Optimal input reverberation and homeostatic self-organization toward the edge of synchronization.

Transient or partial synchronization can be used to do computations, although a fully synchronized network is sometimes related to the onset of epileptic seizures. Here, we propose a homeostatic mechanism that is capable of maintaining a neuronal network at the edge of a synchronization transition, thereby avoiding the harmful consequences of a fully synchronized network. We model neurons by maps since they are dynamically richer than integrate-and-fire models and more computationally efficient than conductance-based approaches. We first describe the synchronization phase transition of a dense network of neurons with different tonic spiking frequencies coupled by gap junctions. We show that at the transition critical point, inputs optimally reverberate through the network activity through transient synchronization. Then, we introduce a local homeostatic dynamic in the synaptic coupling and show that it produces a robust self-organization toward the edge of this phase transition. We discuss the potential biological consequences of this self-organization process, such as its relation to the Brain Criticality hypothesis, its input processing capacity, and how its malfunction could lead to pathological synchronization and the onset of seizure-like activity.

CYP2D6 Activity Is Correlated with Changes in Plasma Concentrations of Taurocholic Acid during Pregnancy and Postpartum in CYP2D6 Extensive Metabolizers.

Cytochrome P450 2D6 (CYP2D6) is involved in the metabolism of >20% of marketed drugs. CYP2D6 expression and activity exhibit high interindividual variability and is induced during pregnancy. The farnesoid X receptor (FXR) is a transcriptional regulator of CYP2D6 that is activated by bile acids. In pregnancy, elevated plasma bile acid concentrations are associated with maternal and fetal risks. However, modest changes in bile acid concentrations may occur during healthy pregnancy, thereby altering FXR signaling. A previous study demonstrated that hepatic tissue concentrations of bile acids positively correlated with the hepatic mRNA expression of CYP2D6. This study sought to characterize the plasma bile acid metabolome in healthy women (n = 47) during midpregnancy (25-28 weeks gestation) and ≥3 months postpartum and to determine if plasma bile acids correlate with CYP2D6 activity. It is hypothesized that during pregnancy, plasma bile acids would favor less hydrophobic bile acids (cholic acid vs. chenodeoxycholic acid) and that plasma concentrations of cholic acid and its conjugates would positively correlate with the urinary ratio of dextrorphan/dextromethorphan. At 25-28 weeks gestation, taurine-conjugated bile acids comprised 23% of the quantified serum bile acids compared with 7% ≥3 months postpartum. Taurocholic acid positively associated with the urinary ratio of dextrorphan/dextromethorphan, a biomarker of CYP2D6 activity. Collectively, these results confirm that the bile acid plasma metabolome differs between pregnancy and postpartum and provide evidence that taurocholic acid may impact CYP2D6 activity during pregnancy. SIGNIFICANCE STATEMENT: Bile acid homeostasis is altered in pregnancy, and plasma concentrations of taurocholic acid positively correlate with CYP2D6 activity. Differences between plasma and/or tissue concentrations of farnesoid X receptor ligands such as bile acids may contribute to the high interindividual variability in CYP2D6 expression and activity.

Plasma hydrogen sulfide, nitric oxide, and thiocyanate levels are lower during pregnancy compared to postpartum in a cohort of women from the Pacific northwest of the United States.

AIMS: Pregnancy alters multiple physiological processes including angiogenesis, vasodilation, inflammation, and cellular redox, which are partially modulated by the gasotransmitters hydrogen sulfide (H2S) and nitric oxide (NO). In this study, we sought to determine how plasma levels of H2S, NO, and the H2S-related metabolites thiocyanate (SCN-), and methanethiol (CH3SH) change during pregnancy progression. MATERIALS AND METHODS: Plasma was collected from 45 women at three points: 25-28 weeks gestation, 28-32 week gestation, and at ≥3 months postpartum. Plasma levels of H2S, SCN-, and CH3SH were measured following derivatization using monobromobimane followed by LC-MS/MS. Plasma NO was measured indirectly using the Griess reagent. KEY FINDINGS: NO and SCN- were significantly lower in women at 25-28 weeks gestation and 28-32 weeks gestation than postpartum while plasma H2S levels were significantly lower at 28-32 weeks gestation than postpartum. No significant differences were observed in CH3SH. SIGNIFICANCE: Previous reports demonstrated that the production of H2S and NO are stimulated during pregnancy, but we observed lower levels during pregnancy compared to postpartum. Previous reports on NO have been mixed, but given the related effects of H2S and NO, it is expected that their levels would be higher during pregnancy vs. postpartum. Future studies determining the mechanism for decreased H2S and NO during pregnancy will elucidate the role of these gasotransmitters during normal and pathological progression of pregnancy.

