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1.
PLoS One ; 11(6): e0155191, 2016.
Article in English | MEDLINE | ID: mdl-27333071

ABSTRACT

The heterogeneity of spontaneous preterm birth (SPTB) requires an interdisciplinary approach to determine potential predictive risk factors of early delivery. The aim of this study was to investigate maternal whole blood gene expression profiles associated with spontaneous preterm birth (SPTB, <37 weeks) in asymptomatic pregnant women. The study population was a matched subgroup of women (51 SPTBs, 114 term delivery controls) who participated in the All Our Babies community based cohort in Calgary (n = 1878). Maternal blood at 17-23 (sampling time point 1, T1) and 27-33 weeks of gestation (T2) were collected. Total RNA was extracted and microarray was performed on 326 samples (165 women). Univariate analyses determined significant clinical factors and differential gene expression associated with SPTB. Thirteen genes were validated using qRT-PCR. Three multivariate logistic models were constructed to identify gene expression at T1 (Model A), T2 (Model B), and gene expression fold change from T1 to T2 (Model C) associated with SPTB. All models were adjusted for clinical factors. Model C can predict SPTB with 65% sensitivity and 88% specificity in asymptomatic women after adjusting for history of abortion and anaemia (occurring before T2). Clinical data enhanced the sensitivity of the Models to predict SPTB. In conclusion, clinical factors and whole blood gene expression are associated with SPTB in asymptomatic women. An effective screening tool for SPTB during pregnancy would enable targeted preventive approaches and personalised antenatal care.


Subject(s)
Gene Expression Regulation, Developmental , Premature Birth/blood , Premature Birth/genetics , Adult , Area Under Curve , Demography , Female , Humans , Labor, Obstetric , Models, Genetic , Multivariate Analysis , Pregnancy , Real-Time Polymerase Chain Reaction , Reproducibility of Results
2.
J Proteome Res ; 14(1): 457-66, 2015 Jan 02.
Article in English | MEDLINE | ID: mdl-25299736

ABSTRACT

Threatened preterm labor (TPTL) accounts for ∼30% of pregnancy-related hospital admissions. Maternal peripheral leukocytes can be used to monitor a variety of physiological processes occurring in the body. Two high-throughput mass spectrometry methodologies, SWATH and iTRAQ, were used to study differentially expressed peripheral blood leukocyte lysate proteins in symptomatic women admitted for TPTL who had a preterm birth within 48 h (n = 16) and those who did not (n = 24). The SWATH spectral library consisted of 783 proteins. SWATH methodology quantified 258 proteins (using ≥2 peptides) and 5 proteins (ALBU, ANXA6, HNRPK, HSP90A, and PDIA1) were differentially expressed (p < 0.05, Mann-Whitney U). iTRAQ workflow identified 765 proteins; 354 proteins were quantified and 14 proteins (MIF, UBIQ, HXK3, ALBU, HNRPD, ST1A2, RS15A, RAP1B, CAN1, IQGA2, ST1A1, COX5A, ADDA, and UBQL1) were significantly different between the two groups of women (p < 0.05, Mann-Whitney U). Albumin was the only common differentially expressed protein in both SWATH (28% decrease) and iTRAQ studies (45% decrease). This decrease in albumin was validated using ELISA (11% decrease, p < 0.05, Mann-Whitney U) in another 23 TPTL women. This work suggests that albumin is a broad indicator of leukocyte activation with impending preterm birth and provides new future work directions to understand the pathophysiology of TPTL.


Subject(s)
Gene Expression Regulation/physiology , Obstetric Labor, Premature/blood , Obstetric Labor, Premature/physiopathology , Premature Birth/physiopathology , Serum Albumin/metabolism , Enzyme-Linked Immunosorbent Assay , Female , High-Throughput Screening Assays/methods , Humans , Mass Spectrometry/methods , Pregnancy , Premature Birth/blood , Statistics, Nonparametric , Time Factors , Western Australia
4.
Pharmacotherapy ; 30(9): 966, 2010 Sep.
Article in English | MEDLINE | ID: mdl-20795851

ABSTRACT

In 2008, the American College of Clinical Pharmacy appointed the Task Force on Research in the Professional Curriculum to review and make recommendations on the essential research curriculum that should be part of doctor of pharmacy (Pharm.D.) degree programs. The essential research curriculum provides all students with critical and analytical thinking and lifelong learning skills, which will apply to current and future practice and stimulate some students to pursue a career in this field. Eight key curricular competencies are as follows: identifying relevant problems and gaps in pharmacotherapeutic knowledge; generating a research hypothesis; designing a study to test the hypothesis; analyzing data results using appropriate statistical tests; interpreting and applying the results of a research study to practice; effectively communicating research and clinical findings to pharmacy, medical, and basic science audiences; interpreting and effectively communicating research and clinical findings to patients and caregivers; and applying regulatory and ethical principles when conducting research or using research results. Faculty are encouraged to use research-related examples across the curriculum in nonresearch courses and to employ interactive teaching methods to promote student engagement. Examples of successful strategies used by Pharm.D. degree programs to integrate research content into the curriculum are provided. Current pharmacy school curricula allow variable amounts of time for instructional content in research, which may or may not include hands-on experiences for students to develop research-related skills. Therefore, an important opportunity exists for schools to incorporate the essential research curriculum. Despite the challenges of implementing these recommendations, the essential research curriculum will position pharmacy school graduates to understand the importance of research and its applications to practice. This perspective is provided as an aid and a challenge to those in leadership and teaching positions within schools and colleges of pharmacy.


Subject(s)
Curriculum , Education, Pharmacy , Research , Faculty , Learning , Schools, Pharmacy , Teaching
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