Iron status and anemia in a representative sample of US pregnant women is not associated with pre-pregnancy BMI: Results from the NHANES (1999-2010) study.

Iron deficiency in pregnancy is related to many poor health outcomes, including anemia and low birth weight. A small number of previous studies have identified maternal body mass index (BMI) as a potential risk factor for poor iron status. Our objective was to examine the association between pre-pregnancy BMI, iron status, and anemia in a nationally representative sample of US adult women. We used data from the National Health and Nutrition Examination Survey (NHANES; 1999-2010) for pregnant women ages 18-49 years (n = 1156). BMI (kg/m2) was calculated using pre-pregnancy weight (self-reported) and height (measured at examination). Iron deficiency (ID) was defined as total body iron (calculated from serum ferritin and transferrin receptor using Cook's equation) < 0 mg/kg and anemia as hemoglobin < 11 g/dL. Associations were examined using weighted linear and Poisson regression models, adjusted for confounders (age, race/ethnicity, education, and trimester). Approximately 14% of pregnant women had ID and 8% had anemia in this sample. Ferritin and total body iron trended slightly lower (p = 0.12, p = 0.14) in women with pre-pregnancy BMI in the normal and overweight categories compared to the underweight and obese categories; hemoglobin concentrations were similar across BMI groups (p = 0.76). There were no differences in the prevalence of ID or anemia in women with pre-pregnancy overweight and obesity (ID: overweight, adjusted prevalence ratio (PR) = 1.27, 95%CI: 0.89-1.82; obesity, PR = 0.75, 95%CI: 0.39-1.45; anemia: overweight, PR = 1.08, 95%CI: 0.53-2.19; obesity, PR = 0.99, 95%CI: 0.49-2.01) compared to women with a normal BMI. Findings from these US nationally representative data indicate that total body iron, serum hemoglobin, ID, and anemia in pregnancy do not differ by pre-pregnancy BMI. Since ID and anemia during pregnancy remain significant public health concerns, NHANES should consider measuring current iron status in upcoming cycles.

Maternal Vitamin B12 in Pregnancy and Placental Development.

Vitamin B12, or cobalamin, is an essential nutrient required for diverse physiological functions secondary to its role as a critical cofactor for two mammalian enzymes, methionine synthase and methylmalonyl-CoA mutase. While essential throughout all life stages, several pathways that require vitamin B12, including hematopoiesis, myelination, and DNA/histone methylation, are particularly critical during pregnancy and fetal development. This narrative review aims to describe vitamin B12 in pregnancy, with emphasis on the placenta's role in ensuring adequate nutrition of the fetus and impacts of vitamin B12 deficiency on placental development and function. Our literature search included preclinical model systems and human cohorts and interventions. Our review identified evidence of B12 deficiency resulting in impaired placental development, greater placental inflammation, and modulation of placental docosahexaenoic acid concentration, collectively suggestive of vitamin B12 deficiency as a determinant of both maternal and fetal health outcomes. Heterogeneity in study design complicated generalization of findings. Future studies should consider selecting a B12 marker that is relatively stable across pregnancy, such as holotranscobalamin, while accounting for important confounders such as maternal folate.

Impacts of the COVID-19 Pandemic on Newly Licensed Critical Care Nurses.

Newly licensed registered nurses (NLRNs) were significantly impacted by the COVID-19 pandemic. NLRNs experienced interruptions or significant alterations across, academia, clinical rotations, precepted experiences, and transition to practice programs. All NLRNs were impacted, especially those in critical care who cared for the most acutely ill patients. This article represents a program evaluation of NLRNs in the critical care area during the COVID-19 pandemic and a comprehensive review of the literature related to COVID-19s impact on NLRNs.

Placental pathology reports: A qualitative study in a US university hospital setting on perceived clinical utility and areas for improvement.

