FRI0570 IDENTIFICATION OF OSTEOPONTIN/SECRETED PHOSPHOPROTEIN 1 AS A BIOMARKER FOR PSORIATIC ARTHRITIS

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 887.1-887
Author(s):  
F. Abji ◽  
R. Machhar ◽  
K. Liang ◽  
J. Ye ◽  
K. Oikonomopoulou ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Logistic Regression ◽  
Psoriatic Arthritis ◽  
Synovial Fluid ◽  
Literature Review ◽  
Proteomic Analysis ◽  
Phase 1 ◽  
Serum Levels ◽  
Phase 2 ◽  
Skin Biopsies

Background:Early diagnosis of psoriatic arthritis (PsA) can be facilitated by appropriate referral of psoriasis patients to rheumatologists. Soluble biomarkers for PsA may help screen psoriasis patients for PsA.Objectives:To identify novel biomarkers for PsA by investigating serum levels of candidate biomarkers identified through proteomic analysis of synovial fluid (SF) and skin biopsies and literature review.Methods:We first (discovery phase) identified markers using: i) proteomic analysis of SF1, ii) proteomic analysis of skin biopsies2, and iii) literature review. In verification phase 1, we measured serum levels of the selected potential protein markers, using commercially available ELISA kits, to identify differentially expressed markers in healthy controls and patients with PsA (≥3 swollen joints, not treated with biologics) and psoriasis without PsA (PsC; matched with PsA patients on age, sex and psoriasis duration) (100 subjects each group). In verification phase 2, using less strict criteria (no restriction on pharmacotherapy or disease activity) and larger sample size, we confirmed the association with PsA of markers identified in phase 1 using samples from 200 patients each with PsA and PsC. Statistical methods used included descriptive statistics, t-tests and logistic regression.Results:The discovery phase identified the following 31 markers for testing in verification phase 1- hsCRP, MMP3, CD5L, M2BP, MPO, ITGB5, DKK1, FGF23, IL-6, IL-1β, leptin, osteocalcin, OPG, OPN, SOST, TNFα, adiponectin, periostin, RANKL, YKL40, KLK6, KLK8, CS846, C2C, CPII, TNFSF14, COMP, ALP, CXCL10, S100A8/A9 and DEFA. The following 21 markers remained differentially upregulated in PsA after testing in verification phase 1- hsCRP, MMP-3, M2BP, ITGB5, leptin, OPG, OPN, SOST,TNFα, periostin, RANKL, YKL40, KLK8, C2C, CPII, TNFSF14, COMP, ALP, CXCL10, S100A8/A9 and DEFA. Univariate logistic regression analyses adjusted for age, sex, and disease duration confirmed the association between hsCRP, OPN, S100A8/A9, OPG and the ratio CPII/C2C in verification phase 2. Multivariate logistic regression demonstrated that hsCRP and OPN (both p<0.001) are independently associated with PsA.Conclusion:OPN, a cytokine involved in enhancing production of IFNγ and IL-12, reducing production of IL-10 and promoting attachment of osteoclasts to mineralized bone matrix, is a potential biomarker of PsA.References:[1] Cretu D, Prassas I, Saraon P, Batruch I, Gandhi R, Diamandis EP, Chandran V. Identification of psoriatic arthritis mediators in synovial fluid by quantitative mass spectrometry. Clin Proteomics. 2014 Jul 1;11(1):27.[2] Cretu D, Liang K, Saraon P, Batruch I, Diamandis EP, Chandran V. Quantitative tandem mass-spectrometry of skin tissue reveals putative psoriatic arthritis biomarkers. Clin Proteomics. 2015 Jan 13;12(1):1.Disclosure of Interests:Fatima Abji: None declared, Rohan Machhar: None declared, Kun Liang: None declared, Justine Ye: None declared, Katerina Oikonomopoulou: None declared, Vinod Chandran Grant/research support from: Abbvie, Celgene, Consultant of: Abbvie, Amgen, Bristol-Myers Squibb, Celgene, Eli Lily, Janssen, Novartis, Pfizer, UCB, Employee of: Spouse employed by Eli Lily

scholarly journals Different Dietary Protein Sources in Low-Protein Diets Induces Changes in Antioxidant Capacity, Immunity, Fecal Microbiota and Metabolites of Weaned Piglets

2021 ◽  
Author(s):  
Lianhua Zhang ◽  
Xiangshu Piao
Keyword(s):  
Antioxidant Capacity ◽  
Soybean Meal ◽  
Phase 1 ◽  
Serum Levels ◽  
Fecal Microbiota ◽  
Phase 2 ◽  
Weaned Piglets ◽  
Low Protein ◽  
Dietary Treatments ◽  
Protein Diets

