POTRA domains of the TamA insertase interact with the outer membrane and modulate membrane properties.

The outer membrane (OM) of gram-negative bacteria serves as a vital organelle that is densely populated with OM proteins (OMPs) and plays pivotal roles in cellular functions and virulence. The assembly and insertion of these OMPs into the OM represent a fundamental process requiring specialized molecular chaperones. One example is the translocation and assembly module (TAM), which functions as a transenvelope chaperone promoting the folding of specific autotransporters, adhesins, and secretion systems. The catalytic unit of TAM, TamA, comprises a catalytic ß-barrel domain anchored within the OM and three periplasmic polypeptide-transport-associated (POTRA) domains that recruit the TamB subunit. The latter acts as a periplasmic ladder that facilitates the transport of unfolded OMPs across the periplasm. In addition to their role in recruiting the auxiliary protein TamB, our data demonstrate that the POTRA domains mediate interactions with the inner surface of the OM, ultimately modulating the membrane properties. Through the integration of X-ray crystallography, molecular dynamic simulations, and biomolecular interaction methodologies, we located the membrane-binding site on the first and second POTRA domains. Our data highlight a binding preference for phosphatidylglycerol, a minor lipid constituent present in the OM, which has been previously reported to facilitate OMP assembly. In the context of the densely OMP-populated membrane, this association may serve as a mechanism to secure lipid accessibility for nascent OMPs through steric interactions with existing OMPs, in addition to creating favorable conditions for OMP biogenesis.

Florida Doulas' Perspectives on Their Role in Reducing Maternal Morbidity and Health Disparities.

BACKGROUND: Maternal mortality rates continue to rise in the United States. Considerable racial disparities exist, as Black women face two to three times the risks of dying from pregnancy-related complications compared with white women. Doulas have been associated with improved maternal outcomes. This study aimed to 1) investigate Florida doulas' perspectives and influence on severe maternal morbidity/mortality and related inequities, as well as 2) identify opportunities for actionable change. The social ecological model, which acknowledges how individual, interpersonal, institutional, community, and public policy factors intersect, informed our analysis. METHODS: This qualitative study included seven online in-depth interviews and seven focus groups with doulas (N = 31) in Florida. Interview guides investigated how doulas perceive their role in the context of a) maternal morbidity and b) health disparities. RESULTS: Doulas associated maternal morbidity and health disparities with Black pregnant people, identifying racism as a major contributor. Doulas identified their role as one that most often intersects with the individual and interpersonal levels of the social ecological model. Doulas report providing positive social surveillance and emotional support, contributing education and resources, and championing for advocacy in health care settings. Actionable steps recommended by doulas to further mitigate health disparities include the integration of implicit bias training into doula certification programs, increasing public health funding to bolster a doula workforce that can serve racial and ethnic communities, establishing doula-hospital partnerships to improve relational communication, providing tailored resources for clients featuring representative messaging, and doulas' continued engagement in positive social surveillance of their clients. CONCLUSIONS: Doulas perceived their role as integral to mitigating maternal morbidity and health disparities, particularly in the context of supporting and advocating for birthing persons on all levels of the social ecological model. Equitable access to doulas for low-income and/or minoritized populations may be one key strategy to improve maternal health equity.

Child Health Needs and the Adolescent Medicine Workforce Supply: 2020-2040.

Adolescent medicine (AM) subspecialists provide primary, subspecialty, and consultative care to adolescents and young adults (AYAs). Given insufficient numbers of AM subspecialists to care for all AYAs, the workforce supports AYAs health care capacity through education, research, advocacy, and the development of policies and programs sensitive to their unique needs. A modeling project funded by the American Board of Pediatrics Foundation was developed to forecast the pediatric subspecialty workforce in the United States from 2020 to 2040 on the basis of current trends in each subspecialty. The model predicts workforce supply at baseline and across alternative scenarios, and reports results in headcount and headcount adjusted for percentage of time spent in clinical care, termed "clinical workforce equivalent." For the AM subspecialty, several scenarios were considered that modified the number of fellows and/or clinical time. The baseline model predicted low growth nationally (27% and 13% increase in total AM subspecialists and AM subspecialists per 100 000 children, respectively) and declines in AM workforce relative to population growth in census divisions with existing geographic workforce disparities. In the alternative scenarios, fellow number and clinical time changes did not significantly change predictions relative to the baseline model, but a 12.5% decrease in fellows predicted a 40% reduction in the workforce from baseline with a widening of geographic workforce disparities. On the basis of the expansive clinical and nonclinical roles of AM subspecialists and these forecasted workforce challenges, significant educational, practice, and policy changes will be necessary to bolster the supply of well-trained clinicians addressing the dynamic health care needs of AYAs.

