Nulliparous Individuals with Class III Obesity: Adverse Outcomes with Labor versus Planned Cesarean Delivery.

Individuals with class III obesity (body mass index [BMI] > 40 kg/m2) are at increased risk of cesarean delivery and peripartum complications. We ascertained compositive neonatal and maternal adverse outcomes among individuals with class III obesity who labored versus had planned cesarean delivery (CD). This was a retrospective cohort study from 2016-2021 using the National Vital Statistics System database. Nulliparous individuals with class III obesity pre-pregnancy were included if they had singleton, non-anomalous pregnancies and delivered at 37 to 41 weeks of gestation. Individuals were excluded if they had hypertensive disorders or diabetes. The primary outcome was a composite neonatal adverse outcome (CNAO), consisting of Apgar score less than 5 at 5 minutes, assisted ventilation > 6 hours, neonatal seizure, or neonatal death. The secondary outcome was a composite maternal adverse outcome (CMAO) that included admission to the intensive care unit (ICU), maternal transfusion, uterine rupture, or unplanned hysterectomy. A sensitivity analysis using a CMAO without transfusion was performed. A multivariable Poisson regression model was performed to calculate adjusted relative risks (RR) with 95% confidence intervals (CI). Of 192,298 individuals who met inclusion criteria, 169,676 (88.2%) labored and 22,622 (11.8%) had a planned CD. Compared to neonates delivered by planned CD, the risk of CNAO was significantly lower in those who delivered after labor (aRR 0.79, 95% CI 0.71 - 0.87). There was no significant difference in the risk of CMAO between groups (aRR 1.11, 95% CI 0.87-1.41). However, the risk of CMAO without transfusion was lower in individuals who labored (aRR 0.57, 95% CI 0.40 - 0.83). In nulliparous individuals with class III obesity, the risk of CNAO and of CMAO without transfusion were significantly lower in individuals who labored, versus those who had a planned cesarean delivery.

Fibrin drives thromboinflammation and neuropathology in COVID-19.

Life-threatening thrombotic events and neurological symptoms are prevalent in COVID-19 and are persistent in patients with long COVID experiencing post-acute sequelae of SARS-CoV-2 infection1-4. Despite the clinical evidence1,5-7, the underlying mechanisms of coagulopathy in COVID-19 and its consequences in inflammation and neuropathology remain poorly understood and treatment options are insufficient. Fibrinogen, the central structural component of blood clots, is abundantly deposited in the lungs and brains of patients with COVID-19, correlates with disease severity and is a predictive biomarker for post-COVID-19 cognitive deficits1,5,8-10. Here we show that fibrin binds to the SARS-CoV-2 spike protein, forming proinflammatory blood clots that drive systemic thromboinflammation and neuropathology in COVID-19. Fibrin, acting through its inflammatory domain, is required for oxidative stress and macrophage activation in the lungs, whereas it suppresses natural killer cells, after SARS-CoV-2 infection. Fibrin promotes neuroinflammation and neuronal loss after infection, as well as innate immune activation in the brain and lungs independently of active infection. A monoclonal antibody targeting the inflammatory fibrin domain provides protection from microglial activation and neuronal injury, as well as from thromboinflammation in the lung after infection. Thus, fibrin drives inflammation and neuropathology in SARS-CoV-2 infection, and fibrin-targeting immunotherapy may represent a therapeutic intervention for patients with acute COVID-19 and long COVID.

Virus entéricos distintos de rotavirus y norovirus en menores de 5 años con gastroenteritis en Argentina, 2010-2021. Estudio descriptivo / Enteric viruses other than rotavirus and norovirus in children under 5 years of age with gastroenteritis in Argentina, 2010­2021. A descriptive study

