevant rubber additives is mandatory when HE in HCWs is investigated. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Additive renoprotective effect of candesartan and tetrahydrobiopterin in rats after 5/6 nephrectomy.

PubMed

Podjarny, Eduardo; Bernheim, Joelle; Hasdan, Galit; Karsh, Dorit; Rashid, Gloria; Green, Janice; Katz, Bernardo; Bernheim, Jacques

2007-07-01

Chronic treatment with candesartan cilexetil (C) improves the outcome of rats after 5/6 nephrectomy (Nx). Tetrahydrobiopterin (BH4), an essential cofactor for appropriate endothelial nitric oxide synthase (eNOS) activity, prevents an increase in blood pressure (BP) in Nx rats when given immediately after surgery. In the present study, we evaluated the renoprotective effect of a combined treatment. Five groups of rats were studied: SHAM (sham-operated rats, n=12); SNx (untreated 5/6 nephrectomized rats, n=15); C (SNx rats treated with candesartan cilexetil, 5 mg/kg/day per os, n=11); C+BH4 (SNx rats treated with candesartan cilexetil and BH4, 10 mg/kg/day intraperitoneally, n=11); and BH4 (SNx rats treated with BH4, 10 mg/kg/day intraperitoneally, n=11). Treatment began 30 days after surgery, when hypertension and renal insufficiency have developed. This day was considered as day 1 of treatment for statistical comparisons. The study was continued until 50% mortality was achieved in the SNx rats (4 months after surgery). The survival rates were 100% for SHAM, 47% for SNx, 50% for BH4, 64% for C and 80% for C+BH4 (P<0.05 vs all). Untreated Nx rats developed hypertension, proteinuria (UP) and severe renal insufficiency. Mortality was associated with a lower renal function and increased urine protein excretion. In C and C+BH4 rats, systolic blood pressure (SBP) decreased significantly. BH4 alone had a mild non-significant effect on SBP. C and C+BH4 treatments attenuated significantly the increase in proteinuria found in SNx animals. The weight of the remnant kidneys as well as the severity of glomerulosclerosis were significantly lower in the C+BH4 rats. This study shows that in subnephrectomized rats, addition of BH4 to a treatment with candesartan had an additive renoprotective effect. The mechanism of such action may include a better control of BP associated with a blockade of actions of angiotensin II (Ag II), an improvement in nitric oxide synthesis and a balanced

Co-occurring nonnative woody shrubs have additive and non-additive soil legacies.

PubMed

Kuebbing, Sara E; Patterson, Courtney M; Classen, Aimée T; Simberloff, Daniel

2016-09-01

To maximize limited conservation funds and prioritize management projects that are likely to succeed, accurate assessment of invasive nonnative species impacts is essential. A common challenge to prioritization is a limited knowledge of the difference between the impacts of a single nonnative species compared to the impacts of nonnative species when they co-occur, and in particular predicting when impacts of co-occurring nonnative species will be non-additive. Understanding non-additivity is important for management decisions because the management of only one co-occurring invader will not necessarily lead to a predictable reduction in the impact or growth of the other nonnative plant. Nonnative plants are frequently associated with changes in soil biotic and abiotic characteristics, which lead to plant-soil interactions that influence the performance of other species grown in those soils. Whether co-occurring nonnative plants alter soil properties additively or non-additively relative to their effects on soils when they grow in monoculture is rarely addressed. We use a greenhouse plant-soil feedback experiment to test for non-additive soil impacts of two common invasive nonnative woody shrubs, Lonicera maackii and Ligustrum sinense, in deciduous forests of the southeastern United States. We measured the performance of each nonnative shrub, a native herbaceous community, and a nonnative woody vine in soils conditioned by each shrub singly or together in polyculture. Soils conditioned by both nonnative shrubs had non-additive impacts on native and nonnative performance. Root mass of the native herbaceous community was 1.5 times lower and the root mass of the nonnative L. sinense was 1.8 times higher in soils conditioned by both L. maackii and L. sinense than expected based upon growth in soils conditioned by either shrub singly. This result indicates that when these two nonnative shrubs co-occur, their influence on soils disproportionally favors persistence

The effect of additional physiotherapy to hospital inpatients outside of regular business hours: a systematic review.

PubMed

Brusco, Natasha K; Paratz, Jennifer

2006-12-01

Provision of out of regular business hours (OBH) physiotherapy to hospital inpatients is widespread in the hospital setting. This systematic review evaluated the effect of additional OBH physiotherapy services on patient length of stay (LOS), pulmonary complications, discharge destination, discharge mobility status, quality of life, cost saving, adverse events, and mortality compared with physiotherapy only within regular business hours. A literature search was completed on databases with citation tracking using key words. Two reviewers completed data extraction and quality assessment independently by using modified scales for historical cohorts and case control studies as well as the PEDro scale for randomized controlled trials and quasi-randomised controlled trials. This search identified nine articles of low to medium quality. Four reported a significant reduction in LOS associated with additional OBH physiotherapy, with two articles reporting overall significance and two reporting only for specific subgroups. Two studies reported significant reduction in pulmonary complications for two different patient groups in an intensive care unit (ICU) with additional OBH physiotherapy. Three studies accounted for discharge destination and/or discharge mobility status with no significant difference reported. Quality of life, adverse events, and mortality were not reported in any studies. Cost savings were considered in three studies, with two reporting a cost saving. This systematic review was unable to conclude that the provision of additional OBH physiotherapy made significant improvement to patient outcomes for all subgroups of inpatients. One study in critical care reported that overnight physiotherapy decreased LOS and reduced pulmonary complications of patients in the ICU. However, the studies in the area of orthopaedics, neurology, postcardiac surgery, and rheumatology, which all considered additional daytime weekend physiotherapy intervention, did not provide

Prognostic significance of 5T4 oncofetal antigen expression in colorectal carcinoma.

PubMed Central

Starzynska, T.; Marsh, P. J.; Schofield, P. F.; Roberts, S. A.; Myers, K. A.; Stern, P. L.

1994-01-01

The 5T4 oncofetal antigen is a 72 kDa glycoprotein defined by a monoclonal antibody raised against human placental trophoblast and is expressed in many different carcinomas but detected only at low levels in some normal epithelia. Immunohistochemical analysis of the patterns of expression in colorectal carcinomas has indicated a significant association between the presence of the antigen in tumour cells and metastatic spread. The 5T4 antigen phenotype of 72 colorectal cancers has been compared with the clinical outcome of the patients in order to assess its relationship with prognosis. Forty per cent of tumours were 5T4 positive; the remainder were either unlabelled or exhibited stroma-associated labelling only. There was a significant correlation between 5T4 expression in the malignant cells and unfavourable course of disease (P < 0.001). The 5 year survival with 5T4-positive tumours was 22% compared with 75% for patients with 5T4-negative tumours; median survival was 24 versus > 90 months respectively. Stratified analysis showed that 5T4 antigen tumour positivity was acting independently of each of stage, site of tumour, age or sex. There were significant differences in survival for patients with Dukes' B and C stage carcinomas (P = 0.001 and P = 0.034). The results suggest that in colorectal cancer immunohistochemical assessment of 5T4 expression may be useful in identifying patients at high risk for tumour recurrence and for whom additional treatment strategies might be most appropriate. Images Figure 1 PMID:8180020

Genome-wide association study of 40,000 individuals identifies two novel loci associated with bipolar disorder

PubMed Central

Hou, Liping; Bergen, Sarah E.; Akula, Nirmala; Song, Jie; Hultman, Christina M.; Landén, Mikael; Adli, Mazda; Alda, Martin; Ardau, Raffaella; Arias, Bárbara; Aubry, Jean-Michel; Backlund, Lena; Badner, Judith A.; Barrett, Thomas B.; Bauer, Michael; Baune, Bernhard T.; Bellivier, Frank; Benabarre, Antonio; Bengesser, Susanne; Berrettini, Wade H.; Bhattacharjee, Abesh Kumar; Biernacka, Joanna M.; Birner, Armin; Bloss, Cinnamon S.; Brichant-Petitjean, Clara; Bui, Elise T.; Byerley, William; Cervantes, Pablo; Chillotti, Caterina; Cichon, Sven; Colom, Francesc; Coryell, William; Craig, David W.; Cruceanu, Cristiana; Czerski, Piotr M.; Davis, Tony; Dayer, Alexandre; Degenhardt, Franziska; Del Zompo, Maria; DePaulo, J. Raymond; Edenberg, Howard J.; Étain, Bruno; Falkai, Peter; Foroud, Tatiana; Forstner, Andreas J.; Frisén, Louise; Frye, Mark A.; Fullerton, Janice M.; Gard, Sébastien; Garnham, Julie S.; Gershon, Elliot S.; Goes, Fernando S.; Greenwood, Tiffany A.; Grigoroiu-Serbanescu, Maria; Hauser, Joanna; Heilbronner, Urs; Heilmann-Heimbach, Stefanie; Herms, Stefan; Hipolito, Maria; Hitturlingappa, Shashi; Hoffmann, Per; Hofmann, Andrea; Jamain, Stephane; Jiménez, Esther; Kahn, Jean-Pierre; Kassem, Layla; Kelsoe, John R.; Kittel-Schneider, Sarah; Kliwicki, Sebastian; Koller, Daniel L.; König, Barbara; Lackner, Nina; Laje, Gonzalo; Lang, Maren; Lavebratt, Catharina; Lawson, William B.; Leboyer, Marion; Leckband, Susan G.; Liu, Chunyu; Maaser, Anna; Mahon, Pamela B.; Maier, Wolfgang; Maj, Mario; Manchia, Mirko; Martinsson, Lina; McCarthy, Michael J.; McElroy, Susan L.; McInnis, Melvin G.; McKinney, Rebecca; Mitchell, Philip B.; Mitjans, Marina; Mondimore, Francis M.; Monteleone, Palmiero; Mühleisen, Thomas W.; Nievergelt, Caroline M.; Nöthen, Markus M.; Novák, Tomas; Nurnberger, John I.; Nwulia, Evaristus A.; Ösby, Urban; Pfennig, Andrea; Potash, James B.; Propping, Peter; Reif, Andreas; Reininghaus, Eva; Rice, John; Rietschel, Marcella; Rouleau, Guy A.; Rybakowski, Janusz K.; Schalling, Martin; Scheftner, William A.; Schofield, Peter R.; Schork, Nicholas J.; Schulze, Thomas G.; Schumacher, Johannes; Schweizer, Barbara W.; Severino, Giovanni; Shekhtman, Tatyana; Shilling, Paul D.; Simhandl, Christian; Slaney, Claire M.; Smith, Erin N.; Squassina, Alessio; Stamm, Thomas; Stopkova, Pavla; Streit, Fabian; Strohmaier, Jana; Szelinger, Szabolcs; Tighe, Sarah K.; Tortorella, Alfonso; Turecki, Gustavo; Vieta, Eduard; Volkert, Julia; Witt, Stephanie H.; Wright, Adam; Zandi, Peter P.; Zhang, Peng; Zollner, Sebastian; McMahon, Francis J.