OBJECTIVE: To explore how placental pathology is currently used by clinicians and what placental information would be most useful in the immediate hours after delivery. STUDY DESIGN: We used a qualitative study design to conduct in-depth, semi-structured interviews with obstetric and neonatal clinicians who provide delivery or postpartum care at an academic medical center in the US (n = 19). Interviews were transcribed and analyzed using descriptive content analysis. RESULTS: Clinicians valued placental pathology information yet cited multiple barriers that prevent the consistent use of pathology. Four main themes were identified. First, the placenta is sent to pathology for consistent reasons, however, the pathology report is accessed by clinicians inconsistently due to key barriers: difficult to find in the electronic medical record, understand, and get quickly. Second, clinicians value placental pathology for explanatory capability as well as for contributions to current and future care, particularly when there is fetal growth restriction, stillbirth, or antibiotic use. Third, a rapid placental exam (specifically including placental weight, infection, infarction, and overall assessment) would be helpful in providing clinical care. Fourth, placental pathology reports that connect clinically relevant findings (similar to radiology) and that are written with plain, standardized language and that non-pathologists can more readily understand are preferred. CONCLUSION: Placental pathology is important to clinicians that care for mothers and newborns (particularly those that are critically ill) after birth, yet many problems stand in the way of its usefulness. Hospital administrators, perinatal pathologists, and clinicians should work together to improve access to and contents of reports. Support for new methods to provide quick placenta information is warranted.

Determining the Location of the α-Synuclein Dimer Interface Using Native Top-Down Fragmentation and Isotope Depletion-Mass Spectrometry.

α-Synuclein (αSyn), a 140-residue intrinsically disordered protein, comprises the primary proteinaceous component of pathology-associated Lewy body inclusions in Parkinson's disease (PD). Due to its association with PD, αSyn is studied extensively; however, the endogenous structure and physiological roles of this protein are yet to be fully understood. Here, ion mobility-mass spectrometry and native top-down electron capture dissociation fragmentation have been used to elucidate the structural properties associated with a stable, naturally occurring dimeric species of αSyn. This stable dimer appears in both wild-type (WT) αSyn and the PD-associated variant A53E. Furthermore, we integrated a novel method for generating isotopically depleted protein into our native top-down workflow. Isotope depletion increases signal-to-noise ratio and reduces the spectral complexity of fragmentation data, enabling the monoisotopic peak of low abundant fragment ions to be observed. This enables the accurate and confident assignment of fragments unique to the αSyn dimer to be assigned and structural information about this species to be inferred. Using this approach, we were able to identify fragments unique to the dimer, which demonstrates a C-terminal to C-terminal interaction between the monomer subunits. The approach in this study holds promise for further investigation into the structural properties of endogenous multimeric species of αSyn.

Harmonization of maternal balanced energy-protein supplementation studies for individual participant data (IPD) meta-analyses - finding and creating similarities in variables and data collection.

BACKGROUND: Public health and clinical recommendations are established from systematic reviews and retrospective meta-analyses combining effect sizes, traditionally, from aggregate data and more recently, using individual participant data (IPD) of published studies. However, trials often have outcomes and other meta-data that are not defined and collected in a standardized way, making meta-analysis problematic. IPD meta-analysis can only partially fix the limitations of traditional, retrospective, aggregate meta-analysis; prospective meta-analysis further reduces the problems. METHODS: We developed an initiative including seven clinical intervention studies of balanced energy-protein (BEP) supplementation during pregnancy and/or lactation that are being conducted (or recently concluded) in Burkina Faso, Ethiopia, India, Nepal, and Pakistan to test the effect of BEP on infant and maternal outcomes. These studies were commissioned after an expert consultation that designed recommendations for a BEP product for use among pregnant and lactating women in low- and middle-income countries. The initiative goal is to harmonize variables across studies to facilitate IPD meta-analyses on closely aligned data, commonly called prospective meta-analysis. Our objective here is to describe the process of harmonizing variable definitions and prioritizing research questions. A two-day workshop of investigators, content experts, and advisors was held in February 2020 and harmonization activities continued thereafter. Efforts included a range of activities from examining protocols and data collection plans to discussing best practices within field constraints. Prior to harmonization, there were many similar outcomes and variables across studies, such as newborn anthropometry, gestational age, and stillbirth, however, definitions and protocols differed. As well, some measurements were being conducted in several but not all studies, such as food insecurity. Through the harmonization process, we came to consensus on important shared variables, particularly outcomes, added new measurements, and improved protocols across studies. DISCUSSION: We have fostered extensive communication between investigators from different studies, and importantly, created a large set of harmonized variable definitions within a prospective meta-analysis framework. We expect this initiative will improve reporting within each study in addition to providing opportunities for a series of IPD meta-analyses.

