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Abstract Background Biologic strain such as oxidative stress has been associated with short leukocyte telomere length (LTL), as well as with preeclampsia and spontaneous preterm birth, yet little is known about their relationships with each other. We investigated associations of postpartum maternal LTL with preeclampsia and spontaneous preterm birth. Methods This pilot nested case control study included independent cohorts of pregnant people with singleton gestations from two academic institutions: Cohort 1 (hereafter referred to as Suburban) were enrolled prior to 20 weeks’ gestation between 2012 and 2018; and Cohort 2 (hereafter referred to as Urban) were enrolled at delivery between 2000 and 2012. Spontaneous preterm birth or preeclampsia were the selected pregnancy complications and served as cases. Cases were compared with controls from each study cohort of uncomplicated term births. Blood was collected between postpartum day 1 and up to 6 months postpartum and samples were frozen, then simultaneously thawed for analysis. Postpartum LTL was the primary outcome, measured using quantitative polymerase chain reaction (PCR) and compared using linear multivariable regression models adjusting for maternal age. Secondary analyses were done stratified by mode of delivery and self-reported level of stress during pregnancy. Results 156 people were included; 66 from the Suburban Cohort and 90 from the Urban Cohort. The Suburban Cohort was predominantly White, Hispanic, higher income and the Urban Cohort was predominantly Black, Haitian, and lower income. We found a trend towards shorter LTLs among people with preeclampsia in the Urban Cohort (6517 versus 6913 bp, p = 0.07), but not in the Suburban Cohort. There were no significant differences in LTLs among people with spontaneous preterm birth compared to term controls in the Suburban Cohort (6044 versus 6144 bp, p = 0.64) or in the Urban Cohort (6717 versus 6913, p = 0.37). No differences were noted by mode of delivery. When stratifying by stress levels in the Urban Cohort, preeclampsia was associated with shorter postpartum LTLs in people with moderate stress levels (p = 0.02). Conclusion Our exploratory results compare postpartum maternal LTLs between cases with preeclampsia or spontaneous preterm birth and controls in two distinct cohorts. These pilot data contribute to emerging literature on LTLs in pregnancy.

The measurement of fecal cortisol/corticosterone metabolites (FCMs) is often used to quantify the stress response. The sampling method is relatively non-invasive, reduces concern for elevation of cortisol from the sampling method, and has been shown to measure cortisol more consistently without the daily diurnal rhythm observed in blood. Commercial ELISA (enzyme-linked immunoassay) kits offer benefits over previously validated immunoassay methods but lack validation. The objective of this study was to evaluate a commercial ELISA kit (Arbor AssaysTM DetectX® Cortisol ELISA kit, K003-H1, Ann Arbor, MI, USA) and provide analytical and biologic validation of equine fecal and plasma samples. Horses (4 male, 4 female, mean ± SD: 4 ± 5 yr) were transported for 15 min with limited physical and visual contact via a livestock trailer. Blood and fecal samples were collected pre- and post-transportation. Parallelism, accuracy, and precision tests were used to analytically validate this kit. Data were analyzed using PROC MIXED in SAS 9.4. Plasma cortisol concentrations increased in response to trailering (254.5 ± 26.4 nmol/L, 0 min post-transportation) compared to pre-transportation (142.8 ± 26.4 nmol/L). FCM concentrations increased 24 h post-trailering (10.8 ± 1.7 ng/g) when compared to pre-transportation (7.4 ± 1.7 ng/g). These data support that changes in FCMs can be observed 24 h post-stressor. In conclusion, the Arbor AssaysTM DetectX® Cortisol ELISA kit is a reliable, economic option for the measurement of biologically relevant changes in cortisol in equine plasma and FCMs.

Objective The four initial severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected pregnant women presenting at term gestation to our institution presented with transaminitis. Three of the four were diagnosed with intrahepatic cholestasis of pregnancy (IHCP). Growing evidence exists of an associated transaminitis in nonpregnant SARS-CoV-2 patients. However, there are limited data of hepatic involvement of SARS-CoV-2 in pregnancy, and no previous studies have assessed the association with IHCP in patients with coronavirus disease 2019 (COVID-19).