2016-01-01

Bipolar disorder (BD) is a genetically complex mental illness characterized by severe oscillations of mood and behaviour. Genome-wide association studies (GWAS) have identified several risk loci that together account for a small portion of the heritability. To identify additional risk loci, we performed a two-stage meta-analysis of >9 million genetic variants in 9,784 bipolar disorder patients and 30,471 controls, the largest GWAS of BD to date. In this study, to increase power we used ∼2,000 lithium-treated cases with a long-term diagnosis of BD from the Consortium on Lithium Genetics, excess controls, and analytic methods optimized for markers on the X-chromosome. In addition to four known loci, results revealed genome-wide significant associations at two novel loci: an intergenic region on 9p21.3 (rs12553324, P =  5.87 × 10 − 9; odds ratio (OR) = 1.12) and markers within ERBB2 (rs2517959, P =  4.53 × 10 − 9; OR = 1.13). No significant X-chromosome associations were detected and X-linked markers explained very little BD heritability. The results add to a growing list of common autosomal variants involved in BD and illustrate the power of comparing well-characterized cases to an excess of controls in GWAS. PMID:27329760

Genome-Wide Association Study of Personality Traits in the Long Life Family Study

PubMed Central

Bae, Harold T.; Sebastiani, Paola; Sun, Jenny X.; Andersen, Stacy L.; Daw, E. Warwick; Terracciano, Antonio; Ferrucci, Luigi; Perls, Thomas T.

2013-01-01

Personality traits have been shown to be associated with longevity and healthy aging. In order to discover novel genetic modifiers associated with personality traits as related with longevity, we performed a genome-wide association study (GWAS) on personality factors assessed by NEO-five-factor inventory in individuals enrolled in the Long Life Family Study (LLFS), a study of 583 families (N up to 4595) with clustering for longevity in the United States and Denmark. Three SNPs, in almost perfect LD, associated with agreeableness reached genome-wide significance (p < 10−8) and replicated in an additional sample of 1279 LLFS subjects, although one (rs9650241) failed to replicate and the other two were not available in two independent replication cohorts, the Baltimore Longitudinal Study of Aging and the New England Centenarian Study. Based on 10,000,000 permutations, the empirical p-value of 2 × 10−7 was observed for the genome-wide significant SNPs. Seventeen SNPs that reached marginal statistical significance in the two previous GWASs (p-value <10−4 and 10−5), were also marginally significantly associated in this study (p-value <0.05), although none of the associations passed the Bonferroni correction. In addition, we tested age-by-SNP interactions and found some significant associations. Since scores of personality traits in LLFS subjects change in the oldest ages, and genetic factors outweigh environmental factors to achieve extreme ages, these age-by-SNP interactions could be a proxy for complex gene–gene interactions affecting personality traits and longevity. PMID:23658558

Additional effects of topical tranexamic acid in on-pump cardiac surgery.

PubMed

Taksaudom, Noppon; Siwachat, Sophon; Tantraworasin, Apichat

2017-01-01

Objective Postoperative bleeding after cardiac surgery is commonly associated with hyperfibrinolysis. This study was designed to evaluate the efficacy of topical tranexamic acid in addition to intravenous tranexamic acid in reducing bleeding in cardiac surgery cases. Methods From July 1, 2014 to September 30, 2015, 82 patients who underwent elective on-pump cardiac surgery were randomized into a tranexamic acid group and a placebo group. In the tranexamic acid group, 1 g of tranexamic acid dissolved in 100 mL of normal saline solution was poured into the pericardium during sternal closure; the placebo group had 100 mL of saline only. Two patients were excluded from the study due to obvious surgical bleeding. The primary endpoint was total blood loss 24 h after surgery. Repeated measures with mixed models was used to analyze bleeding over time. Results There was no significant difference in demographic and intraoperative data except for a significantly lower platelet count preoperatively in the tranexamic acid group ( p = 0.030). There was no significant difference in postoperative drainage volumes at 8, 16, and 24 h, postoperative bleeding over time (coefficient = 0.713, p = 0.709), or blood product transfusion between the groups. There were no serious complications. Conclusions Topical tranexamic acid is safe but it adds no additional efficacy to the intravenous application in reducing postoperative blood loss. Intravenous tranexamic acid administration alone is sufficient antifibrinolytic treatment to enhance the hemostatic effects during on-pump cardiac surgery.

Genome-wide association study of alcohol dependence

PubMed Central

Treutlein, Jens; Cichon, Sven; Ridinger, Monika; Wodarz, Norbert; Soyka, Michael; Zill, Peter; Maier, Wolfgang; Moessner, Rainald; Gaebel, Wolfgang; Dahmen, Norbert; Fehr, Christoph; Scherbaum, Norbert; Steffens, Michael; Ludwig, Kerstin U.; Frank, Josef; Wichmann, H.- Erich; Schreiber, Stefan; Dragano, Nico; Sommer, Wolfgang; Leonardi-Essmann, Fernando; Lourdusamy, Anbarasu; Gebicke-Haerter, Peter; Wienker, Thomas F.; Sullivan, Patrick F.; Nöthen, Markus M.; Kiefer, Falk; Spanagel, Rainer; Mann, Karl; Rietschel, Marcella

2014-01-01

Context Identification of genes contributing to alcohol dependence will improve our understanding of the mechanisms underlying this disorder. Objective To identify susceptibility genes for alcohol dependence through a genome-wide association study (GWAS) and follow-up study in a population of German male inpatients with an early age at onset. Design The GWAS included 487 male inpatients with DSM-IV alcohol dependence with an age at onset below 28 years and 1,358 population based control individuals. The follow-up study included 1,024 male inpatients and 996 age-matched male controls. All subjects were of German descent. The GWAS tested 524,396 single nucleotide polymorphisms (SNPs). All SNPs with p<10-4 were subjected to the follow-up study. In addition, nominally significant SNPs from those genes that had also shown expression changes in rat brains after chronic alcohol consumption were selected for the follow-up step. Results The GWAS produced 121 SNPs with nominal p<10-4. These, together with 19 additional SNPs from homologs of rat genes showing differential expression, were genotyped in the follow-up sample. Fifteen SNPs showed significant association with the same allele as in the GWAS. In the combined analysis, two closely linked intergenic SNPs met genome-wide significance (rs7590720 p=9.72×10-9; rs1344694 p=1.69×10-8). They are located on chromosome 2q35, a region which has been implicated in linkage studies for alcohol phenotypes. Nine SNPs were located in genes, including CDH13 and ADH1C genes which have been reported to be associated with alcohol dependence. Conclusion This is the first GWAS and follow-up study to identify a genome-wide significant association in alcohol dependence. Further independent studies are required to confirm these findings. PMID:19581569

The prognostic significance of UCA1 for predicting clinical outcome in patients with digestive system malignancies

PubMed Central

Zhu, Zheng-Ming

2017-01-01

Background Urothelial Carcinoma Associated 1 (UCA1) was an originally identified lncRNA in bladder cancer. Previous studies have reported that UCA1 played a significant role in various types of cancer. This study aimed to clarify the prognostic value of UCA1 in digestive system cancers. Results The meta-analysis of 15 studies were included, comprising 1441 patients with digestive system cancers. The pooled results of 14 studies indicated that high expression of UCA1 was significantly associated with poorer OS in patients with digestive system cancers (HR: 1.89, 95 % CI: 1.52–2.26). In addition, UCA1 could be as an independent prognostic factor for predicting OS of patients (HR: 1.85, 95 % CI: 1.45–2.25). The pooled results of 3 studies indicated a significant association between UCA1 and DFS in patients with digestive system cancers (HR = 2.50; 95 % CI = 1.30–3.69). Statistical significance was also observed in subgroup meta-analysis. Furthermore, the clinicopathological values of UCA1 were discussed in esophageal cancer, colorectal cancer and pancreatic cancer. Materials and methods A comprehensive retrieval was performed to search studies evaluating the prognostic value of UCA1 in digestive system cancers. Many databases were involved, including PubMed, Web of Science, Embase and Chinese National Knowledge Infrastructure and Wanfang database. Quantitative meta-analysis was performed with standard statistical methods and the prognostic significance of UCA1 in digestive system cancers was qualified. Conclusions Elevated level of UCA1 indicated the poor clinical outcome for patients with digestive system cancers. It may serve as a new biomarker related to prognosis in digestive system cancers. PMID:28380443

The prognostic significance of UCA1 for predicting clinical outcome in patients with digestive system malignancies.