A systematic review of contaminants in donor human milk.

Donor human milk (DHM) from a milk bank is the recommended feeding method for preterm infants when the mother's own milk (MOM) is not available. Despite this recommendation, information on the possible contamination of donor human milk and its impact on infant health outcomes is poorly characterised. The aim of this systematic review is to assess contaminants present in DHM samples that preterm and critically ill infants consume. The data sources used include PubMed, EMBASE, CINAHL and Web of Science. A search of the data sources targeting DHM and its potential contaminants yielded 426 publications. Two reviewers (S. T. and D. L.) conducted title/abstract screening through Covidence software, and predetermined inclusion/exclusion criteria yielded 26 manuscripts. Contaminant types (bacterial, chemical, fungal, viral) and study details (e.g., type of bacteria identified, study setting) were extracted from each included study during full-text review. Primary contaminants in donor human milk included bacterial species and environmental pollutants. We found that bacterial contaminants were identified in 100% of the papers in which bacterial contamination was sought (16 papers) and 61.5% of the full data set (26 papers), with the most frequently identified genera being Staphylococcus (e.g., Staphylococcus aureus and coagulase-negative Staphylococcus) and Bacillus (e.g., Bacillus cereus). Chemical pollutants were discovered in 100% of the papers in which chemical contamination was sought (eight papers) and 30.8% of the full data set (26 papers). The most frequently identified chemical pollutants included perfluoroalkyl substances (six papers), toxic metal (one paper) and caffeine (one paper). Viral and fungal contamination were identified in one paper each. Our results highlight the importance of establishing standardisation in assessing DHM contamination and future studies are needed to clarify the impact of DHM contaminants on health outcomes.

Diabetic Retinopathy during pregnancy in Hispanic women with latent Toxoplasma gondii infection.

BACKGROUND: Retinal photography was performed in pregnancy and postpartum in pregnant Hispanic women with latent Toxoplasma gondii (TG) infection in order to screen for characteristic retinal lesions or the particular scars found in people with active T. gondii infection. A comparison group of TG negative women was included in the study but they did not have retinal photography. OBJECTIVE: The goal of the parent study was to assess for adverse pregnancy events and evidence for parasite reactivation in TG positive (TG + ) women, through examination of the eyes for characteristic lesions. Retinal photography, usually at prenatal visits 2 (17 +/- 3.35 weeks) and 3 (26.3+/-1.75) weeks, was done on TG + women. Fifty-six of these women also (43 %) had retinal photography at the postpartum visit. Health and demographic data were obtained at the first prenatal visit for all women. STUDY DESIGN: From the 690 recruited at the first prenatal visit, 128 TG- women and 158 TG + women were enrolled in a prospective study through pregnancy and the postpartum. All TG- women (n = 532) provided data at the first prenatal visit and throughout their pregnancy and birth through the EHR. This allowed comparison of health and outcome data for the TG + compared to a larger number of TG- Hispanic pregnant women. RESULTS: While there was no evidence of ocular toxoplasmosis during pregnancy, there was a surprisingly large number (42 %) of TG + women with diabetic retinopathy (DR). We also observed that TG + women had a 20 % incidence of gestational diabetes mellitus (GDM) compared to 11.3 % in the TG- women (p = 0.01). At postpartum (mean 5.6 weeks), 23 of 30 women with pregnancy DR showed no DR in the postpartum. CONCLUSIONS: No characteristic T. gondii lesions were discovered. Retinal photography serendipitously revealed DR in these T. gondii positive women. It was also found that latent TG infection was associated with increased incidence of GDM. Hispanic pregnant women's increased risk for latent TG infection, GDM and DR are underappreciated. Retinal photography may need to be considered an innovative approach to screening.