Introducción. Los datos de frecuencia de los adenovirus entéricos, sapovirus y astrovirus en casos de gastroenteritis aguda esporádica en Argentina son escasos. Métodos. Diseño descriptivo sobre una selección de muestras de heces de menores de 5 años con diarrea remitidas durante el período 2010-2021, con resultado previo negativo para rotavirus y norovirus. Se estudió la presencia de adenovirus entéricos, sapovirus y astrovirus por métodos moleculares, con posterior genotipificación de las muestras positivas. Resultados. De 574 muestras seleccionadas, en 226 (39,4 %) se identificó al menos uno de los virus estudiados. En particular, se detectaron adenovirus, sapovirus y astrovirus en el 30,7 %, el 5,6 % y el 3,1 %, respectivamente. El adenovirus 41, los sapovirus GI.1 y GI.2, y el astrovirus 1 fueron los más frecuentemente detectados. Se identificaron dos muestras con astrovirus no clásicos. Conclusiones. A pesar de ser menos frecuentes, estos enteropatógenos son responsables de un número considerable de episodios de diarrea esporádica. Por lo tanto, su estudio y vigilancia contribuye significativamente a reducir la brecha de casos no diagnosticados.

Introduction. Data on the frequency of enteric adenoviruses, sapoviruses, and astroviruses in cases of sporadic acute gastroenteritis in Argentina are scarce. Methods. Descriptive design of a selection of fecal samples of children with diarrhea younger than 5 years referred between 2010 and 2021, with a previous negative result for rotavirus and norovirus. The presence of enteric adenovirus, sapovirus, and astrovirus was tested by molecular methods, with subsequent genotyping of positive samples. Results. At least 1 of the tested viruses was detected in 226 (39.4%) of the 574 selected samples. Specifically, adenovirus, sapovirus, and astrovirus were detected in 30.7%, 5.6%, and 3.1% of the samples, respectively. The most frequent viruses detected were adenovirus 41, sapoviruses GI.1 and GI.2, and astrovirus 1. Non-classic astroviruses were detected in 2 samples. Conclusions. Despite being less frequent, these enteropathogens are responsible for a large number of sporadic diarrhea events. Therefore, their study and surveillance contribute significantly to reduce the gap of undiagnosed cases.

Keypoint-MoSeq: parsing behavior by linking point tracking to pose dynamics.

Keypoint tracking algorithms can flexibly quantify animal movement from videos obtained in a wide variety of settings. However, it remains unclear how to parse continuous keypoint data into discrete actions. This challenge is particularly acute because keypoint data are susceptible to high-frequency jitter that clustering algorithms can mistake for transitions between actions. Here we present keypoint-MoSeq, a machine learning-based platform for identifying behavioral modules ('syllables') from keypoint data without human supervision. Keypoint-MoSeq uses a generative model to distinguish keypoint noise from behavior, enabling it to identify syllables whose boundaries correspond to natural sub-second discontinuities in pose dynamics. Keypoint-MoSeq outperforms commonly used alternative clustering methods at identifying these transitions, at capturing correlations between neural activity and behavior and at classifying either solitary or social behaviors in accordance with human annotations. Keypoint-MoSeq also works in multiple species and generalizes beyond the syllable timescale, identifying fast sniff-aligned movements in mice and a spectrum of oscillatory behaviors in fruit flies. Keypoint-MoSeq, therefore, renders accessible the modular structure of behavior through standard video recordings.

A systematic review and meta-analysis of the association between e-cigarette use among non-tobacco users and initiating smoking of combustible cigarettes.

