Spinal projecting neurons in rostral ventromedial medulla co-regulate motor and sympathetic tone.

Many behaviors require the coordinated actions of somatic and autonomic functions. However, the underlying mechanisms remain elusive. By opto-stimulating different populations of descending spinal projecting neurons (SPNs) in anesthetized mice, we show that stimulation of excitatory SPNs in the rostral ventromedial medulla (rVMM) resulted in a simultaneous increase in somatomotor and sympathetic activities. Conversely, opto-stimulation of rVMM inhibitory SPNs decreased both activities. Anatomically, these SPNs innervate both sympathetic preganglionic neurons and motor-related regions in the spinal cord. Fiber-photometry recording indicated that the activities of rVMM SPNs correlate with different levels of muscle and sympathetic tone during distinct arousal states. Inhibiting rVMM excitatory SPNs reduced basal muscle and sympathetic tone, impairing locomotion initiation and high-speed performance. In contrast, silencing the inhibitory population abolished muscle atonia and sympathetic hypoactivity during rapid eye movement (REM) sleep. Together, these results identify rVMM SPNs as descending spinal projecting pathways controlling the tone of both the somatomotor and sympathetic systems.

Clinical implications of crown-rump length discordance at 11 to 14 weeks in dichorionic twins.

BACKGROUND: Crown-rump length discordance, defined as ≥10% discordance, has been investigated as an early sonographic marker of subsequent growth abnormalities and is associated with an increased risk of fetal loss in twin pregnancies. Previous studies have not investigated the prevalence of fetal aneuploidy or structural anomalies in twins with discordance or the independent association of crown-rump length discordance with adverse perinatal outcomes. Moreover, data are limited on cell-free DNA screening for aneuploidy in dichorionic twins with discordance. OBJECTIVE: This study aimed to evaluate whether crown-rump length discordance in dichorionic twins between 11 and 14 weeks of gestation is associated with a higher risk of aneuploidy, structural anomalies, or adverse perinatal outcomes and to assess the performance of cell-free DNA screening in dichorionic twin pregnancies with crown-rump length discordance. STUDY DESIGN: This was a secondary analysis of a multicenter retrospective cohort study that evaluated the performance of cell-free DNA screening for the common trisomies in twin pregnancies from December 2011 to February 2020. For this secondary analysis, we included live dichorionic pregnancies with crown-rump length measurements between 11 and 14 weeks of gestation. First, we compared twin pregnancies with discordant crown-rump lengths with twin pregnancies with concordant crown-rump lengths and analyzed the prevalence of aneuploidy and fetal structural anomalies in either twin. Second, we compared the prevalence of a composite adverse perinatal outcome, which included preterm birth at <34 weeks of gestation, hypertensive disorders of pregnancy, stillbirth or miscarriage, small-for-gestational-age birthweight, and birthweight discordance. Moreover, we assessed the performance of cell-free DNA screening in pregnancies with and without crown-rump length discordance. Outcomes were compared with multivariable regression to adjust for confounders. RESULTS: Of 987 dichorionic twins, 142 (14%) had crown-rump length discordance. The prevalence of aneuploidy was higher in twins with crown-rump length discordance than in twins with concordance (9.9% vs 3.9%, respectively; adjusted relative risk, 2.7; 95% confidence interval, 1.4-4.9). Similarly, structural anomalies (adjusted relative risk, 2.5; 95% confidence interval, 1.4-4.4]) and composite adverse perinatal outcomes (adjusted relative risk, 1.2; 95% confidence interval, 1.04-1.3) were significantly higher in twins with discordance. A stratified analysis demonstrated that even without other ultrasound markers, there were increased risks of aneuploidy (adjusted relative risk, 3.5; 95% confidence interval, 1.5-8.4) and structural anomalies (adjusted relative risk, 2.7; 95% confidence interval, 1.5-4.8) in twins with CRL discordance. Cell-free DNA screening had high negative predictive values for trisomy 21, trisomy 18, and trisomy 13, regardless of crown-rump length discordance, with 1 false-negative for trisomy 21 in a twin pregnancy with discordance. CONCLUSION: Crown-rump length discordance in dichorionic twins is associated with an increased risk of aneuploidy, structural anomalies, and adverse perinatal outcomes, even without other sonographic abnormalities. Cell-free DNA screening demonstrated high sensitivity and negative predictive values irrespective of crown-rump length discordance; however, 1 false-negative result illustrated that there is a role for diagnostic testing. These data may prove useful in identifying twin pregnancies that may benefit from increased screening and surveillance and are not ascertained by other early sonographic markers.