We present a new analysis of the KELT-24 system, comprising a well-aligned hot Jupiter, KELT-24 b, and a bright ( V = 8.3), nearby ( d = 96.9 pc) F-type host star. KELT-24 b was independently discovered by two groups in 2019, with each reporting best-fit stellar parameters that were notably inconsistent. Here, we present three independent analyses of the KELT-24 system, each incorporating a broad range of photometric and spectroscopic data, including eight sectors of Transiting Exoplanet Survey Satellite (TESS) photometry and more than 200 new radial velocities (RVs) from the MINiature Exoplanet Radial Velocity Array. Two of these analyses use KELT-24's observed spectral energy distribution (SED) through a direct comparison to stellar evolutionary models, while our third analysis assumes an unknown additional body contributing to the observed broadband photometry and excludes the SED. Ultimately, we find that the models that include the SED are a poor fit to the available data, so we adopt the system parameters derived without it. We also highlight a single transit-like event observed by TESS, deemed likely to be an eclipsing binary bound to KELT-24, that will require follow-up observations to confirm. We discuss the potential of these additional bodies in the KELT-24 system as a possible explanation for the discrepancies between the results of the different modeling approaches, and explore the system for longer-period planets that may be weakly evident in the RV observations. The comprehensive investigations that we present not only increase the fidelity of our understanding of the KELT-24 system but also serve as a blueprint for future stellar modeling in global analyses of exoplanet systems.

Abstract Background Short leukocyte telomere length is a biomarker associated with stress and morbidity in non-pregnant adults. Little is known, however, about maternal telomere dynamics in pregnancy. To address this, we examined changes in maternal leukocyte telomere length (LTL) during uncomplicated pregnancies and explored correlations with perceived stress. Methods In this pilot study, maternal LTL was measured in blood collected from nulliparas who delivered live, term, singleton infants between 2012 and 2018 at a single institution. Participants were excluded if they had diabetes or hypertensive disease. Samples were collected over the course of pregnancy and divided into three time periods:

There is a chaotic scenario that exists in the field of prostate cancer (PCa) screening. To balance goals, such as decreasing mortality, avoiding unnecessary procedures, and decreasing the cost of medical care, the pendulum seems to have swung to the side of more restricted screening. The decrease in PCa screening has led to a slowly creeping decline in the favourable outcomes that existed among patients with PCa. If a potential patient or a family member is trying to get clear guidance about PCa screening by searching the internet, they will end up confused by several recommendations from many organisations. It is even more challenging to obtain any clarity about PCa screening for special populations, such as those with a family history of PCa, those of African descent/African Americans, and the elderly. The advent of genomic medicine and precision medicine is an opportunity to identify those at a very high risk of developing aggressive PCa, so that PCa screening can be more actively undertaken among them. In this paper, the authors review the current recommendations by different entities and summarise emerging molecular markers that may help bring clarity to PCa screening. The authors predict that concrete, consensual guidelines will emerge in less than one decade. Meanwhile, this article suggests intermediary steps that will help save lives from PCa mortality, especially for under-represented populations. This paper is a catalyst to stimulate further discussion and serves as a guide to noncancer-specialists for the near future as precision medicine progresses to better understand risk–benefit and cost–benefit ratios in PCa screening.

Stressful conditions in animal production facilities may exacerbate the fecal shedding and foodborne transmission of non-typhoidal Salmonella enterica subsp. enterica. Dairy cows are reservoirs of this zoonotic microorganism, and its prevalence has roughly doubled in the past decade on dairy farms in United States. Dairy cows are commonly overstocked at the feed bunk, and stressors placed on the animal prior to parturition may exacerbate Salmonella shedding. However, no studies have evaluated the impact of overstocking and metabolic stress on fecal concentrations of the pathogen. Therefore, we conducted a field trial with 120 multiparous dairy cows randomized into one of four treatment groups with different stocking densities at the feed bunk during the periparturient period as follows: US, understocked from −60 to −1 DRC; OS, overstocked from −60 to −1 DRC; USOS, understocked from −60 to −26 DRC/overstocked from −25 to −1 DRC; and OSUS, overstocked from −60 to −26 DRC/ understocked from −25 to −1 DRC. Fecal and blood samples were collected at four time points relative to calving. qPCR assays were used to quantify Salmonella invA gene and total bacterial community from fecal samples, and a subset of isolates recovered from fecal bacterial culture were characterized using pulsed field gel electrophoresis and serotyping. Serum non-esterified fatty acids (NEFA) were measured as a metabolic stress indicator using an immunoassay. Multivariable analyses were performed to test if changes in Salmonella concentrations were associated with stocking density, energy balance, or days relative to calving. From fecal isolates, three Salmonella serovars were identified, S. Cerro; Kentucky; Meleagridis. Concentrations of Salmonella increased as cows approached calving. Higher stocking densities at the feed bunk did not impact total bacterial community or NEFA; however, cows in the overstocked groups had higher Salmonella fecal concentrations. Further, cows with higher NEFA concentrations after calving had a higher likelihood of detection of Salmonella. Future farm interventions should aim to reduce environmental and metabolic stress during the periparturient period to decrease the dissemination of Salmonella to cattle, the environment, and humans.

