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OBJECTIVE: Hospitalized children are a potentially underimmunized population. We sought to determine the proportion of patients admitted to our pediatric medicine inpatient units who are underimmunized or unimmunized and to identify barriers to immunization faced by families of children admitted to hospital. METHODS: We conducted a prospective study of children aged 2 months to 18 years admitted to our pediatric medicine inpatient units between July 2021 and October 2022. Immunization and demographic data were collected from electronic medical charts. Immunization status of each child was categorized as up-to-date if they had received all eligible vaccine doses in accordance with the provincial immunization schedule. Caregivers completed a survey on barriers to immunizations; results were compared between caregivers of children whose vaccines were up-to-date and those who were not. RESULTS: Hospitalized children were missing more doses of the preschool vaccines than the general population based on published provincial data. Only 142 of 244 (58.2%) of study patients were up-to-date on all their immunizations. Caregivers of children whose immunizations were not up-to-date reported significantly more barriers to vaccination in all survey categories: access to shots, concerns about shots, and importance of shots. CONCLUSIONS: There is a disparity in immunization status between children admitted to hospital in a Canadian setting compared with national targets and community immunization rates. Caregivers of underimmunized hospitalized children cited significantly more barriers to immunization when compared with hospitalized children who are up-to-date. Pursuing a hospital-based immunization strategy could lead to improved immunization status for hospitalized children.
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Enfant hospitalisé , Humains , Enfant d'âge préscolaire , Nourrisson , Enfant , Mâle , Études prospectives , Femelle , Enfant hospitalisé/statistiques et données numériques , Adolescent , Aidants/statistiques et données numériques , Vaccination/statistiques et données numériques , Immunisation/statistiques et données numériques , Calendrier vaccinal , Hospitalisation/statistiques et données numériques , Canada , Accessibilité des services de santé/statistiques et données numériquesRÉSUMÉ
OBJECTIVE: To describe the characteristics of research training and scholarly activity during pediatrics residency in Canada and identify facilitators and barriers to resident scholarly activity. STUDY DESIGN: We conducted a mixed-methods, cross-sectional survey of pediatrics residents in Canada from April to June 2023. Trainees and medical education experts developed the 55-item survey, pilot tested, and distributed electronically to residents in all 17 Canadian residency programs. Responses were complemented with program-level data from pediatrics residency program directors. RESULTS: Of 644 Canadian pediatrics residents, 230 (36%) responded. Resident respondents conducted various types of scholarly projects, including retrospective clinical study (22%), qualitative research (15%), quality improvement (13%), and medical education research (12%). Discordance between the field of career interests and primary scholarly projects was common. Among respondents, 20% had abstracts accepted at national or international conferences, and 12% had manuscripts submitted to peer-reviewed journals. Resident respondents' self-perceived progress in their scholarly projects were discrepant from their actual progress. Key themes related to barriers and facilitators to scholarly activity included protected time for research, mentorship, and research skills training. CONCLUSIONS: The research training and scholarly activity of pediatrics residents in Canada is variable. Establishing national standards, implementing progress monitoring mechanisms with tailored support, and offering flexible protected research time are important next steps.
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Cardiac fibroblasts are pivotal regulators of cardiac homeostasis and are essential in the repair of the heart after myocardial infarction (MI), but their function can also become dysregulated, leading to adverse cardiac remodelling involving both fibrosis and hypertrophy. MicroRNAs (miRNAs) are noncoding RNAs that target mRNAs to prevent their translation, with specific miRNAs showing differential expression and regulation in cardiovascular disease. Here, we show that miR-214-3p is enriched in the fibroblast fraction of the murine heart, and its levels are increased with cardiac remodelling associated with heart failure, or in the acute phase after experimental MI. Tandem mass tagging proteomics and in-silico network analyses were used to explore protein targets regulated by miR-214-3p in cultured human cardiac fibroblasts from multiple donors. Overexpression of miR-214-3p by miRNA mimics resulted in decreased expression and activity of the Piezo1 mechanosensitive cation channel, increased expression of the entire lysyl oxidase (LOX) family of collagen cross-linking enzymes, and decreased expression of an array of mitochondrial proteins, including mitofusin-2 (MFN2), resulting in mitochondrial dysfunction, as measured by citrate synthase and Seahorse mitochondrial respiration assays. Collectively, our data suggest that miR-214-3p is an important regulator of cardiac fibroblast phenotypes and functions key to cardiac remodelling, and that this miRNA represents a potential therapeutic target in cardiovascular disease.