Low-dose aspirin, maternal cardiometabolic health, and offspring respiratory health 9 to 14 years after delivery: Findings from the EAGeR Follow-up Study.

BACKGROUND: Accumulating evidence shows that peri-conceptional and in-utero exposures have lifetime health impacts for mothers and their offspring. OBJECTIVES: We conducted a Follow-Up Study of the Effects of Aspirin in Gestation and Reproduction (EAGeR) trial with two objectives. First, we determined if women who enrolled at the Utah site (N = 1001) of the EAGeR trial (2007-2011, N = 1228) could successfully be contacted and agree to complete an online questionnaire on their reproductive, cardio-metabolic, and offspring respiratory health 9-14 years after original enrollment. Second, we evaluated if maternal exposure to low-dose aspirin (LDA) during pregnancy was associated with maternal cardio-metabolic health and offspring respiratory health. METHODS: The original EAGeR study population included women, 18-40 years of age, who had 1-2 prior pregnancy losses, and who were trying to become pregnant. At follow-up (2020-2021), participants from the Utah cohort completed a 13-item online questionnaire on reproductive and cardio-metabolic health, and those who had a live birth during EAGeR additionally completed a 7-item questionnaire on the index child's respiratory health. Primary maternal outcomes included hypertension and hypercholesterolemia; primary offspring outcomes included wheezing and asthma. RESULTS: Sixty-eight percent (n = 678) of participants enrolled in the follow-up study, with 10% and 15% reporting maternal hypertension and hypercholesterolemia, respectively; and 18% and 10% reporting offspring wheezing and asthma. We found no association between maternal LDA exposure and hypertension (risk difference [RD] -0.001, 95% confidence interval [CI] -0.05, 0.04) or hypercholesterolemia (RD -0.01, 95% CI -0.06, 0.05) at 9-14 years follow-up. Maternal LDA exposure was not associated with offspring wheezing (RD -0.002, 95% CI -0.08, 0.08) or asthma (RD 0.13, 95% CI 0.11, 0.37) at follow-up. Findings remained robust after considering potential confounding and selection bias. CONCLUSIONS: We observed no association between LDA exposure during pregnancy and maternal cardiometabolic or offspring respiratory health.

Copy number variants and fetal structural abnormalities in stillborn fetuses: A secondary analysis of the Stillbirth Collaborative Research Network study.

OBJECTIVE: To examine the association of placental and fetal DNA copy number variants (CNVs) with fetal structural malformations (FSMs) in stillborn fetuses. DESIGN: A secondary analysis of stillbirth cases in the Stillbirth Collaborative Research Network (SCRN) study. SETTING: Multicenter, 59 hospitals in five geographic regions in the USA. POPULATION: 388 stillbirth cases of the SCRN study (2006-2008). METHODS: Fetal structural malformations were grouped by anatomic system and specific malformation type (e.g. central nervous system, thoracic, cardiac, gastrointestinal, skeletal, umbilical cord and craniofacial defects). Single-nucleotide polymorphism array detected CNVs of at least 500 kb. CNVs were classified into two groups: normal, defined as no CNVs >500 kb or benign CNVs, and abnormal, defined as pathogenic or variants of unknown clinical significance. MAIN OUTCOME MEASURES: The proportions of abnormal CNVs and normal CNVs were compared between stillbirth cases with and without FSMs using the Wald Chi-square test. RESULTS: The proportion of stillbirth cases with any FSMs was higher among those with abnormal CNVs than among those with normal CNVs (47.5 versus 19.1%; P-value <0.001). The most common organ system-specific FSMs associated with abnormal CNVs were cardiac defects, followed by hydrops, craniofacial defects and skeletal defects. A pathogenic deletion of 1q21.1 involving 46 genes (e.g. CHD1L) and a duplication of 21q22.13 involving four genes (SIM2, CLDN14, CHAF1B, HLCS) were associated with a skeletal and cardiac defect, respectively. CONCLUSION: Specific CNVs involving several genes were associated with FSMs in stillborn fetuses. The findings warrant further investigation and may inform counselling and care surrounding pregnancies affected by FSMs at risk for stillbirth.

First-Trimester Cell-Free DNA Fetal Fraction and Birth Weight in Twin Pregnancies.