Abstract Background: The inclusion of high-quality proteins and the protein restriction are commonly used in swine production. Our study was conducted to evaluate the effects of hydrolyzed wheat protein (HWP), fermented soybean meal (FSBM), and enzyme-treated soybean meal (ESBM) in low-protein diets on antioxidant capacity, immunity, fecal microbiota and metabolites of weaned piglets.Methods: A total of 144 weaned piglets were randomly assigned to 3 dietary treatments with 6 replications of 8 piglets per pen. The experiment was divided into phase 1 ( days 0-14) and phase 2 (days 15-28). The dietary treatments contained 15.90% HWP, 15.80% FSBM, and 15.10% ESBM in phase 1, and 7.90% HWP, 7.80% FSBM, and 7.50% ESBM in phase 2, respectively.Results: The ADG of piglets in the ESBM group was higher (P < 0.05) than HWP and FSBM during days 1-28. Compared with HWP and FSBM, piglets in ESBM had higher (P < 0.05) serum levels of FRAP and SOD on days 14, as well as higher (P < 0.05) serum FRAP level on days 28. Piglets in ESBM had lower (P < 0.05) serum levels of DAO and IL-1β than HWP on day 28. ESBM significantly increased the abundance of Bacteroidetes, Oscillospiraceae and Christensenellaceae and decreased the Clostridiaceae abundance in the feces compared with HWP and FSBM. The PICRUSt analysis revealed that the number of gene tags involved in valine, leucine and isoleucine degradation and lysine degradation in ESBM were lower (P < 0.05) than HWP and FSBM. Piglets in ESBM had higher (P < 0.05) fecal butyrate content compared with FSBM, and ESBM tended to decrease (P = 0.076) fecal cadaverine level.Conclusions: Overall, ESBM had advantages over HWP and FSBM in improving antioxidant capacity, immunity, and fecal microbiota and metabolites of weaned piglets.

scholarly journals Relating Instructional Design Components to the Effectiveness of Internet-Based Mindfulness Interventions: A Critical Interpretive Synthesis (Preprint)

2018 ◽  
Author(s):  
Marie Lippmann ◽  
Helena Laudel ◽  
Marlene Heinzle ◽  
Susanne Narciss
Keyword(s):  
Instructional Design ◽  
Literature Review ◽  
Phase 1 ◽  
Just In Time ◽  
Phase 2 ◽  
Effective Interventions ◽  
Critical Interpretive Synthesis ◽  
Task Practice ◽  
Mindfulness Interventions ◽  
Time Information

BACKGROUND Internet-based mindfulness interventions are a promising approach to address challenges in the dissemination and implementation of mindfulness interventions, but it is unclear how the instructional design components of such interventions are associated with intervention effectiveness. OBJECTIVE The objective of this study was to identify the instructional design components of the internet-based mindfulness interventions and provide a framework for the classification of those components relative to the intervention effectiveness. METHODS The critical interpretive synthesis method was applied. In phase 1, a strategic literature review was conducted to generate hypotheses for the relationship between the effectiveness of internet-based mindfulness interventions and the instructional design components of those interventions. In phase 2, the literature review was extended to systematically explore and revise the hypotheses from phase 1. RESULTS A total of 18 studies were identified in phase 1; 14 additional studies were identified in phase 2. Of the 32 internet-based mindfulness interventions, 18 were classified as more effective, 11 as less effective, and only 3 as ineffective. The effectiveness of the interventions increased with the level of support provided by the instructional design components. The main difference between effective and ineffective interventions was the presence of just-in-time information in the form of reminders. More effective interventions included more supportive information (scores: 1.91 in phases 1 and 2) than less effective interventions (scores: 1.00 in phase 1 and 1.80 in phase 2), more part-task practice (scores: 1.18 in phase 1 and 1.60 in phase 2) than less effective interventions (scores: 0.33 in phase 1 and 1.40 in phase 2), and provided more just-in-time information (scores: 1.35 in phase 1 and 1.67 in phase 2) than less effective interventions (scores: 0.83 in phase 1 and 1.60 in phase 2). The average duration of more effective, less effective, and ineffective interventions differed for the studies of phase 1, with more effective interventions taking up more time (7.45 weeks) than less effective (4.58 weeks) or ineffective interventions (3 weeks). However, this difference did not extend to the studies of phase 2, with comparable average durations of effective (5.86 weeks), less effective (5.6 weeks), and ineffective (7 weeks) interventions. CONCLUSIONS Our results suggest that to be effective, internet-based mindfulness interventions must contain 4 instructional design components: formal learning tasks, supportive information, part-task practice, and just-in-time information. The effectiveness of the interventions increases with the level of support provided by each of these instructional design components.

scholarly journals Proteomic analysis of synovial fluid in osteoarthritis using SWATH‑mass spectrometry