Seizures in trisomy 18: Prevalence, description, and treatment.

Changes in medical intervention over the last decade have improved outcomes for individuals with trisomy 18, the second most common human aneuploidy syndrome at birth. As children with trisomy 18 live longer, a shared concern of medical experts and parents is the occurrence and treatment of seizures. Previously published surveillance guidelines for this condition have not addressed seizure management. Using parent-reported data collected as part of the Tracking Rare Incidence Syndromes project, we report on the prevalence, course, and management of seizures in individuals with trisomy 18. Twenty-eight percent (52/186) of individuals diagnosed with trisomy 18 in our retrospective cohort experienced generalized, focal, or mixed seizures at some point in their lifetime. For many individuals, seizures were effectively managed by broad-spectrum anti-seizure medications. Correlation analysis showed that focal and generalized seizures were more likely to occur in individuals who had previously experienced infantile spasms or central apnea. Electroencephalogram testing should be considered as part of a standard screening approach in individuals with trisomy 18 to enable early diagnosis and treatment of seizures. An international registry that incorporates parent-reported and clinical data for patients with trisomy 18 may facilitate ongoing research and recruitment into clinical trials for seizure management.

Uveitis in Sarcoidosis - Clinical Features and Comparison with Other Non-infectious Uveitis.

PURPOSE: Comparison of sarcoid uveitis with other non-infectious uveitis treatment and visual outcomes. METHODS: Retrospective study of 287 eyes with sarcoid uveitis and 1517 eyes with other non-infectious uveitis (15,029 eye-years follow-up). RESULTS: Sarcoid uveitis patients presented at age 43.1 ± 0.8 years, and 66.2% were female. Panuveitis was the most frequent presentation (48.3%), and 90.1% were bilateral. Moderate visual loss (≤20/50) developed in 19 eyes (6.6%), and severe visual loss (≤20/200) in 13 eyes (4.5%). Sarcoid uveitis had better visual outcomes than other non-infectious uveitis (10-year BCVA anterior uveitis 0.06 vs 0.24 p = .002; posterior disease 0.17 vs 0.38 p = .001). Oral corticosteroid use was more common with sarcoid uveitis (anterior uveitis 45.9% vs 16.4% p < .0005; posterior disease 64.0% vs 61.7% p = .635), but second-line immunosuppression was required less frequently (p = .008). CONCLUSIONS: Compared to other non-infectious uveitis, sarcoid uveitis has better visual acuity outcomes and is less likely to require second-line immunosuppression.

Abdominal and robotic sacrocolpopexy costs following implementation of enhanced recovery after surgery.

OBJECTIVE: To compare perioperative costs and morbidity between open and robotic sacrocolpopexy after implementation of enhanced recovery after surgery (ERAS) pathway. METHODS: The present retrospective cohort study of patients undergoing open or robotic sacrocolpopexy (January 1, 2014, through November 30, 2017) used an ERAS protocol with liposomal bupivacaine infiltration of laparotomy incisions. Primary outcomes were costs associated with index surgery and hospitalization, determined with Medicare cost-to-charge ratios and reimbursement rates and adjusted for variables expected to impact costs. Secondary outcomes included narcotic use, length of stay (LOS), and complications from index hospitalization to postoperative day 30. RESULTS: For the total of 231 patients (open cohort, 90; robotic cohort, 141), the adjusted mean cost of robotic surgery was $3239 higher compared with open sacrocolpopexy (95% confidence interval [CI] $1331-$5147; P < 0.001). Rates were not significantly different for intraoperative complications (robotic, 4.3% [6/141]; open, 5.6% [5/90]; P = 0.754), 30-day postoperative complications (robotic, 11.4% [16/141]; open, 16.7% [15/90]; P = 0.322), or readmissions (robotic, 5.7% [8/141]; open, 3.3% [3/90]; P = 0.535). The percentage of patients dismissed on postoperative day 1 was greater in the robotic group (89.4% [126/141] vs. 48.9% [44/90], P < 0.001). CONCLUSIONS: Decreased LOS associated with ERAS provided significant cost savings with open sacrocolpopexy versus robotic sacrocolpopexy without adverse impacts on perioperative complications or readmissions.