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Fibroblastes , Canaux ioniques , microARN , microARN/génétique , microARN/métabolisme , Humains , Fibroblastes/métabolisme , Animaux , Souris , Canaux ioniques/métabolisme , Canaux ioniques/génétique , Régulation de l'expression des gènes , Infarctus du myocarde/métabolisme , Infarctus du myocarde/génétique , Infarctus du myocarde/anatomopathologie , Myocarde/métabolisme , Myocarde/cytologie , Myocarde/anatomopathologie , Défaillance cardiaque/génétique , Défaillance cardiaque/métabolisme , Défaillance cardiaque/anatomopathologie , Mitochondries/métabolisme , Mitochondries/génétique , Cellules cultivéesRÉSUMÉ
BACKGROUND: Indigenous Peoples in Canada bear a disproportionate burden of disease and experience poorer health outcomes as compared to non-Indigenous populations within Canada; these conditions are said to be mediated and exacerbated by pervasive and uninterrupted anti-Indigenous racism. Third and fourth-year medical students at a Canadian medical school were asked to reflect on their experiences working with Indigenous patients in clinical settings, and how their preclinical Indigenous health curriculum impacted these experiences. METHOD: Phenomenology was used, guided by Goffman's theory of social stigma. Eleven undergraduate medical students were recruited using purposeful sampling. Semi-structured phone interviews were conducted to gain an in-depth understanding of the participants' experiences. Interviews were recorded and transcribed verbatim. Data were analyzed using the four main processes for phenomenological analysis. RESULTS: Four main themes emerged from students' descriptions of clinical experiences involving Indigenous patients: 1) students describe how their Indigenous patients encounter the health care system and their own lack of cultural sensitivity in this context; 2) racism was evident in students' clinical interactions with Indigenous patients, but students do not always perceive these biases nor the impact of this on patient care; 3) identifying the impact of racism on care is complicated by situational clinical encounters; and 4) practicality of preclinical Indigenous health education is desired by students to prepare them for working with Indigenous patients in the clinical setting. CONCLUSIONS: In their clinical experiences, students witness racism against Indigenous peoples yet are unprepared to stand up against it. Findings highlight the importance of enhancing undergraduate medical training to allow students to better understand the unique experiences and perspectives of Indigenous patients. The results support the need for ongoing Indigenous health education, to foster culturally sensitive experiences while learning about Indigenous patients.
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Racisme , Étudiant médecine , Humains , Étudiant médecine/psychologie , Canada , Racisme/psychologie , Femelle , Mâle , Services de santé pour autochtones/organisation et administration , Compétence culturelle , Entretiens comme sujet , Enseignement médical premier cycle , Recherche qualitative , Peuples autochtones/psychologie , Adulte , Attitude du personnel soignantRÉSUMÉ
OBJECTIVES: 'Early' specialist palliative care (SPC) has been shown to improve outcomes for patients with advanced cancer, yet patients are often referred late. 'Enhanced supportive care' (ESC) aims to facilitate earlier integrated supportive care for those with incurable cancer. This study aimed to explore clinicians' understanding of ESC/SPC delivery through description of current service provision. METHODS: This national cross-sectional survey of 53 cancer centres had two parts. Part 1: Service details, was directed to lead ESC/SPC nurses or consultants about service configuration, and Part 2: Clinician understanding, targeting conceptual understanding of service aims including ESC/SPC teams and oncology consultants (n=262 surveys). Multiple-choice questions explored service provision, referral triggers and evidence of integration with oncology, with free-text responses. Quantitative results were analysed with Fischer's exact test. Qualitative free text was line-by-line coded by two authors independently to derive themes. RESULTS: 56% (30/53) of SPC and ESC teams and 14% (14/100) of oncologists responded. Those involved in ESC self-reported greater integration with oncology compared with non-ESC teams, for example, joint case discussions (64.3%, 9/14 vs 23.1%, 3/13, p=0.05), and timelier patient referral ((>6 months before death vs <6 months) (10/14 vs 4/13, p=0.06)). Qualitative themes described ambiguity in definitions of supportive and palliative terms and a perception of timelier identification of patients when ESC was involved. CONCLUSION: Providers of ESC perceive greater integration with oncology and potentially timelier referral for patients compared with teams not delivering ESC. Terminology around SPC and ESC remains uncertain across England.