Enhancing Automatic Placenta Analysis through Distributional Feature Recomposition in Vision-Language Contrastive Learning.

The placenta is a valuable organ that can aid in understanding adverse events during pregnancy and predicting issues post-birth. Manual pathological examination and report generation, however, are laborious and resource-intensive. Limitations in diagnostic accuracy and model efficiency have impeded previous attempts to automate placenta analysis. This study presents a novel framework for the automatic analysis of placenta images that aims to improve accuracy and efficiency. Building on previous vision-language contrastive learning (VLC) methods, we propose two enhancements, namely Pathology Report Feature Recomposition and Distributional Feature Recomposition, which increase representation robustness and mitigate feature suppression. In addition, we employ efficient neural networks as image encoders to achieve model compression and inference acceleration. Experiments validate that the proposed approach outperforms prior work in both performance and efficiency by significant margins. The benefits of our method, including enhanced efficacy and deployability, may have significant implications for reproductive healthcare, particularly in rural areas or low- and middle-income countries.

An Evaluation of Traditional Versus Virtual Nurse Residency Programs on New Graduate Nurses' Perceptions of Preparedness to Provide Safe Patient Care.

The impact of the COVID-19 pandemic on nurse residents' perceptions of preparedness while learning in a virtual environment remains unknown. This cohort study compared nurse residents' perceptions of preparedness in traditional in-person versus virtual learning environments. Results found no statistically significant differences between these two groups over 1 year. This demonstrates that a virtual learning format can achieve comparable outcomes to a traditional in-person learning format in successfully transitioning newly licensed nurses into the profession.

Pore dynamics and asymmetric cargo loading in an encapsulin nanocompartment.

Encapsulins are protein nanocompartments that house various cargo enzymes, including a family of decameric ferritin-like proteins. Here, we study a recombinant Haliangium ochraceum encapsulin:encapsulated ferritin complex using cryo-electron microscopy and hydrogen/deuterium exchange mass spectrometry to gain insight into the structural relationship between the encapsulin shell and its protein cargo. An asymmetric single-particle reconstruction reveals four encapsulated ferritin decamers in a tetrahedral arrangement within the encapsulin nanocompartment. This leads to a symmetry mismatch between the protein cargo and the icosahedral encapsulin shell. The encapsulated ferritin decamers are offset from the interior face of the encapsulin shell. Using hydrogen/deuterium exchange mass spectrometry, we observed the dynamic behavior of the major fivefold pore in the encapsulin shell and show the pore opening via the movement of the encapsulin A-domain. These data will accelerate efforts to engineer the encapsulation of heterologous cargo proteins and to alter the permeability of the encapsulin shell via pore modifications.

Extending Native Top-Down Electron Capture Dissociation to MDa Immunoglobulin Complexes Provides Useful Sequence Tags Covering Their Critical Variable Complementarity-Determining Regions.