PubMed

Liu, Fang-Teng; Dong, Qing; Gao, Hui; Zhu, Zheng-Ming

2017-06-20

Urothelial Carcinoma Associated 1 (UCA1) was an originally identified lncRNA in bladder cancer. Previous studies have reported that UCA1 played a significant role in various types of cancer. This study aimed to clarify the prognostic value of UCA1 in digestive system cancers. The meta-analysis of 15 studies were included, comprising 1441 patients with digestive system cancers. The pooled results of 14 studies indicated that high expression of UCA1 was significantly associated with poorer OS in patients with digestive system cancers (HR: 1.89, 95 % CI: 1.52-2.26). In addition, UCA1 could be as an independent prognostic factor for predicting OS of patients (HR: 1.85, 95 % CI: 1.45-2.25). The pooled results of 3 studies indicated a significant association between UCA1 and DFS in patients with digestive system cancers (HR = 2.50; 95 % CI = 1.30-3.69). Statistical significance was also observed in subgroup meta-analysis. Furthermore, the clinicopathological values of UCA1 were discussed in esophageal cancer, colorectal cancer and pancreatic cancer. A comprehensive retrieval was performed to search studies evaluating the prognostic value of UCA1 in digestive system cancers. Many databases were involved, including PubMed, Web of Science, Embase and Chinese National Knowledge Infrastructure and Wanfang database. Quantitative meta-analysis was performed with standard statistical methods and the prognostic significance of UCA1 in digestive system cancers was qualified. Elevated level of UCA1 indicated the poor clinical outcome for patients with digestive system cancers. It may serve as a new biomarker related to prognosis in digestive system cancers.

Clinical Significance of Epigenetic Alterations in Human Hepatocellular Carcinoma and Its Association with Genetic Mutations.

PubMed

Nishida, Naoshi; Kudo, Masatoshi

Accumulation of genetic and epigenetic alterations is a hallmark of cancer genomes, including those in hepatocellular carcinoma (HCC). Particularly, in human HCC, epigenetic changes are more frequently observed than genetic changes in a variety of cancer-related genes, suggesting a potential role for epigenetic alterations during hepatocarcinogenesis. Several environmental factors, such as inflammation, obesity, and steatosis, are reported to affect the epigenetic status in hepatocytes, which could play a role in HCC development. In addition, genetic mutations in histone modulators and chromatin regulators would be critical for the acceleration of epigenetic alteration. It is also possible that major genetic mutations of HCC, such as TP53 and CNTTB1 mutations, are associated with the disturbance of epigenetic integrity. For example, specific TP53 mutations frequently induced by aflatoxin B1 exposure might affect histone modifiers and nucleosome remodelers. Generally, epigenetic alteration is reversible, because of which dysregulation of transcription takes place, without affecting protein structure. Therefore, differentiation therapy is one of the potential approaches for HCC with advanced epigenetic alterations. On the other hand, a tumor carrying an accumulation of genetic mutations would result in many abnormal proteins that could be recognized as non-self and could be targets for immune reactions; thus, immune-checkpoint blockers should be effective for HCCs with genetic hypermutation. Although the emergence of genetic and epigenetic alterations could be linked to each other and there could be some crossover or convergence between these cancer pathways, characterization of the mutation spectrum of genetic and epigenetic alterations could influence future HCC treatment. © 2016 S. Karger AG, Basel.

The effect of gyrolite additive on the hydration properties of Portland cement

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

Eisinas, A., E-mail: anatolijus.eisinas@ktu.lt; Baltakys, K.; Siauciunas, R.

2012-01-15

The influence of gyrolite additive on the hydration properties of ordinary Portland cement was examined. It was found that the additive of synthetic gyrolite accelerates the early stage of hydration of OPC. This compound binds alkaline ions and serves as a nucleation site for the formation of hydration products (stage I). Later on, the crystal lattice of gyrolite becomes unstable and turns into C-S-H, with higher basicity (C/S {approx} 0.8). This recrystallization process is associated with the consumption of energy (the heat of reaction) and with a decrease in the rate of heat evolution of the second exothermic reaction (stagemore » II). The experimental data and theoretical hypothesis were also confirmed by thermodynamic and the apparent kinetic parameters of the reaction rate of C{sub 3}S hydration calculations. The changes occur in the early stage of hydration of OPC samples and do not have a significant effect on the properties of cement stone.« less

Scope and Significance of Eating Disorders.

ERIC Educational Resources Information Center

Mitchell, James E.; Eckert, Elke D.

1987-01-01

Describes the increasing prevalence of anorexia nervosa and bulimia in many industrialized societies, and their association with significant morbidity and mortality. Discusses the genetic risks for the development of anorexia nervosa, and treatment strategies. Of these, pharmacotherapy and psychotherapy, particularly those incorporating…

Genome-wide association analysis identifies six new loci associated with forced vital capacity.

PubMed

Loth, Daan W; Soler Artigas, María; Gharib, Sina A; Wain, Louise V; Franceschini, Nora; Koch, Beate; Pottinger, Tess D; Smith, Albert Vernon; Duan, Qing; Oldmeadow, Chris; Lee, Mi Kyeong; Strachan, David P; James, Alan L; Huffman, Jennifer E; Vitart, Veronique; Ramasamy, Adaikalavan; Wareham, Nicholas J; Kaprio, Jaakko; Wang, Xin-Qun; Trochet, Holly; Kähönen, Mika; Flexeder, Claudia; Albrecht, Eva; Lopez, Lorna M; de Jong, Kim; Thyagarajan, Bharat; Alves, Alexessander Couto; Enroth, Stefan; Omenaas, Ernst; Joshi, Peter K; Fall, Tove; Viñuela, Ana; Launer, Lenore J; Loehr, Laura R; Fornage, Myriam; Li, Guo; Wilk, Jemma B; Tang, Wenbo; Manichaikul, Ani; Lahousse, Lies; Harris, Tamara B; North, Kari E; Rudnicka, Alicja R; Hui, Jennie; Gu, Xiangjun; Lumley, Thomas; Wright, Alan F; Hastie, Nicholas D; Campbell, Susan; Kumar, Rajesh; Pin, Isabelle; Scott, Robert A; Pietiläinen, Kirsi H; Surakka, Ida; Liu, Yongmei; Holliday, Elizabeth G; Schulz, Holger; Heinrich, Joachim; Davies, Gail; Vonk, Judith M; Wojczynski, Mary; Pouta, Anneli; Johansson, Asa; Wild, Sarah H; Ingelsson, Erik; Rivadeneira, Fernando; Völzke, Henry; Hysi, Pirro G; Eiriksdottir, Gudny; Morrison, Alanna C; Rotter, Jerome I; Gao, Wei; Postma, Dirkje S; White, Wendy B; Rich, Stephen S; Hofman, Albert; Aspelund, Thor; Couper, David; Smith, Lewis J; Psaty, Bruce M; Lohman, Kurt; Burchard, Esteban G; Uitterlinden, André G; Garcia, Melissa; Joubert, Bonnie R; McArdle, Wendy L; Musk, A Bill; Hansel, Nadia; Heckbert, Susan R; Zgaga, Lina; van Meurs, Joyce B J; Navarro, Pau; Rudan, Igor; Oh, Yeon-Mok; Redline, Susan; Jarvis, Deborah L; Zhao, Jing Hua; Rantanen, Taina; O'Connor, George T; Ripatti, Samuli; Scott, Rodney J; Karrasch, Stefan; Grallert, Harald; Gaddis, Nathan C; Starr, John M; Wijmenga, Cisca; Minster, Ryan L; Lederer, David J; Pekkanen, Juha; Gyllensten, Ulf; Campbell, Harry; Morris, Andrew P; Gläser, Sven; Hammond, Christopher J; Burkart, Kristin M; Beilby, John; Kritchevsky, Stephen B; Gudnason, Vilmundur; Hancock, Dana B; Williams, O Dale; Polasek, Ozren; Zemunik, Tatijana; Kolcic, Ivana; Petrini, Marcy F; Wjst, Matthias; Kim, Woo Jin; Porteous, David J; Scotland, Generation; Smith, Blair H; Viljanen, Anne; Heliövaara, Markku; Attia, John R; Sayers, Ian; Hampel, Regina; Gieger, Christian; Deary, Ian J; Boezen, H Marike; Newman, Anne; Jarvelin, Marjo-Riitta; Wilson, James F; Lind, Lars; Stricker, Bruno H; Teumer, Alexander; Spector, Timothy D; Melén, Erik; Peters, Marjolein J; Lange, Leslie A; Barr, R Graham; Bracke, Ken R; Verhamme, Fien M; Sung, Joohon; Hiemstra, Pieter S; Cassano, Patricia A; Sood, Akshay; Hayward, Caroline; Dupuis, Josée; Hall, Ian P; Brusselle, Guy G; Tobin, Martin D; London, Stephanie J

2014-07-01

Forced vital capacity (FVC), a spirometric measure of pulmonary function, reflects lung volume and is used to diagnose and monitor lung diseases. We performed genome-wide association study meta-analysis of FVC in 52,253 individuals from 26 studies and followed up the top associations in 32,917 additional individuals of European ancestry. We found six new regions associated at genome-wide significance (P < 5 × 10(-8)) with FVC in or near EFEMP1, BMP6, MIR129-2-HSD17B12, PRDM11, WWOX and KCNJ2. Two loci previously associated with spirometric measures (GSTCD and PTCH1) were related to FVC. Newly implicated regions were followed up in samples from African-American, Korean, Chinese and Hispanic individuals. We detected transcripts for all six newly implicated genes in human lung tissue. The new loci may inform mechanisms involved in lung development and the pathogenesis of restrictive lung disease.

