Associations between anxiety, sleep, and blood pressure parameters in pregnancy: a prospective pilot cohort study.

BACKGROUND: The potential effect modification of sleep on the relationship between anxiety and elevated blood pressure (BP) in pregnancy is understudied. We evaluated the relationship between anxiety, insomnia, and short sleep duration, as well as any interaction effects between these variables, on BP during pregnancy. METHODS: This was a prospective pilot cohort of pregnant people between 23 to 36 weeks' gestation at a single institution between 2021 and 2022. Standardized questionnaires were used to measure clinical insomnia and anxiety. Objective sleep duration was measured using a wrist-worn actigraphy device. Primary outcomes were systolic (SBP), diastolic (DBP), and mean (MAP) non-invasive BP measurements. Separate sequential multivariable linear regression models fit with generalized estimating equations (GEE) were used to separately assess associations between anxiety (independent variable) and each BP parameter (dependent variables), after adjusting for potential confounders (Model 1). Additional analyses were conducted adding insomnia and the interaction between anxiety and insomnia as independent variables (Model 2), and adding short sleep duration and the interaction between anxiety and short sleep duration as independent variables (Model 3), to evaluate any moderating effects on BP parameters. RESULTS: Among the 60 participants who completed the study, 15 (25%) screened positive for anxiety, 11 (18%) had subjective insomnia, and 34 (59%) had objective short sleep duration. In Model 1, increased anxiety was not associated with increases in any BP parameters. When subjective insomnia was included in Model 2, increased DBP and MAP was significantly associated with anxiety (DBP: ß 6.1, p = 0.01, MAP: ß 6.2 p < 0.01). When short sleep was included in Model 3, all BP parameters were significantly associated with anxiety (SBP: ß 9.6, p = 0.01, DBP: ß 8.1, p < 0.001, and MAP: ß 8.8, p < 0.001). No moderating effects were detected between insomnia and anxiety (p interactions: SBP 0.80, DBP 0.60, MAP 0.32) or between short sleep duration and anxiety (p interactions: SBP 0.12, DBP 0.24, MAP 0.13) on BP. CONCLUSIONS: When including either subjective insomnia or objective short sleep duration, pregnant people with anxiety had 5.1-9.6 mmHg higher SBP, 6.1-8.1 mmHg higher DBP, and 6.2-8.8 mmHg higher MAP than people without anxiety.

Evaluation of Sleep in Pregnant Inpatients Compared With Outpatients.

OBJECTIVE: To evaluate whether antepartum hospitalization was associated with differences in sleep duration or disrupted sleep patterns. METHODS: This was a prospective cohort study with enrollment of pregnant people aged 18-55 years with singleton gestations at 16 weeks of gestation or more between 2021 and 2022. Each enrolled antepartum patient was matched by gestational age to outpatients recruited from obstetric clinics at the same institution. Participants responded to the ISI (Insomnia Severity Index) and wore actigraph accelerometer watches for up to 7 days. The primary outcome was total sleep duration per 24 hours. Secondary outcomes included sleep efficiency (time asleep/time in bed), ISI score, clinical insomnia (ISI score higher than 15), short sleep duration (less than 300 minutes/24 hours), wakefulness after sleep onset, number of awakenings, and sleep fragmentation index. Outcomes were evaluated with multivariable generalized estimating equations adjusted for body mass index (BMI), sleep aid use, and insurance type, accounting for gestational age correlations. An interaction term assessed the joint effects of time and inpatient status. RESULTS: Overall 58 participants were included: 18 inpatients and 40 outpatients. Inpatients had significantly lower total sleep duration than outpatients (mean 4.4 hours [SD 1.6 hours] inpatient vs 5.2 hours [SD 1.5 hours] outpatient, adjusted ß=-1.1, 95% CI, -1.8 to -0.3, P =.01). Awakenings (10.1 inpatient vs 13.8, P =.01) and wakefulness after sleep onset (28.3 inpatient vs 35.5 outpatient, P =.03) were lower among inpatients. There were no differences in the other sleep outcomes, and no interaction was detected for time in the study and inpatient status. Inpatients were more likely to use sleep aids (39.9% vs 12.5%, P =.03). CONCLUSION: Hospitalized pregnant patients slept about 1 hour/day less than outpatients. Fewer awakenings and reduced wakefulness after sleep onset among inpatients may reflect increased use of sleep aids in hospitalized patients.