INTRODUCTION: The rapid increase in e-cigarette use over the past decade has triggered an important public health question on the potential association between e-cigarette use and combustible cigarette smoking. Following AMSTAR 2 and PRISMA guidelines, this evidence synthesis sought to identify and characterize any associations between e-cigarette use among individuals not smoking cigarettes and initiation of cigarette smoking. METHODS: The protocol was registered on September 24, 2018 (PROSPERO 2018 CRD42018108540). Three databases were queried from January 01, 2007 to April 26, 2023. Search results were screened using the PICOS review method. RESULTS: Among 55 included studies (40 "good" and 15 "fair"; evidence grade: "high") that adjusted for gender, age, and race/ethnicity between groups, generally, there was a significant association between non-regular e-cigarette use and initiation of cigarette smoking, further supported by the meta-analytic results (AOR 3.71; 95% CI 2.86-4.81). However, smoking initiation was most often measured as ever/current cigarette smoking. Two studies (quality: 2 "good") evaluated progression to regular cigarette smoking among individuals with regular use of e-cigarettes, and generally found no significant associations. One study ("good") evaluated smoking initiation among individuals with regular use of e-cigarettes, finding an increasing probability of ever smoking cigarettes with increased e-cigarette use. Twelve studies (10 "good" and two "fair") examining progression to regular smoking among individuals with non-regular use of e-cigarettes reported inconsistent findings. CONCLUSIONS: Numerous methodological flaws in the body of literature limit the generalizability of these results to all individuals who are not smoking cigarettes with few studies measuring established/regular use/smoking of e-cigarettes and cigarettes. Further, studies did not control adequately for specific confounding variables representing common liabilities between e-cigarette use and cigarette smoking, nor did they account for sufficient follow-up durations. Collectively, these flaws limit the generalizability of findings to the question of an association between e-cigarette use and cigarette smoking initiation.

The 2023 WSES guidelines on the management of trauma in elderly and frail patients

The trauma mortality rate is higher in the elderly compared with younger patients. Ageing is associated with physiological changes in multiple systems and correlated with frailty. Frailty is a risk factor for mortality in elderly trauma patients. We aim to provide evidence-based guidelines for the management of geriatric trauma patients to improve it and reduce futile procedures. Six working groups of expert acute care and trauma surgeons reviewed extensively the literature according to the topic and the PICO question assigned. Statements and recommendations were assessed according to the GRADE methodology and approved by a consensus of experts in the field at the 10th international congress of the WSES in 2023. The management of elderly trauma patients requires knowledge of ageing physiology, a focused triage, including drug history, frailty assessment, nutritional status, and early activation of trauma protocol to improve outcomes. Acute trauma pain in the elderly has to be managed in a multimodal analgesic approach, to avoid side effects of opioid use. Antibiotic prophylaxis is recommended in penetrating (abdominal, thoracic) trauma, in severely burned and in open fractures elderly patients to decrease septic complications. Antibiotics are not recommended in blunt trauma in the absence of signs of sepsis and septic shock. Venous thromboembolism prophylaxis with LMWH or UFH should be administrated as soon as possible in high and moderate-risk elderly trauma patients according to the renal function, weight of the patient and bleeding risk. A palliative care team should be involved as soon as possible to discuss the end of life in a multidisciplinary approach considering the patient's directives, family feelings and representatives' desires, and all decisions should be shared. The management of elderly trauma patients requires knowledge of ageing physiology, a focused triage based on assessing frailty and early activation of trauma protocol to improve outcomes. Geriatric Intensive Care Units are needed to care for elderly and frail trauma patients in a multidisciplinary approach to decrease mortality and improve outcomes.

Hospice and palliative care utilization in 16 004 232 medicare claims: comparing trauma to surgical and medical inpatients.

Background: Hospice and palliative care (PC) utilization is increasing in geriatric inpatients, but limited research exists comparing rates among trauma, surgical and medical specialties. The goal of this study was to determine whether there are differences among these three groups in rates of hospice and PC utilization. Methods: Patients from Centers for Medicare & Medicaid Services (CMS) Inpatient Standard Analytical Files for 2016-2020 aged ≥65 years were analyzed. Patients with a National Trauma Data Standard-qualifying ICD-10 injury code with abbreviated injury score ≥2 were classified as 'trauma'; the rest as 'surgical' or 'medical' using CMS MS-DRG definitions. Patients were classified as having PC if they had an ICD-10 diagnosis code for PC (Z51.5) and as hospice discharge (HD) if their hospital disposition was 'hospice' (home or inpatient). Use proportions for specialties were compared by group and by subgroups with increasing risk of poor outcome. Results: There were 16M hospitalizations from 1024 hospitals (9.3% trauma, 26.3% surgical and 64.4% medical) with 53.7% women, 84.5% white and 38.7% >80 years. Overall, 6.2% received PC and 4.1% a HD. Both rates were higher in trauma patients (HD: 3.6%, PC: 6.3%) versus surgical patients (HD: 1.5%, PC: 3.0%), but lower than in medical patients (HD: 5.2%, PC: 7.5%). PC rates increased in higher risk patient subgroups and were highest for inpatient HD. Conclusions: In this large study of Medicare patients, HD and PC rates varied significantly among specialties. Trauma patients had higher HD and PC utilization rates than surgical, but lower than medical. The presence of comorbidities, frailty and/or severe traumatic brain injury (in addition to advanced age) may be valuable criteria in selection of trauma patients for hospice and PC services. Further studies are needed to inform the most efficient use of hospice and PC resources, with particular focus on both timing and selection of subgroups most likely to benefit from these valuable yet limited resources. Level of evidence: Level III, therapeutic/care management.