A Common Variant of NGEF Is Associated with Abdominal Visceral Fat in Korean Men.

PubMed

Kim, Hyun-Jin; Park, Jin-Ho; Lee, Seungbok; Son, Ho-Young; Hwang, Jinha; Chae, Jeesoo; Yun, Jae Moon; Kwon, Hyuktae; Kim, Jong-Il; Cho, Belong

2015-01-01

Central adiposity, rather than body mass index (BMI), is a key pathophysiological feature of the development of obesity-related diseases. Although genetic studies by anthropometric measures such as waist circumference have been widely conducted, genetic studies for abdominal fat deposition measured by computed tomography (CT) have been rarely performed. A total of 1,243 participants who were recruited from two health check-up centers were included in this study. We selected four and three single-nucleotide polymorphisms (SNPs) in NGEF and RGS6, respectively, and analyzed the associations between the seven SNPs and central adiposity measured by CT using an additive, dominant, or recessive model. The participants were generally healthy middle-aged men (50.7 ± 5.3 years). In the additive model, the rs11678490 A allele of NGEF was significantly associated with total adipose tissue, visceral adipose tissue (VAT), and subcutaneous adipose tissue (all P < 0.05). The AA genotype of this SNP in the recessive model showed a more significant association with all adiposity traits, and its association with VAT remained significant even after adjustment for BMI (P = 0.005). In the overall or visceral obesity group analysis, the AA genotype of rs11678490 showed no association with overall obesity (P = 0.148), whereas it was significantly associated with visceral obesity both before (P = 0.010) and after (P = 0.029) adjustment for BMI. In particular, an AA genotype effect was conspicuous between lower and upper groups with 5% extreme VAT phenotypes (OR = 9.59, 95% CI = 1.50-61.31). However, we found no significant association between SNPs of RGS6 and central adiposity. We identified a visceral-fat-associated SNP, rs11678490 of NGEF, in Korean men. This study suggests that the genetic background of central adiposity and BMI is different, and that additional efforts should be made to find the unique genetic architecture of intra-abdominal fat accumulation.

Additive interaction between heterogeneous environmental ...

EPA Pesticide Factsheets

BACKGROUND Environmental exposures often occur in tandem; however, epidemiological research often focuses on singular exposures. Statistical interactions among broad, well-characterized environmental domains have not yet been evaluated in association with health. We address this gap by conducting a county-level cross-sectional analysis of interactions between Environmental Quality Index (EQI) domain indices on preterm birth in the Unites States from 2000-2005.METHODS: The EQI, a county-level index constructed for the 2000-2005 time period, was constructed from five domain-specific indices (air, water, land, built and sociodemographic) using principal component analyses. County-level preterm birth rates (n=3141) were estimated using live births from the National Center for Health Statistics. Linear regression was used to estimate prevalence differences (PD) and 95% confidence intervals (CI) comparing worse environmental quality to the better quality for each model for a) each individual domain main effect b) the interaction contrast and c) the two main effects plus interaction effect (i.e. the “net effect”) to show departure from additive interaction for the all U.S counties. Analyses were also performed for subgroupings by four urban/rural strata. RESULTS: We found the suggestion of antagonistic interactions but no synergism, along with several purely additive (i.e., no interaction) associations. In the non-stratified model, we observed antagonistic interac

Role of serine/threonine kinase 33 methylation in colorectal cancer and its clinical significance

PubMed Central

Yin, Ming-Di; Ma, Si-Ping; Liu, Fang; Chen, Yu-Ze

2018-01-01

Serine/threonine kinase 33 (STK33) is a novel protein that has been the focus of an increasing number of studies in recent years; however, the role of STK33 in tumorigenesis remains controversial. Previous studies have demonstrated that STK33 is overexpressed in several human cancers and exerts a pro-tumorigenic effect through the promotion of cell proliferation. However, the role of STK33 in colorectal cancer (CRC), which is one of the most aggressive human malignancies, remains unclear. The aim of the current study was to investigate the methylation status of STK33 in CRC and to determine its clinical significance. The results demonstrated that STK33 was hypermethylated in CRC cell lines and promoted the proliferation of CRC cells. In addition, the methylation status and expression of STK33 in 94 pairs of cancer and noncancerous tissues obtained from patients with CRC was investigated. STK33 methylation was significantly increased in cancer tissues when compared with adjacent noncancerous tissues (P<0.001). STK33 methylation was associated with lymph node metastasis (P<0.05), tumor invasion (P<0.05), distant metastases (P<0.01) and tumor stage (P<0.01). Reduced STK33 mRNA and protein expression in CRC was associated with STK33 hypermethylation (P<0.001). In addition, patients with hypermethylated STK33 exhibited shorter overall survival rates when compared with those with unmethylated STK33 (P<0.01). In conclusion, the results of the current study suggest that STK33 hypermethylation may be a promising novel biomarker for the diagnosis, prognosis and suitable treatment of CRC. PMID:29434919

45 CFR 162.930 - Additional rules for health care clearinghouses.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 45 Public Welfare 1 2010-10-01 2010-10-01 false Additional rules for health care clearinghouses. 162.930 Section 162.930 Public Welfare DEPARTMENT OF HEALTH AND HUMAN SERVICES ADMINISTRATIVE DATA... Additional rules for health care clearinghouses. When acting as a business associate for another covered...

Dose-dependent folic acid and memantine treatments promote synergistic or additive protection against Aβ(25-35) peptide-induced apoptosis in SH-SY5Y cells mediated by mitochondria stress-associated death signals.

PubMed

Chen, Ta-Fu; Tang, Ming-Chi; Chou, Chia-Hui; Chiu, Ming-Jang; Huang, R-F S

2013-12-01

Increased dietary folic acid (FA) is associated with reduced risks of Alzheimer's disease (AD). The AD drug memantine (Mn) has had limited therapeutic effects for the treatment of patients with moderate to severe AD. This study investigated whether and the underlying mechanisms by which the combination of Mn and FA may have synergistic or additive effects in protecting against amyloid-β(25-35) peptide (Aβ)-induced neurocytotoxicity. Aβ treatment of human neuroblastoma SH-SY5Y cells significantly induced a 6-fold increase of apoptotic cells compared with the Aβ-untreated group. Preincubation of Aβ-exposed cells with FA (500 μM) or Mn (20 μM) caused a 22% and 10% reduction of apoptotic cells, respectively, whereas the combo-treatments at such doses synergistically alleviated Aβ-induced apoptosis by 60% (P<0.05). The apoptotic protection by the combo-treatments coincided with attenuating Aβ-elicited mitochondrial (mt) membrane depolarization and abolishing Aβ-induced mt cytochrome c release to the cytosol. Increased levels of FA at 1000 μM in combination with 20 μM Mn exerted an additive protection against Aβ(25-35)-induced-apoptosis as compared to the isolate Mn group (P<0.05). The combo-treatments reversed Aβ-elicited mt membrane depolarization, attenuated Aβ-elicited mt cytochrome c release to the cytosol, and diminished Aβ-promoted superoxide generation. The apoptotic-protection by such combo-treatments was partially abolished by carbonyl cyanide 3-chlorophenylhydrazone (mt membrane potential uncoupler) and sodium azide (mt cytochrome c oxidase inhibitor). Taken together, the data demonstrated that dose-dependent FA and Mn synergistically or additively protected SH-SY5Y cells against Aβ-induced apoptosis, which was partially, if not completely, mediated by mt stress-associated death signals. Copyright © 2013 Elsevier Ltd. All rights reserved.

An integrative neuroscience model of "significance" processing.

PubMed

Williams, Leanne M

2006-03-01

The Gordon [37-40] framework of Integrative Neuroscience is used to develop a continuum model for understanding the central role of motivationally-determined "significance" in organizing human information processing. Significance is defined as the property which gives a stimulus relevance to our core motivation to minimize danger and maximize pleasure. Within this framework, the areas of cognition and emotion, theories of motivational arousal and orienting, and the current understanding of neural systems are brought together. The basis of integration is a temporal continuum in which significance processing extends from the most rapid millisecond time scale of automatic, nonconscious mechanisms to the time scale of seconds, in which memory is shaped, to the controlled and conscious mechanisms unfolding over minutes. Over this continuum, significant stimuli are associated with a spectrum of defensive (or consumptive) behaviors through to volitional regulatory behaviors for danger (versus pleasure) and associated brainstem, limbic, medial forebrain bundle and prefrontal circuits, all of which reflect a balance of excitatory (predominant at rapid time scales) to inhibitory mechanisms. Across the lifespan, the negative and positive outcomes of significance processing, coupled with constitutional and genetic factors, will contribute to plasticity, shaping individual adaptations and maladaptions in the balance of excitatory-inhibitory mechanisms.