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WHAT WAS THE EDUCATIONAL CHALLENGE?: Medical students experience high rates of anxiety; frequent examinations are one contributing source. Students may perceive the observed structured clinical examinations (OSCEs) as particularly stressful. Strategies to reduce anxiety during OSCEs have not been described. WHAT WAS THE SOLUTION?: We sought to implement and evaluate a simple, in-the-moment intervention aimed at reducing students' OSCE-related anxiety by making stress-reducing activities available during break stations during a summative pediatric OSCE. HOW WAS THE SOLUTION IMPLEMENTED?: Three break stations were included in an end-of-rotation, summative OSCE. Students were block-randomized to either control group with standard break stations, or intervention group with stress-reducing activities available in the break room. All participants completed the State-Trait Anxiety Inventory (STAI) before and after the OSCE, and a short questionnaire after OSCE completion. WHAT LESSONS WERE LEARNED THAT ARE RELEVANT TO A WIDER GLOBAL AUDIENCE?: Third-year medical students have high levels of stress before and after OSCEs. More than half of students in the intervention group felt their anxiety improved with activities. While the inclusion of stress-reducing activities in break stations did not impact exam performance, some students subjectively felt their performance improved. If OSCE break stations are logistically required, they can be employed to allow students to briefly relax during a high-stress exam without negatively impacting performance. WHAT ARE THE NEXT STEPS?: Next steps include exploration of opportunities for integration of stress-reducing activities during OSCEs with other learner groups, and identification of other stress-inducing aspects of medical training to provide similar opportunities.
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Anxiété , Évaluation des acquis scolaires , Étudiant médecine , Humains , Étudiant médecine/psychologie , Évaluation des acquis scolaires/méthodes , Stress psychologique , Compétence clinique , Femelle , Mâle , Enseignement médical premier cycleRÉSUMÉ
BACKGROUND: This study explores the impacts of the Council on Medical Student Education in Pediatrics (COMSEP) Journal Club, a unique means of providing monthly professional development for a large international community of pediatric undergraduate medical educators. In particular, we sought to establish member engagement with the Journal Club, identify factors impacting member contributions to the Journal Club, and determine perceived benefits of and barriers to participation as a Journal Club reviewer. METHODS: Using an established Annual Survey as a study instrument, six survey questions were distributed to members of COMSEP. Items were pilot tested prior to inclusion. Quantitative data were analyzed using descriptive statistics and chi-square analysis.. RESULTS: Of 125 respondents who completed the survey, 38% reported reading the Journal Club most months or always. Level of engagement varied. Reasons for reading included a topic of interest, keeping up to date on medical education literature, gaining practical tips for teaching and implementing new curricula. Motivators for writing a review included keeping up to date, contributing to a professional organization, and developing skill in analyzing medical education literature, with a minority citing reasons of enhancing their educational portfolio or academic promotion. The most commonly cited barriers were lack of time and lack of confidence or training in ability to analyze medical education literature. CONCLUSION: As a strategy to disseminate the latest evidence in medical education to its membership, the COMSEP Journal Club is effective. Its format is ideally suited for busy educators and may help in members' professional development and in the development of a community of practice.
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Enseignement médical , Étudiant médecine , Humains , Enfant , Enquêtes et questionnaires , Programme d'études , Processus mentauxRÉSUMÉ
BACKGROUND AND AIMS: The World Health Assembly recommends integration of palliative care into treatment of patients with any life-limiting condition, yet patients with non-malignant disease are less likely to receive specialist palliative care (SPC). This study compares SPC offered to patients with hepatocellular carcinoma (HCC) versus patients with chronic liver disease without HCC (CLD without HCC). METHODS: Patients who died from CLD or HCC over 5 years (2013-2017) in England were identified using a dataset linking national data on all hospital admissions (Hospital Episode Statistics - HES) with national mortality data from the Office for National Statistics (HES - ONS). The primary outcome was the proportion of patients who received inpatient SPC in their last year of life (LYOL). Secondary outcomes were (1) early inpatient SPC input and (2) the proportion dying in a hospice. The outcomes were compared between patients with HCC and CLD without HCC. RESULTS: 29 669 patients were identified, 8143 of whom had HCC. Patients with HCC were significantly more likely to receive inpatient SPC input-adjusted OR 3.74 (95% CI 3.52-3.97) and early inpatient SPC input-adjusted OR 7.26 (95% CI 6.38-8.25) and die in a hospice OR 8.23 (95% CI 7.33-9.24) than patients with CLD without HCC. CONCLUSIONS: These data highlight the stark inequity in access to SPC services between patients with HCC and patients with CLD without HCC in England. Addressing these inequities will improve end-of-life care for patients with CLD.