Meiotic nuclear pore complex remodeling provides key insights into nuclear basket organization.

Nuclear pore complexes (NPCs) are large proteinaceous assemblies that mediate nuclear compartmentalization. NPCs undergo large-scale structural rearrangements during mitosis in metazoans and some fungi. However, our understanding of NPC remodeling beyond mitosis remains limited. Using time-lapse fluorescence microscopy, we discovered that NPCs undergo two mechanistically separable remodeling events during budding yeast meiosis in which parts or all of the nuclear basket transiently dissociate from the NPC core during meiosis I and II, respectively. Meiosis I detachment, observed for Nup60 and Nup2, is driven by Polo kinase-mediated phosphorylation of Nup60 at its interface with the Y-complex. Subsequent reattachment of Nup60-Nup2 to the NPC core is facilitated by a lipid-binding amphipathic helix in Nup60. Preventing Nup60-Nup2 reattachment causes misorganization of the entire nuclear basket in gametes. Strikingly, meiotic nuclear basket remodeling also occurs in the distantly related fission yeast, Schizosaccharomyces pombe. Our study reveals a conserved and developmentally programmed aspect of NPC plasticity, providing key mechanistic insights into the nuclear basket organization.

Impact of Pregnancy and Vitamin A Supplementation on CYP2D6 Activity.

The mechanism of cytochrome P450 2D6 (CYP2D6) induction during pregnancy has not been evaluated in humans. This study assessed the changes in CYP2D6 and CYP3A activities during pregnancy and postpartum, and the effect of vitamin A administration on CYP2D6 activity. Forty-seven pregnant CYP2D6 extensive metabolizers (with CYP2D6 activity scores of 1 to 2) received dextromethorphan (DM) 30 mg orally as a single dose during 3 study windows (at 25 to 28 weeks of gestation, study day 1; at 28 to 32 weeks of gestation, study day 2; and at ≥3 months postpartum, study day 3). Participants were randomly assigned to groups with no supplemental vitamin A (control) or with supplemental vitamin A (10 000 IU/day orally for 3 to 4 weeks) after study day 1. Concentrations of DM and its metabolites, dextrorphan (DX) and 3-hydroxymorphinan (3HM), were determined from a 2-hour post-dose plasma sample and cumulative 4-hour urine sample using liquid chromatography-mass spectrometry. Change in CYP2D6 activity was assessed using DX/DM plasma and urine metabolic ratios. The activity change in CYP3A was also assessed using the 3HM/DM urine metabolic ratio. The DX/DM urine ratio was significantly higher (43%) in pregnancy compared with postpartum (P = .03), indicating increased CYP2D6 activity. The DX/DM plasma ratio was substantially higher in the participants, with an activity score of 1.0 during pregnancy (P = .04) compared with postpartum. The 3HM/DM urinary ratio was significantly higher (92%) during pregnancy, reflecting increased CYP3A activity (P = .02). Vitamin A supplementation did not change CYP2D6 activity during pregnancy; however, plasma all-trans retinoic acid (atRA) concentrations were positively correlated with increased CYP2D6 activity during pregnancy and postpartum. Further research is needed to elucidate the mechanisms of increased CYP2D6 activity during pregnancy.

Depression, anxiety, stress, and physical activity of Australian adults during COVID-19: A combined longitudinal and repeated cross-sectional study.

Background: The COVID-19 pandemic has led to a worsening of mental health and health behaviors. While physical activity is positively associated mental health, there is limited understanding of how mental health and physical activity evolve throughout the COVID-19 pandemic. This study aimed to examine changes in depression, anxiety and stress and physical activity, and associations between depression, anxiety, and stress with physical activity in Australian adults across three-time points during the COVID-19 pandemic. Materials and methods: This study collected both longitudinal and cross-sectional data at three-time points during the COVID-19 pandemic in Australia (i.e., April, July/August, and December 2020). Australians aged 18 years and over were invited to complete online surveys hosted on Qualtrics survey platform. Linear mixed models with random subject effect and general linear models were used to analyze the longitudinal and repeated cross-sectional data respectively. Results: The number of participants in cross-sectional surveys and longitudinal surveys was 1,877 and 849, respectively. There was an overall reduction between time 2 vs. time 3 in depression (d = 1.03, 95% CI = 0.20, 1.85), anxiety (d = 0.57, 95% CI = 0.02, 1.12), and stress (d = 1.13, 95% CI = 0.21, 2.04) scores but no significant differences in physical activity across three-time points. On average, participants who met the physical activity guidelines had lower depression (d = -2.08, 95% CI = -2.90, -1.26), anxiety (d = -0.88, 95% CI = -1.41, -0.34), and stress (d = -1.35, 95% CI = -2.13, -0.56) scores compared to those not meeting the guidelines. Conclusion: In the context of the ongoing COVID-19 pandemic, both governments and service providers should continue to provide the public with timely mental health support and promote the benefits of physical activity, as a cost-effective strategy to improve mental health and wellbeing.