Expression and clinical significance of glucose transporter-1 in pancreatic cancer

PubMed Central

LU, KAI; YANG, JIAN; LI, DE-CHUN; HE, SONG-BING; ZHU, DONG-MING; ZHANG, LI-FENG; ZHANG, XU; CHEN, XIAO-CHEN; ZHANG, BING; ZHOU, JIAN

2016-01-01

Increasing evidence has demonstrated that malignant cells exhibit increased glucose uptake, which facilitates survival and growth in a hypoxic environment. The glucose transporter-1 (GLUT-1) is overexpressed in a variety of malignant tumors. However, the association between GLUT-1 expression and clinicopathological factors, 18F-fluorodeoxyglucose uptake and tumor proliferation in pancreatic cancer has not been investigated to date. In the present study, the expression of GLUT-1 in 53 pancreatic cancer tissues was analyzed, which revealed that GLUT-1 was overexpressed in pancreatic tissue and correlated with poor prognosis and clinicopathological characteristics, including increased tumor size, clinical stage and lymph node metastasis, maximum standardized uptake value (SUVmax) and Ki-67 expression. The receiver operating characteristic curve analysis indicated that a cut-off SUVmax value of 4.830 was associated with optimal sensitivity (88%) and specificity (71.4%) for the detection of strong positive GLUT-1 expression. In addition, as the expression of GLUT-1 was found to correlate with Ki-67 expression, GLUT-1 may exhibit a significant effect on cell proliferation in pancreatic cancer. Overall, these findings indicate that GLUT-1 may represent a prognostic indicator, and a potential therapeutic target for pancreatic cancer. PMID:27347132

Small area clustering of under-five children's mortality and associated factors using geo-additive Bayesian discrete-time survival model in Kersa HDSS, Ethiopia.

PubMed

Dedefo, Melkamu; Oljira, Lemessa; Assefa, Nega

2016-02-01

Child mortality reflects a country's level of socio-economic development and quality of life. In Ethiopia, limited studies were conducted on under-five mortality and almost none of them tried to identify the spatial effect on mortality. Thus, this study explored the small area clustering of under-five mortality and associated factors in Kersa HDSS, Eastern Ethiopia. The study population included all children under the age of five years during the time September, 2008-august 31, 2012 which are registered in Kersa Health and Demographic Surveillance System (Kersa HDSS). A flexible Bayesian geo-additive discrete-time survival mixed model was used. Some of the factors that are significantly associated with under-five mortality, with posterior odds ratio and 95% credible intervals, are maternal educational status 1.31(1.13,-1.49), place of delivery 1.016(1.013-1.12), no of live birth at a delivery 0.35(0.23,1.83), low household wealth index 1.26(1.10 1.43) middle level household wealth index 0.95 (0.84 1.07) pre-term duration of pregnancy 1.95(1.27,2.91), post-term duration of pregnancy 0.74(0.60,0.93) and antenatal visit 1.19(1.06, 1.35). Variation was noted in the risk of under-five mortality by the selected small administrative regions (kebeles). This study reveals geographic patterns in rates of under-five mortality in those selected small administrative regions and shows some important determinants of under-five mortality. More importantly, we observed clustering of under-five mortality, which indicates the importance of spatial effects and presentation of this clustering through maps that facilitates visuality and highlights differentials across geographical areas that would, otherwise, be overlooked in traditional data-analytic methods. Copyright © 2015 Elsevier Ltd. All rights reserved.

Significant social events and increasing use of life-sustaining treatment: trend analysis using extracorporeal membrane oxygenation as an example.

PubMed

Chen, Yen-Yuan; Chen, Likwang; Huang, Tien-Shang; Ko, Wen-Je; Chu, Tzong-Shinn; Ni, Yen-Hsuan; Chang, Shan-Chwen

2014-03-04

Most studies have examined the outcomes of patients supported by extracorporeal membrane oxygenation as a life-sustaining treatment. It is unclear whether significant social events are associated with the use of life-sustaining treatment. This study aimed to compare the trend of extracorporeal membrane oxygenation use in Taiwan with that in the world, and to examine the influence of significant social events on the trend of extracorporeal membrane oxygenation use in Taiwan. Taiwan's extracorporeal membrane oxygenation uses from 2000 to 2009 were collected from National Health Insurance Research Dataset. The number of the worldwide extracorporeal membrane oxygenation cases was mainly estimated using Extracorporeal Life Support Registry Report International Summary July 2012. The trend of Taiwan's crude annual incidence rate of extracorporeal membrane oxygenation use was compared with that of the rest of the world. Each trend of extracorporeal membrane oxygenation use was examined using joinpoint regression. The measurement was the crude annual incidence rate of extracorporeal membrane oxygenation use. Each of the Taiwan's crude annual incidence rates was much higher than the worldwide one in the same year. Both the trends of Taiwan's and worldwide crude annual incidence rates have significantly increased since 2000. Joinpoint regression selected the model of the Taiwan's trend with one joinpoint in 2006 as the best-fitted model, implying that the significant social events in 2006 were significantly associated with the trend change of extracorporeal membrane oxygenation use following 2006. In addition, significantly social events highlighted by the media are more likely to be associated with the increase of extracorporeal membrane oxygenation use than being fully covered by National Health Insurance. Significant social events, such as a well-known person's successful extracorporeal membrane oxygenation use highlighted by the mass media, are associated with the use of

Trophic significance of the kelp Laminaria digitata (Lamour.) for the associated food web: a between-sites comparison

NASA Astrophysics Data System (ADS)

Schaal, Gauthier; Riera, Pascal; Leroux, Cédric

2009-12-01

This study aimed at establishing the trophic significance of the kelp Laminaria digitata for consumers inhabiting two rocky shores of Northern Brittany (France), displaying contrasted ecological conditions. The general trophic structure did not vary between these two sites, with a wide diversity of filter-feeders and predators, and only 14% of the species sampled belonging to the grazers' trophic group. The diversity of food sources fueling the food web appeared also similar. The food webs comprised four trophic levels and the prevalence of omnivory appeared relatively low compared to previous studies in the same area. Conversely, to the food web structure, which did not differ, the biochemical composition of L. digitata differed between the two sites, and was correlated to a larger diversity of grazers feeding on this kelp in sheltered conditions. This indicated that the spatial variability occurring in the nutritive value of L. digitata is likely to deeply affect the functioning of kelp-associated food webs. The contribution of L. digitata-derived organic matter to the diet of filter-feeders inhabiting these two environments was assessed using the mixing model Isosource, which showed the higher contribution of kelp matter in sheltered conditions. These results highlight the spatial variability that may occur in the functioning of kelp-associated food webs. Moreover, this suggests that hydrodynamics is likely to control the availability of kelp-derived organic matter to local filter-feeders, probably through an increase of detritus export in exposed areas.

The Soil Microbiome Influences Grapevine-Associated Microbiota

PubMed Central

Zarraonaindia, Iratxe; Owens, Sarah M.; Weisenhorn, Pamela; West, Kristin; Hampton-Marcell, Jarrad; Lax, Simon; Bokulich, Nicholas A.; Mills, David A.; Martin, Gilles; Taghavi, Safiyh; van der Lelie, Daniel

2015-01-01

ABSTRACT Grapevine is a well-studied, economically relevant crop, whose associated bacteria could influence its organoleptic properties. In this study, the spatial and temporal dynamics of the bacterial communities associated with grapevine organs (leaves, flowers, grapes, and roots) and soils were characterized over two growing seasons to determine the influence of vine cultivar, edaphic parameters, vine developmental stage (dormancy, flowering, preharvest), and vineyard. Belowground bacterial communities differed significantly from those aboveground, and yet the communities associated with leaves, flowers, and grapes shared a greater proportion of taxa with soil communities than with each other, suggesting that soil may serve as a bacterial reservoir. A subset of soil microorganisms, including root colonizers significantly enriched in plant growth-promoting bacteria and related functional genes, were selected by the grapevine. In addition to plant selective pressure, the structure of soil and root microbiota was significantly influenced by soil pH and C:N ratio, and changes in leaf- and grape-associated microbiota were correlated with soil carbon and showed interannual variation even at small spatial scales. Diazotrophic bacteria, e.g., Rhizobiaceae and Bradyrhizobium spp., were significantly more abundant in soil samples and root samples of specific vineyards. Vine-associated microbial assemblages were influenced by myriad factors that shape their composition and structure, but the majority of organ-associated taxa originated in the soil, and their distribution reflected the influence of highly localized biogeographic factors and vineyard management. PMID:25805735

The soil microbiome influences grapevine-associated microbiota

DOE PAGES

Zarraonaindia, Iratxe; Owens, Sarah M.; Weisenhorn, Pamela; ...