OBJECTIVE: The relationship between fetal fraction and birth weight in twin gestations is poorly understood. This study aimed to investigate the relationship between first-trimester cell-free DNA (cfDNA) fetal fraction and birth weight <10th percentile in twin gestations. STUDY DESIGN: This is a planned secondary analysis of the Twin cfDNA Study, a 17-center retrospective cohort of twin pregnancies screened for aneuploidy using cfDNA in the first trimester from December 2011 to February 2022, excluding those with positive screen results for chromosomal aneuploidy. cfDNA testing was performed by a single laboratory using massively parallel sequencing. Baseline characteristics and birth weight of pregnancies with normal fetal fraction were compared with those with low (<5%) and high (>95%) fetal fraction using univariable analyses and multivariable regression. RESULTS: A total of 1,041 twin pregnancies were included. Chronic hypertension, elevated body mass index, and self-identified Black race were associated with fetal fraction <5th percentile. There was no difference in median fetal fraction between those with birth weight <10th percentile in at least one twin (median [interquartile range (IQR)] fetal fraction: 12.2% [9.8, 14.8] vs. those with normal birth weight (≥10th percentile) in both twins (median [IQR] fetal fraction: 12.3% [9.7, 15.2] for normal birth weight, p = 0.49). There was no association between high or low fetal fraction and birth weight <10th percentile for one (p = 0.45) or both (p = 0.81) twins, and there was no association between high or low fetal fraction and birth weight <5th percentile for one (p = 0.44) or both (p = 0.74) twins. The results were unchanged after adjustment for potential confounders. CONCLUSION: In this large cohort, there was no association between the extremes of cfDNA fetal fraction and birth weight <10th percentile, suggesting that first-trimester fetal fraction may not predict impaired fetal growth in twin gestations. KEY POINTS: · No association between fetal fraction and small for gestational age birth weight in twins.. · Results suggest that fetal fraction does not predict birth weight in twin gestations.. · These results differ from the relationship between fetal fraction and birth weight in singletons..

Endometriosis Typology and Ovarian Cancer Risk.

Importance: Endometriosis has been associated with an increased risk of ovarian cancer; however, the associations between endometriosis subtypes and ovarian cancer histotypes have not been well-described. Objective: To evaluate the associations of endometriosis subtypes with incidence of ovarian cancer, both overall and by histotype. Design, Setting, and Participants: Population-based cohort study using data from the Utah Population Database. The cohort was assembled by matching 78 893 women with endometriosis in a 1:5 ratio to women without endometriosis. Exposures: Endometriosis cases were identified via electronic health records and categorized as superficial endometriosis, ovarian endometriomas, deep infiltrating endometriosis, or other. Main Outcomes and Measures: Estimated adjusted hazard ratios (aHRs), adjusted risk differences (aRDs) per 10 000 women, and 95% CIs for overall ovarian cancer, type I ovarian cancer, and type II ovarian cancer comparing women with each type of endometriosis with women without endometriosis. Models accounted for sociodemographic factors, reproductive history, and past gynecologic operations. Results: In this Utah-based cohort, the mean (SD) age at first endometriosis diagnosis was 36 (10) years. There were 597 women with ovarian cancer. Ovarian cancer risk was higher among women with endometriosis compared with women without endometriosis (aHR, 4.20 [95% CI, 3.59-4.91]; aRD, 9.90 [95% CI, 7.22-12.57]), and risk of type I ovarian cancer was especially high (aHR, 7.48 [95% CI, 5.80-9.65]; aRD, 7.53 [95% CI, 5.46-9.61]). Ovarian cancer risk was highest in women with deep infiltrating endometriosis and/or ovarian endometriomas for all ovarian cancers (aHR, 9.66 [95% CI, 7.77-12.00]; aRD, 26.71 [95% CI, 20.01-33.41]), type I ovarian cancer (aHR, 18.96 [95% CI, 13.78-26.08]; aRD, 19.57 [95% CI, 13.80-25.35]), and type II ovarian cancer (aHR, 3.72 [95% CI, 2.31-5.98]; aRD, 2.42 [95% CI, -0.01 to 4.85]). Conclusions and Relevance: Ovarian cancer risk was markedly increased among women with ovarian endometriomas and/or deep infiltrating endometriosis. This population may benefit from counseling regarding ovarian cancer risk and prevention and could be an important population for targeted screening and prevention studies.

