Project description:A lactobacilli dominated microbiota in most pre and post-menopausal women is an indicator of vaginal health. A Nugent scoring system serves as a proxy for determining the ratio of lactobacilli to other vaginal inhabitants where a high score usually represents a diseased state, whilst an intermediate score represents a warning zone. The objective of this double blinded, placebo-controlled crossover study was to evaluate in 14 post-menopausal women with an intermediate score, the effect of vaginal administration of probiotic L. rhamnosus GR-1 and L. reuteri RC-14 on the microbiota and host response. The probiotic treatment did not result in changes to clinical parameters such as dryness, irritation and comfort, compared to when placebo was applied. Analysis using 16S rRNA sequencing and metabolomics profiling revealed that the proportional abundance of Lactobacillus was increased following probiotic administration as compared to placebo, which was weakly associated with an increase in lactate levels. Analysis of host responses by microarray showed the probiotics had an immune-modulatory response and multiplex cytokine analysis showed up-regulation of IL-5. This is the first study to use an interactomic approach for the study of vaginal probiotic administration in post-menopausal women. It shows that in some cases multifaceted approaches are required to detect the subtle trigger molecular changes induced by the host to instillation of probiotic strains. A total of 35 total RNA samples extracted from vaginal brushes were analyzed on Affymetrix Gene 2.0 ST arrays from 14 Participants collected over multiple visits including administration of either a probiotic supplement or placebo control.
Project description:The CLARITY trial (NCT00213135) was designed as a double-blind, placebo-controlled study to allow the best comparison of absolute efficacy and safety of oral cladribine in RRMS subjects. 1326 patients with relapsing MS were randomized (1:1:1) to receive cladribine tablets 3.5 mg/kg or 5.25 mg/kg bodyweight or placebo. Gene expression data in whole blood samples at 96 weeks were prepared according to standard Affymetrix protocols Gene expression data in whole blood samples at 96 weeks were available from patients randomized to placebo (n=57), cladribine tablets 3.5 mg/kg (n=62), and cladribine tablets 5.25 mg/kg (n=70).
Project description:Gene expresion profiles from the scAT following 6 week LC n-3 PUFA and 6 week placebo supplementation were compared Women with PCOS were supplemented with 4g n-3 PUFA (containing 1.8g EPA and DHA) daily for 6 weeks and changes in subcutaneous adipose tissue gene expression was compared with 6 week placebo supplementation. This was a cross-over placebo, controlled dietary intervention wherein women with PCOS received both treatments.
Project description:Vitamin D deficiency is a risk factor for developing multiple sclerosis (MS). Both in vitro and animal studies suggest an immunomodulatory effect of vitamin D. The PrevANZ trial, a phase IIb randomized placebo-controlled trial of oral vitamin D3 supplementation in people with a first demyelinating event (FDE), was conducted to determine if supplementation can prevent recurrent disease activity in this cohort at high risk of developing definite MS. As a sub-study of this trial, we used whole blood transcriptomic analyses to investigate the effect of vitamin D3 supplementation on peripheral immune cells in people with an FDE, and to gain insight into potential mechanisms by which vitamin D3 may regulate MS risk and disease activity. The PrevANZ trial randomized participants to 1000 IU, 5000 IU or 10,000 IU daily of oral vitamin D3 or placebo. Peripheral blood was collected at baseline and 12 weeks in PAXgene Blood RNA tubes. Transcriptomic datasets were generated by RNA sequencing.
Project description:A lactobacilli dominated microbiota in most pre and post-menopausal women is an indicator of vaginal health. A Nugent scoring system serves as a proxy for determining the ratio of lactobacilli to other vaginal inhabitants where a high score usually represents a diseased state, whilst an intermediate score represents a warning zone. The objective of this double blinded, placebo-controlled crossover study was to evaluate in 14 post-menopausal women with an intermediate score, the effect of vaginal administration of probiotic L. rhamnosus GR-1 and L. reuteri RC-14 on the microbiota and host response. The probiotic treatment did not result in changes to clinical parameters such as dryness, irritation and comfort, compared to when placebo was applied. Analysis using 16S rRNA sequencing and metabolomics profiling revealed that the proportional abundance of Lactobacillus was increased following probiotic administration as compared to placebo, which was weakly associated with an increase in lactate levels. Analysis of host responses by microarray showed the probiotics had an immune-modulatory response and multiplex cytokine analysis showed up-regulation of IL-5. This is the first study to use an interactomic approach for the study of vaginal probiotic administration in post-menopausal women. It shows that in some cases multifaceted approaches are required to detect the subtle trigger molecular changes induced by the host to instillation of probiotic strains.
Project description:We present the biopsy sub-study results from the first randomized, placebo-controlled clinical trial in patients with alopecia areata (AA) with ≥50% scalp hair loss and ≤7 years since the last AA episode. In this sub-study, we evaluated the molecular responses to PF-06651600, an oral inhibitor of JAK3 and the tyrosine kinase expressed in hepatocellular carcinoma (TEC) kinase family, and PF-06700841, an oral TYK2/JAK1 inhibitor, versus placebo in nonlesional and lesional scalp biopsies of biopsy samples from patients with AA.
Project description:Expression profiling of vastus lateralis muscle of young, healthy, non-obese men supplemented with creatine monohydrate vs. placebo for 10 days. Results identify transcriptional pathways activated in skeletal muscles as a result of acute creatine monohydrate supplementation. Keywords: Supplementation response. In a randomized, placebo-controlled, crossover, double-blind design, 12 young, healthy, non-obese men were supplemented with either a placebo or creatine monohydrate (loading phase, 20 g/d x 3 d; maintenance phase, 5 g/d x 7 d) for 10 d. Following a 28 day washout period, subjects were put on the alternate supplementation for 10 days. Muscle biopsies of the vastus lateralis were obtained and were assessed for global mRNA expression using cDNA microarrays.
Project description:The goal of this study is to define the molecular signatures of SLE patients at baseline in BMS IM101042 trial. IM101042 (NCT00119678) is a phase IIb, multi-center, randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of abatacept vs placebo on a background of oral glucocorticosteroids in the treatment of subjects with systemic lupus erythematosus and the prevention of subsequent lupus flares, sponsored by Bristol-Myers Squibb.