2015-03-24

Grapevine is a well-studied, economically relevant crop, whose associated bacteria could influence its organoleptic properties. In this study, the spatial and temporal dynamics of the bacterial communities associated with grapevine organs (leaves, flowers, grapes, and roots) and soils were characterized over two growing seasons to determine the influence of vine cultivar, edaphic parameters, vine developmental stage (dormancy, flowering, preharvest), and vineyard. Belowground bacterial communities differed significantly from those aboveground, and yet the communities associated with leaves, flowers, and grapes shared a greater proportion of taxa with soil communities than with each other, suggesting that soil may serve as a bacterialmore » reservoir. A subset of soil microorganisms, including root colonizers significantly enriched in plant growth-promoting bacteria and related functional genes, were selected by the grapevine. In addition to plant selective pressure, the structure of soil and root microbiota was significantly influenced by soil pH and C:N ratio, and changes in leaf- and grape-associated microbiota were correlated with soil carbon and showed interannual variation even at small spatial scales. Diazotrophic bacteria, e.g., Rhizobiaceae and Bradyrhizobium spp., were significantly more abundant in soil samples and root samples of specific vineyards. Vine-associated microbial assemblages were influenced by myriad factors that shape their composition and structure, but the majority of organ-associated taxa originated in the soil, and their distribution reflected the influence of highly localized biogeographic factors and vineyard management.« less

Genome-wide association study of kidney function decline in individuals of European descent.

PubMed

Gorski, Mathias; Tin, Adrienne; Garnaas, Maija; McMahon, Gearoid M; Chu, Audrey Y; Tayo, Bamidele O; Pattaro, Cristian; Teumer, Alexander; Chasman, Daniel I; Chalmers, John; Hamet, Pavel; Tremblay, Johanne; Woodward, Marc; Aspelund, Thor; Eiriksdottir, Gudny; Gudnason, Vilmundur; Harris, Tamara B; Launer, Lenore J; Smith, Albert V; Mitchell, Braxton D; O'Connell, Jeffrey R; Shuldiner, Alan R; Coresh, Josef; Li, Man; Freudenberger, Paul; Hofer, Edith; Schmidt, Helena; Schmidt, Reinhold; Holliday, Elizabeth G; Mitchell, Paul; Wang, Jie Jin; de Boer, Ian H; Li, Guo; Siscovick, David S; Kutalik, Zoltan; Corre, Tanguy; Vollenweider, Peter; Waeber, Gérard; Gupta, Jayanta; Kanetsky, Peter A; Hwang, Shih-Jen; Olden, Matthias; Yang, Qiong; de Andrade, Mariza; Atkinson, Elizabeth J; Kardia, Sharon L R; Turner, Stephen T; Stafford, Jeanette M; Ding, Jingzhong; Liu, Yongmei; Barlassina, Cristina; Cusi, Daniele; Salvi, Erika; Staessen, Jan A; Ridker, Paul M; Grallert, Harald; Meisinger, Christa; Müller-Nurasyid, Martina; Krämer, Bernhard K; Kramer, Holly; Rosas, Sylvia E; Nolte, Ilja M; Penninx, Brenda W; Snieder, Harold; Fabiola Del Greco, M; Franke, Andre; Nöthlings, Ute; Lieb, Wolfgang; Bakker, Stephan J L; Gansevoort, Ron T; van der Harst, Pim; Dehghan, Abbas; Franco, Oscar H; Hofman, Albert; Rivadeneira, Fernando; Sedaghat, Sanaz; Uitterlinden, André G; Coassin, Stefan; Haun, Margot; Kollerits, Barbara; Kronenberg, Florian; Paulweber, Bernhard; Aumann, Nicole; Endlich, Karlhans; Pietzner, Mike; Völker, Uwe; Rettig, Rainer; Chouraki, Vincent; Helmer, Catherine; Lambert, Jean-Charles; Metzger, Marie; Stengel, Benedicte; Lehtimäki, Terho; Lyytikäinen, Leo-Pekka; Raitakari, Olli; Johnson, Andrew; Parsa, Afshin; Bochud, Murielle; Heid, Iris M; Goessling, Wolfram; Köttgen, Anna; Kao, W H Linda; Fox, Caroline S; Böger, Carsten A

2015-05-01

Genome-wide association studies (GWASs) have identified multiple loci associated with cross-sectional eGFR, but a systematic genetic analysis of kidney function decline over time is missing. Here we conducted a GWAS meta-analysis among 63,558 participants of European descent, initially from 16 cohorts with serial kidney function measurements within the CKDGen Consortium, followed by independent replication among additional participants from 13 cohorts. In stage 1 GWAS meta-analysis, single-nucleotide polymorphisms (SNPs) at MEOX2, GALNT11, IL1RAP, NPPA, HPCAL1, and CDH23 showed the strongest associations for at least one trait, in addition to the known UMOD locus, which showed genome-wide significance with an annual change in eGFR. In stage 2 meta-analysis, the significant association at UMOD was replicated. Associations at GALNT11 with Rapid Decline (annual eGFR decline of 3 ml/min per 1.73 m(2) or more), and CDH23 with eGFR change among those with CKD showed significant suggestive evidence of replication. Combined stage 1 and 2 meta-analyses showed significance for UMOD, GALNT11, and CDH23. Morpholino knockdowns of galnt11 and cdh23 in zebrafish embryos each had signs of severe edema 72 h after gentamicin treatment compared with controls, but no gross morphological renal abnormalities before gentamicin administration. Thus, our results suggest a role in the deterioration of kidney function for the loci GALNT11 and CDH23, and show that the UMOD locus is significantly associated with kidney function decline.

Genome-wide association study of kidney function decline in individuals of European descent

PubMed Central

Gorski, Mathias; Tin, Adrienne; Garnaas, Maija; McMahon, Gearoid M.; Chu, Audrey Y.; Tayo, Bamidele O.; Pattaro, Cristian; Teumer, Alexander; Chasman, Daniel I.; Chalmers, John; Hamet, Pavel; Tremblay, Johanne; Woodward, Marc; Aspelund, Thor; Eiriksdottir, Gudny; Gudnason, Vilmundur; Harris, Tammara B.; Launer, Lenore J.; Smith, Albert V.; Mitchell, Braxton D.; O'Connell, Jeffrey R.; Shuldiner, Alan R.; Coresh, Josef; Li, Man; Freudenberger, Paul; Hofer, Edith; Schmidt, Helena; Schmidt, Reinhold; Holliday, Elizabeth G.; Mitchell, Paul; Wang, Jie Jin; de Boer, Ian H.; Li, Guo; Siscovick, David S.; Kutalik, Zoltan; Corre, Tanguy; Vollenweider, Peter; Waeber, Gérard; Gupta, Jayanta; Kanetsky, Peter A.; Hwang, Shih-Jen; Olden, Matthias; Yang, Qiong; de Andrade, Mariza; Atkinson, Elizabeth J.; Kardia, Sharon L.R.; Turner, Stephen T.; Stafford, Jeanette M.; Ding, Jingzhong; Liu, Yongmei; Barlassina, Cristina; Cusi, Daniele; Salvi, Erika; Staessen, Jan A; Ridker, Paul M; Grallert, Harald; Meisinger, Christa; Müller-Nurasyid, Martina; Krämer, Bernhard K.; Kramer, Holly; Rosas, Sylvia E.; Nolte, Ilja M.; Penninx, Brenda W.; Snieder, Harold; Del Greco, Fabiola; Franke, Andre; Nöthlings, Ute; Lieb, Wolfgang; Bakker, Stephan J.L.; Gansevoort, Ron T.; van der Harst, Pim; Dehghan, Abbas; Franco, Oscar H.; Hofman, Albert; Rivadeneira, Fernando; Sedaghat, Sanaz; Uitterlinden, André G.; Coassin, Stefan; Haun, Margot; Kollerits, Barbara; Kronenberg, Florian; Paulweber, Bernhard; Aumann, Nicole; Endlich, Karlhans; Pietzner, Mike; Völker, Uwe; Rettig, Rainer; Chouraki, Vincent; Helmer, Catherine; Lambert, Jean-Charles; Metzger, Marie; Stengel, Benedicte; Lehtimäki, Terho; Lyytikäinen, Leo-Pekka; Raitakari, Olli; Johnson, Andrew; Parsa, Afshin; Bochud, Murielle; Heid, Iris M.; Goessling, Wolfram; Köttgen, Anna; Kao, H. Linda; Fox, Caroline S.; Böger, Carsten A.