Biosignature Detection and MinION Sequencing of Antarctic Cryptoendoliths After Exposure to Mars Simulation Conditions.

In the search for life in our Solar System, Mars remains a promising target based on its proximity and similarity to Earth. When Mars transitioned from a warmer, wetter climate to its current dry and freezing conditions, any putative extant life probably retreated into habitable refugia such as the subsurface or the interior of rocks. Terrestrial cryptoendolithic microorganisms (i.e., those inhabiting rock interiors) thus represent possible modern-day Mars analogs, particularly those from the hyperarid McMurdo Dry Valleys in Antarctica. As DNA is a strong definitive biosignature, given that there is no known abiotic chemistry that can polymerize nucleobases, we investigated DNA detection with MinION sequencing in Antarctic cryptoendoliths after an ∼58-sol exposure in MARTE, a Mars environmental chamber capable of simulating martian temperature, pressure, humidity, ultraviolet (UV) radiation, and atmospheric composition, in conjunction with protein and lipid detection. The MARTE conditions resulted in changes in community composition and DNA, proteins, and cell membrane-derived lipids remained detectable postexposure. Of the multitude of extreme environmental conditions on Mars, UV radiation (specifically UVC) is the most destructive to both cells and DNA. As such, we further investigated if a UVC exposure corresponding to ∼278 martian years would impede DNA detection via MinION sequencing. The MinION was able to successfully detect and sequence DNA after this UVC radiation exposure, suggesting its utility for life detection in future astrobiology missions focused on finding relatively recently exposed biomarkers inside possible martian refugia.

Ethnic disparity in diagnosing asymptomatic bacterial vaginosis using machine learning.

While machine learning (ML) has shown great promise in medical diagnostics, a major challenge is that ML models do not always perform equally well among ethnic groups. This is alarming for women's health, as there are already existing health disparities that vary by ethnicity. Bacterial Vaginosis (BV) is a common vaginal syndrome among women of reproductive age and has clear diagnostic differences among ethnic groups. Here, we investigate the ability of four ML algorithms to diagnose BV. We determine the fairness in the prediction of asymptomatic BV using 16S rRNA sequencing data from Asian, Black, Hispanic, and white women. General purpose ML model performances vary based on ethnicity. When evaluating the metric of false positive or false negative rate, we find that models perform least effectively for Hispanic and Asian women. Models generally have the highest performance for white women and the lowest for Asian women. These findings demonstrate a need for improved methodologies to increase model fairness for predicting BV.

Silver and Copper Nitride Cooperate for CO Electroreduction to Propanol.

The need of carbon sources for the chemical industry, alternative to fossil sources, has pointed to CO2 as a possible feedstock. While CO2 electroreduction (CO2 R) allows production of interesting organic compounds, it suffers from large carbon losses, mainly due to carbonate formation. This is why, quite recently, tandem CO2 R, a two-step process, with first CO2 R to CO using a solid oxide electrolysis cell followed by CO electroreduction (COR), has been considered, since no carbon is lost as carbonate in either step. Here we report a novel copper-based catalyst, silver-doped copper nitride, with record selectivity for formation of propanol (Faradaic efficiency: 45 %), an industrially relevant compound, from CO electroreduction in gas-fed flow cells. Selective propanol formation occurs at metallic copper atoms derived from copper nitride and is promoted by silver doping as shown experimentally and computationally. In addition, the selectivity for C2+ liquid products (Faradaic efficiency: 80 %) is among the highest reported so far. These findings open new perspectives regarding the design of catalysts for production of C3 compounds from CO2 .

Prenatal Counseling and Preparation for Breastfeeding.

Breastfeeding is the gold standard of infant nutrition and current guidelines suggest exclusive breastfeeding for 6 months, with continued breastfeeding through 24 months or beyond. Obstetric care professionals can encourage and educate their patients about breastfeeding through the prenatal period when many expectant parents make decisions about their infant feeding choices. Education and support should extend through the postpartum period and include parents who may have concerns surrounding medical comorbidities, breast augmentation, or substance use disorders.

Improving Racial and Ethnic Equity in Clinical Trials Enrolling Pregnant and Lactating Individuals.