Logic model development for the exercise is medicine-on campus initiative.

One strategy to encourage college students to meet physical activity and public health guidelines is the Exercise is Medicine on Campus Initiative (EIM-OC), whose goal is to promote physical activity as a vital health sign within universities. To develop, implement, and evaluate the EIM-OC Initiative, it is critical to understand the mechanics of the program via a logic model. Objective: The objective is to present a conceptual logic model for EIM-OC Initiative implementation. Methods: Using an activities-approach framework, a logic model was developed using inputs, activities, outputs, and outcomes. Results: This logic model serves as a guide for the conceptual relationships within the EIM-OC Initiative. It was hypothesized that the EIM-OC Initiative would have an overarching outcome of improving physical activity levels in the university setting to promote overall community wellness and health. Conclusion: The authors anticipate this logic model will serve as a framework for other universities implementing EIM-OC.

Bempegaldesleukin plus Nivolumab in First-line Metastatic Urothelial Carcinoma: Results from PIVOT-02.

BACKGROUND: Despite recent changes in the treatment landscape, there remains an unmet need for effective, tolerable, chemotherapy-free treatments for patients with advanced/metastatic urothelial carcinoma (mUC), especially cisplatin-ineligible patients. OBJECTIVE: To evaluate the immunostimulatory interleukin-2 cytokine prodrug bempegaldesleukin (BEMPEG) plus nivolumab in patients with advanced/mUC from the phase 2 multicenter PIVOT-02 study. DESIGN, SETTING, AND PARTICIPANTS: This open-label, multicohort phase 1/2 study enrolled patients with previously untreated locally advanced/surgically unresectable or mUC (N = 41). INTERVENTION: Patients received BEMPEG 0.006 mg/kg plus nivolumab 360 mg intravenously every 3 wk. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary objectives were safety and the objective response rate (ORR) in patients with measurable disease at baseline and at least one postbaseline tumor response assessment (response-evaluable). Secondary objectives were overall survival (OS) and progression-free survival (PFS). Exploratory biomarker analyses via univariate logistic regression were performed to test the association between potential biomarkers (CD8+ tumor-infiltrating lymphocytes, tumor mutational burden, and IFN-γ gene expression profile) and response. RESULTS AND LIMITATIONS: The ORR was 35% (13/37 evaluable patients) and the complete response rate was 19% (7/37 patients); the median duration of response was not reached. Median PFS was 4.1 mo (95% confidence interval [CI] 2.1-8.7) and median OS was 23.7 mo (95% CI 15.8-not reached). Overall, 40/41 patients (98%) experienced at least one treatment-related adverse event (TRAE); grade 3/4 TRAEs occurred in 11 patients (27%), most commonly pyrexia (4.9%; 2 patients). Exploratory biomarker analyses showed no association between biomarkers and response. Limitations include the small sample size and single-arm design. CONCLUSIONS: BEMPEG plus nivolumab was well tolerated and showed antitumor activity as first-line treatment in patients with locally advanced/mUC. PATIENT SUMMARY: We investigated an immune-stimulating prodrug called bempegaldesleukin plus the antibody nivolumab as the first therapy for patients with advanced or metastatic cancer of the urinary tract. This combination had manageable treatment-related side effects and was effective in a subset of patients. This trial is registered at ClinicalTrials.gov as NCT02983045.

A Trauma-informed Approach to Postpartum Care.