Lineage-tracing hematopoietic stem cell origins in vivo to efficiently make human HLF+ HOXA+ hematopoietic progenitors from pluripotent stem cells.

The developmental origin of blood-forming hematopoietic stem cells (HSCs) is a longstanding question. Here, our non-invasive genetic lineage tracing in mouse embryos pinpoints that artery endothelial cells generate HSCs. Arteries are transiently competent to generate HSCs for 2.5 days (∼E8.5-E11) but subsequently cease, delimiting a narrow time frame for HSC formation in vivo. Guided by the arterial origins of blood, we efficiently and rapidly differentiate human pluripotent stem cells (hPSCs) into posterior primitive streak, lateral mesoderm, artery endothelium, hemogenic endothelium, and >90% pure hematopoietic progenitors within 10 days. hPSC-derived hematopoietic progenitors generate T, B, NK, erythroid, and myeloid cells in vitro and, critically, express hallmark HSC transcription factors HLF and HOXA5-HOXA10, which were previously challenging to upregulate. We differentiated hPSCs into highly enriched HLF+ HOXA+ hematopoietic progenitors with near-stoichiometric efficiency by blocking formation of unwanted lineages at each differentiation step. hPSC-derived HLF+ HOXA+ hematopoietic progenitors could avail both basic research and cellular therapies.

Eph-ephrin signaling couples endothelial cell sorting and arterial specification.

Cell segregation allows the compartmentalization of cells with similar fates during morphogenesis, which can be enhanced by cell fate plasticity in response to local molecular and biomechanical cues. Endothelial tip cells in the growing retina, which lead vessel sprouts, give rise to arterial endothelial cells and thereby mediate arterial growth. Here, we have combined cell type-specific and inducible mouse genetics, flow experiments in vitro, single-cell RNA sequencing and biochemistry to show that the balance between ephrin-B2 and its receptor EphB4 is critical for arterial specification, cell sorting and arteriovenous patterning. At the molecular level, elevated ephrin-B2 function after loss of EphB4 enhances signaling responses by the Notch pathway, VEGF and the transcription factor Dach1, which is influenced by endothelial shear stress. Our findings reveal how Eph-ephrin interactions integrate cell segregation and arteriovenous specification in the vasculature, which has potential relevance for human vascular malformations caused by EPHB4 mutations.

Evolution and genetic architecture of sex-limited polymorphism in cuckoos.

Sex-limited polymorphism has evolved in many species including our own. Yet, we lack a detailed understanding of the underlying genetic variation and evolutionary processes at work. The brood parasitic common cuckoo (Cuculus canorus) is a prime example of female-limited color polymorphism, where adult males are monochromatic gray and females exhibit either gray or rufous plumage. This polymorphism has been hypothesized to be governed by negative frequency-dependent selection whereby the rarer female morph is protected against harassment by males or from mobbing by parasitized host species. Here, we show that female plumage dichromatism maps to the female-restricted genome. We further demonstrate that, consistent with balancing selection, ancestry of the rufous phenotype is shared with the likewise female dichromatic sister species, the oriental cuckoo (Cuculus optatus). This study shows that sex-specific polymorphism in trait variation can be resolved by genetic variation residing on a sex-limited chromosome and be maintained across species boundaries.

