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.

Innovative design of 3D-printed nasopharyngeal pediatric swab for COVID-19 detection.

3-dimensional (3D) printing technology provides a solution to meet the high demand for producing adult nasal swabs. A smaller, more flexible nasopharyngeal swab needs to be developed for children and infants suspected of having coronavirus. The information shared here presents a novel 3D-printed pediatric swab for the purpose of collecting upper respiratory clinical specimens.

Low-Cost Polyester-Tipped Three-Dimensionally Printed Nasopharyngeal Swab for the Detection of Severe Acute Respiratory Syndrome-Related Coronavirus 2 (SARS-CoV-2).

Case identification, isolation, and contact tracing are fundamental strategies used to control the spread of coronavirus disease 2019 (COVID-19). This has led to widespread testing that interrupted the supply chain for testing materials around the world. A prospective study was conducted to compare inexpensive and easily sourced 3-dimensionally (3D)-printed polylactic acid and polyester nasopharyngeal swabs to commercially manufactured swabs for the detection of severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2). During the study period, 287 laboratory-confirmed hospitalized COVID-19 patients, at multiple stages of their illness, were enrolled. The median age for the study population was 47.6 years (interquartile range [IQR], 34.4 to 56.6 years), and two-thirds (67.6%) of the subjects were male. The median duration of hospitalization, at the time of sampling, was 13 days (IQR, 10 to 16 days). Overall concordance between the prototype and control swabs was 80.8% (Cohen's kappa coefficient, 0.61). Most discrepant results were due to prototype-positive control-negative results. When considering all positive results to be true positives, the prototype swab had a higher sensitivity (90.6% versus 80.8%; 95% confidence interval [CI], 85.7% to 94.0% and 74.7% to 85.7%, respectively; P < 0.015). The cost to produce the prototype swab was estimated to be $0.05 per swab. Polylactic acid 3D-printed polyester-tipped swabs were shown to be effective for nasopharyngeal sample collection. We believe that this design can easily be adopted in countries where commercial swabs are not readily available and can play a vital role in public health efforts for disease control in low-income countries.

Effects of Progesterone, Dydrogesterone and Estrogen on the Production of Th1/Th2/Th17 Cytokines by Lymphocytes from Women with Recurrent Spontaneous Miscarriage.

Anti-inflammatory Th2 cytokines have been shown to be associated with healthy, successful pregnancy while pro-inflammatory Th1 and Th17 cytokines are associated with pregnancy loss due to recurrent spontaneous miscarriage. This nexus between unexplained recurrent spontaneous miscarriage (uRSM) and maternal inflammatory has led to the possibility of using pregnancy-related hormones to modify the maternal cytokine bias in a manner that is conducive to successful pregnancy. We investigated the ability of progesterone, dydrogesterone and estrogen to modulate cytokine production by peripheral blood lymphocytes from women undergoing uRSM. Peripheral blood mononuclear cells (PBMC) from females with uRSM were stimulated in vitro with phytohemagglutinin (PHA) in the presence and absence of progesterone or dydrogesterone or 17ß-estradiol. Culture supernatants were assayed for IFN-α, TNF-γ, IL-2, IL-6, IL-10, IL-13, IL-17A, and IL-23 by ELISA. Progesterone and dydrogesterone significantly down-regulated the secretion of the Th1 cytokines IFN-α and TNF-γ, and the Th17 cytokine IL-17A, and IL-23. Additionally, the secretion of the Th2 cytokine IL-6 was up-regulated. Estrogen, on the other hand, decreased the production of IFN-α and IL-2, increased the production of IL-6 but did not affect IL-17A and IL-23 secretion. Progestogens and estrogen can decrease the production of some Th1/Th17 inflammatory cytokines secreted by lymphocytes from uRSM and upregulate the production of anti-inflammatory cytokines. These data support the notion that progestogens can be used for altering maternal cytokine profiles to manage pregnancy complications.