Physical activity among pregnant inpatients and outpatients and associations with anxiety.

OBJECTIVE: Physical activity is linked to lower anxiety, but little is known about the association during pregnancy. This is especially important for antepartum inpatients, who are known to have increased anxiety yet may not be able to achieve target levels of physical activity during hospitalization. We compared physical activity metrics between pregnant inpatients and outpatients and explored correlations with anxiety. MATERIALS AND METHODS: This was a prospective cohort between 2021 and 2022 of pregnant people aged 18-55 years carrying singleton gestations ≥ 16 weeks. Three exposure groups were matched for gestational age: 1) outpatients from general obstetric clinics; 2) outpatients from high-risk Maternal-Fetal Medicine obstetric clinics; and 3) antepartum inpatients. Participants wore Actigraph GT9X Link accelerometer watches for up to 7 days to measure physical activity. The primary outcome was mean daily step count. Secondary outcomes were metabolic equivalent tasks (METs), hourly kilocalories (kcals), moderate to vigorous physical activity (MVPA) bursts, and anxiety (State-Trait Anxiety Inventory [STAI]). Step counts were compared using multivariable generalized estimating equations adjusting for maternal age, body-mass index, and insurance type as a socioeconomic construct, accounting for within-group clustering by gestational age. Spearman correlations were used to correlate anxiety scores with step counts. RESULTS: 58 participants were analyzed. Compared to outpatients, inpatients had significantly lower mean daily steps (primary outcome, adjusted beta -2185, 95 % confidence interval [CI] -3146, -1224, p < 0.01), METs (adjusted beta -0.18, 95 % CI -0.23, -0.13, p < 0.01), MVPAs (adjusted beta -38.2, 95 % CI -52.3, -24.1, p < 0.01), and kcals (adjusted beta -222.9, 95 % CI -438.0, -7.8, p = 0.04). Over the course of the week, steps progressively decreased for inpatients (p-interaction 0.01) but not for either of the outpatient groups. Among the entire cohort, lower step counts correlated with higher anxiety scores (r = 0.30, p = 0.02). CONCLUSION: We present antenatal population norms and variance for step counts, metabolic equivalent tasks, moderate to vigorous physical activity bursts, and kcals, as well as correlations with anxiety. Antepartum inpatients had significantly lower physical activity than outpatients, and lower step counts correlated with higher anxiety levels. These results highlight the need for physical activity interventions, particularly for hospitalized pregnant people.

The USH3A causative gene clarin1 functions in Müller glia to maintain retinal photoreceptors.

Mutations in CLRN1 cause Usher syndrome type IIIA (USH3A), an autosomal recessive disorder characterized by hearing and vision loss, and often accompanied by vestibular balance issues. The identity of the cell types responsible for the pathology and mechanisms leading to vision loss in USH3A remains elusive. To address this, we employed CRISPR/Cas9 technology to delete a large region in the coding and untranslated (UTR) region of zebrafish clrn1. Retina of clrn1 mutant larvae exhibited sensitivity to cell stress, along with age-dependent loss of function and degeneration in the photoreceptor layer. Investigation revealed disorganization in the outer retina in clrn1 mutants, including actin-based structures of the Müller glia and photoreceptor cells. To assess cell-specific contributions to USH3A pathology, we specifically re-expressed clrn1 in either Müller glia or photoreceptor cells. Müller glia re-expression of clrn1 prevented the elevated cell death observed in larval clrn1 mutant zebrafish exposed to high-intensity light. Notably, the degree of phenotypic rescue correlated with the level of Clrn1 re-expression. Surprisingly, high levels of Clrn1 expression enhanced cell death in both wild-type and clrn1 mutant animals. However, rod- or cone-specific Clrn1 re-expression did not rescue the extent of cell death. Taken together, our findings underscore three crucial insights. First, clrn1 mutant zebrafish exhibit key pathological features of USH3A; second, Clrn1 within Müller glia plays a pivotal role in photoreceptor maintenance, with its expression requiring controlled regulation; third, the reliance of photoreceptors on Müller glia suggests a structural support mechanism, possibly through direct interactions between Müller glia and photoreceptors mediated in part by Clrn1 protein.