Distressing or traumatic perinatal experiences and adverse health outcomes can lead to particularly challenging postpartum experiences for patients and families. By adopting a trauma-informed care approach, the health care team can provide much-needed support, prevent additional harm, and promote healing. We propose practical communication, behavioral, and procedural considerations for integrating trauma-informed care principles into routine postpartum care, with attention to populations that have been marginalized. We see postpartum care as a critical component of holistic patient recovery and an opportunity to facilitate posttraumatic growth so that all families can thrive.

Treatment With Etirinotecan Pegol for Patients With Metastatic Breast Cancer and Brain Metastases: Final Results From the Phase 3 ATTAIN Randomized Clinical Trial.

Importance: Patients with breast cancer and brain metastases (BM) have a poor prognosis and high clinical need for novel treatments; however, historically, studies have often excluded these patients. Although the BEACON study did not meet its primary end point, treatment with etirinotecan pegol vs chemotherapy of the physician's choice for patients with advanced breast cancer demonstrated a significant improvement in overall survival (OS) for the prespecified patient subgroup with preexisting, pretreated, and nonprogressive BM. Objective: To compare clinical outcomes in patients with BM treated with etirinotecan pegol vs chemotherapy of the physician's choice in a confirmatory trial. Design, Setting, and Participants: This study was a phase 3, open-label, randomized clinical trial (ATTAIN) in patients with metastatic breast cancer and a history of stable pretreated BM who experienced disease progression while receiving chemotherapy in the metastatic setting. The trial took place at 47 sites in 10 countries, and patients were enrolled between March 7, 2017, and November 6, 2019. Interventions: Patients were randomized to receive etirinotecan pegol, 145 mg/m2, every 21 days or chemotherapy (eribulin, ixabepilone, vinorelbine, gemcitabine, paclitaxel, docetaxel, or nab-paclitaxel). Main Outcomes and Measures: The primary end point was OS. Key secondary end points included progression-free survival, objective response rate, duration of response, and the clinical benefit rate. Results: A total of 178 female patients (9 [5.1%] Asian, 8 [4.5%] Black or African American, and 123 [69.1] White individuals) were randomized to receive treatment with etirinotecan pegol (92 [51.7%]; median [range] age, 53 [27-79] years) or chemotherapy (86 [48.3%]; median [range] age, 52 [24-77] years). Median OS was similar in both groups (etirinotecan pegol, 7.8 months; chemotherapy, 7.5 months; hazard ratio [HR], 0.90; 95% CI, 0.61-1.33; P = .60). Median progression-free survival for non-central nervous system metastases per blinded independent central review for etirinotecan pegol vs chemotherapy was 2.8 and 1.9 months (HR, 0.72; 95% CI, 0.45-1.16; P = .18) and 3.9 vs 3.3 months, respectively, for central nervous system metastases (HR, 0.59; 95% CI, 0.33-1.05; P = .07). Safety profiles between the groups were largely comparable. Conclusions and Relevance: The results of the ATTAIN randomized clinical trial found no statistically significant difference in outcomes between treatment with etirinotecan pegol and chemotherapy in patients with BM. However, this study represents one of the largest published trials dedicated to patients with breast cancer and BM and may help to inform further research. Trial Registration: ClinicalTrials.gov Identifier: NCT02915744.

Impact of enhanced recovery implementation in women undergoing abdominal sacrocolpopexy.

OBJECTIVE: To assess the effect of Enhanced Recovery After Surgery (ERAS) with and without liposomal bupivacaine (LB) on opioid use, hospital length of stay (LOS), costs, and morbidity of women undergoing sacrocolpopexy. METHODS: Retrospective cohort of women who underwent abdominal sacrocolpopexy between April 1, 2009 and November 30, 2017. Costs for relevant healthcare services were determined by assigning 2017 charges multiplied by 2017 Medicare Cost Report's cost to charge ratios. Outcomes were compared among periods with multivariable regression models adjusted for age, American Society of Anesthesiologists score, and concurrent hysterectomy and posterior repair. RESULTS: Patients were subdivided into pre-ERAS (G1, n = 128), post-ERAS (G2, n = 83), and post-ERAS plus LB (G3, n = 91). The proportion of patients needing opioids during postoperative days 0-2 was significantly less for G3 (75.8%) compared with G1 (97.7%) and G2 (92.8%); P < 0.001). The median morphine equivalent units (MEU) with interquartile ranges, mean LOS, and adjusted mean standardized costs were significantly lower in G3 compared with the other two groups (35 [20-75] vs. 67 [31-109], and 60 [30-122] MEUs; 1.8 vs. 2.3 vs. 2.9 days; and $2391, $2975, and $3844, for G3, G2, and G1, respectively; P < 0.001). CONCLUSION: Implementation of an ERAS pathway led to significant decreases in opioid use, LOS, and costs. Supplementation with LB further improved these measures.