Heavy ion signatures of coronal mass ejections (CMEs) indicate that rapid and strong heating takes place during the eruption and early stages of propagation. However, the nature of the heating that produces the highly ionized charge states often observed in situ is not fully constrained. An MHD simulation of the Bastille Day CME serves as a test bed to examine the origin and conditions of the formation of heavy ions evolving within the CME in connection with those observed during its passage at L1. In particular, we investigate the bimodal nature of the Fe charge state distribution, which is a quintessential heavy ion signature of CME substructure, as well as the source of the highly ionized plasma. We find that the main heating experienced by the tracked plasma structures linked to the ion signatures examined is due to field-aligned thermal conduction via shocked plasma at the CME front. Moreover, the bimodal Fe distributions can be generated through significant heating and rapid cooling of prominence material. However, although significant heating was achieved, the highest ionization stages of Fe ions observed in situ were not reproduced. In addition, the carbon and oxygen charge state distributions were not well replicated owing to anomalous heavy ion dropouts observed throughout the ejecta. Overall, the results indicate that additional ionization is needed to match observation. An important driver of ionization could come from suprathermal electrons, such as those produced via Fermi acceleration during reconnection, suggesting that the process is critical to the development and extended heating of extreme CME eruptions, like the Bastille Day CME.

Cancer growth is predicted to require substantial rates of substrate catabolism and ATP turnover to drive unrestricted biosynthesis and cell growth. While substrate limitation can dramatically alter cell behavior, the effects of substrate limitation on total cellular ATP production rate is poorly understood. Here, we show that MCF7 breast cancer cells, given different combinations of the common cell culture substrates glucose, glutamine, and pyruvate, display ATP production rates 1.6-fold higher than when cells are limited to each individual substrate. This increase occurred mainly through faster oxidative ATP production, with little to no increase in glycolytic ATP production. In comparison, non-transformed C2C12 myoblast cells show no change in ATP production rate when substrates are limited. In MCF7 cells, glutamine allows unexpected access to oxidative capacity that pyruvate, also a strictly oxidized substrate, does not. Pyruvate, when added with other exogenous substrates, increases substrate-driven oxidative ATP production, by increasing both ATP supply and demand. Overall, we find that MCF7 cells are highly flexible with respect to maintaining total cellular ATP production under different substrate-limited conditions, over an acute (within minutes) timeframe that is unlikely to result from more protracted (hours or more) transcription-driven changes to metabolic enzyme expression. The near-identical ATP production rates maintained by MCF7 and C2C12 cells given single substrates reveal a potential difficulty in using substrate limitation to selectively starve cancer cells of ATP. In contrast, the higher ATP production rate conferred by mixed substrates in MCF7 cells remains a potentially exploitable difference.