Native top-down mass spectrometry (MS) is gaining traction for the analysis and sequencing of intact proteins and protein assemblies, giving access to their mass and composition, as well as sequence information useful for identification. Herein, we extend and apply native top-down MS, using electron capture dissociation, to two submillion Da IgM- and IgG-based oligomeric immunoglobulins. Despite structural similarities, these two systems are quite different. The ∼895 kDa noncovalent IgG hexamer consists of six IgG subunits hexamerizing in solution due to three specifically engineered mutations in the Fc region, whereas the ∼935 kDa IgM oligomer results from the covalent assembly of one joining (J) chain and 5 IgM subunits into an asymmetric "pentamer" stabilized by interchain disulfide bridges. Notwithstanding their size, structural differences, and complexity, we observe that their top-down electron capture dissociation spectra are quite similar and straightforward to interpret, specifically providing informative sequence tags covering the highly variable CDR3s and FR4s of the Ig subunits they contain. Moreover, we show that the electron capture dissociation fragmentation spectra of immunoglobulin oligomers are essentially identical to those obtained for their respective monomers. Demonstrated for recombinantly produced systems, the approach described here opens up new prospects for the characterization and identification of IgMs circulating in plasma, which is important since IgMs play a critical role in the early immune response to pathogens such as viruses and bacteria.

Chorioamnionitis and Risk for Maternal and Neonatal Sepsis: A Systematic Review and Meta-analysis.

OBJECTIVE: To estimate the risk of maternal and neonatal sepsis associated with chorioamnionitis. DATA SOURCES: PubMed, BIOSIS, and ClinicalTrials.gov databases were systematically searched for full-text articles in English from inception until May 11, 2020. METHODS OF STUDY SELECTION: We screened 1,251 studies. Randomized controlled trials, case-control, or cohort studies quantifying a relationship between chorioamnionitis and sepsis in mothers (postpartum) or neonates born at greater than 22 weeks of gestation were eligible. Studies were grouped for meta-analyses according to exposures of histologic or clinical chorioamnionitis and outcomes of maternal or neonatal sepsis. TABULATION, INTEGRATION, AND RESULTS: One hundred three studies were included, and 55 met criteria for meta-analysis (39 studies of preterm neonates, 10 studies of general populations of preterm and term neonates, and six studies of late preterm and term neonates). Study details and quantitative data were abstracted. Random-effects models were used to generate pooled odds ratios (ORs); most studies only reported unadjusted results. Histologic chorioamnionitis was associated with confirmed and any early-onset neonatal sepsis (unadjusted pooled ORs 4.42 [95% CI 2.68-7.29] and 5.88 [95% CI 3.68-9.41], respectively). Clinical chorioamnionitis was also associated with confirmed and any early-onset neonatal sepsis (unadjusted pooled ORs 6.82 [95% CI 4.93-9.45] and 3.90 [95% CI 2.74-5.55], respectively). Additionally, histologic and clinical chorioamnionitis were each associated with higher odds of late-onset sepsis in preterm neonates. Confirmed sepsis incidence was 7% (early-onset) and 22% (late-onset) for histologic and 6% (early-onset) and 26% (late-onset) for clinical chorioamnionitis-exposed neonates. Three studies evaluated chorioamnionitis and maternal sepsis and were inconclusive. CONCLUSION: Both histologic and clinical chorioamnionitis were associated with early- and late-onset sepsis in neonates. Overall, our findings support current guidelines for preventative neonatal care. There was insufficient evidence to determine the association between chorioamnionitis and maternal sepsis. SYSTEMATIC REVIEW REGISTRATION: PROSPERO, CRD42020156812.

Maternal-Fetal Inflammation in the Placenta and the Developmental Origins of Health and Disease.

Events in fetal life impact long-term health outcomes. The placenta is the first organ to form and is the site of juxtaposition between the maternal and fetal circulations. Most diseases of pregnancy are caused by, impact, or are reflected in the placenta. The purpose of this review is to describe the main inflammatory processes in the placenta, discuss their immunology, and relate their short- and long-term disease associations. Acute placental inflammation (API), including maternal and fetal inflammatory responses corresponds to the clinical diagnosis of chorioamnionitis and is associated with respiratory and neurodevelopmental diseases. The chronic placental inflammatory pathologies (CPI), include chronic villitis of unknown etiology, chronic deciduitis, chronic chorionitis, eosinophilic T-cell vasculitis, and chronic histiocytic intervillositis. These diseases are less-well studied, but have complex immunology and show mechanistic impacts on the fetal immune system. Overall, much work remains to be done in describing the long-term impacts of placental inflammation on offspring health.