Racial Inequities in Palliative Referral for Children with High-Intensity Neurologic Impairment.

OBJECTIVE: To evaluate whether racial and socioeconomic inequities in pediatric palliative care utilization extend to children with high-intensity neurologic impairment (HI-NI), which is a chronic neurological diagnosis resulting in substantial functional morbidity and mortality. STUDY DESIGN: We conducted a retrospective study of patients with HI-NI who received primary care services at a tertiary care center from 2014 through 2019. HI-NI diagnoses that warranted a palliative care referral were identified by consensus of a multidisciplinary team. The outcome was referral to palliative care. The primary exposure was race, categorized as Black or non-Black to represent the impact of anti-Black racism. Additional exposures included ethnicity (Hispanic/non-Hispanic) and insurance status (Medicaid/non-Medicaid). Descriptive statistics, bivariate analyses, and multivariable logistic regression models were performed to assess associations between exposures and palliative care referral. RESULTS: A total of 801 patients with HI-NI were included; 7.5% received a palliative referral. There were no differences in gestational age, sex, or ethnicity between patients who received a referral and those who did not. In multivariable analysis, adjusting for ethnicity, sex, gestational age, and presence of complex chronic conditions, Black children (aOR 0.47, 95% CI 0.26, 0.84) and children with Medicaid insurance (aOR 0.40, 95% CI 0.23, 0.70) each had significantly lower odds of palliative referral compared with their non-Black and non-Medicaid-insured peers, respectively. CONCLUSIONS: We identified inequities in pediatric palliative care referral among children with HI-NI by race and insurance status. Future work is needed to develop interventions, with families, aimed at promoting more equitable, antiracist systems of palliative care.

Implementation of a Peer-to-Peer Support Program in a Quaternary Pediatric Medical Center.

Healthcare worker burnout is a growing epidemic associated with multiple negative outcomes. Compounding the routine stresses of clinical practice, involvement in adverse events can be emotionally devastating. Healthcare organizations have an obligation to mitigate burnout and promote engagement and resiliency. Many institutions have launched wellness initiatives, but the value of these programs is unclear. Here, we describe the implementation of a peer-to-peer support program at our quaternary pediatric medical center. This proactive program is unique in its referral process and scope and has demonstrated efficacy in mitigating the emotional impact of adverse effects. In total, our institution has trained 125 peer supporters. Since initiation, there have been a total of 2187 referrals made to the program. Data collected in 2022 from these referrals showed a 60.3% (n = 1220) response rate to the offer of support. A survey was sent to frontline clinicians from divisions with trained supporters. Of 963 respondents, 71.8% (n = 691) agreed that this program was a valuable resource, and 81.3% (n = 783) recommended peer support to be offered to those involved in adverse and stressful events. Our experience supports that the implementation of a proactive, peer-to-peer support program is both feasible and valuable.

Vitamin D and infertility.

PURPOSE OF REVIEW: Vitamin D deficiency has been implicated as a contributing factor to a spectrum of reproductive health burden, including difficulty conceiving, pathogenesis of gynaecological disorders such as uterine fibroids and endometriosis, to metabolic and endocrine burden of polycystic ovarian syndrome (PCOS). RECENT FINDINGS: There have been recent publications showing that in infertile women who are supplemented with vitamin D, there are higher pregnancy rates; there are improved ovarian reserve parameters in women with diminished ovarian reserve; curtailed fibroid growth in those with uterine myomas; lessened dysmenorrhea in endometriosis patients; and improved menstrual regularity, lowered testosterone, AMH and insulin levels in women with PCOS. In infertile men, sperm parameters, especially motility, are positively correlated with vitamin D serum levels. SUMMARY: Vitamin D status appears to be relevant to reproductive physiology, and to physiological processes underlying common gynaecological disorders as well as for reproductive success.