Preeclampsia is one of the most severe pregnancy complications and a leading cause of maternal death. However, early diagnosis of preeclampsia remains a clinical challenge. Alterations in the normal immune adaptations necessary for the maintenance of a healthy pregnancy are central features of preeclampsia. However, prior analyses primarily focused on the static assessment of select immune cell subsets have provided limited information for the prediction of preeclampsia. Here, we used a high-dimensional mass cytometry immunoassay to characterize the dynamic changes of over 370 immune cell features (including cell distribution and functional responses) in maternal blood during healthy and preeclamptic pregnancies. We found a set of eight cell-specific immune features that accurately identified patients well before the clinical diagnosis of preeclampsia (median area under the curve (AUC) 0.91, interquartile range [0.82–0.92]). Several features recapitulated previously known immune dysfunctions in preeclampsia, such as elevated pro-inflammatory innate immune responses early in pregnancy and impaired regulatory T (Treg) cell signaling. The analysis revealed additional novel immune responses that were strongly associated with, and preceded the onset of preeclampsia, notably abnormal STAT5ab signaling dynamics in CD4+T cell subsets (AUC 0.92, p = 8.0E-5). These results provide a global readout of the dynamics of the maternal immune system early in pregnancy and lay the groundwork for identifying clinically-relevant immune dysfunctions for the prediction and prevention of preeclampsia.

In the Netherlands a need is felt for more flexible Child Health Care services, both efficient and tailored to needs. We set up a study on impact and feasibility of task delegation to child health care nurses performing all regular checkups on children aged 2 months to 4 years. Abnormal findings were discussed with the attending child health care doctor. This article describes impact and feasibility of this task delegation from four viewpoints: competences of nurses; percentage of children assigned to the nurse; change in abnormal findings and referrals; experiences of professionals and parents.Two experiment teams and two control teams were compared before and after starting task delegation. Nurses in the experiment teams were trained to carry out regular checkups on healthy children. Assignment to the experiment schedule was a joint decision by doctor and nurse. Nursing competences were measured by means of questionnaires. Percentage of children assigned to the nurse and screening results of eyes, heart, hips, growth and development were extracted from the electronic health record. Difference in change was compared between experiment and control teams. Mann-Whitney tests and logistic generalized estimating equations were used to test for significance. Experiences of professionals and parents were evaluated through focus group interviews, which were subjected to a qualitative analysis.Nurses in the experiment regions showed improvement in medical screening skills. No difference in change was perceived in general nursing competences. In the experiment group, 69% of all children were assigned to the nurse. There were no significant differences in change in the percentages of abnormal findings or referrals in the experiment teams compared to the control teams, except for hips. Interviews showed that both doctors and nurses thought positively of the new working method, yet made some recommendations for improvements. Parents felt well-informed and experienced an equal level of proficiency but less continuity in person.This experiment shows that task delegation from doctor to nurse in preventive child health care is feasible. It is important to pay attention to the acceptation process of professionals during implementation. More investigation is needed in order to assess effectiveness and efficacy of task delegation.

There are various system identification approaches typically used to extract the rotordynamic coefficients from simultaneously measured dynamic force and motion signals. Since the coefficient values extracted can vary significantly as a function of the system identification approach used, more attention is needed to treat this issue than is typically included in the rotor dynamics literature. This paper describes system identification and data reduction methods used for extracting rotordynamic coefficients of fluid-film journal bearings. Data is used from a test apparatus incorporating a double-spoolshaft spindle which permits independent control over the journal spin speed and the frequency of an adjustable-magnitude circular orbit, for both forward and backward whirling. For example, a least squares linear regression on the force-displacement equations of the experiment provides only one of the rational approaches to extract the anisotropic rotordynamic coefficients (stiffness, damping and fluid inertia effects). Rotordynamic coefficients are also extracted with both first and second order orbital frequency dependencies. To assess the quality of the measured signals, coherence functions are calculated to relate the time-averaged input motion signals and the time-averaged output force signals.

