Differential impact of prenatal PTSD symptoms and preconception trauma exposure on placental NR3C1 and FKBP5 methylation.

Perinatal stress is associated with altered placental methylation, which plays a critical role in fetal development and infant outcomes. This proof-of-concept pilot study investigated the impact of lifetime trauma exposure and perinatal PTSD symptoms on epigenetic regulation of placenta glucocorticoid signaling genes (NR3C1 and FKBP5). Lifetime trauma exposure and PTSD symptoms during pregnancy were assessed in a racially/ethnically diverse sample of pregnant women (N = 198). Participants were categorized into three groups: (1) No Trauma (-T); (2) Trauma, No Symptoms (T - S); and (3) Trauma and Symptoms (T + S). Placental tissue was analyzed via bisulfite pyrosequencing for degree of methylation at the NR3C1 promoter and FKBP5 regulatory regions. Analyses of covariance were used to test group differences in percentages of NR3C1 and FKBP5 methylation overall and at each CpG site. We found a significant impact of PTSD symptoms on placental NR3C1 methylation. Compared to the -T group, the T + S group had greater NR3C1 methylation overall and at CpG6, CpG8, CpG9, and CpG13, but lower methylation at CpG5. The T + S group had significantly higher NR3C1 methylation overall and at CpG8 compared to the T - S group. There were no differences between the T - S group and - T group. Additionally, no group differences emerged for FKBP5 methylation. Pregnant trauma survivors with PTSD symptoms exhibited differential patterns of placental NR3C1 methylation compared to trauma survivors without PTSD symptoms and pregnant women unexposed to trauma. Results highlight the critical importance of interventions to address the mental health of pregnant trauma survivors.

NICU-Specific Stress Following Traumatic Childbirth and Its Relationship With Posttraumatic Stress.

This mixed-methods pilot study investigated maternal perceived stress specific to infant neonatal intensive care unit (NICU) hospitalization as a moderator of the relationship between traumatic childbirth appraisal and symptoms of posttraumatic stress disorder (PTSD). NICU mothers (N = 77) were recruited via social media 1 to 4 months postpartum for a cross-sectional survey about perinatal experiences. Measures included traumatic childbirth, PTSD Checklist for DSM-5, and Parental Stressor Scale (PSS): NICU. Quantitative results indicated that, only at high levels of stress, women who reported traumatic childbirth (68%) reported significantly higher PTSD symptoms [b = 18.00, standard error = 7.18, t = 2.51, P = .015, 95% confidence interval (3.65, 32.36)]. Qualitative analysis identified additional stressors: maternal emotional well-being, dissatisfaction with care, infant health problems, breastfeeding, and additional characteristics of the NICU environment. Results provide supportive evidence that NICU mothers are at high risk for childbirth-related trauma and PTSD. Perceived stress related to the NICU may be an important intervention target when developing trauma-informed patient care. In addition to the domains captured by the PSS: NICU, maternal emotional well-being, interpersonal relationships with NICU staff, and stress related to breastfeeding are additional areas for improvement in the family-centered NICU.

Sleep Quality in High-Risk Pregnancies: Mixed Methods Results from a Randomized Controlled Trial of a Mindfulness Training Intervention.

Objectives: Sleep difficulties in pregnancy are common and increase the risk for obstetric complications. Past research shows that mindfulness training (MT) is helpful for improving sleep in non-pregnant adults and may improve sleep during pregnancy. However, it is unknown if MT improves sleep among pregnant people at risk for obstetric complications. We examined the effects of MT on sleep quality in individuals at risk of developing hypertensive disorders of pregnancy. Methods: Twenty-nine participants (mean age, 32 ± 4 years; mean gestational age, 16 ± 3weeks) at risk for hypertensive disorders in pregnancy (HDP) were randomized to an 8-week phone-delivered MT intervention (n = 15) or treatment as usual (TAU; n = 14), designed to test MT feasibility and acceptability. As part of the study, participants completed the Pittsburgh Sleep Quality Index and participated in a semi-structured individual qualitative interview which queried for sleep changes over pregnancy. Results: Participants randomized to MT reported less daytime sleep dysfunction compared to TAU (F = 5.79, p = 0.03, ηp2 = 0.28). Qualitative data illustrated the common experiences of sleep disturbance across both study groups; however, MT participants reported an improved ability to initiate sleep and return to sleep using mindfulness skills. About half of the participants in the MT condition reported an improvement in overall sleep quality due to less interference related to anxiety and restlessness, while other MT participants reported no change in sleep quality. Conclusions: Results from this study confirm that pregnant individuals frequently encounter sleep challenges. Findings also suggest that MT may be a helpful tool in improving sleep quality among pregnant people at risk for obstetric complications.