Copy number variants and fetal growth in stillbirths.

BACKGROUND: Fetal growth abnormalities are associated with a higher incidence of stillbirth, with small and large for gestational age infants incurring a 3 to 4- and 2 to 3-fold increased risk, respectively. Although clinical risk factors such as diabetes, hypertension, and placental insufficiency have been associated with fetal growth aberrations and stillbirth, the role of underlying genetic etiologies remains uncertain. OBJECTIVE: This study aimed to assess the relationship between abnormal copy number variants and fetal growth abnormalities in stillbirths using chromosomal microarray. STUDY DESIGN: A secondary analysis utilizing a cohort study design of stillbirths from the Stillbirth Collaborative Research Network was performed. Exposure was defined as abnormal copy number variants including aneuploidies, pathogenic copy number variants, and variants of unknown clinical significance. The outcomes were small for gestational age and large for gestational age stillbirths, defined as a birthweight <10th percentile and greater than the 90th percentile for gestational age, respectively. RESULTS: Among 393 stillbirths with chromosomal microarray and birthweight data, 16% had abnormal copy number variants. The small for gestational age outcome was more common among those with abnormal copy number variants than those with a normal microarray (29.5% vs 16.5%; P=.038). This finding was consistent after adjusting for clinically important variables. In the final model, only abnormal copy number variants and maternal age remained significantly associated with small for gestational age stillbirths, with an adjusted odds ratio of 2.22 (95% confidence interval, 1.12-4.18). Although large for gestational age stillbirths were more likely to have an abnormal microarray: 6.2% vs 3.3% (P=.275), with an odds ratio of 2.35 (95% confidence interval, 0.70-7.90), this finding did not reach statistical significance. CONCLUSION: Genetic abnormalities are more common in the setting of small for gestational age stillborn fetuses. Abnormal copy number variants not detectable by traditional karyotype make up approximately 50% of the genetic abnormalities in this population.

Cell-free DNA screening for trisomy 21 in twin pregnancy: a large multicenter cohort study.

BACKGROUND: Analysis of cell-free DNA from maternal blood provides effective screening for trisomy 21 in singleton pregnancies. Data on cell-free DNA screening in twin gestations are promising although limited. In previous twin studies, cell-free DNA screening was primarily performed in the second trimester and many studies did not report chorionicity. OBJECTIVE: This study aimed to evaluate the screening performance of cell-free DNA for trisomy 21 in twin pregnancies in a large, diverse cohort. A secondary aim was to evaluate screening performance for trisomy 18 and trisomy 13. STUDY DESIGN: This was a retrospective cohort study of twin pregnancies from 17 centers for which cell-free DNA screening was performed from December 2011 to February 2020 by one laboratory using massively parallel sequencing technology. Medical record review was conducted for all newborns and data on the birth outcome, the presence of any congenital abnormalities, phenotypic appearance at birth, and any chromosomal testing that was undertaken in the antenatal or postnatal period were extracted. Cases with a possible fetal chromosomal abnormality with no genetic test results were reviewed by a committee of maternal-fetal medicine geneticists. Cases with a vanishing twin and inadequate follow-up information were excluded. A minimum of 35 confirmed cases of trisomy 21 was required to capture a sensitivity of at least 90% with a prevalence of at least 1.9% with 80% power. Test characteristics were calculated for each outcome. RESULTS: A total of 1764 samples were sent for twin cell-free DNA screening. Of those, 78 cases with a vanishing twin and 239 cases with inadequate follow-up were excluded, leaving a total of 1447 cases for inclusion in the analysis. The median maternal age was 35 years and the median gestational age at cell-free DNA testing was 12.3 weeks. In total, 81% of the twins were dichorionic. The median fetal fraction was 12.4%. Trisomy 21 was detected in 41 of 42 pregnancies, yielding a detection rate of 97.6% (95% confidence interval, 83.8-99.7). There was 1 false negative and no false positive cases. Trisomy 21 was detected in 38 out of 39 dichorionic twin pregnancies, yielding a detection rate of 97.4% (95% confidence interval, 82.6-99.7). Trisomy 18 was detected in 10 of the 10 affected pregnancies. There was 1 false positive case. Trisomy 13 was detected in 4 of the 5 cases, yielding a detection rate of 80% (95% confidence interval, 11.1-99.2). There was one false negative and no false positive cases. The nonreportable rate was low at 3.9 %. CONCLUSION: Cell-free DNA testing is effective in screening for trisomy 21 in twin gestations from the first trimester of pregnancy. Detection of trisomy 21 was high in dichorionic and monochorionic twins, and the nonreportable result rates were low. This study included high numbers of cases of trisomy 18 and 13 when compared with the current literature. Although screening for these conditions in twins seems to be promising, the numbers were too small to make definitive conclusions regarding the screening efficacy for these conditions. It is possible that cell-free DNA testing performance may differ among laboratories and vary with screening methodologies.