Dissecting the structural and functional roles of a putative metal entry site in encapsulated ferritins.

Encapsulated ferritins belong to the universally distributed ferritin superfamily, whose members function as iron detoxification and storage systems. Encapsulated ferritins have a distinct annular structure and must associate with an encapsulin nanocage to form a competent iron store that is capable of holding significantly more iron than classical ferritins. The catalytic mechanism of iron oxidation in the ferritin family is still an open question because of the differences in organization of the ferroxidase catalytic site and neighboring secondary metal-binding sites. We have previously identified a putative metal-binding site on the inner surface of the Rhodospirillum rubrum encapsulated ferritin at the interface between the two-helix subunits and proximal to the ferroxidase center. Here we present a comprehensive structural and functional study to investigate the functional relevance of this putative iron-entry site by means of enzymatic assays, MS, and X-ray crystallography. We show that catalysis occurs in the ferroxidase center and suggest a dual role for the secondary site, which both serves to attract metal ions to the ferroxidase center and acts as a flow-restricting valve to limit the activity of the ferroxidase center. Moreover, confinement of encapsulated ferritins within the encapsulin nanocage, although enhancing the ability of the encapsulated ferritin to undergo catalysis, does not influence the function of the secondary site. Our study demonstrates a novel molecular mechanism by which substrate flux to the ferroxidase center is controlled, potentially to ensure that iron oxidation is productively coupled to mineralization.

Isotope Depletion Mass Spectrometry (ID-MS) for Accurate Mass Determination and Improved Top-Down Sequence Coverage of Intact Proteins.

Top-down mass spectrometry (MS) is an increasingly important technique for protein characterization. However, in many biological MS experiments, the practicality of applying top-down methodologies is still limited at higher molecular mass. In large part, this is due to the detrimental effect resulting from the partitioning of the mass spectral signal into an increasing number of isotopic peaks as molecular mass increases. Reducing the isotopologue distribution of proteins via depletion of heavy stable isotopes was first reported over 20 years ago (Marshall, A. G.; Senko, M. W.; Li, W.; Li, M.; Dillon, S., Guan, S.; Logan, T. M.. Protein Molecular Mass to 1 Da by 13C, 15N Double-Depletion and FT-ICR Mass Spectrometry. J. Am. Chem. Soc. 1997, 119, 433-434.) and has been demonstrated for several small proteins. Here we extend this approach, introducing a new highly efficient method for the production of recombinant proteins depleted in 13C and 15N and demonstrating its advantages for top-down analysis of larger proteins (up to ∼50 kDa). FT-ICR MS of isotopically depleted proteins reveals dramatically reduced isotope distributions with monoisotopic signal observed up to 50 kDa. In top-down fragmentation experiments, the reduced spectral complexity alleviates fragment-ion signal overlap, the presence of monoisotopic signals allows assignment with higher mass accuracy, and the dramatic increase in signal-to-noise ratio (up to 7-fold) permits vastly reduced acquisition times. These compounding benefits allow the assignment of ∼3-fold more fragment ions than comparable analyses of proteins with natural isotopic abundances. Finally, we demonstrate greatly increased sequence coverage in time-limited top-down experiments-highlighting advantages for top-down LC-MS/MS workflows and top-down proteomics.

Postpartum Weight Retention in Primiparous Women and Weight Outcomes in Their Offspring.