2017 ◽  
Author(s):  
Weixiong Liao ◽  
Zhongli Li ◽  
Tanshi Li ◽  
Qiang Zhang ◽  
Heng Zhang ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Synovial Fluid ◽  
Proteomic Analysis

Clinical pharmacologic considerations for the phase II/III dose/regimen of the investigational Aurora A kinase (AAK) inhibitor MLN8237 (alisertib): Pharmacokinetics (PK), pharmacodynamics (PD), and exposure-safety relationships.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 2597-2597
Author(s):  
Karthik Venkatakrishnan ◽  
Xiaofei Zhou ◽  
Jeffrey Ecsedy ◽  
Hadi Danaee ◽  
Hugh Xiao ◽  
...  
Keyword(s):  
Logistic Regression ◽  
Body Size ◽  
Tumor Cells ◽  
Dose Regimen ◽  
Phase 1 ◽  
Geometric Mean ◽  
Dose Range ◽  
Systemic Exposure ◽  
Phase 2 ◽  
Pharmacologically Active

2597 Background: MLN8237, an oral selective AAK inhibitor, is primarily metabolized by multiple glucuronidation enzymes including the polymorphic UGT1A1. Phase 1 studies included comprehensive PK and PD sampling. We report integrated PK, PD, and PK-safety analyses in support of dose/regimen selection for phase 2/3 studies. Methods: Phase 1 studies in adults with advanced cancers evaluated dosing on d 1-7 in 21-d cycles or d 1-21 in 35-d cycles. Data from 294 patients in 4 phase 1 and 2 phase 2 studies contributed to population PK modeling. PD endpoints included mitotic index (MI) in skin and chromosome alignment and spindle bipolarity (CA/SB) in mitotic tumor cells. Logistic regression analyses evaluated relationships between MLN8237 PK parameters and DLTs (N=86) or CNS adverse events (AEs; n=134) in 2 phase 1 studies. Results: MLN8237 displayed dose-linear PK (5-200 mg/d), described by a 2-compartment model with first order absorption. Covariate analyses did not reveal significant effects of age, body size, sex, UGT1A1 genotype, or creatinine clearance (≥30 mL/min). Exposure-related increases in skin MI and decreases in CA/SB in tumor mitotic cells confirmed AAK inhibition by MLN8237. At the MTD of 50 mg BID (d 1-7 dosing) geometric mean steady-state exposures (48,200 nM.hr) were comparable to those associated with ≥50% CA/SB reductions in mitotic tumor cells (57,300 nM.hr). Exposures at the 21-d MTD (QD dosing) were lower, favoring 50 mg BID (d 1-7 dosing) for further development. At 50 mg BID (d 1-7 dosing) logistic regression relating MLN8237 AUC to DLT rate estimated a DLT probability of 8% (95% CI 3-20%). Similar analyses identified Cmax rather than AUC as the predictor of CNS AEs, supporting BID dosing in adults to reduce peak concentrations while preserving total systemic exposure. Conclusions: MLN8237 exhibits dose-linear PK independent of age, body size, mild or moderate renal impairment, or UGT1A1*28 polymorphism. Exposures achieved at or near 50 mg BID are expected to result in tumor AAK inhibition, supporting a pharmacologically active dose range for future clinical development.

scholarly journals Understanding Complementary Feeding Practices in Children 6–23 Months in the West and Central Africa Region: A Mixed Methods Regional Analysis of 24 Countries

2020 ◽  
Vol 4 (Supplement_2) ◽  
pp. 871-871
Author(s):  
Muzi Na ◽  
Anne-Sophie Le Dain ◽  
Stephen Kodish ◽  
Laura Murray-Kolb ◽  
Raphia Ngoutane ◽  
...  
Keyword(s):  
Mixed Methods ◽  
Literature Review ◽  
Vitamin A ◽  
Complementary Feeding ◽  
Dietary Diversity ◽  
Phase 1 ◽  
Feeding Practices ◽  
Phase 2 ◽  
Factors Influencing ◽  
Modifiable Factors