Racial and ethnic marginalized populations have historically been poorly represented, underrecruited, and underprioritized across clinical trials enrolling pregnant and lactating individuals. The objectives of this review are to describe the current state of racial and ethnic representation in clinical trials enrolling pregnant and lactating individuals and to propose evidence-based tangible solutions to achieving equity in these clinical trials. Despite efforts from federal and local organizations, only marginal progress has been made toward achieving equity in clinical research. This continued limited inclusion and transparency in pregnancy trials exacerbates health disparities, limits the generalizability of research findings, and may heighten the maternal child health crisis in the United States. Racial and ethnic underrepresented communities are willing to participate in research; however, they face unique barriers to access and participation. Multifaceted approaches are required to facilitate the participation of marginalized individuals in clinical trials including partnering with the local community to understand their priorities, needs, and assets; establishing accessible recruitment strategies; creating flexible protocols; supporting participants for their time; and increasing culturally congruent and/or culturally sensitive research staff. This article also highlights exemplars in pregnancy research.

Skin to Skin Contact Correlated with Improved Production and Consumption of Mother's Own Milk.

Background: Human milk diet, preferably mother's own milk (MOM) over donor milk (DM), is recommended for preterm infants. Expression of MOM in proximity to preterm infants, especially during or immediately after skin-to-skin contact (SSC), is associated with greater milk production. However, the correlation between SSC and MOM production during hospital admission in preterm infants has not yet been studied. Our study investigated the relationship between SSC and MOM production and consumption in preterm infants during the first postnatal month of life. Materials and Methods: This was a prospective cohort study. Mothers and their preterm infants born at <35 weeks by gestational age (GA) and eligible for SSC within the first 5 postnatal days were eligible for the study. Mothers were given a binder to document pumped breast milk volumes and SSC sessions. Pumped breast milk volumes, enteral feeding type and volume, and SSC duration and frequency were collected daily over the first 28 days of life, along with demographic, perinatal, and feeding data from electronic medical records (EMR). Results: Mean birth GA and weight were 30 ± 3 weeks and 1,443 ± 576 g, respectively. SSC duration was inversely correlated with GA and weight. The SSC duration was positively correlated with ingested MOM volume after correcting for birth GA. The SSC duration was predictive of increased volumes of pumped MOM. Conclusion: Our findings suggest that SSC duration is associated with improved MOM production and consumption. SSC can be a useful tool to increase MOM exposure and improve long-term health outcomes in preterm infants.

Microbial Characterization of Arctic Glacial Ice Cores with a Semiautomated Life Detection System.

The search for extant microbial life will be a major focus of future astrobiology missions; however, no direct extant life detection instrumentation is included in current missions to Mars. In this study, we developed the semiautomated MicroLife detection platform that collects and processes environmental samples, detects biosignatures, and characterizes microbial activity. This platform is composed of a drill for sample collection, a redox dye colorimetric system for microbial metabolic activity detection and assessment (µMAMA [microfluidics Microbial Activity MicroAssay]), and a MinION sequencer for biosignature detection and characterization of microbial communities. The MicroLife platform was field-tested on White Glacier on Axel Heiberg Island in the Canadian high Arctic, with two extracted ice cores. The µMAMA successfully detected microbial metabolism from the ice cores within 1 day of incubation. The MinION sequencing of the ice cores and the positive µMAMA card identified a microbial community consistent with cold and oligotrophic environments. Furthermore, isolation and identification of microbial isolates from the µMAMA card corroborated the MinION sequencing. Together, these analyses support the MicroLife platform's efficacy in identifying microbes natively present in cryoenvironments and detecting their metabolic activity. Given our MicroLife platform's size and low energy requirements, it could be incorporated into a future landed platform or rovers for life detection.

Maternal gut microbiota in the postpartum Period: A Systematic review.