2014-01-01

Genome wide association studies (GWAS) have identified multiple loci associated with cross-sectional eGFR, but a systematic genetic analysis of kidney function decline over time is missing. Here we conducted a GWAS meta-analysis among 63,558 participants of European descent, initially from 16 cohorts with serial kidney function measurements within the CKDGen Consortium, followed by independent replication among additional participants from 13 cohorts. In stage 1 GWAS meta-analysis, SNPs at MEOX2, GALNT11, IL1RAP, NPPA, HPCAL1 and CDH23 showed the strongest associations for at least one trait, in addition to the known UMOD locus which showed genome-wide significance with an annual change in eGFR. In stage 2 meta-analysis, the significant association at UMOD was replicated. Associations at GALNT11 with Rapid Decline (annual eGFRdecline of 3ml/min/1.73m2 or more), and CDH23 with eGFR change among those with CKD showed significant suggestive evidence of replication. Combined stage 1 and 2 meta-analyses showed significance for UMOD, GALNT11 and CDH23. Morpholino knockdowns of galnt11 and cdh23 in zebrafish embryos each had signs of severe edema 72 hours after gentamicin treatment compared to controls, but no gross morphological renal abnormalities before gentamicin administration. Thus, our results suggest a role in the deterioration of kidney function for the loci GALNT11 and CDH23, and show that the UMOD locus is significantly associated with kidney function decline. PMID:25493955

Additive direct-write microfabrication for MEMS: A review

NASA Astrophysics Data System (ADS)

Teh, Kwok Siong

2017-12-01

Direct-write additive manufacturing refers to a rich and growing repertoire of well-established fabrication techniques that builds solid objects directly from computer- generated solid models without elaborate intermediate fabrication steps. At the macroscale, direct-write techniques such as stereolithography, selective laser sintering, fused deposition modeling ink-jet printing, and laminated object manufacturing have significantly reduced concept-to-product lead time, enabled complex geometries, and importantly, has led to the renaissance in fabrication known as the maker movement. The technological premises of all direct-write additive manufacturing are identical—converting computer generated three-dimensional models into layers of two-dimensional planes or slices, which are then reconstructed sequentially into threedimensional solid objects in a layer-by-layer format. The key differences between the various additive manufacturing techniques are the means of creating the finished layers and the ancillary processes that accompany them. While still at its infancy, direct-write additive manufacturing techniques at the microscale have the potential to significantly lower the barrier-of-entry—in terms of cost, time and training—for the prototyping and fabrication of MEMS parts that have larger dimensions, high aspect ratios, and complex shapes. In recent years, significant advancements in materials chemistry, laser technology, heat and fluid modeling, and control systems have enabled additive manufacturing to achieve higher resolutions at the micrometer and nanometer length scales to be a viable technology for MEMS fabrication. Compared to traditional MEMS processes that rely heavily on expensive equipment and time-consuming steps, direct-write additive manufacturing techniques allow for rapid design-to-prototype realization by limiting or circumventing the need for cleanrooms, photolithography and extensive training. With current direct-write additive

Predicting significant torso trauma.

PubMed

Nirula, Ram; Talmor, Daniel; Brasel, Karen

2005-07-01

Identification of motor vehicle crash (MVC) characteristics associated with thoracoabdominal injury would advance the development of automatic crash notification systems (ACNS) by improving triage and response times. Our objective was to determine the relationships between MVC characteristics and thoracoabdominal trauma to develop a torso injury probability model. Drivers involved in crashes from 1993 to 2001 within the National Automotive Sampling System were reviewed. Relationships between torso injury and MVC characteristics were assessed using multivariate logistic regression. Receiver operating characteristic curves were used to compare the model to current ACNS models. There were a total of 56,466 drivers. Age, ejection, braking, avoidance, velocity, restraints, passenger-side impact, rollover, and vehicle weight and type were associated with injury (p < 0.05). The area under the receiver operating characteristic curve (83.9) was significantly greater than current ACNS models. We have developed a thoracoabdominal injury probability model that may improve patient triage when used with ACNS.

Does Emotion Dysregulation Mediate the Association Between Sluggish Cognitive Tempo and College Students' Social Impairment?

PubMed

Flannery, Andrew J; Becker, Stephen P; Luebbe, Aaron M

2016-09-01

Studies demonstrate an association between sluggish cognitive tempo (SCT) and social impairment, although no studies have tested possible mechanisms of this association. This study aimed to (a) examine SCT in relation to college students' social functioning; (b) test if SCT is significantly associated with emotion dysregulation beyond depressive, anxious, and ADHD symptoms; and (c) test if emotion dysregulation mediates the association between SCT symptoms and social impairment. College students (N = 158) completed measures of psychopathology symptoms, emotion dysregulation, and social functioning. Participants with elevated SCT (12%) had higher ADHD, depressive, and anxious symptoms in addition to poorer emotion regulation and social adjustment than participants without elevated SCT. Above and beyond other psychopathologies, SCT was significantly associated with social impairment but not general interpersonal functioning. SCT was also associated with emotion dysregulation, even after accounting for the expectedly strong association between depression and emotion dysregulation. Further analyses supported emotion dysregulation as a mediator of the association between SCT and social impairment. These findings are important for theoretical models of SCT and underscore the need for additional, longitudinal research. © The Author(s) 2014.

Can gravity waves significantly impact PSC occurrence in the Antarctic?

NASA Astrophysics Data System (ADS)

McDonald, A. J.; George, S. E.; Woollands, R. M.

2009-11-01

A combination of POAM III aerosol extinction and CHAMP RO temperature measurements are used to examine the role of atmospheric gravity waves in the formation of Antarctic Polar Stratospheric Clouds (PSCs). POAM III aerosol extinction observations and quality flag information are used to identify Polar Stratospheric Clouds using an unsupervised clustering algorithm. A PSC proxy, derived by thresholding Met Office temperature analyses with the PSC Type Ia formation temperature (TNAT), shows general agreement with the results of the POAM III analysis. However, in June the POAM III observations of PSC are more abundant than expected from temperature threshold crossings in five out of the eight years examined. In addition, September and October PSC identified using temperature thresholding is often significantly higher than that derived from POAM III; this observation probably being due to dehydration and denitrification. Comparison of the Met Office temperature analyses with corresponding CHAMP observations also suggests a small warm bias in the Met Office data in June. However, this bias cannot fully explain the differences observed. Analysis of CHAMP data indicates that temperature perturbations associated with gravity waves may partially explain the enhanced PSC incidence observed in June (relative to the Met Office analyses). For this month, approximately 40% of the temperature threshold crossings observed using CHAMP RO data are associated with small-scale perturbations. Examination of the distribution of temperatures relative to TNAT shows a large proportion of June data to be close to this threshold, potentially enhancing the importance of gravity wave induced temperature perturbations. Inspection of the longitudinal structure of PSC occurrence in June 2005 also shows that regions of enhancement are geographically associated with the Antarctic Peninsula; a known mountain wave "hotspot". The latitudinal variation of POAM III observations means that we only

Genetic polymorphisms in ALDH2 are associated with drug addiction in a Chinese Han population

PubMed Central

Zhang, Chan; Ding, Heng; Cheng, Yujing; Chen, Wanlu; Li, Qi; Li, Qing; Dai, Run; Luo, Manlin

2017-01-01

We investigated the association between single nucleotide polymorphisms (SNPs) in ALDH2, which has been associated with alcohol dependence and several types of diseases, and the risk of drug addiction in a Chinese Han population. In a case-control study that included 692 cases and 700 healthy controls, eight SNPs in ALDH2 were selected and genotyped using the Sequenom MassARRAY platform. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using unconditional logistic regression after adjusting for age and gender. We determined that rs671 is significantly associated with a 1.551-fold increased drug addiction risk (95% CI = 1.263-1.903; p < 0.001). In the genetic model analysis, we found that rs671 is associated with an increased risk of drug addiction under additive, dominant and recessive models (p < 0.001), while rs886205, rs441 and rs4646778 displayed a decreased drug addiction risk under additive and recessive model, respectively (p < 0.05). SNP rs671 remained significant after Bonferroni correction (p<0.00125). Additionally, we observed that haplotype “GTCAC” was associated with increased drug addiction risk (OR = 1.668; 95% CI, 1.328–2.094, p < 0.001); in contrast, “ATCGC” was a protective haplotype for drug addiction risk (OR = 0.444; 95% CI, 0.281–0.704, p < 0.001). Our findings showed that ALDH2 polymorphisms are significantly associated with the risk of drug addiction in the Chinese Han population. PMID:28052001

Genetic polymorphisms in ALDH2 are associated with drug addiction in a Chinese Han population.

PubMed

Zhang, Chan; Ding, Heng; Cheng, Yujing; Chen, Wanlu; Li, Qi; Li, Qing; Dai, Run; Luo, Manlin

2017-01-31

We investigated the association between single nucleotide polymorphisms (SNPs) in ALDH2, which has been associated with alcohol dependence and several types of diseases, and the risk of drug addiction in a Chinese Han population. In a case-control study that included 692 cases and 700 healthy controls, eight SNPs in ALDH2 were selected and genotyped using the Sequenom MassARRAY platform. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using unconditional logistic regression after adjusting for age and gender. We determined that rs671 is significantly associated with a 1.551-fold increased drug addiction risk (95% CI = 1.263-1.903; p < 0.001). In the genetic model analysis, we found that rs671 is associated with an increased risk of drug addiction under additive, dominant and recessive models (p < 0.001), while rs886205, rs441 and rs4646778 displayed a decreased drug addiction risk under additive and recessive model, respectively (p < 0.05). SNP rs671 remained significant after Bonferroni correction (p<0.00125). Additionally, we observed that haplotype "GTCAC" was associated with increased drug addiction risk (OR = 1.668; 95% CI, 1.328-2.094, p < 0.001); in contrast, "ATCGC" was a protective haplotype for drug addiction risk (OR = 0.444; 95% CI, 0.281-0.704, p < 0.001). Our findings showed that ALDH2 polymorphisms are significantly associated with the risk of drug addiction in the Chinese Han population.

Clinical significance of J-wave in elite athletes.