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Carcinome hépatocellulaire , Accompagnement de la fin de la vie , Tumeurs du foie , Soins terminaux , Humains , Carcinome hépatocellulaire/thérapie , Tumeurs du foie/thérapie , Soins palliatifs , Maladie chroniqueRÉSUMÉ
The origin of embryo implantation in mammals ~148 million years ago was a dramatic shift in reproductive strategy, yet the molecular changes that established mammal implantation are largely unknown. Although progesterone receptor signalling predates the origin of mammals and is highly conserved in, and critical for, successful mammal pregnancy, it alone cannot explain the origin and subsequent diversity of implantation strategies throughout the placental mammal radiation. MiRNAs are known to be flexible and dynamic regulators with a well-established role in the pathophysiology of mammal placenta. We propose that a dynamic core microRNA (miRNA) network originated early in placental mammal evolution, responds to conserved mammal pregnancy cues (e.g. progesterone), and facilitates species-specific responses. Here we identify 13 miRNA gene families that arose at the origin of placental mammals and were subsequently retained in all descendent lineages. The expression of these miRNAs in response to early pregnancy molecules is regulated in a species-specific manner in endometrial epithelia of species with extreme implantation strategies (i.e. bovine and human). Furthermore, this set of miRNAs preferentially target proteins under positive selective pressure on the ancestral eutherian lineage. Discovery of this core embryo implantation toolkit and specifically adapted proteins helps explain the origin and evolution of implantation in mammals.
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microARN , Placenta , Grossesse , Humains , Bovins , Animaux , Femelle , Placenta/métabolisme , Eutheria/génétique , Implantation embryonnaire/génétique , Mammifères/génétique , microARN/génétique , microARN/métabolisme , GénomiqueRÉSUMÉ
BACKGROUND: Surgeons routinely care for patients with life-limiting illness, requiring communication and symptom management skills supported by appropriate training. The objective of this study was to appraise and synthesize studies that assessed surgeon-directed training interventions that aimed to optimize communication and symptom management for patients with life-limiting illness. METHODS: A PRISMA-concordant systematic review was undertaken. MEDLINE, Embase, Allied and Complementary Medicine Database (AMED), and the Cochrane Central Register of Controlled Trials were searched from inception until October 2022 for studies reporting on the evaluation of surgeon-training interventions intending to improve surgeons' communication or symptom management of patients with life-limiting disease. Data on the design, trainer and patient participants, and the intervention were extracted. Risk of bias was assessed. RESULTS: Of 7794 articles, 46 were included. Most studies employed a before-after approach (29 studies) and nine included control groups with five being randomized studies. General surgery was the most frequently included sub-specialty (22 studies). Trainers were described in 25 of 46 studies. Most training interventions aimed to improve communication skills (45 studies) and 13 different training interventions were described. Eight studies reported a measurable improvement in patient care, such as increased documentation of advance care discussions. Most study outcomes focused on surgeons' knowledge (12 studies), skills (21 studies), and confidence/comfort (18 studies) in palliative communication skills. Studies had a high risk of bias. CONCLUSION: Whilst interventions exist to improve the training of surgeons managing patients with life-threatening conditions, evidence is limited, and studies measure the direct impact on patient care insufficiently. Improved research is needed to lead to better methods for training surgeons to benefit patients.
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Communication , Chirurgiens , HumainsRÉSUMÉ
In high income countries, approximately 10% of pregnancies are complicated by pre-eclampsia (PE), preterm birth (PTB), fetal growth restriction (FGR) and/or macrosomia resulting from gestational diabetes (GDM). Despite the burden of disease this places on pregnant people and their newborns, there are still few, if any, effective ways of preventing or treating these conditions. There are also gaps in our understanding of the underlying pathophysiologies and our ability to predict which mothers will be affected. The placenta plays a crucial role in pregnancy, and alterations in placental structure and function have been implicated in all of these conditions. As extracellular vesicles (EVs) have emerged as important molecules in cell-to-cell communication in health and disease, recent research involving maternal- and placental-derived EV has demonstrated their potential as predictive and diagnostic biomarkers of obstetric disorders. This review will consider how placental and maternal EVs have been investigated in pregnancies complicated by PE, PTB, FGR and GDM and aims to highlight areas where further research is required to enhance the management and eventual treatment of these pathologies.