Demonstrating Attachment-Based Family Therapy for Transgender and Gender Diverse Youth with Suicidal Thoughts and Behavior: A Case Study.

Suicide is a growing public health issue among adolescents. While the majority of transgender and gender diverse (TGD) youth are healthy, many experience suicidal thoughts and behavior (STB). Due to discrimination and stigma, TGD youth attempt suicide at higher rates then heterosexual, cisgender and even cisgender, LGBQ youth. Despite this vulnerability to suicide, few treatments have been developed and tested for this population. One treatment, attachment-based family therapy (ABFT) has been adapted to work with LGBQ youth and may be promising for TGD adolescents at risk for suicide. This article provides an overview of our ABFT modifications for TGD youth with thoughts of suicide. Specifically, we illustrate how treatment outcomes, in a single case study, relate to processes within clinical treatment tasks. The case study demonstrates the application of these ABFT modifications with a self-identified, gender nonconforming adolescent (who had recently attempted suicide) and his caregivers. Treatment evaluation measures were collected over the course of 24 weeks to illustrate the youth's clinical progress. The youth's suicidal symptoms diminished markedly by the end of treatment. Further, the family reported an increased ability for problem solving and more open communication by treatment conclusion.

El suicidio es un problema de salud pública cada vez mayor entre los adolescentes. Si bien la mayoría de los jóvenes transgénero y de géneros diversos (TGD) son saludables, muchos tienen pensamientos y conductas suicidas. Debido a la discriminación y al estigma, los índices de intento de suicidio en los jóvenes TGD son más altos que en los jóvenes heterosexuales, cisgénero e incluso LGBQ cisgénero. A pesar de esta vulnerabilidad al suicidio, se han desarrollado y se han evaluado pocos tratamientos para esta población. Un tratamiento, la terapia familiar basada en el apego (TFBA), se ha adaptado para trabajar con jóvenes LGBQ y puede ser prometedor para adolescentes TGD en riesgo de suicidio. Este artículo ofrece un resumen de nuestras modificaciones a la TFBA para los jóvenes TGD con pensamientos de suicidio. Específicamente, ilustramos cómo los resultados del tratamiento, en un solo caso práctico, se relacionan con los procesos dentro de las tareas del tratamiento clínico. El caso práctico demuestra la aplicación de estas modificaciones de la TFBA con un adolescente que se identificó como de género no conforme (y que recientemente había intentado suicidarse) y sus cuidadores. Se recopilaron las valoraciones de una evaluación del tratamiento durante el transcurso de 24 semanas para ilustrar el avance clínico del joven. Los síntomas de suicidio del joven disminuyeron notablemente al final del tratamiento. Además, la familia informó una mayor capacidad para resolver problemas y una comunicación más abierta al concluir el tratamiento.

The ASQ-TRAK: Validating a culturally adapted developmental screening tool for Australian Aboriginal children.

BACKGROUND: Developmental monitoring, performed using culturally relevant tools, is of critical importance for all young children. The ASQ-TRAK is the culturally and linguistically adapted Ages and Stages Questionnaire (ASQ-3), a developmental screening tool, for Australian Aboriginal children. While the ASQ-TRAK has been well received in practice, investigating its psychometric properties will enable professionals to make informed decisions about its use. AIMS: To conduct a rigorous validation study of the ASQ-TRAK by applying Kane's argument-based approach. SUBJECTS: The ASQ-TRAK, Bayley-III and/or BDI-2 were administered cross-sectionally to 336 Australian Aboriginal children aged 2-48 months across ten participating sites in the Northern Territory and South Australia. A sample of staff and caregivers completed feedback surveys about the ASQ-TRAK. RESULTS: ASQ-TRAK domain scores were moderately positively correlated with corresponding domain scores on the Bayley-III or BDI-2. Inter-rater and inter-instrument reliability were high. Sensitivity (83%), specificity (83%) and negative predictive value (99%) were acceptable. Staff and caregivers expressed high levels of satisfaction with the ASQ-TRAK. CONCLUSIONS: Regular developmental screening can provide important information about developmental vulnerability and the need for services. The ASQ-TRAK should be administered by trained Aboriginal community-based workers and the implementation approach carefully planned. Areas for future research include longitudinal follow-up of children, investigating existing norms and cut-off scores, and considering the appropriateness of the ASQ-TRAK with Aboriginal people from different locations. The ASQ-TRAK has the potential to fill an important gap by enabling better access to high-quality developmental monitoring and targeted early intervention.