Bempegaldesleukin plus nivolumab in first-line renal cell carcinoma: results from the PIVOT-02 study.

BACKGROUND: Immune checkpoint inhibitor-based combinations have expanded the treatment options for patients with renal cell carcinoma (RCC); however, tolerability remains challenging. The aim of this study was to evaluate the safety and efficacy of the immunostimulatory interleukin-2 cytokine prodrug bempegaldesleukin (BEMPEG) plus nivolumab (NIVO) as first-line therapy in patients with advanced clear-cell RCC. METHODS: This was an open-label multicohort, multicenter, single-arm phase 1/2 study; here, we report results from the phase 1/2 first-line RCC cohort (N=49). Patients received BEMPEG 0.006 mg/kg plus NIVO 360 mg intravenously every 3 weeks. The primary objectives were safety and objective response rate (ORR; patients with measurable disease at baseline and at least one postbaseline tumor response assessment). Secondary objectives included overall survival (OS) and progression-free survival (PFS). Exploratory biomarker analyses: association between baseline biomarkers and ORR. RESULTS: At a median follow-up of 32.7 months, the ORR was 34.7% (17/49 patients); 3/49 patients (6.1%) had a complete response. Of the 17 patients with response, 14 remained in response for >6 months, and 6 remained in response for >24 months. Median PFS was 7.7 months (95% CI 3.8 to 13.9), and median OS was not reached (95% CI 37.3 to not reached). Ninety-eight per cent (48/49) of patients experienced ≥1 treatment-related adverse event (TRAE) and 38.8% (19/49) had grade 3/4 TRAEs, most commonly syncope (8.2%; 4/49) and increased lipase (6.1%; 3/49). No association between exploratory biomarkers and ORR was observed. Limitations include the small sample size and single-arm design. CONCLUSIONS: BEMPEG plus NIVO showed preliminary antitumor activity as first-line therapy in patients with advanced clear-cell RCC and was well tolerated. These findings warrant further investigation.

Split-GFP Complementation to Study the Nuclear Membrane Proteome Using Microscopy.

Defining the proteome of any given subcellular compartment provides insight into the activities and functions within that organelle. Understanding the composition of the nuclear envelope (NE) using traditional methods such as biochemical subcellular fractionation has been challenging due to the continuity of the NE and the endoplasmic reticulum. Here, we describe how split green fluorescent protein (split-GFP) was adapted to determine and define the NE proteome. This system is able to resolve protein topology and distinguish localization to the inner or outer nuclear membranes (INM or ONM).

Plasma Retinoid Concentrations Are Altered in Pregnant Women.

Vitamin A is vital to maternal-fetal health and pregnancy outcomes. However, little is known about pregnancy associated changes in maternal vitamin A homeostasis and concentrations of circulating retinol metabolites. The goal of this study was to characterize retinoid concentrations in healthy women (n = 23) during two stages of pregnancy (25-28 weeks gestation and 28-32 weeks gestation) as compared to ≥3 months postpartum. It was hypothesized that plasma retinol, retinol binding protein 4 (RBP4), transthyretin and albumin concentrations would decline during pregnancy and return to baseline by 3 months postpartum. At 25-28 weeks gestation, plasma retinol (-27%), 4-oxo-13-cis-retinoic acid (-34%), and albumin (-22%) concentrations were significantly lower, and all-trans-retinoic acid (+48%) concentrations were significantly higher compared to ≥3 months postpartum in healthy women. In addition, at 28-32 weeks gestation, plasma retinol (-41%), retinol binding protein 4 (RBP4; -17%), transthyretin (TTR; -21%), albumin (-26%), 13-cis-retinoic acid (-23%) and 4-oxo-13-cis-retinoic acid (-48%) concentrations were significantly lower, whereas plasma all-trans-retinoic acid concentrations (+30%) were significantly higher than ≥3 months postpartum. Collectively, the data demonstrates that in healthy pregnancies, retinol plasma concentrations are lower, but all-trans-retinoic acid concentrations are higher than postpartum.