BACKGROUND: Placental dysfunction underlies numerous complications of pregnancy. A major obstacle to understanding the roles of potential mediators of placental pathology has been the absence of suitable methods for tissue-specific gene manipulation and sensitive assays for studying gene functions in the placentas of intact animals. We describe a sensitive and noninvasive method of repetitively tracking placenta-specific gene expression throughout pregnancy using lentivirus-mediated transduction of optical reporter genes in mouse blastocysts. METHODOLOGY/PRINCIPAL FINDINGS: Zona-free blastocysts were incubated with lentivirus expressing firefly luciferase (Fluc) and Tomato fluorescent fusion protein for trophectoderm-specific infection and transplanted into day 3 pseudopregnant recipients (GD3). Animals were examined for Fluc expression by live bioluminescence imaging (BLI) at different points during pregnancy, and the placentas were examined for tomato expression in different cell types on GD18. In another set of experiments, blastocysts with maximum photon fluxes in the range of 2.0E+4 to 6.0E+4 p/s/cm(2)/sr were transferred. Fluc expression was detectable in all surrogate dams by day 5 of pregnancy by live imaging, and the signal increased dramatically thereafter each day until GD12, reaching a peak at GD16 and maintaining that level through GD18. All of the placentas, but none of the fetuses, analyzed on GD18 by BLI showed different degrees of Fluc expression. However, only placentas of dams transferred with selected blastocysts showed uniform photon distribution with no significant variability of photon intensity among placentas of the same litter. Tomato expression in the placentas was limited to only trophoblast cell lineages. CONCLUSIONS/SIGNIFICANCE: These results, for the first time, demonstrate the feasibility of selecting lentivirally-transduced blastocysts for uniform gene expression in all placentas of the same litter and early detection and quantitative analysis of gene expression throughout pregnancy by live BLI. This method may be useful for a wide range of applications involving trophoblast-specific gene manipulations in utero.

This study investigates the use of atomic layer deposition (ALD) to mitigate multipacting phenomena inside superconducting radio frequency cavities used in particle accelerators while preserving high quality factors in the 1010 range. The unique ALD capability to control the film thickness down to the atomic level on arbitrary complex shape objects enables the fine-tuning of TiN film resistivity and total electron emission yield (TEEY) from coupons to devices. This level of control allows us to adequately choose a TiN film thickness that provides both high resistivity to prevent Ohmic losses and a low TEEY to mitigate multipacting for the application of interest. The methodology presented in this work can be scaled to other domains and devices subject to RF fields in vacuum and sensitive to multipacting or electron discharge processes with their own requirements in resistivities and TEEY values. [ABSTRACT FROM AUTHOR]

Estimating the time of delivery is of high clinical importance because pre- and postterm deviations are associated with complications for the mother and her offspring. However, current estimations are inaccurate. As pregnancy progresses toward labor, major transitions occur in fetomaternal immune, metabolic, and endocrine systems that culminate in birth. The comprehensive characterization of maternal biology that precedes labor is key to understanding these physiological transitions and identifying predictive biomarkers of delivery. Here, a longitudinal study was conducted in 63 women who went into labor spontaneously. More than 7000 plasma analytes and peripheral immune cell responses were analyzed using untargeted mass spectrometry, aptamer-based proteomic technology, and single-cell mass cytometry in serial blood samples collected during the last 100 days of pregnancy. The high-dimensional dataset was integrated into a multiomic model that predicted the time to spontaneous labor [R = 0.85, 95% confidence interval (CI) [0.79 to 0.89], P = 1.2 × 10-40, N = 53, training set; R = 0.81, 95% CI [0.61 to 0.91], P = 3.9 × 10-7, N = 10, independent test set]. Coordinated alterations in maternal metabolome, proteome, and immunome marked a molecular shift from pregnancy maintenance to prelabor biology 2 to 4 weeks before delivery. A surge in steroid hormone metabolites and interleukin-1 receptor type 4 that preceded labor coincided with a switch from immune activation to regulation of inflammatory responses. Our study lays the groundwork for developing blood-based methods for predicting the day of labor, anchored in mechanisms shared in preterm and term pregnancies.

MotivationMultiple biological clocks govern a healthy pregnancy. These biological mechanisms produce immunologic, metabolomic, proteomic, genomic and microbiomic adaptations during the course of pregnancy. Modeling the chronology of these adaptations during full-term pregnancy provides the frameworks for future studies examining deviations implicated in pregnancy-related pathologies including preterm birth and preeclampsia.ResultsWe performed a multiomics analysis of 51 samples from 17 pregnant women, delivering at term. The datasets included measurements from the immunome, transcriptome, microbiome, proteome and metabolome of samples obtained simultaneously from the same patients. Multivariate predictive modeling using the Elastic Net (EN) algorithm was used to measure the ability of each dataset to predict gestational age. Using stacked generalization, these datasets were combined into a single model. This model not only significantly increased predictive power by combining all datasets, but also revealed novel interactions between different biological modalities. Future work includes expansion of the cohort to preterm-enriched populations and in vivo analysis of immune-modulating interventions based on the mechanisms identified.Availability and implementationDatasets and scripts for reproduction of results are available through: https://nalab.stanford.edu/multiomics-pregnancy/.Supplementary informationSupplementary data are available at Bioinformatics online.