Peri-implantation cytokine profile differs between singleton and twin IVF pregnancies.

PROBLEM: It is unknown whether maternal cytokine production differs between twin and singleton gestations in the implantation phase. A difference in maternal serum cytokine concentrations in twins would imply a dose-response to the invading embryos, as opposed to a general immune reaction. METHOD OF STUDY: A prospective longitudinal cohort of women aged 18-45 at an academic fertility center undergoing in vitro fertilization and embryo transfer (IVF-ET) underwent routine collection of serial serum samples starting 9 days after ET and then approximately every 48 hours thereafter. Cryopreserved aliquots of these samples were assayed for interleukin-10 (IL-10), tumor necrosis factor-alpha (TNF-α), and C-X-C motif chemokine ligand 10 (CXCL10) using the SimplePlex immunoassay platform. Pregnancies were followed until delivery. Serial measures of serum concentrations of IL-10, CXCL10, and TNF-α in singleton or di-di twin pregnancies from 9 to 15 days after IVF-ET were compared. RESULTS: Maternal serum levels of CXCL10 are significantly lower in women with di-di twin pregnancies in early implantation compared to those with singleton gestation (day 9-11, P = .02). Serum levels of TNF-α and IL-10 were comparable at all studied time points (P > .05). CONCLUSION: Maternal serum levels of CXCL10 are significantly lower in the earliest implantation phase in di-di twins compared to singleton conceptions. Given the known anti-angiogenic role of CXCL10, we hypothesize that lower CXCL10 levels in twin implantations allow an environment that is conducive for the greater vascularization required for the establishment of dual placentation in di-di twins.

A Pediatric Patient With Ascites, Proteinuria, and Thrombocytopenia: A Rare Presentation for a Common Illness.

ABSTRACT: A 7-year-old female patient presented to our pediatric emergency department with 5 days of fever, sore throat, abdominal pain, vomiting, headache, and 2 days of periorbital swelling. Her initial laboratory evaluation revealed a negative monospot test, neutropenia, atypical lymphocytosis, and thrombocytopenia in addition to transaminitis and proteinuria. An abdominal ultrasound obtained identified hepatosplenomegaly, moderate ascites, acalculous cholecystitis, and a distended appendix with periappendiceal fluid. She was admitted to gastroenterology for further management with antibiotics and surgery and hematology consults. Ultimately, Epstein-Barr virus polymerase chain reaction was positive. This case highlights an atypical presentation of Epstein-Barr virus and the collaborative approach to diagnosis.

Prenatally diagnosed vasa previa: association with adverse obstetrical and neonatal outcomes.

BACKGROUND: Vasa previa represents a rare prenatal finding with potentially life-threatening risk to the fetus. OBJECTIVE: This study aimed to describe the natural history of prenatally diagnosed vasa previa and evaluate the association between antenatally diagnosed vasa previa and adverse obstetrical and neonatal outcomes. STUDY DESIGN: This was a multicenter descriptive and retrospective study of patients diagnosed prenatally with vasa previa on transvaginal ultrasound in the New York City Maternal-Fetal Medicine Research Consortium centers between 2012 and 2018. Outcomes evaluated included persistence of vasa previa at the time of delivery, gestational age at delivery, indications for unplanned unscheduled delivery, and neonatal course. RESULTS: A total of 165 pregnancies with vasa previa were included, of which 16 were twin gestations. Forty-three cases (26.1%) were noted to resolve on subsequent ultrasound. Of the remaining 122 cases with persistent vasa previa, 46 (37.7%) required unscheduled delivery. Twin gestations were nearly 3 times as likely to require unscheduled delivery as singleton gestations (73.3% vs 25.2%; P<.001). Most infants (70%) were admitted to the neonatal intensive care unit. There was 1 neonatal death (0.9%) because of complications related to prematurity. CONCLUSION: Despite the low neonatal mortality rate with prenatal detection of vasa previa, one-third of patients required unscheduled delivery, and more than half of neonates experienced complications related to prematurity.