Prenatal Mindfulness Training and Interoceptive Awareness in Pregnant People at Risk for Hypertensive Disorders.

Aim: In this secondary analysis of a pilot randomized controlled trial (RCT), we sought to examine whether mindfulness training (MT) is associated with change in interoceptive awareness in pregnant people at risk for hypertension using quantitative and qualitative methods. Interoceptive awareness is the perception, regulation, and integration of bodily sensations. Interoceptive awareness increases following MT and has been proposed as a psychosomatic process underlying hypertension outside of pregnancy. Methods: Twenty-nine participants (mean age 32 ± 4 years; 67% White) with a history of hypertensive disorders of pregnancy (HDP) were enrolled at 16 weeks' gestation (SD = 3) for a RCT assessing the feasibility and acceptability of an 8-week phone-delivered MT intervention. Fifteen participants were randomized to MT, whereas 14 were randomized to usual prenatal care. Before and after the intervention, all participants completed the Multidimensional Assessment of Interoceptive Awareness (MAIA) measure and participated an individual interview, which queried for mind-body changes noticed across the study period. Results: Adjusting for baseline interoceptive awareness and gestational age, participants randomized to MT reported less worry about physical sensations on the MAIA after the intervention compared to those randomized to usual care. Qualitative data corroborated these results; MT participants described improved awareness of body and breath sensations, ability to notice blood pressure changes, non-judgmental observation of thoughts, and improved responses to interpersonal challenges. Conclusions: MT may improve the ability to notice body sensations that arise in pregnancy in a way that promotes healthy responding rather than worry. Results provide support for interoceptive awareness as a potential mechanism through which mindfulness may modulate blood pressure and potentially reduce the prevalence of HDP. Clinical Trial Registration: ClinicalTrials.gov (NCT03679117).

Experiences of maltreatment in childhood are associated with increasing anxiety and lower body acceptance over pregnancy.

OBJECTIVE: Prior studies have established that childhood sexual abuse (CSA) survivors are at increased risk for anxiety during pregnancy. Less is known about the course of anxiety throughout pregnancy for CSA survivors as well as underlying mechanisms linking CSA and perinatal anxiety. We assessed change in anxiety over the course of pregnancy for CSA survivors and examined whether acceptance and awareness of pregnancy-related body changes mediated this change. METHODS: 299 pregnant participants from two larger longitudinal cohort studies were grouped into CSA (n = 67), "other Maltreatment" (OM; n = 111); and "no abuse" (NA; n = 121) based on responses to the Adverse Childhood Events scale. We used a general linear mixed model with repeated measures to examine change in anxiety (Hamilton Anxiety Scale) at two time points (MEGA = 26.2 weeks and 34.9) by abuse/maltreatment group and then examined whether group differences in anxiety were mediated by body awareness/acceptance (from Maternal Fetal Attachment Scale) using structural equation modeling. RESULTS: The CSA group demonstrated higher anxiety at both gestational time-points and significantly greater increase in anxiety over gestation compared to OM and NA groups (F(1, 280) p = .046). CSA and OM groups reported significantly lower body acceptance than those without abuse/maltreatment (F(2, 287) = 3.486, p = .032). A small proportion of the total effect of CSA on change in anxiety (0.5%) was attributable to body acceptance. CONCLUSION: Pregnant CSA survivors experienced a greater increase in anxiety over pregnancy compared to other groups. Both abuse/maltreatment groups exhibited lower body acceptance, yet this contributed little to the association between CSA and anxiety.