Familial aggregation of stillbirth: A pedigree analysis of a matched case-control study.

OBJECTIVE: To determine whether stillbirth aggregates in families and quantify its familial risk using extended pedigrees. DESIGN: State-wide matched case-control study. SETTING: Utah, United States. POPULATION: Stillbirth cases (n = 9404) and live birth controls (18 808) between 1978 and 2019. METHODS: Using the Utah Population Database, a population-based genealogical resource linked with state fetal death and birth records, we identified high-risk pedigrees with excess familial aggregation of stillbirth using the Familial Standardised Incidence Ratio (FSIR). Stillbirth odds ratio (OR) for first-degree relatives (FDR), second-degree relatives (SDR) and third-degree relatives (TDR) of parents with a stillbirth (affected) and live birth (unaffected) were estimated using logistic regression models. MAIN OUTCOME MEASURES: Familial aggregation estimated using FSIR, and stillbirth OR estimated for FDR, SDR and TDR of affected and unaffected parents using logistic regression models. RESULTS: We identified 390 high-risk pedigrees with evidence for excess familial aggregation (FSIR ≥2.00; P-value <0.05). FDRs, SDRs and TDRs of affected parents had 1.14-fold (95% confidence interval [CI]: 1.04-1.26), 1.22-fold (95% CI 1.11-1.33) and 1.15-fold (95% CI 1.08-1.21) higher stillbirth odds compared with FDRs, SDRs and TDRs of unaffected parents, respectively. Parental sex-specific analyses showed male FDRs, SDRs and TDRs of affected fathers had 1.22-fold (95% CI 1.02-1.47), 1.38-fold (95% CI 1.17-1.62) and 1.17-fold (95% CI 1.05-1.30) higher stillbirth odds compared with those of unaffected fathers, respectively. FDRs, SDRs and TDRs of affected mothers had 1.12-fold (95% CI 0.98-1.28), 1.09-fold (95% CI 0.96-1.24) and 1.15-fold (95% CI 1.06-1.24) higher stillbirth odds compared with those of unaffected mothers, respectively. CONCLUSIONS: We provide evidence for familial aggregation of stillbirth. Our findings warrant investigation into genes associated with stillbirth and underscore the need to design large-scale studies to determine the genetic architecture of stillbirth.

Fetomaternal hemorrhage: Evidence from a multihospital healthcare system that up to 40% of severe cases are missed.

BACKGROUND: We previously reported fetomaternal hemorrhage (FMH) in 1/9160 births, and only one neonatal death from FMH among 219,853 births. Recent reports indicate FMH is not uncommon among stillbirths. Consequently, we speculated we were missing cases among early neonatal deaths. We began a new FMH initiative to determine the current incidence. METHODS: We analyzed births from 2011 to 2020 where FMH was diagnosed. We also evaluated potential cases among neonates receiving an emergent transfusion just after birth, whose mothers were not tested for FMH. RESULTS: Among 297,403 births, 1375 mothers were tested for FMH (1/216 births). Fourteen percent tested positive (1/1599 births). Of those, we found 25 with clinical and laboratory evidence of FMH adversely affecting the neonate. Twenty-one received one or more emergency transfusions on the day of birth; all but two lived. We found 17 others who received an emergency transfusion on the day of birth where FMH was not tested for, but was likely; eight of those died. The 42 severe (proven + probable) cases equate to 1/7081 births. We judged that 10 of the 42 had an acute FMH, and in the others it likely had more than a day before birth. CONCLUSIONS: We estimate that we fail to diagnose >40% of our severe FMH cases. Needed improvements include (1) education to request maternal FMH testing when neonates are born anemic, (2) education on false-negative FMH tests, and (3) improved FMH communications between neonatology, obstetrics, and blood bank.

Copy number variants and placental abnormalities in stillborn fetuses: A secondary analysis of the Stillbirth Collaborative Research Network study.

