Quantitative analyses of cytokine profiles reveal hormone-mediated modulation of cytokine profiles in recurrent spontaneous miscarriage.

PURPOSE: Cytokines play important roles in pregnancy complications. Some hormones such as estrogen, progesterone, and dydrogesterone have been shown to alter cytokine profiles. Understanding how cytokine profiles are affected by these hormones is therefore an important step towards immunomodulatory therapies for pregnancy complications. We analyse previously published data on the effects of estrogen, progesterone, and dydrogesterone on cytokine balances in women having recurrent spontaneous miscarriages. MATERIALS AND METHODS: Levels of eight cytokines (IFN-γ, IL-2, IL-6, IL-10, IL-13, IL-17, IL-23, TNF-α) from n = 22 women presenting unexplained recurrent spontaneous miscarriages were studied. Cytokine values were recorded after in vitro exposure of peripheral blood cells to estrogen, progesterone, and dydrogesterone. We expand on earlier analysis of the dataset by employing different statistical techniques including effect sizes for individual cytokine values, a more powerful statistical test, and adjusting p-values for multiple comparisons. We employ multivariate analysis methods, including to determine the relative magnitude of the effects of the hormone therapies on cytokines. A new statistical method is introduced based on pairwise distances able to accommodate complex relations in cytokine profiles. RESULTS: We report several statistically significant differences in individual cytokine values between the control group and each hormone treated group, with estrogen affecting the fewest cytokines, and progesterone and dydrogesterone both affecting seven out of eight cytokines. Exposure to estrogen produces no large effects sizes however, while IFN-γ and IL-17 show large effect sizes for both progesterone and dydrogesterone, among other cytokines. Our new method for identifying which collections (i.e. subsets) of cytokines best distinguish contrasting groups identifies IFN-γ, IL-10 and IL-23 as especially noteworthy for both progesterone and dydrogesterone treatments. CONCLUSIONS: While some statistically significant differences in cytokine levels after exposure to estrogen are found, these have small effect sizes and are unlikely to be clinically relevant. Progesterone and dydrogesterone both induce statistically significant and large effect-size differences in cytokine levels, hence therapy with these two progestogens is more likely to be clinically relevant. Univariate and multivariate methods for identifying cytokine importances provide insight into which groups of cytokines are most affected and in what ways by therapies.

CytokineExplore: An Online Tool for Statistical Analysis of Cytokine Concentration Datasets.

PURPOSE: Cytokine data sets are increasing both in the number of different cytokines measured and the number of samples assayed. Further, typically data from different groups may be contrasted, eg, normal vs complication subjects. Many univariate and multivariate statistical techniques exist to study such cytokine datasets, but the ability to implement these techniques may be lacking for some practitioners, or may not be available quickly and conveniently. Here, we introduce CytokineExplore, an online tool for multi-cytokine and multi-group data analysis of user-provided Microsoft Excel data files. MATERIALS AND METHODS: In order to illustrate the tool features, we use data from intrauterine growth retardation (IUGR), a pregnancy complication, and normal healthy subjects as a control. The dataset contains levels for 10 cytokines, namely: IL-4, IL-6, IL-8, IL-10, IL-12, IL-13, IL-18, IL-23, interferon-gamma (IFN-γ) and tumour necrosis-alpha (TNF-α), obtained from 34 women with IUGR (further divided into 17 symmetric and 17 asymmetric cases) and 24 gestationally age-matched normal controls. RESULTS: The online tool automatically generates box-plots, histograms, PCA and PLSDA plots, t-tests and Mann-Whitney statistical tests, cytokine importance values for separating two groups, heatmaps for comparing multiple groups, and other functionalities. Figures generated can be directly downloaded for use in presentations or journal articles. CONCLUSION: The tool facilitates quick and easy numerical exploration and multivariate analysis of cytokine datasets, to aid basic understanding and hypothesis generation.

Contamination and ecological risk assessment of the Red Sea coastal sediments, southwest Saudi Arabia.

The level of heavy metals (HMs) in coastal sediments has attracted the environmental researchers due to their persistence, abundance, biomagnification and toxicity. The present study was conducted to assess the contamination and ecological risk assessment of HMs in Jazan coastal sediments, Red Sea, Saudi Arabia utilizing pollution indices and multivariate statistical analyses. A total of 32 surface samples were collected for Cu, Sb, Zn, Cr, Cd, Pb, Fe, Co, Ni, Al, and total organic matter analysis using an atomic absorption spectrophotometer. The results indicate the following descending order of metal concentrations: Al > Fe > Cr > Cu > Zn > Ni > Co > Pb > Cd > Sb. Average level of Cd is significantly higher than those from many neighboring and worldwide coastal sediments; and recorded very severe enrichment, severe contamination and very high risk in the investigated sediments. The pollution indices and statistical analyses revealed that proportion of Zn, Fe, Ni, Cr, Al, Cu, Sb and Pb were formed from lithogenic sources of weathering Quaternary units and atmospheric deposition. Most of the Cd, Sb, and Pb levels were derived from anthropogenic sources of industrial, agricultural, and fishing activities. The higher contribution of organic matter may be attributed to the mangrove roots and organic fertilizers; and played a key role in adsorbing, transferring and accumulating of elements.

High-resolution constructive interference in steady-state imaging in tethered cord syndrome: technical note.

BACKGROUND: Differentiation between nerve roots and the tethered filum terminale in magnetic resonance images remains challenging. It is, however, crucial to select patients for surgical intervention. METHOD: In 1 patient with progressive and 2 patients with stable clinical signs of tethered cord syndrome (TCS), images reconstructed from a 3D constructive interference in steady-state (CISS) sequence were compared with those obtained from a regular T2-weighted fast spin echo sequence. RESULTS: Nerve roots of the cauda equina were suppressed, whereas visualization of the filum terminale was much improved in high-resolution CISS sequences. In addition, the level of adhesion of the filum could be localized in relation to elements of the spinal cord. The imaging results were confirmed during surgery and the patient improved considerably after the intervention. The advantages of CISS were also apparent in 2 other patients who are still being observed. CONCLUSION: Constructive interference in steady-state imaging should be considered in the presurgical routine for patients with TCS.