Abstract Objectives 1) To describe the trends of complementary feeding since 2010; 2) to understand the factors influencing the sub-optimal feeding practices; and 3) to generate recommendations to inform future interventions. Methods Mixed methods study with an iterative, two phase design. Phase 1: quantitative data analysis of 13 key complementary feeding indicators reported in 68 national survey reports from 2010 to 2018. Phase 2: semi-structured qualitative interviews with 14 regional informants (UN, Government, NGO, and donor communities). We conducted a literature review of grey and peer-reviewed publications in 2010–2019 to contextualize the results. Results Phase 1. Across 24 WCAR countries, mean continued breastfeeding at 1y was 89%, but halved to 44% by 2y. Introduction of complementary foods occurred in 64% of children 6–8 mos. Minimum meal frequency in children 6–23 mos increased over time from 27% to 38% while minimum dietary diversity and minimum acceptable diet were stagnant (22% and 10%, respectively) since 2010. Intake of nutrient rich foods (vitamin A, animal source, iron-rich) were reported in about half of children, respectively. The proportion of children (only reported for &lt; 5 y) receiving vitamin A (66%), or iron supplements (15%), or iodized salt (79%) varied. Phase 2. Regionally, we identified policy, community, institutional, household, interpersonal, and individual level barriers. Additionally, non-modifiable factors including environmental shocks/hazards and security issues (i.e., violence), were said to disrupt food systems. From a systems perspective, major facilitators to optimal complementary feeding fell within the ‘health and nutrition’ or ‘food system’ sectors; fewer were ascribed to ‘WASH’ or ‘social protection’. Preliminary recommendations from key informants and supported by the literature review were largely multi-sectorial, yet a strong emphasis was placed on the policy level. Conclusions Since 2010, complementary feeding practices in WCAR have remained nearly unchanged. Inter-related factors influencing complementary feeding distribute across levels and sectors, suggesting the need for more multi-sectorial, integrated intervention strategies to improve child nutrition in WCAR. Funding Sources Bill & Melinda Gates Foundation funding to UNICEF-WCARO.

scholarly journals Identification of psoriatic arthritis mediators in synovial fluid by quantitative mass spectrometry

2014 ◽  
Vol 11 (1) ◽  
pp. 27 ◽  
Author(s):  
Daniela Cretu ◽  
Ioannis Prassas ◽  
Punit Saraon ◽  
Ihor Batruch ◽  
Rajiv Gandhi ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Psoriatic Arthritis ◽  
Synovial Fluid ◽  
Quantitative Mass Spectrometry

scholarly journals Relating Instructional Design Components to the Effectiveness of Internet-Based Mindfulness Interventions: A Critical Interpretive Synthesis

10.2196/12497 ◽  
2019 ◽  
Vol 21 (11) ◽  
pp. e12497 ◽  
Author(s):  
Marie Lippmann ◽  
Helena Laudel ◽  
Marlene Heinzle ◽  
Susanne Narciss
Keyword(s):  
Instructional Design ◽  
Literature Review ◽  
Phase 1 ◽  
Just In Time ◽  
Phase 2 ◽  
Effective Interventions ◽  
Critical Interpretive Synthesis ◽  
Task Practice ◽  
Mindfulness Interventions ◽  
Time Information

Background Internet-based mindfulness interventions are a promising approach to address challenges in the dissemination and implementation of mindfulness interventions, but it is unclear how the instructional design components of such interventions are associated with intervention effectiveness. Objective The objective of this study was to identify the instructional design components of the internet-based mindfulness interventions and provide a framework for the classification of those components relative to the intervention effectiveness. Methods The critical interpretive synthesis method was applied. In phase 1, a strategic literature review was conducted to generate hypotheses for the relationship between the effectiveness of internet-based mindfulness interventions and the instructional design components of those interventions. In phase 2, the literature review was extended to systematically explore and revise the hypotheses from phase 1. Results A total of 18 studies were identified in phase 1; 14 additional studies were identified in phase 2. Of the 32 internet-based mindfulness interventions, 18 were classified as more effective, 11 as less effective, and only 3 as ineffective. The effectiveness of the interventions increased with the level of support provided by the instructional design components. The main difference between effective and ineffective interventions was the presence of just-in-time information in the form of reminders. More effective interventions included more supportive information (scores: 1.91 in phases 1 and 2) than less effective interventions (scores: 1.00 in phase 1 and 1.80 in phase 2), more part-task practice (scores: 1.18 in phase 1 and 1.60 in phase 2) than less effective interventions (scores: 0.33 in phase 1 and 1.40 in phase 2), and provided more just-in-time information (scores: 1.35 in phase 1 and 1.67 in phase 2) than less effective interventions (scores: 0.83 in phase 1 and 1.60 in phase 2). The average duration of more effective, less effective, and ineffective interventions differed for the studies of phase 1, with more effective interventions taking up more time (7.45 weeks) than less effective (4.58 weeks) or ineffective interventions (3 weeks). However, this difference did not extend to the studies of phase 2, with comparable average durations of effective (5.86 weeks), less effective (5.6 weeks), and ineffective (7 weeks) interventions. Conclusions Our results suggest that to be effective, internet-based mindfulness interventions must contain 4 instructional design components: formal learning tasks, supportive information, part-task practice, and just-in-time information. The effectiveness of the interventions increases with the level of support provided by each of these instructional design components.

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