Effect of an Arsenic Mitigation Program on Arsenic Exposure in American Indian Communities: A Cluster Randomized Controlled Trial of the Community-Led Strong Heart Water Study Program.

BACKGROUND: Chronic arsenic exposure has been associated with an increased risk of cardiovascular disease; diabetes; cancers of the lung, pancreas and prostate; and all-cause mortality in American Indian communities in the Strong Heart Study. OBJECTIVE: The Strong Heart Water Study (SHWS) designed and evaluated a multilevel, community-led arsenic mitigation program to reduce arsenic exposure among private well users in partnership with Northern Great Plains American Indian Nations. METHODS: A cluster randomized controlled trial (cRCT) was conducted to evaluate the effectiveness of the SHWS arsenic mitigation program over a 2-y period on a) urinary arsenic, and b) reported use of arsenic-safe water for drinking and cooking. The cRCT compared the installation of a point-of-use arsenic filter and a mobile Health (mHealth) program (3 phone calls; SHWS mHealth and Filter arm) to a more intensive program, which included this same program plus three home visits (3 phone calls and 3 home visits; SHWS Intensive arm). RESULTS: A 47% reduction in urinary arsenic [geometric mean (GM)=13.2 to 7.0µg/g creatinine] was observed from baseline to the final follow-up when both study arms were combined. By treatment arm, the reduction in urinary arsenic from baseline to the final follow-up visit was 55% in the mHealth and Filter arm (GM=14.6 to 6.55µg/g creatinine) and 30% in the Intensive arm (GM=11.2 to 7.82µg/g creatinine). There was no significant difference in urinary arsenic levels by treatment arm at the final follow-up visit comparing the Intensive vs. mHealth and Filter arms: GM ratio of 1.21 (95% confidence interval: 0.77, 1.90). In both arms combined, exclusive use of arsenic-safe water from baseline to the final follow-up visit significantly increased for water used for cooking (17% to 53%) and drinking (12% to 46%). DISCUSSION: Delivery of the interventions for the community-led SHWS arsenic mitigation program, including the installation of a point-of-use arsenic filter and a mHealth program on the use of arsenic-safe water (calls only, no home visits), resulted in a significant reduction in urinary arsenic and increases in reported use of arsenic-safe water for drinking and cooking during the 2-y study period. These results demonstrate that the installation of an arsenic filter and phone calls from a mHealth program presents a promising approach to reduce water arsenic exposure among private well users. https://doi.org/10.1289/EHP12548.

Would you be surprised? Prospective multicenter study of the Surprise Question as a screening tool to predict mortality in trauma patients.

BACKGROUND: The Surprise Question (SQ) ("Would I be surprised if the patient died within the next year?") is a validated tool used to identify patients with limited life expectancy. Because it may have potential to expedite palliative care interventions per American College of Surgeons Trauma Quality Improvement Program Palliative Care Best Practices Guidelines, we sought to determine if trauma team members could use the SQ to accurately predict 1-year mortality in trauma patients. METHODS: A multicenter, prospective, cohort study collected data (August 2020 to February 2021) on trauma team members' responses to the SQ at 24 hours from admission. One-year mortality was obtained via social security death index records. Positive/negative predictive values and accuracy were calculated overall, by provider role and by patient age. RESULTS: Ten Level I/II centers enrolled 1,172 patients (87.9% blunt). The median age was 57 years (interquartile range, 36-74 years), and the median Injury Severity Score was 10 (interquartile range, 5-14 years). Overall 1-year mortality was 13.3%. Positive predictive value was low (30.5%) regardless of role. Mortality prediction minimally improved as age increased (positive predictive value highest between 65 and 74 years old, 34.5%) but consistently trended to overprediction of death, even in younger patients. CONCLUSION: Trauma team members' ability to forecast 1-year mortality using the SQ at 24 hours appears limited perhaps because of overestimation of injury effects, preinjury conditions, and/or team bias. This has implications for the Trauma Quality Improvement Program Guidelines and suggests that more research is needed to determine the optimal time to screen trauma patients with the SQ. LEVEL OF EVIDENCE: Prognostic and Epidemiological; Level III.