The association between anti-Müllerian hormone and vitamin 25(OH)D serum levels and polycystic ovarian syndrome in adolescent females.

BACKGROUND: High anti-Müllerian hormone (AMH) levels and 25-hydroxyvitamin D [25(OH)D] deficiency have been associated with polycystic ovarian syndrome (PCOS) in adult women, and implicated in its pathogenesis. Herein we determined if the level of both AMH and 25(OH)D are altered in adolescent females with clinical features of PCOS. METHODS: This is a cross-sectional study utilizing a retrospective chart review of 128 patients aged 12-20 referred to an academic adolescent gynecology and endocrinology clinic for an evaluation of suspected PCOS. Unadjusted comparisons of AMH and 25(OH)D distributions between subjects with and without PCOS were performed using the Wilcoxon Rank Sum test. Quantile regression was used to compare the median AMH and 25(OH)D between subject groups; adjusting for race, ethnicity, BMI, insurance type, age, and season when bloodwork was performed. RESULTS: Seventy-four subjects were classified as having PCOS by meeting ≥2 of the three Rotterdam diagnostic criteria, and 47 subjects met only one Rotterdam diagnostic criteria, and were used as the comparative non-PCOS group. There were statistically significant unadjusted differences in median levels of AMH and 25(OH)D. In the adjusted analyses, median AMH was significantly higher in the PCOS group compared to the non-PCOS group (+ 2.39 ng/mL, 95% CI 0.43, 4.35, p = 0.018); 25(OH)D was significantly lower in the PCOS group (- 9.01 ng/mL, 95% CI -14.49, - 3.53 p = 0.001). In our sample, adolescents in both groups had insufficient 25(OH)D level (22 ng/mL) and elevated BMI (32.2 kg/m2). CONCLUSIONS: Adolescents with PCOS display high levels of AMH and low 25(OH)D levels. Since traditional clinical markers of PCOS may be physiologic in adolescents, AMH and 25(OH)D may be used as surrogate markers of PCOS risk in adolescents.

Acceptability of the culturally adapted ASQ-TRAK developmental screening tool to caregivers of Aboriginal children.

AIM: The Ages and Stages Questionnaire-Talking about Raising Aboriginal Kids (ASQ-TRAK) culturally adapted developmental screening tool is widely used in Australian Aboriginal communities. However, there has been limited exploration of the tool's acceptability to caregivers. The aim of the study is to determine the acceptability of the ASQ-TRAK developmental screening tool to caregivers of Aboriginal children in urban, regional and remote South Australia. METHODS: Caregivers of Aboriginal children completed a survey regarding acceptability of the ASQ-TRAK. Convenience samples of caregivers were invited to a telephone interview. RESULTS: Ninety-two caregivers completed the survey (96% response). Acceptability (92%) and caregiver satisfaction (73%) were high. Families perceived the screen as easy to use and understand, strengths-based and providing valuable information about their child's development. CONCLUSIONS: The ASQ-TRAK tool was highly acceptable to caregivers in Aboriginal communities in South Australia. The study highlights the importance of culturally safe practice and supports ASQ-TRAK implementation. Broader use and further evaluation of the ASQ-TRAK in Aboriginal communities needs consideration.

Trophoblast-secreted soluble-PD-L1 modulates macrophage polarization and function.