Internalized Weight Bias, Weight-Related Experiences, And Peripartum Weight.

INTRODUCTION: The purpose of this study was to investigate internalized weight bias (IWB) and its relationship with pregnancy-related weight changes and postpartum depression. IWB is defined as the internalization of negative attitudes and beliefs about people due to their weight. Although IWB has been linked with weight change and depression in other samples, it has never been investigated in the postpartum period. METHODS: We used a cross-sectional survey design. Participants were 251 women recruited via social media who were living in the United States and 6 to 12 months postpartum. We calculated percentage of body weight gained during pregnancy and percentage of that weight that was retained postpartum from self-reported weights. Participants completed self-report measures of IWB (modified version of the Weight Bias Internalization Scale) and postpartum depression (Edinburgh Postnatal Depression Scale). RESULTS: Gestational weight gain was not significantly associated with IWB or depression. Postpartum retention of gestational weight was significantly positively associated with both IWB and depressive symptoms. Furthermore, IWB mediated the relationship between postpartum weight retention and depressive symptoms. DISCUSSION: Postpartum retention of weight gained during pregnancy, but not weight gain itself, was related to both IWB and depressive symptoms. The relationship between pregnancy-related weight changes and psychological distress is complex. Sociocultural pressures to return to a prepregnancy physical state swiftly after giving birth may increase risk for IWB during a time in life when stress is already likely to be high, posing additional psychological risk. IWB existing prepregnancy may also worsen postpartum self-concept, contributing to depression. This is the first study, to our knowledge, to directly assess associations among gestational weight change, IWB, and postpartum depression. In addition to discussing weight in pregnancy, perinatal care providers could improve postpartum health by helping women set realistic, body-positive goals postpartum.

Hydrophobic analogues of the winter flounder 'antifreeze' protein.

The synthesis, solution conformation and ice-growth inhibition properties of four new analogues of the type I 37-residue winter flounder 'antifreeze' protein are reported. All four analogues contain two extra salt bridges to facilitate comparison of results with previously published data. In two analogues, all four threonine residues in the native polypeptide were mutated to 2-amino butyric acid (an unnatural amino acid) and isoleucine, respectively. The butyric acid analogue was approximately 85% helical at 3 degrees C, modified the shape of ice growth, and exhibited reduced hysteresis compared to the native protein (9% at 4 mM). These results show that the gamma-methyl group of threonine, which is present in the sidechain of 2-amino butyric acid, is not sufficient for activity. The isoleucine analogue, in which the threonine hydroxyl group is replaced by an ethyl group, was 100% helical at 3 degrees C, showed no hysteresis but was able to modify the shape of ice crystal growth. In the third and fourth analogues, mutations of the aspartic acids 1 and 5 to alanine, and asparagines 16 and 27 to leucine in the threonine- and valine-substituted analogues did not affect the helicity of the polypeptides, but removed the ability to inhibit ice growth.

Valine substituted winter flounder 'antifreeze': preservation of ice growth hysteresis.

Three mutant polypeptides of the type I 37-residue winter flounder 'antifreeze' protein have been synthesized. All four threonine residues in the native peptide were been mutated to serine, valine and glycine respectively and two additional salt bridges were incorporated into the sequences in order to improve aqueous solubility. The peptides were analyzed by nanoliter osmometry, the 'ice hemisphere' test, the 'crystal habit' test, measurement of ice growth hysteresis and CD spectroscopy. While the valine and serine mutants retain the alpha-helical structure, only the valine mutant retains 'antifreeze' activity similar to that of the native protein. These data show that the threonine hydroxyl groups do not play a crucial role in the accumulation of the native 'antifreeze' protein at the ice/water interface and the inhibition of ice growth below the equilibrium melting temperature.

The effects of intraoperative administration of OKT3 during renal transplantation.