INTRODUCTION: To explore the effect of prepregnancy body mass index (BMI) and gestational weight gain on postpartum weight retention in nulliparous women and weight-for-length percentiles of offspring to 2 years following birth. METHODS: A retrospective secondary analysis of a large, prospective longitudinal study of women conducted during pregnancy and after their first birth was completed to examine outcomes associated with postpartum weight retention. A chart review of the offspring of these women was completed to explore the relationship between maternal prepregnancy BMI and gestational weight gain on offspring weight-for-length percentiles. RESULTS: Data from 652 woman-infant dyads were available for analysis. Average postpartum weight retention was 4.0 kg at one year for all groups. At 6 weeks postpartum, women who were obese prior to pregnancy retained significantly less weight than did women who were normal weight prior to pregnancy (P < .05). Women who were normal weight or overweight at the onset of pregnancy and had gestational weight gain within Institute of Medicine recommendations retained significantly less weight at 6 weeks, 6 months, and 1 year postpartum (P < .01) when compared with women in those same weight groups who had a gestational weight gain in excess of the recommended guideline. Women who entered pregnancy obese and who had a gestational weight gain within the recommended weight range during pregnancy retained significantly less weight compared with women who were obese and who gained in excess of the guideline at 6 weeks postpartum only (P < .05). No statistically significant differences were seen in offspring weight-for-length percentiles at any time point based on maternal prepregnancy BMI or weight gain within guidelines. DISCUSSION: Many women retained weight up to one year postpartum. In this study, we saw no statistically significant differences between the prepregnant BMI groups or between gestational weight gain within guidelines or in excess of guidelines on offspring weight-for-length percentiles.

Assessing the Policy gaps for achieving China's climate targets in the Paris Agreement.

China committed to peak its carbon emissions around 2030, with best efforts to peak early, and also to achieve 20% non-fossil energy as a proportion of primary energy supply by 2030. These commitments were included in China's nationally-determined contribution to the 2015 Paris Agreement on climate change. We develop and apply a mixed-method methodology for analyzing the likelihood of current Chinese policies reducing greenhouse gas emissions in accordance with China's Paris commitments. We find that China is likely to peak its emissions well in advance of 2030 and achieve its non-fossil target conditional on full and effective implementation of all current policies, successful conclusion of power-sector reform, and full implementation of a national emissions-trading system (ETS) for the power and additional major industrial sectors after 2020. Several policy gaps are identified and discussed.

Phase 2, randomized dose-finding study of tapinarof (GSK2894512 cream) for the treatment of plaque psoriasis.

BACKGROUND: There is a significant need for novel, safe, and efficacious topical treatments for psoriasis. OBJECTIVE: We assessed the safety and efficacy of tapinarof in a new cream formulation at 2 concentrations and with 2 application frequencies in adults with psoriasis. METHODS: Double-blind, vehicle-controlled, randomized, 6-arm trial (1:1:1:1:1:1) in adults, with psoriasis with body surface involvement ≥1% and ≤15% and Physician Global Assessment (PGA) score ≥2 at baseline. Primary endpoint included PGA of 0 or 1 at week 12 and a 2-grade improvement from baseline. Additional analyses included assessment of ≥75% improvement of Psoriasis Area and Severity Index and mean percent change in Psoriasis Area and Severity Index and body surface area involvement. RESULTS: Treatment success defined by PGA 0 or 1 and a 2-grade improvement at week 12 was statistically significantly higher (at a .05 significance level) in the tapinarof groups (65% [1% twice daily], 56% [1% once daily], 46% [0.5% twice daily], and 36% [0.5% once daily]) than in the vehicle groups (11% [twice daily] and 5% [once daily]) and was maintained for 4 weeks posttreatment. Treatment-emergent adverse events were more frequent in patients treated with tapinarof (85/152, 56%) than vehicle (19/75, 25%) and mild-to-moderate in intensity. Severe treatment-emergent adverse events were reported in all tapinarof groups except the 0.5% once daily group. LIMITATIONS: Large confirmation trials are needed. CONCLUSIONS: Tapinarof cream is efficacious and well tolerated in adult patients with psoriasis.