Decidual macrophages are in close contact with trophoblast cells during placenta development, and an appropriate crosstalk between these cellular compartments is crucial for the establishment and maintenance of a healthy pregnancy. During different phases of gestation, macrophages undergo dynamic changes to adjust to the different stages of fetal development. Trophoblast-secreted factors are considered the main modulators responsible for macrophage differentiation and function. However, the phenotype of these macrophages induced by trophoblast-secreted factors and the factors responsible for their polarization has not been elucidated. In this study, we characterized the phenotype and function of human trophoblast-induced macrophages. Using in vitro models, we found that human trophoblast-educated macrophages were CD14+ CD206+ CD86- and presented an unusual transcriptional profile in response to TLR4/LPS activation characterized by the expression of type I IFN-ß expression. IFN-ß further enhances the constitutive production of soluble programmed cell death ligand 1 (PD-L1) from trophoblast cells. PD-1 blockage inhibited trophoblast-induced macrophage differentiation. Soluble PD-L1 (sPD-L1) was detected in the blood of pregnant women and increased throughout the gestation. Collectively, our data suggest the existence of a regulatory circuit at the maternal fetal interface wherein IFN-ß promotes sPD-L1 expression/secretion by trophoblast cells, which can then initiate a PD-L1/PD-1-mediated macrophage polarization toward an M2 phenotype, consequently decreasing inflammation. Macrophages then maintain the expression of sPD-L1 by the trophoblasts through IFN-ß production induced through TLR4 ligation.

Human Chorionic Gonadotropin modulates CXCL10 Expression through Histone Methylation in human decidua.

The process of implantation, trophoblast invasion and placentation demand continuous adaptation and modifications between the trophoblast (embryonic) and the decidua (maternal). Within the decidua, the maternal immune system undergoes continued changes, as the pregnancy progress, in terms of the cell population, phenotype and production of immune factors, cytokines and chemokines. Human chorionic gonadotropin (hCG) is one of the earliest hormones produced by the blastocyst and has potent immune modulatory effects, especially in relation to T cells. We hypothesized that trophoblast-derived hCG modulates the immune population present at the maternal fetal interface by modifying the cytokine profile produced by the stromal/decidual cells. Using in vitro models from decidual samples we demonstrate that hCG inhibits CXCL10 expression by inducing H3K27me3 histone methylation, which binds to Region 4 of the CXCL10 promoter, thereby suppressing its expression. hCG-induced histone methylation is mediated through EZH2, a functional member of the PRC2 complex. Regulation of CXCL10 expression has a major impact on the capacity of endometrial stromal cells to recruit CD8 cells. We demonstrate the existence of a cross talk between the placenta (hCG) and the decidua (CXCL10) in the control of immune cell recruitment. Alterations in this immune regulatory function, such as during infection, will have detrimental effects on the success of the pregnancy.

IL-10 to TNFα ratios throughout early first trimester can discriminate healthy pregnancies from pregnancy losses.

PROBLEM: Embryo implantation and placentation require a careful immunological balance. Cytokines such as IL-10 and TNFα have been implicated as markers of dysregulation, but have only been studied at a single time point or after a pregnancy loss. Our objective was to determine normative patterns of serum levels of IL-10 and TNFα and their ratio throughout the first trimester in healthy pregnancies and to determine if this pattern differs from pregnancy loss. METHOD OF STUDY: Two prospective longitudinal cohorts of gravidae including in vitro fertilization (IVF) and naturally conceived pregnancies with serial blood draws. Cytokines were assayed using Simple Plex. In the IVF cohort, we monitored from the implantation day up to 6 weeks of gestation; whereas in the naturally conceived cohort, sample collection began at 4 weeks and throughout the whole first trimester. RESULTS: IL-10 concentrations in normal pregnancies were significantly higher than in pregnancies ending in a loss starting at 6-8 weeks of gestation, while TNFα concentrations were significantly lower in normal than in pregnancies ending in a loss starting at 3-5 of gestation weeks. The IL-10 to TNFα ratio in normal pregnancies was significantly higher from 4 to 9 weeks compared to pregnancies that were lost (t test, P < .05). Changes were observed before any symptoms of miscarriage were present. CONCLUSION: We provide evidences of differences in early immunomodulation in healthy pregnancies vs those destined to end in first-trimester loss. The ratio of IL-10 to TNFα rises significantly higher in viable pregnancies as early as 4.5 weeks compared to pregnancies loss.

Extragonadal Yolk Sac Tumor Limited to the Myometrium: Report of a Case With Potential Fertility Preservation and Molecular Analysis Suggesting Germ Cell Origin.