OBJECTIVE: To examine the association of fetal/placental DNA copy number variants (CNVs) with pathologic placental lesions (PPLs) in pregnancies complicated by stillbirth. DESIGN: A secondary analysis of stillbirth cases in the Stillbirth Collaborative Research Network case-control study. SETTING: Multicenter, 59 hospitals in five geographical regions in the USA. POPULATION: 387 stillbirth cases (2006-2008). METHODS: Using standard definitions, PPLs were categorised by type including maternal vascular, fetal vascular, inflammatory and immune/idiopathic lesions. Single-nucleotide polymorphism array detected CNVs of at least 500 kb. CNVs were classified into two groups: normal, defined as no CNV >500 kb or benign CNVs, and abnormal, defined as pathogenic or variants of unknown clinical significance. MAIN OUTCOME MEASURES: The proportions of abnormal CNVs and normal CNVs compared between stillbirth cases with and without PPLs using the Wald Chi-square test. RESULTS: Of 387 stillborn fetuses, 327 (84.5%) had maternal vascular PPLs and 60 (15.6%) had abnormal CNVs. Maternal vascular PPLs were more common in stillborn fetuses with abnormal CNVs than in those with normal CNVs (81.7% versus 64.2%; P = 0.008). The proportions of fetal vascular, maternal/fetal inflammatory and immune/idiopathic PPLs were similar among stillborn fetuses with abnormal CNVs and those with normal CNVs. Pathogenic CNVs in stillborn fetuses with maternal vascular PPLs spanned several known genes. CONCLUSIONS: Abnormal placental/fetal CNVs were associated with maternal vascular PPLs in stillbirth cases. The findings may provide insight into the mechanisms of specific genetic abnormalities associated with placental dysfunction and stillbirth.

Social EEG: A novel neurodevelopmental approach to studying brain-behavior links and brain-to-brain synchrony during naturalistic toddler-parent interactions.

Despite increasing emphasis on emergent brain-behavior patterns supporting language, cognitive, and socioemotional development in toddlerhood, methodologic challenges impede their characterization. Toddlers are notoriously difficult to engage in brain research, leaving a developmental window in which neural processes are understudied. Further, electroencephalography (EEG) and event-related potential paradigms at this age typically employ structured, experimental tasks that rarely reflect formative naturalistic interactions with caregivers. Here, we introduce and provide proof of concept for a new "Social EEG" paradigm, in which parent-toddler dyads interact naturally during EEG recording. Parents and toddlers sit at a table together and engage in different activities, such as book sharing or watching a movie. EEG is time locked to the video recording of their interaction. Offline, behavioral data are microcoded with mutually exclusive engagement state codes. From 216 sessions to date with 2- and 3-year-old toddlers and their parents, 72% of dyads successfully completed the full Social EEG paradigm, suggesting that it is possible to collect dual EEG from parents and toddlers during naturalistic interactions. In addition to providing naturalistic information about child neural development within the caregiving context, this paradigm holds promise for examination of emerging constructs such as brain-to-brain synchrony in parents and children.

DLK1: A Novel Biomarker of Placental Insufficiency in Stillbirth and Live Birth.

OBJECTIVE: Delta-like homolog 1 (DLK1) is a growth factor that is reduced in maternal sera in pregnancies with small for gestational age neonates. We sought to determine if DLK1 is associated with stillbirth (SB), with and without placental insufficiency. STUDY DESIGN: A nested case-control study was performed using maternal sera from a multicenter case-control study of SB and live birth (LB). SB and LB were stratified as placental insufficiency cases (small for gestational age <5% or circulatory lesions on placental histopathology) or normal placenta controls (appropriate for gestational age and no circulatory lesions). Enzyme-linked immunosorbent assay (ELISA) was used to measure DLK1. The mean difference in DLK1 was compared on the log scale in an adjusted linear regression model with pairwise differences, stratified by term/preterm deliveries among DLK1 results in the quantifiable range. In exploratory analysis, geometric means were compared among all data and the proportion of "low DLK1" (less than the median value for gestational age) was compared between groups and modeled using linear and logistic regression, respectively. RESULTS: Overall, 234 SB and 234 LB were analyzed; 246 DLK1 values were quantifiable within the standard curve. Pairwise comparisons of case and control DLK1 geometric means showed no significant differences between groups. In exploratory analysis of all data, adjusted analysis revealed a significant difference for the LB comparison only (SB: 71.9 vs. 99.1 pg/mL, p = 0.097; LB: 37.6 vs. 98.1 pg/mL, p = 0.005). In exploratory analysis of "low DLK1," there was a significant difference between the odds ratio of having "low DLK1" between preterm cases and controls for both SB and LB. There were no significant differences in geometric means nor "low DLK1" between SB and LB. CONCLUSION: In exploratory analysis, more placental insufficiency cases in preterm SB and LB had "low DLK1." However, low DLK1 levels were not associated with SB. KEY POINTS: · Maternally circulating DLK1 is correlated with placental insufficiency.. · Maternally circulating DLK1 is not correlated with SB.. · DLK1 is a promising marker for placental insufficiency..