Studies have demonstrated the importance of the gut microbiota during pregnancy, and there is emerging literature on the postpartum maternal gut microbiota. The primary objective of this paper was to synthesize the literature on the postpartum gut microbiome composition and diversity measured in stool samples from healthy mothers of predominantly term infants. The secondary objectives were (1) to identify biological and environmental factors that influence postpartum maternal gut microbiota and (2) to assess health conditions and clinical intermediate measures associated with postpartum gut microbiota changes in all mothers. Electronic searches were conducted November 9, 2020 and updated July 25, 2021 without publication time limits on PubMed, Embase, CINHAL, Scopus, Cochrane Library, BioArchives, and OpenGrey.eu. Primary research on maternal gut microbiota in the postpartum (up to one year after childbirth) were eligible. Postpartum gut microbiota comparisons to pregnancy or non-pregnancy gut microbiota were of interest, therefore, studies examining these in addition to the postpartum were included. Studies were excluded if they were only conducted in animals, infants, pregnancy, or microbiome of other body locations (e.g., vaginal). Data extraction of microbial composition and diversity were completed and synthesized narratively. Studies were assessed for risk of bias. A total of 2512 articles were screened after deduplication and 27 were included in this review. Of the 27 included studies, 22 addressed the primary objective. Firmicutes was the predominant phylum in the early (<6 weeks) and late postpartum (6 weeks to 1 year). In early postpartum, Bacteroides was the predominant genus. Findings from longitudinal assessments of alpha and beta diversity from the early to the late postpartum varied. Nineteen of the 27 studies assessed biological and environmental factors influencing the postpartum gut microbial profile changes. Timing of delivery, probiotic supplementation, triclosan exposure, and certain diets influenced the postpartum gut microbiota. Regarding health conditions and intermediate clinical measures assessed in 8 studies; inflammatory bowel disease, postpartum depression, early-onset preeclampsia, gestational diabetes, excessive gestational weight gain, and anthropometric measures such as body mass index and waist-to-hip ratio were related to gut microbiota changes. There is limited data on the maternal postpartum gut microbiota and how it influences maternal health. We need to understand the postpartum maternal gut microbiome, establish how it differs from non-pregnancy and pregnancy states, and determine biological and environmental influencers. Future research of the gut microbiome's significance for the birthing parent in the postpartum could lead to a new understanding of how to improve maternal short and long-term health.

Perinatal Health Outcomes Across Rural and Nonrural Counties Within a Single Health System Catchment.

Background: Perinatal health outcomes are influenced by a variety of socioeconomic, behavioral, and economic factors that reduce access to health services. Despite these observations, rural communities continue to face barriers, including a lack of resources and the fragmentation of health services. Objective: To evaluate patterns in health outcomes, health behaviors, socioeconomic vulnerability, and sociodemographic characteristics across rural and nonrural counties within a single health system catchment area. Methods: Socioeconomic vulnerability metrics, health care access as determined by licensed provider metrics, and behavioral data were obtained from FlHealthCHARTS.gov and the County Health Rankings. County-level birth and health data were obtained from the Florida Department of Health. The University of Florida Health Perinatal Catchment Area (UFHPCA) was defined as all Florida counties where ≥5% of all infants were delivered at Shands Hospital between June 2011 and April 2017. Results: The UFHPCA included 3 nonrural and 10 rural counties that represented more than 64,000 deliveries. Nearly 1 in 3 infants resided in a rural county, and 7 out of 13 counties did not have a licensed obstetrician gynecologist. Maternal smoking rates (range 6.8%-24.8%) were above the statewide rate (6.2%). Except for Alachua County, breastfeeding initiation rates (range 54.9%-81.4%) and access to household computing devices (range 72.8%-86.4%) were below the statewide rate (82.9% and 87.9%, respectively). Finally, we found that childhood poverty rates (range 16.3%-36.9%) were above the statewide rate (18.5%). Furthermore, risk ratios suggested negative health outcomes for residents of counties within the UFHPCA for each measure, except for infant mortality and maternal deaths, which lacked sample sizes to adequately test. Conclusions: The health burden of the UFHPCA is characterized by rural counties with increased maternal death, neonatal death, and preterm birth, as well as adverse health behaviors that included increased smoking during pregnancy and lower levels of breastfeeding relative to nonrural counties. Understanding perinatal health outcomes across a single health system has potential to not only estimate community needs but also facilitate planning of health care initiatives and interventions in rural and low-resource communities.

Novel filamin C (FLNC) variant causes a severe form of familial mixed hypertrophic-restrictive cardiomyopathy.

