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| 512. |
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| 513. |
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| 514. |
- Faulin, TDS, et al.
(author)
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Proinflammatory Action of a New Electronegative Low-Density Lipoprotein Epitope
- 2019
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In: Biomolecules. - : MDPI AG. - 2218-273X. ; 9:8
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Journal article (peer-reviewed)abstract
- The electronegative low-density lipoprotein, LDL (−), is an endogenously modified LDL subfraction with cytotoxic and proinflammatory actions on endothelial cells, monocytes, and macrophages contributing to the progression of atherosclerosis. In this study, epitopes of LDL (−) were mapped using a phage display library of peptides and monoclonal antibodies reactive to this modified lipoprotein. Two different peptide libraries (X6 and CX8C for 6- and 8-amino acid-long peptides, respectively) were used in the mapping. Among all tested peptides, two circular peptides, P1A3 and P2C7, were selected based on their high affinities for the monoclonal antibodies. Small-angle X-ray scattering analysis confirmed their structures as circular rings. P1A3 or P2C7 were quickly internalized by bone marrow-derived murine macrophages as shown by confocal microscopy. P2C7 increased the expression of TNFα, IL-1 β and iNOS as well as the secretion of TNFα, CCL2, and nitric oxide by murine macrophages, similar to the responses induced by LDL (−), although less intense. In contrast, P1A3 did not show pro-inflammatory effects. We identified a mimetic epitope associated with LDL (−), the P2C7 circular peptide, that activates macrophages. Our data suggest that this conformational epitope represents an important danger-associated molecular pattern of LDL (−) that triggers proinflammatory responses.
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| 515. |
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| 516. |
- Gehlen, J., et al.
(author)
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First genome-wide association study of esophageal atresia identifies three genetic risk loci at CTNNA3, FOXF1/FOXC2/FOXL1, and HNF1B
- 2022
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In: Human Genetics and Genomics Advances. - : Elsevier BV. - 2666-2477. ; 3:2
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Journal article (peer-reviewed)abstract
- Esophageal atresia with or without tracheoesophageal fistula (EA/TEF) is the most common congenital malformation of the upper digestive tract. This study represents the first genome-wide association study (GWAS) to identify risk loci for EA/TEF. We used a European case-control sample comprising 764 EA/TEF patients and 5,778 controls and observed genome-wide significant associations at three loci. On chromosome 10q21 within the gene CTNNA3 (p = 2.11 × 10−8; odds ratio [OR] = 3.94; 95% confidence interval [CI], 3.10–5.00), on chromosome 16q24 next to the FOX gene cluster (p = 2.25 × 10−10; OR = 1.47; 95% CI, 1.38–1.55) and on chromosome 17q12 next to the gene HNF1B (p = 3.35 × 10−16; OR = 1.75; 95% CI, 1.64–1.87). We next carried out an esophageal/tracheal transcriptome profiling in rat embryos at four selected embryonic time points. Based on these data and on already published data, the implicated genes at all three GWAS loci are promising candidates for EA/TEF development. We also analyzed the genetic EA/TEF architecture beyond the single marker level, which revealed an estimated single-nucleotide polymorphism (SNP)-based heritability of around 37% ± 14% standard deviation. In addition, we examined the polygenicity of EA/TEF and found that EA/TEF is less polygenic than other complex genetic diseases. In conclusion, the results of our study contribute to a better understanding on the underlying genetic architecture of ET/TEF with the identification of three risk loci and candidate genes. © 2022 The Authors
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| 517. |
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| 518. |
- Hodges, P. W., et al.
(author)
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Building a Collaborative Model of Sacroiliac Joint Dysfunction and Pelvic Girdle Pain to Understand the Diverse Perspectives of Experts
- 2019
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In: PM&R. - : Wiley. - 1934-1482 .- 1934-1563. ; 11:Suppl. 1
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Journal article (peer-reviewed)abstract
- Background: Pelvic girdle pain (PGP) and sacroiliac joint (SIJ) dysfunction/pain are considered frequent contributors to low back pain (LBP). Like other persistent pain conditions, PGP is increasingly recognized as a multifactorial problem involving biological, psychological, and social factors. Perspectives differ between experts and a diversity of treatments (with variable degrees of evidence) have been utilized. Objective: To develop a collaborative model of PGP that represents the collective view of a group of experts. Specific goals were to analyze structure and composition of conceptual models contributed by participants, to aggregate them into a metamodel, to analyze the metamodel's composition, and to consider predicted efficacy of treatments. Design: To develop a collaborative model of PGP, models were generated by invited individuals to represent their understanding of PGP using fuzzy cognitive mapping (FCM). FCMs involved proposal of components related to causes, outcomes, and treatments for pain, disability, and quality of life, and their connections. Components were classified into thematic categories. Weighting of connections was summed for components to judge their relative importance. FCMs were aggregated into a metamodel for analysis of the collective opinion it represented and to evaluate expected efficacy of treatments. Results: From 21 potential contributors, 14 (67%) agreed to participate (representing six disciplines and seven countries). Participants' models included a mean (SD) of 22 (5) components each. FCMs were refined to combine similar terms, leaving 89 components in 10 categories. Biomechanical factors were the most important in individual FCMs. The collective opinion from the metamodel predicted greatest efficacy for injection, exercise therapy, and surgery for pain relief. Conclusions: The collaborative model of PGP showed a bias toward biomechanical factors. Most efficacious treatments predicted by the model have modest to no evidence from clinical trials, suggesting a mismatch between opinion and evidence. The model enables integration and communication of the collection of opinions on PGP.
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| 519. |
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| 520. |
- Kaye, S, et al.
(author)
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Persistence and Subtype Stability of ADHD Among Substance Use Disorder Treatment Seekers
- 2019
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In: Journal of attention disorders. - : SAGE Publications. - 1557-1246 .- 1087-0547. ; 23:12, s. 1438-1453
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Journal article (peer-reviewed)abstract
- Objective: To examine ADHD symptom persistence and subtype stability among substance use disorder (SUD) treatment seekers. Method: In all, 1,276 adult SUD treatment seekers were assessed for childhood and adult ADHD using Conners’ Adult ADHD Diagnostic Interview for Diagnostic and Statistical Manual of Mental Disorders (4th ed.; DSM-IV; CAADID). A total of 290 (22.7%) participants met CAADID criteria for childhood ADHD and comprise the current study sample. Results: Childhood ADHD persisted into adulthood in 72.8% ( n = 211) of cases. ADHD persistence was significantly associated with a family history of ADHD, and the presence of conduct disorder and antisocial personality disorder. The combined subtype was the most stable into adulthood (78.6%) and this stability was significantly associated with conduct disorder and past treatment of ADHD. Conclusion: ADHD is highly prevalent and persistent among SUD treatment seekers and is associated with the more severe phenotype that is also less likely to remit. Routine screening and follow-up assessment for ADHD is indicated to enhance treatment management and outcomes.
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