Extent and predictors of work-related distress in community correction officers: a systematic review.

Research indicates that indirect exposure to trauma can have a detrimental psychological impact on professionals working within, and interfacing with, law enforcement and the criminal justice system. This systematic review aimed to explore the extent and predictors of work-related distress amongst community corrections personnel. A search of five databases identified 19 papers eligible for inclusion; 16 addressed burnout, and the remainder investigated secondary trauma, vicarious trauma and compassion fatigue. Synthesis revealed that community corrections personnel reported burnout at levels akin to those of other professions working in forensic contexts, though reports of secondary trauma appeared higher. Predictive factors encompassed personal, role-based and organisational factors. Research reporting work-related distress in correctional officers is focused on burnout but uses divergent models of stress, reveals methodological weaknesses, and to date has little examined responses to indirect trauma. The limitations of this review are discussed, alongside clinical implications and areas for future research.

Nonrapid eye movement sleep characteristics and relations with motor, memory, and cognitive ability from infancy to preadolescence.

Sleep plays a critical role in neural neurodevelopment. Hallmarks of sleep reflected in the electroencephalogram during nonrapid eye movement (NREM) sleep are associated with learning processes, cognitive ability, memory, and motor functioning. Research in adults is well-established; however, the role of NREM sleep in childhood is less clear. Growing evidence suggests the importance of two NREM sleep features: slow-wave activity and sleep spindles. These features may be critical for understanding maturational change and the functional role of sleep during development. Here, we review the literature on NREM sleep from infancy to preadolescence to provide insight into the network dynamics of the developing brain. The reviewed findings show distinct relations between topographical and maturational aspects of slow waves and sleep spindles; however, the direction and consistency of these relationships vary, and associations with cognitive ability remain unclear. Future research investigating the role of NREM sleep and development would benefit from longitudinal approaches, increased control for circadian and homeostatic influences, and in early childhood, studies recording daytime naps and overnight sleep to yield increased precision for detecting age-related change. Such evidence could help explicate the role of NREM sleep and provide putative physiological markers of neurodevelopment.

Point-of-Care Tissue Analysis Using Miniature Mass Spectrometer.

The combination of direct sampling ionization and miniature mass spectrometer presents a promising technical pathway of point-of-care analysis in clinical applications. In this work, a miniature mass spectrometry system was used for analysis of tissue samples. Direct tissue sampling coupled with extraction spray ionization was used with a home-built miniature mass spectrometer, Mini 12. Lipid species in tissue samples were well profiled in rat brain, kidney, and liver in a couple of minutes. By incorporating a photochemical (Paternò-Büchi) reaction, fast identification of lipid C═C location was realized. Relative quantitation of the lipid C═C isomer was performed by calculating the intensity ratio C═C diagnostic product ions, by which FA 18:1 (Δ9)/FA 18:1 (Δ11) was found to change significantly in mouse cancerous breast tissue samples. Accumulation of 2-hydroxylglutarate in human glioma samples, not in normal brains, can also be easily identified for rapid diagnosis.

Mapping Lipid C=C Location Isomers in Organ Tissues by Coupling Photochemical Derivatization and Rapid Extractive Mass Spectrometry.