Variants of filamin C (FLNC) have been identified as rare genetic substrate for hypertrophic cardiomyopathy (HCM). Data on the clinical course of FLNC-related HCM are conflicting with some studies suggesting mild phenotypes whereas other studies have reported more severe outcomes. In this study, we present a novel FLNC variant (Ile1937Asn) that was identified in a large family of French-Canadian descent with excellent segregation data. FLNC-Ile1937Asn is a novel missense variant characterized by full penetrance and poor clinical outcomes. End stage heart failure requiring transplantation occurred in 43% and sudden cardiac death in 29% of affected family members. Other particular features of FLNC-Ile1937Asn include an early disease onset (mean age of 19 years) and the development of a marked atrial myopathy (severe biatrial dilatation with remodeling and multiple complex atrial arrhythmias) that was present in all gene carriers. The FLNC-Ile1937Asn variant is a novel, pathogenic mutation resulting in a severe form of HCM with full disease penetrance. The variant is associated with a high proportion of end-stage heart failure, heart transplantation, and disease-related mortality. Close follow-up and appropriate risk stratification of affected individuals at specialized heart centers is recommended.

Peripartum women's perspectives on research study participation in the OneFlorida Clinical Research Consortium during COVID-19 pandemic.

Introduction: The COVID-19 pandemic created an unprecedented need for population-level clinical trials focused on the discovery of life-saving therapies and treatments. However, there is limited information on perception of research participation among perinatal populations, a population of particular interest during the pandemic. Methods: Eligible respondents were 18 years or older, were currently pregnant or had an infant (≤12 months old), and lived in Florida within 50 miles of sites participating in the OneFlorida Clinical Research Consortium. Respondents were recruited via Qualtrics panels between April and September 2020. Respondents completed survey items about barriers and facilitators to participation and answered sociodemographic questions. Results: Of 533 respondents, most were between 25 and 34 years of age (n = 259, 49%) and identified as White (n = 303, 47%) and non-Hispanic (n = 344, 65%). Facebook was the most popular social media platform among our respondents. The most common barriers to research participation included poor explanation of study goals, discomforts to the infant, and time commitment. Recruitment through healthcare providers was perceived as the best way to learn about clinical research studies. When considering research participation, "myself" had the greatest influence, followed by familial ties. Noninvasive biological samples were highly acceptable. Hispanics had higher positive perspectives on willingness to participate in a randomized study (p = 0.009). Education (p = 0.007) had significant effects on willingness to release personal health information. Conclusion: When recruiting women during the pregnancy and postpartum periods for perinatal studies, investigators should consider protocols that account for common barriers and preferred study information sources. Social media-based recruitment is worthy of adoption.

Risk Factors, Symptoms, and Treatment of Lactational Mastitis.

This JAMA Insights Clinical Update reviews the risk factors for and symptoms of lactational mastitis and provides a potential treatment algorithm.

Adverse pregnancy outcomes in Toxoplasma gondii seropositive Hispanic women.

AIMS: Chronic Toxoplasma gondii infection is not thought to affect pregnancy or birth outcomes, but there are few prospective studies. The study aims were T. gondii immunoglobulin G measurement and relationship of chronic T. gondii infection with gestational age at birth and adverse pregnancy outcomes in 690 Hispanic women in Tampa, Florida. METHODS: Hispanic women, born either in the United States or in Latin America or the Caribbean had a venous blood sample drawn to measure T. gondii IgG and T. gondii serotype at the first prenatal visit, along with collection of demographic and health-related measures. Seropositive and seronegative women were followed throughout their pregnancy. Gestational age, infant weights, and adverse pregnancy outcomes (miscarriages, preterm births) were compared in the two groups. RESULTS: There were 740 women of self-reported Hispanic ethnicity screened and enrolled in Tampa, Florida, with 690 having birth data extracted from the electronic health record (538 T. gondii negative and 152 T. gondii seropositive). T. gondii seropositivity was 22.4% and the majority (83%) had high avidity titers, indicating chronic infection. Compared to T. gondii seronegative Hispanic women, seroseropositive women had more smaller for gestational age infants and higher prevalences of miscarriages and preterm birth. CONCLUSION: This is one of the largest longitudinal cohort studies of women with chronic T. gondii infection followed through pregnancy. There was a higher percentages of adverse pregnancy outcomes in this group compared to T. gondii seronegative controls. The mechanism for this is unknown and warrants reexamination of the dogma that chronic T. gondii infection in pregnant women has no significant clinical consequences.