CXCL12 regulates coronary artery dominance in diverse populations and links development to disease.

Mammalian cardiac muscle is supplied with blood by right and left coronary arteries that form branches covering both ventricles of the heart. Whether branches of the right or left coronary arteries wrap around to the inferior side of the left ventricle is variable in humans and termed right or left dominance. Coronary dominance is likely a heritable trait, but its genetic architecture has never been explored. Here, we present the first large-scale multi-ancestry genome-wide association study of dominance in 61,043 participants of the VA Million Veteran Program, including over 10,300 Africans and 4,400 Admixed Americans. Dominance was moderately heritable with ten loci reaching genome wide significance. The most significant mapped to the chemokine CXCL12 in both Europeans and Africans. Whole-organ imaging of human fetal hearts revealed that dominance is established during development in locations where CXCL12 is expressed. In mice, dominance involved the septal coronary artery, and its patterning was altered with Cxcl12 deficiency. Finally, we linked human dominance patterns with coronary artery disease through colocalization, genome-wide genetic correlation and Mendelian Randomization analyses. Together, our data supports CXCL12 as a primary determinant of coronary artery dominance in humans of diverse backgrounds and suggests that developmental patterning of arteries may influence one's susceptibility to ischemic heart disease.

Transcutaneous Temperature Controlled Radiofrequency: Groundbreaking Technology - Female Stress Urinary Incontinence and Overactive Bladder Can Be Treated Noninvasively and with Vulvovaginal Rejuvenation?

It has long been difficult to treat vulvovaginal laxity, genitourinary syndrome of menopause, stress urine incontinence, overactive bladder (OAB), and other indications of sexual dysfunction because women traditionally find it difficult to discuss these difficulties with clinicians and because society generally accepts these diseases. Originating in esthetic medicine, noninvasive feminine rejuvenation that targets vaginal tissue with energy-based methods has recently become more popular. A more youthful-looking vulva, the restoration of vaginal elasticity and "tightness," a significant improvement in stress urinary incontinence, a reduction in symptoms of OAB, and a decrease in sexual dysfunction are all benefits of transcutaneous temperature-controlled radiofrequency (TTCRF) therapy at the vulvovaginal region. It is also becoming more popular as a mild-to-moderate stress urinary incontinence and OAB noninvasive therapy option. Women will likely always be appreciative of their gynecologist for managing stress urinary incontinence with TTCRF therapy without making an incision, it would appear.

A Systematic Review Investigating Associations Between E-Cigarette Use Among Former Cigarette Smokers and Relapse to Smoking Cigarettes.

As e-cigarette use has steadily increased over the recent years, the public health interest in the potential implications of e-cigarette use on cigarette smoking has grown in parallel. With strict adherence to PRISMA guidelines, this systematic review examined the potential associations between e-cigarette use and relapse to cigarette smoking among former cigarette smokers. The protocol was registered on November 06, 2018 (PROSPERO 2018 CRD42018115674). Literature searches were executed from January 01, 2007 to August 20, 2022 and search results were screened according to the PICOS review method. One RCT and 10 adjusted studies examined relapse to cigarette smoking (evidence grade "moderate") among regular e-cigarette users, reporting mixed and inconsistent findings according to varying definitions of e-cigarette use and relapse. Findings were similarly inconsistent among the 8 adjusted studies examining relapse to cigarette smoking among non-regular e-cigarette users. The inconsistency in findings among studies evaluating regular measures of e-cigarette use, combined with the numerous methodological flaws in the overall body of literature, limit the generalizability of results associated with a causal association between e-cigarette use and relapse to cigarette smoking. Based on findings from this review, more robust studies are required to determine whether a causal association exists between e-cigarette use and relapse to cigarette smoking. Future studies should apply consistent measures of regular e-cigarette use to examine causality with future use patterns, and sufficiently account for known or suspected confounding variables to support inform determinations related to e-cigarette use and cigarette smoking behaviors.