Extragonadal pelvic yolk sac tumor (YST) in postpubertal female patients is a rare malignant neoplasm with potentially 2 distinct histogenetic pathways, and no clear treatment algorithm, especially in young patients desiring future fertility. Here we report a case of extragonadal YST arising within the myometrium in a 30-yr-old nulligravid woman. The patient presented with heavy and irregular bleeding, and imaging studies showed an 8.2 cm uterine mass, most consistent with a degenerating uterine leiomyoma. The patient underwent abdominal myomectomy, and intraoperative frozen section evaluation revealed a high-grade malignancy. Because of the patient's strong desire for future fertility, a conservative wedge resection of the surrounding myometrium and surgical staging with uterine closure and retention of the ovaries were performed. On permanent sections the tumor showed an admixture of glandular, reticular, solid and papillary architectural patterns, moderate to marked nuclear atypia and clear cytoplasm with focal eosinophilic hyaline globules. Immunohistochemical stains were diffusely positive for SALL4, AFP, glypican3, and focally positive for CK20, and negative for EMA, and CK7, confirming the diagnosis of extragonadal YST. The endometrium displayed normal secretory phase morphology without involvement by YST, and the myometrial resection margins were negative. Short tandem repeat genotyping analysis of the tumor revealed allelic gains at 7 loci (involving chromosomes 2, 3, 4, 5, 8, 13, and 15) and allelic loss at one locus assessed on chromosome 11, while next-generation sequencing results showed no mutations in 155 genes tested, suggesting germ cell origin. The patient underwent 4 cycles of adjuvant chemotherapy with bleomycin, etoposide, and cisplatin, and she had 1 cycle of successful oocyte cryopreservation 6 months after completing chemotherapy. The clinical follow-up at 12 mo shows no evidence of disease.

Thermal stability of cytokines: A review.

BACKGROUND: The role of cytokines in various disease states is a burgeoning field of academic study and clinical application, however there are no consensus documents on how certain cytokines should be stored prior to quantification. This information is especially of interest to researchers assembling a biobank or clinicians who have to transport specimens to a different location in order to be tested. OBJECTIVE: To review the literature and synthesize prior findings on cytokine storage and freeze/thaw stability. DESIGN: We searched PubMed for articles related to cytokine storage stability. All articles were analyzed for cytokines studied, source of reported cytokine concentration (i.e., human whole blood or serum, concentrations from other species or bodily sources were excluded), and reported statistical results. RESULTS: We identified and synthesized results of 23 peer-reviewed articles which published data on the storage and freeze/thaw stability of 33 different cytokines and chemokines. CONCLUSION: There is a wide variety of reported cytokine storage and freeze/thaw stability. Interleukin-6 and tumor necrosis factor alpha are the most widely studied cytokines in regard to temperature stability. In a few cytokines, a clear consensus can be reached as to storage safety at particular temperatures, but in most, more research needs to be done and we advise the clinician or researcher to use caution in interpreting cytokine concentration results after a long period of storage or several freeze/thaw cycles.

Stability of retrospective self-reports of childhood trauma in first-episode psychosis.

AIM: Childhood trauma (CT), abuse and neglect are commonly reported by individuals experiencing psychosis. However, there are concerns that acute psychotic symptoms, in particular delusions, may contribute to inaccurate reporting of CT. As a result, individuals experiencing psychosis may not be asked about their experiences of abuse when they are being seen in psychiatric settings. This lack of attention can directly impact on the tailoring of their clinical care. This study aimed to investigate the stability of reports of CT by young people experiencing a first psychotic episode (FEP) compared to healthy comparison subjects. METHODS: Responses of 24 young people during the acute FEP and 3 months later to items on the Childhood Trauma Questionnaire (CTQ) were compared to 30 non-psychiatric controls. All participants were aged 15 to 25 years. RESULTS: FEP participants reported higher CT than controls at both time points. Reliability analyses (interclass correlation coefficients [ICCs]) suggested strong agreement between CT reports at baseline and follow-up for FEP participants (.81) and controls (.91). Positive psychotic symptoms were unrelated to CT reports. Although the severity of CT reports fluctuated between assessments, complete retractions of severe abuse claims occurred rarely. CONCLUSIONS: The results suggest that retrospective self-report can be used to reliably assess CT in young people experiencing acute psychosis.