Simple Summary: Cortisol is a very common hormone measured when studying the stress response. While plasma cortisol is commonly utilized, concerns regarding stress caused by the sampling procedure and whether that sample represents acute vs. chronic stress have paved the way for measuring fecal cortisol metabolites (FCMs). The measurement of FCMs can be costly, and some reagents used require special permission. Commercial ELISA kits have become popular as a cost-effective method of cortisol measurement, but it is crucial to validate if these kits can detect a biologically significant change in the hormone being measured within the animal being studied. In our work, we conclude that the Arbor AssaysTM DetectX® Cortisol ELISA kit (K003-H1, Ann Arbor, MI, USA) is a reliable, economic option for the measurement of biologically relevant changes in cortisol in equine plasma and FCMs. This work helps to provide another potential tool for researchers who want to evaluate horse stress and well-being. The measurement of fecal cortisol/corticosterone metabolites (FCMs) is often used to quantify the stress response. The sampling method is relatively non-invasive, reduces concern for elevation of cortisol from the sampling method, and has been shown to measure cortisol more consistently without the daily diurnal rhythm observed in blood. Commercial ELISA (enzyme-linked immunoassay) kits offer benefits over previously validated immunoassay methods but lack validation. The objective of this study was to evaluate a commercial ELISA kit (Arbor AssaysTM DetectX® Cortisol ELISA kit, K003-H1, Ann Arbor, MI, USA) and provide analytical and biologic validation of equine fecal and plasma samples. Horses (4 male, 4 female, mean ± SD: 4 ± 5 yr) were transported for 15 min with limited physical and visual contact via a livestock trailer. Blood and fecal samples were collected pre- and post-transportation. Parallelism, accuracy, and precision tests were used to analytically validate this kit. Data were analyzed using PROC MIXED in SAS 9.4. Plasma cortisol concentrations increased in response to trailering (254.5 ± 26.4 nmol/L, 0 min post-transportation) compared to pre-transportation (142.8 ± 26.4 nmol/L). FCM concentrations increased 24 h post-trailering (10.8 ± 1.7 ng/g) when compared to pre-transportation (7.4 ± 1.7 ng/g). These data support that changes in FCMs can be observed 24 h post-stressor. In conclusion, the Arbor AssaysTM DetectX® Cortisol ELISA kit is a reliable, economic option for the measurement of biologically relevant changes in cortisol in equine plasma and FCMs. [ABSTRACT FROM AUTHOR]

ObjectiveTo examine recurrent preterm birth and early term birth in women's initial and immediately subsequent pregnancies.MethodsThis retrospective cohort study included 163,889 women who delivered their first and second liveborn singleton neonates between 20 and 44 weeks of gestation in California from 2005 through 2011. Data from hospital discharge records and birth certificates were used for analyses. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using logistic regression models adjusted for risk factors.ResultsShorter gestational duration in the first pregnancy increased the risk of subsequent preterm birth (both early, before 32 weeks of gestation, and later, from 32 to 36 weeks of gestation) as well as early term birth (37-38 weeks of gestation). Compared with women with a prior term birth, women with a prior early preterm birth (before 32 weeks of gestation) were at the highest risk for a subsequent early preterm birth (58/935 [6.2%] compared with 367/118,505 [0.3%], adjusted OR 23.3, 95% CI 17.2-31.7). Women with a prior early term birth had more than a twofold increased risk for subsequent preterm birth (before 32 weeks of gestation: 171/36,017 [0.5%], adjusted OR 2.0, 95% CI 1.6-2.3; from 32 to 36 weeks of gestation: 2,086/36,017 [6.8%], adjusted OR 3.0, 95% CI 2.9-3.2) or early term birth (13,582/36,017 [37.7%], adjusted OR 2.2, 95% CI 2.2-2.3).ConclusionBoth preterm birth and early term birth are associated with these outcomes in a subsequent pregnancy. Increased clinical attention and research efforts may benefit from a focus on women with a prior early term birth as well as those with prior preterm birth.