The use of the monoclonal antibody OKT3 for induction immunosuppression in renal transplantation is increasing--however, the safety of intraoperative administration continues to be questioned because of first-dose effects. The current study was designed to examine the effects of intraoperative administration of OKT3 on the cardiovascular and pulmonary systems in 161 consecutive renal transplant recipients. Patients receiving OKT3 intraoperatively during renal transplant (99 cadaver recipients) were compared with 62 patients not administered the drug (31 cadaver, 25 living-related-donor, 6 living-nonrelated donor). Intraoperative airway pressure (highest, average), O2 saturation (SaO2), temperature, blood pressure changes, cardiac rhythm, and bronchospasm were compared in these two groups. Significant physiologic changes noted in the group receiving OKT3 included increased temperature (both intraoperative and postoperative), decreased SaO2 (postoperative), and increased FiO2 (postoperative). Despite these differences, no clinically significant changes were noted in the group receiving OKT3. OKT3 induction given at the time of surgery was associated with a significantly increased one- and three-year graft function. This study demonstrates that first-dose administration of OKT3 intraoperatively during renal transplantation is safe and effective.

Long-term seafloor monitoring at an open ocean aquaculture site in the western Gulf of Maine, USA: development of an adaptive protocol.

The seafloor at an open ocean finfish aquaculture facility in the western Gulf of Maine, USA was monitored from 1999 to 2008 by sampling sites inside a predicted impact area modeled by oceanographic conditions and fecal and food settling characteristics, and nearby reference sites. Univariate and multivariate analyses of benthic community measures from box core samples indicated minimal or no significant differences between impact and reference areas. These findings resulted in development of an adaptive monitoring protocol involving initial low-cost methods that required more intensive and costly efforts only when negative impacts were initially indicated. The continued growth of marine aquaculture is dependent on further development of farming methods that minimize negative environmental impacts, as well as effective monitoring protocols. Adaptive monitoring protocols, such as the one described herein, coupled with mathematical modeling approaches, have the potential to provide effective protection of the environment while minimize monitoring effort and costs.

Type I 'antifreeze' proteins. Structure-activity studies and mechanisms of ice growth inhibition.

The type I 'antifreeze' proteins, found in the body fluids of fish inhabiting polar oceans, are alanine-rich alpha-helical proteins that are able to inhibit the growth of ice. Within this class there are two distinct subclasses of proteins: those related to the winter flounder sequence HPLC6 and which contain 11-residue repeat units commencing with threonine; and those from the sculpins that are unique in the N-terminal region that contains established helix breakers and lacks the 11-residue repeat structure present in the rest of the protein. Although 14 type I proteins have been isolated, almost all research has focused on HPLC6, the 37-residue protein from the winter flounder Pseudopleuronectes americanus. This protein modifies both the rate and shape (or 'habit') of ice crystal growth, displays hysteresis and accumulates specifically at the {2 0 2; 1} ice plane. Until very recently, all models to explain the mechanism for this specific interaction have relied on the interaction of the four threonine hydroxyls, which are spaced equally apart on one face of the helix, with the ice lattice. In contrast, proteins belonging to the sculpin family accumulate specifically at the {2 1; 1; 0} plane. The molecular origin of this difference in specificity between the flounder and sculpin proteins is not understood. This review will summarize the structure-activity and molecular modelling and dynamics studies on HPLC6, with an emphasis on recent studies in which the threonine residues have been mutated. These studies have identified important hydrophobic contributions to the ice growth inhibition mechanism. Some 50 mutants of HPLC6 have been reported and the data is consistent with the following requirements for ice growth inhibition: (a) a minimum length of approx. 25 residues; (b) an alanine-rich sequence in order to induce a highly helical conformation; (c) a hydrophobic face; (d) a number of charged/polar residues which are involved in solubility and/or interaction with the ice surface. The emerging picture, that requires further dynamics studies including accurate modelling of the ice/water interface, suggests that a hydrophobic interaction between the surface of the protein and ice is the key to explaining accumulation at specific ice planes, and thus the molecular level mechanism for ice growth inhibition.