Lipid desaturation plays important roles in biological processes and the disease states. Here, we report a simple but efficient method for mapping unsaturated phospholipids including the spatial distribution of lipid C=C location isomers in animal organs by coupling the C=C specific derivatization with direct analysis mass spectrometry (MS). Lipids are sampled directly by a stainless-steel wire from rat brain or kidney, extracted, and derivatized via the Paternò-Büchi reaction in a glass emitter of the nanoelectrospray ionization (nanoESI) source. Subsequent analysis by nanoESI-tandem mass spectrometry reveals C=C locations and relative quantities of lipid C=C location isomers. Unsaturated lipids, such as phospholipids and free fatty acids, have been identified with ion intensities spanning two orders of magnitude in rat brain. Typical sample consumption is less than 10 µg/measurement and the time for each analysis is about 3 min. This method should serve as a complementary method to high spatial resolution mass spectrometry imaging techniques, because it offers a streamlined experimental workflow for rapid profiling of lipids with C=C specificity to enable such applications as point-of-care disease diagnostics.

Meeting sustainable development challenges in growing cities: Coupled social-ecological systems modeling of land use and water changes.

Ongoing urban expansion may degrade natural resources, ecosystems, and the services they provide to human societies, e.g., through land use and water changes and feedbacks. In order to control and minimize such negative impacts of urbanization, best practices for sustainable urban development must be identified, supported, and reinforced. To accomplish this, assessment methods and tools need to consider the couplings and feedbacks between social and ecological systems, as the basis for improving the planning and management of urban development. Collaborative efforts by academics, urban planners, and other relevant actors are also essential in this context. This will require relevant methods and tools for testing and projecting scenarios of coupled social-ecological system (CSES) behavior, changes, and feedbacks, in support of sustainable development of growing cities. This paper presents a CSES modeling approach that can provide such support, by coupling socio-economically driven land use changes and associated hydrological changes. The paper exemplifies and tests the applicability of this approach for a concrete case study with relevant data availability, the Tyresån catchment in Stockholm County, Sweden. Results show that model integration in the approach can reveal impacts of urbanization on hydrological and water resource, and the implications and feedbacks for urban societies and ecosystems. The CSES approach introduces new model challenges, but holds promise for improved model support towards sustainable urban development.

High-density EEG characterization of brain responses to auditory rhythmic stimuli during wakefulness and NREM sleep.

Auditory rhythmic sensory stimulation modulates brain oscillations by increasing phase-locking to the temporal structure of the stimuli and by increasing the power of specific frequency bands, resulting in Auditory Steady State Responses (ASSR). The ASSR is altered in different diseases of the central nervous system such as schizophrenia. However, in order to use the ASSR as biological markers for disease states, it needs to be understood how different vigilance states and underlying brain activity affect the ASSR. Here, we compared the effects of auditory rhythmic stimuli on EEG brain activity during wake and NREM sleep, investigated the influence of the presence of dominant sleep rhythms on the ASSR, and delineated the topographical distribution of these modulations. Participants (14 healthy males, 20-33 years) completed on the same day a 60 min nap session and two 30 min wakefulness sessions (before and after the nap). During these sessions, amplitude modulated (AM) white noise auditory stimuli at different frequencies were applied. High-density EEG was continuously recorded and time-frequency analyses were performed to assess ASSR during wakefulness and NREM periods. Our analysis revealed that depending on the electrode location, stimulation frequency applied and window/frequencies analysed the ASSR was significantly modulated by sleep pressure (before and after sleep), vigilance state (wake vs. NREM sleep), and the presence of slow wave activity and sleep spindles. Furthermore, AM stimuli increased spindle activity during NREM sleep but not during wakefulness. Thus, (1) electrode location, sleep history, vigilance state and ongoing brain activity needs to be carefully considered when investigating ASSR and (2) auditory rhythmic stimuli during sleep might represent a powerful tool to boost sleep spindles.

Evaluation of stillbirth.

PURPOSE OF REVIEW: To review current evidence regarding the most useful tests for evaluation of potential causes of stillbirth. RECENT FINDINGS: Stillbirth remains one of the most devastating obstetric complications. Recent advances include work investigating the highest yield diagnostic tests for determining a cause of death in stillbirths. Placental pathology and fetal autopsy improve the diagnostic yield when combined with maternal clinical history. Additional tools include genetic evaluation, and testing for antiphospholipid antibodies and fetal-maternal hemorrhage based on the clinical scenario. However, routine testing for heritable thrombophilias or infection has not proven to be useful. In cases in which fetal autopsy is not acceptable to patients or possible for logistical reasons, alternative forms of fetal evaluation should be considered. SUMMARY: A systematic approach to stillbirth evaluation is useful in identifying a potential cause of death. This should incorporate clinical information as well as placental pathology and fetal autopsy. Based on clinical characteristics further testing may be indicated.