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Diabète gestationnel , Vésicules extracellulaires , Pré-éclampsie , Naissance prématurée , Grossesse , Nouveau-né , Femelle , Humains , Placenta , Retard de croissance intra-utérinRÉSUMÉ
BACKGROUND: Clinical reasoning skills are essential to medical practice. The problem lies in assuming junior medical students with limited experience develop clinical reasoning and decision-making skills passively and solely through clinical exposure. To prepare learners for independent practice and care for future patients, explicit teaching and assessment of clinical reasoning in low-stakes, collaborative learning environments are needed. METHODS: The key-feature question (KFQs) format is an assessment approach that focuses on the reasoning and decision-making aspects of medical problems rather than knowledge recall. This report describes the development, implementation, and evaluation of a team-based learning (TBL) approach using KFQs to foster clinical reasoning in the third-year pediatric clerkship at our institution. RESULTS: Over the first 2 years of implementation (2017-18, 2018-19), 278 students participated in TBL sessions. Mean individual student scores significantly improved in the group setting for both academic years (P < .001). Individual scores were moderately positively correlated with their total summative Objective Structured Clinical Examination score (r[275] = 0.51; P < .001). The correlation between individual score and their multiple-choice question examination was weaker at 0.29 (P < .001) but remained positive. CONCLUSIONS: A TBL session using KFQs to both teach and assess clinical reasoning in clerkship students may help educators identify students with gaps in knowledge and/or reasoning. The next steps include developing and implementing individualized coaching opportunities, and expanding this approach within the undergraduate medical curriculum. Outcome measures to assess clinical reasoning in authentic patient encounters require further research and development.
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We tested the hypothesis that conserved placental mammal-specific microRNAs and their targets facilitate endometrial receptivity to implantation. Expression of miR-340-5p, -542-3p, and -671-5p was regulated by exposure of endometrial epithelial cells to progesterone (10 µg/ml) for 24 h coordinate with 1,713 of their predicted targets. Proteomic analysis of cells transfected with miRNA mimic/inhibitor (48 h: n = 3) revealed 1,745 proteins altered by miR-340-5p (mimic; 1,369, inhibitor; 376) of which 171 were predicted targets and P4-regulated. MiR-542-3p altered 2,353 (mimic; 1,378, inhibitor; 975) 100 which were mirDB predicted, including 46 P4-regulated. MiR-671-5p altered 1,744 proteins (mimic; 1,252, inhibitor; 492) 95 of which were predicted targets and 46 P4-regulated. All miRNAs were detected in luteal phase endometrial biopsies, irrespective of pregnancy outcomes. miR-340-5p expression increased in biopsies from individuals suffering previous and subsequent miscarriage compared to those with subsequent live birth. Dysfunction of these miRNAs and their targets contribute to endometrial-derived recurrent pregnancy loss.
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BACKGROUND: Good end-of-life care is essential to ensure dignity and comfort in death. To our knowledge, there has not been a national population-based study in England of community prescribing of all drugs used in end-of-life care for patients with cancer. METHODS: 57 632 people who died from malignant cancer in their own home or in a care home in 2017 in England were included in this study. National routinely collected data were used to examine community prescriptions dispensed for drugs for symptom control and anticipatory prescribing by key sociodemographic factors in the last 4 months of life. RESULTS: 94% of people who died received drugs to control their symptoms and 65% received anticipatory prescribing. Prescribing increased for the symptom control drug group (53% to 75%) and the anticipatory prescribing group (4% to 52%) over the 4-month period to death. CONCLUSIONS: Most individuals who died of cancer in their own home or a care home were dispensed drugs commonly used to control symptoms at the end of life, as recommended by best-practice guidance. Lower prescribing activity was found for those who died in a care home, highlighting a potential need for improved end-of-life service planning.