Switchable Organocatalysis from N-heterocyclic Carbene-Carbodiimide Adducts with Tunable Release Temperature.

N-Heterocyclic carbenes (NHCs) are powerful organocatalysts, but practical applications often require in situ generation from stable precursors that "mask" the NHC reactivity via reversible binding. Previously established "masks" are often simple small molecules, such that the NHC structure is used to control both catalytic activity and activation temperature, leading to undesirable tradeoffs. Herein, we show that NHC-carbodiimide (CDI) adducts can be masked precursors for switchable organocatalysis and that the CDI substituents can control the reaction profile without changing the NHC structure. Large electronic variations on the CDI (e.g., alkyl versus aryl) drastically change the catalytically active temperature, whereas smaller perturbations (e.g., different para-substituted phenyls) tune the catalyst release within a narrower window. This control was demonstrated for three classic NHC-catalyzed reactions, each influencing the NHC-CDI equilibrium in different ways. Our results introduce a new paradigm for controlling NHC organocatalysis as well as present practical considerations for designing appropriate masks for various reactions.

Collaborative relationships between doulas and maternity care providers when supporting migrant women during labour and birth.

OBJECTIVE: To explore the perspectives and experiences of community-based doulas and maternity care providers working with each other in Australia; and to identify the facilitators and barriers to working relationships when supporting migrant women during labour and birth. DESIGN AND METHODS: A qualitative interpretive phenomenological study using in-depth semi-structured interviews. An inductive thematic approach and Capability, Opportunity, and Motivation (COM-B) framework were used in data analysis. SETTING AND PARTICIPANTS: 10 doulas from Birth for Humankind (a community-based doula service), and 13 maternity care providers from a tertiary maternity hospital in Melbourne, Australia were included. FINDINGS: We identified how collaborative working relationships between community-based doulas and maternity care providers may be enhanced by adopting facilitators across all three COM-B domains and by removing identified barriers. Factors facilitating collaborative working relationships included: knowledge and value of doula roles, establishment of rapport and trust between doulas and providers; doulas enhancing respectful care, communication and relationships between migrant women and providers; and community-based doulas differentiated from private practising doulas. Barriers included: limited understanding of doula roles and service; limiting behaviours impacting collaborative relationships; and limited opportunities for doulas and providers to establish rapport. KEY CONCLUSIONS AND IMPLICATIONS FOR PRACTICE: Findings are relevant to other models of doula care including private practice doulas and hospital-based doula services. Positive, collaborative doula-provider working relationships are integral for ensuring that the benefits of doula care continue to reach underserved populations such as migrant women and improve their maternity care experiences and outcomes within hospitals settings.

Sox7-positive endothelial progenitors establish coronary arteries and govern ventricular compaction.

The cardiac endothelium influences ventricular chamber development by coordinating trabeculation and compaction. However, the endothelial-specific molecular mechanisms mediating this coordination are not fully understood. Here, we identify the Sox7 transcription factor as a critical cue instructing cardiac endothelium identity during ventricular chamber development. Endothelial-specific loss of Sox7 function in mice results in cardiac ventricular defects similar to non-compaction cardiomyopathy, with a change in the proportions of trabecular and compact cardiomyocytes in the mutant hearts. This phenotype is paralleled by abnormal coronary artery formation. Loss of Sox7 function disrupts the transcriptional regulation of the Notch pathway and connexins 37 and 40, which govern coronary arterial specification. Upon Sox7 endothelial-specific deletion, single-nuclei transcriptomics analysis identifies the depletion of a subset of Sox9/Gpc3-positive endocardial progenitor cells and an increase in erythro-myeloid cell lineages. Fate mapping analysis reveals that a subset of Sox7-null endothelial cells transdifferentiate into hematopoietic but not cardiomyocyte lineages. Our findings determine that Sox7 maintains cardiac endothelial cell identity, which is crucial to the cellular cross-talk that drives ventricular compaction and coronary artery development.