PubMed

Pelliccia, Antonio; Quattrini, Filippo M

2015-01-01

The J-wave pattern on 12-lead ECG is traditionally defined as a positive deflection at junction between the end of the QRS and the beginning of the ST-segment. This pattern has recently been associated with increased risk for idiopathic ventricular fibrillation in the absence of cardiovascular disease. The interest for the clinical significance of J-wave pattern as a potential ECG hallmark of high risk for cardiac arrest has recently been reinforced by the growing practice of ECG screening, such as occurs in large population of young competitive athletes. The available scientific evidence shows that the J-wave pattern is relatively common in trained athletes (ranging from 14% to 44%) and, differently from subjects who suffered from ventricular fibrillation, commonly localized in lateral leads while it is relatively rare to be found in inferior leads. Furthermore the J-wave pattern has been demonstrated to be a dynamic phenomenon related to the training status, with the larger prominence at the peak of training and with an inverse relation between magnitude of J-wave and heart rate. In addition the J-wave pattern is usually associated with other ECG changes, such as increased QRS voltages and ST-segment elevation, as well as LV remodeling, suggesting that it likely represents another expression of the physiologic athlete's heart. Finally the scientific data available demonstrated that during a medium follow-up period the J-wave pattern does not convey risk for adverse cardiac events, including sudden death or ventricular tachyarrhythmias. Copyright © 2015 Elsevier Inc. All rights reserved.

Effect of organometallic fuel additives on nanoparticle emissions from a gasoline passenger car.

PubMed

Gidney, Jeremy T; Twigg, Martyn V; Kittelson, David B

2010-04-01

Particle size measurements were performed on the exhaust of a car operating on a chassis dynamometer fueled with standard gasoline and gasoline containing low levels of Pb, Fe, and Mn organometallic additives. When additives were present there was a distinct nucleation mode consisting primarily of sub-10 nm nanoparticles. At equal molar dosing Mn and Fe gave similar nanoparticle concentrations at the tailpipe, whereas Pb gave a considerably lower concentration. A catalytic stripper was used to remove the organic component of these particles and revealed that they were mainly solid and, because of their association with inorganic additives, presumably inorganic. Solid nucleation mode nanoparticles of similar size and concentration to those observed here from a gasoline engine with Mn and Fe additives have also been observed from modern heavy-duty diesel engines without aftertreatment at idle, but these solid particles are a small fraction of the primarily volatile nucleation mode particles emitted. The solid nucleation mode particles emitted by the diesel engines are likely derived from metal compounds in the lubrication oil, although carbonaceous particles cannot be ruled out. Significantly, most of these solid nanoparticles emitted by both engine types fall below the 23 nm cutoff of the PMP number regulation.

Risk factors for an additional port in single-incision laparoscopic cholecystectomy in patients with cholecystitis.

PubMed

Araki, Kenichiro; Shirabe, Ken; Watanabe, Akira; Kubo, Norio; Sasaki, Shigeru; Suzuki, Hideki; Asao, Takayuki; Kuwano, Hiroyuki

2017-01-01

Although single-incision laparoscopic cholecystectomy is now widely performed in patients with cholecystitis, some cases require an additional port to complete the procedure. In this study, we focused on risk factor of additional port in this surgery. We performed single-incision cholecystectomy in 75 patients with acute cholecystitis or after cholecystitis between 2010 and 2014 at Gunma University Hospital. Surgical indications followed the TG13 guidelines. Our standard procedure for single-incision cholecystectomy routinely uses two needlescopic devices. We used logistic regression analysis to identify the risk factors associated with use of an additional full-size port (5 or 10 mm). Surgical outcome was acceptable without biliary injury. Nine patients (12.0%) required an additional port, and one patient (1.3%) required conversion to open cholecystectomy because of severe adhesions around the cystic duct and common bile duct. In multivariate analysis, high C-reactive protein (CRP) values (>7.0 mg/dl) during cholecystitis attacks were significantly correlated with the need for an additional port (P = 0.009), with a sensitivity of 55.6%, specificity of 98.5%, and accuracy of 93.3%. This study indicated that the severe inflammation indicated by high CRP values during cholecystitis attacks predicts the need for an additional port. J. Med. Invest. 64: 245-249, August, 2017.

Lack of validation of genetic variants associated with anti-tumor necrosis factor therapy response in rheumatoid arthritis: a genome-wide association study replication and meta-analysis.

PubMed

Márquez, Ana; Ferreiro-Iglesias, Aida; Dávila-Fajardo, Cristina L; Montes, Ariana; Pascual-Salcedo, Dora; Perez-Pampin, Eva; Moreno-Ramos, Manuel J; García-Portales, Rosa; Navarro, Federico; Moreira, Virginia; Magro, César; Caliz, Rafael; Ferrer, Miguel Angel; Alegre-Sancho, Juan José; Joven, Beatriz; Carreira, Patricia; Balsa, Alejandro; Vasilopoulos, Yiannis; Sarafidou, Theologia; Cabeza-Barrera, José; Narvaez, Javier; Raya, Enrique; Cañete, Juan D; Fernández-Nebro, Antonio; Ordóñez, María del Carmen; de la Serna, Arturo R; Magallares, Berta; Gomez-Reino, Juan J; González, Antonio; Martín, Javier

2014-03-11

In this study, our aim was to elucidate the role of four polymorphisms identified in a prior large genome-wide association study (GWAS) in which the investigators analyzed the responses of patients with rheumatoid arthritis (RA) to treatment with tumor necrosis factor inhibitors (TNFi). The authors of that study reported that the four genetic variants were significantly associated. However, none of the associations reached GWAS significance, and two subsequent studies failed to replicate these associations. The four polymorphisms (rs12081765, rs1532269, rs17301249 and rs7305646) were genotyped in a total of 634 TNFi-treated RA patients of Spanish Caucasian origin. Four outcomes were evaluated: changes in the Disease Activity Score in 28 joints (DAS28) after 6 and 12 months of treatment and classification according to the European League Against Rheumatism (EULAR) response criteria at the same time points. Association with DAS28 changes was assessed by linear regression using an additive genetic model. Contingency tables of genotype and allele frequencies between EULAR responder and nonresponder patients were compared. In addition, we combined our data with those of previously reported studies in a meta-analysis including 2,998 RA patients. None of the four genetic variants showed an association with response to TNFi in any of the four outcomes analyzed in our Spanish patients. In addition, only rs1532269 yielded a suggestive association (P = 0.0033) with the response to TNFi when available data from previous studies were combined in the meta-analysis. Our data suggest that the rs12081765, rs1532269, rs17301249 and rs7305646 genetic variants do not have a role as genetic predictors of TNFi treatment outcomes.

Mechanical dyssynchrony is additive to ECG criteria and independently associated with reverse remodelling and clinical response to cardiac resynchronisation therapy in patients with advanced heart failure

PubMed Central

Bank, Alan J; Gage, Ryan M; Marek, Josef J; Onishi, Toshinari; Burns, Kevin V; Schwartzman, David; Saba, Samir; Gorcsan, John

2015-01-01

Background QRS duration and morphology are known established predictors of cardiac resynchronisation therapy (CRT) response, whereas mechanical dyssynchrony is not. Our aim was to determine if mechanical dyssynchrony provides independent prognostic information on CRT response. Methods We studied 369 consecutive patients with heart failure (HF) with low ejection fraction (EF) and widened QRS receiving CRT. Radial dyssynchrony (septal-posterior radial peak strain delay ≥130 ms by speckle tracking) assessment was possible in 318 patients (86%). Associations with left ventricular end-systolic volume (LVESV) changes were examined using linear regression, and clinical outcomes analysed using Cox regression adjusted for multiple established outcome correlates. Results Patients with radial dyssynchrony before CRT (64%) had greater improvements in EF (8.8±9.4 vs 6.1±9.7 units, p=0.04) and LVESV (−30±41 vs −10±30 mL, p<0.01). Radial dyssynchrony was independently associated with reduction in LVESV (regression coefficient −10.5 mL, 95% CI −20.5 to −0.5, p=0.040) as was left bundle-branch block (−17.7 mL, −27.6 to −7.7, p=0.001). Patients with radial dyssynchrony had a 46% lower incidence of death, transplant or implantation of a left ventricular assist device (adjusted HR 0.54, 95% CI 0.31 to 0.92, p=0.02) and a 39% lower incidence of death or HF hospitalisation (0.61, 0.40 to 0.93, p=0.02) over 2 years. Conclusions Radial dyssynchrony was associated with significant improvements in LVESV and clinical outcomes following CRT and is independent of QRS duration or morphology, and additive to current ECG selection criteria to predict response to CRT. PMID:25973213

Polymethylmethacrylate bone cements and additives: A review of the literature

PubMed Central

Arora, Manit; Chan, Edward KS; Gupta, Sunil; Diwan, Ashish D

2013-01-01

Polymethylmethacrylate (PMMA) bone cement technology has progressed from industrial Plexiglass administration in the 1950s to the recent advent of nanoparticle additives. Additives have been trialed to address problems with modern bone cements such as the loosening of prosthesis, high post-operative infection rates, and inflammatory reduction in interface integrity. This review aims to assess current additives used in PMMA bone cements and offer an insight regarding future directions for this biomaterial. Low index (< 15%) vitamin E and low index (< 5 g) antibiotic impregnated additives significantly address infection and inflammatory problems, with only modest reductions in mechanical strength. Chitosan (15% w/w PMMA) and silver (1% w/w PMMA) nanoparticles have strong antibacterial activity with no significant reduction in mechanical strength. Future work on PMMA bone cements should focus on trialing combinations of these additives as this may enhance favourable properties. PMID:23610754

Genetic predisposition to coronary heart disease and stroke using an additive genetic risk score: A population-based study in Greece

PubMed Central