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Services de soins à domicile , Tumeurs , Soins terminaux , Humains , Angleterre , Tumeurs/traitement médicamenteux , MortRÉSUMÉ
BACKGROUND: Maternal diabetes mellitus during pregnancy is associated with an increased risk of pregnancy complications for both the mother and the fetus. One of the most prevalent complications is pathological fetal growth, and particularly infants are born large for gestational age (LGA), which leads to problematic deliveries, including the need for caesarean section, instrumental delivery, and further perinatal complications. Glucose monitoring during pregnancy is essential for ensuring appropriate glycaemic control and to reduce these associated risks. The current methods of glucose monitoring include measuring glycosylated haemoglobin (HbA1c), selfmonitoring of capillary blood glucose (SMBG), and more recently, continuous glucose monitoring (CGM). Observational studies and randomised controlled trials (RCTs) have assessed the appropriate glycaemic targets for HbA1c, SMBG, and CGM in relation to pregnancy outcomes. OBJECTIVE: In this review, we have identified current international guidelines on glycaemic targets and reviewed the supporting evidence. METHODS: We performed an extensive literature search on glycaemic targets in pregnancies affected by diabetes, and we researched international guidelines from recognised societies. RESULTS AND CONCLUSION: The majority of studies used to define the glucose targets associated with the best pregnancy outcomes, across all modalities, were in women with type 1 diabetes. There were limited studies on women with type 2 diabetes and gestational diabetes. We, therefore, suggest that further research needs be conducted on glucose targets and clinical outcomes, specifically in these populations where CGM technology offers the greatest potential for monitoring glucose and improving pregnancy outcomes.
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Autosurveillance glycémique , Glycémie , Diabète gestationnel , Régulation de la glycémie , Humains , Femelle , Grossesse , Diabète de type 1/sang , Diabète de type 2/sang , Issue de la grossesse , Autosurveillance glycémique/méthodes , Hémoglobine glyquée , Glycémie/métabolismeRÉSUMÉ
Transitions to roles with increasing clinical responsibility and independence can be anxiety provoking for many trainees. To support our pediatric residents preparing to transition from the role of junior to senior resident, we developed a novel asynchronous online interactive case-based resource. Our experience suggests that this resource was voluntarily utilized and can effectively increase trainee confidence and reduce anxiety about this key transitional stage. We suggest that interactive case-based resources can be utilized as supplemental support for residents preparing for residency transitions in other programs and settings.
La transition vers des rôles comportant des responsabilités cliniques et une autonomie plus importante peut provoquer de l'anxiété pour de nombreux stagiaires. Pour soutenir nos résidents en pédiatrie qui se préparent à passer du rôle de résident junior à celui de résident senior, nous avons créé une nouvelle ressource interactive en ligne, asynchrone, qui est basée sur une étude de cas. Notre expérience suggère que cette ressource a été utilisée sur une base volontaire et qu'elle peut effectivement accroître la confiance des stagiaires et réduire l'anxiété liée à cette étape clé de leur parcours. Nous estimons que les ressources interactives basées sur des cas peuvent être utilisées à titre complémentaire pour aider les résidents à préparer leurs transitions dans d'autres programmes et contextes de résidence.
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OBJECTIVE: We investigated if women with gestational diabetes mellitus (GDM) in the third trimester of pregnancy exhibit adverse cardiac alterations in myocardial energetics, function, or tissue characteristics. RESEARCH DESIGN AND METHODS: Thirty-eight healthy, pregnant women and 30 women with GDM were recruited. Participants underwent phosphorus MRS and cardiovascular magnetic resonance for assessment of myocardial energetics (phosphocreatine [PCr] to ATP ratio), tissue characteristics, biventricular volumes and ejection fractions, left ventricular (LV) mass, global longitudinal shortening (GLS), and mitral in-flow E-wave to A-wave ratio. RESULTS: Participants were matched for age, gestational age, and ethnicity. The following data are reported as mean ± SD. The women with GDM had higher BMI (27 ± 4 vs. 33 ± 5 kg/m2; P = 0.0001) and systolic (115 ± 11 vs. 121 ± 13 mmHg; P = 0.04) and diastolic (72 ± 7 vs. 76 ± 9 mmHg; P = 0.04) blood pressures. There was no difference in N-terminal pro-brain natriuretic peptide concentrations between the groups. The women with GDM had lower myocardial PCr to ATP ratio (2.2 ± 0.3 vs. 1.9 ± 0.4; P < 0.0001), accompanied by lower LV end-diastolic volumes (76 ± 12 vs. 67 ± 11 mL/m2; P = 0.002) and higher LV mass (90 ± 13 vs. 103 ± 18 g; P = 0.001). Although ventricular ejection fractions were similar, the GLS was reduced in women with GDM (-20% ± 3% vs. -18% ± 3%; P = 0.008). CONCLUSIONS: Despite no prior diagnosis of diabetes, women with obesity and GDM manifest impaired myocardial contractility and higher LV mass, associated with reductions in myocardial energetics in late pregnancy compared with lean women with healthy pregnancy. These findings may aid our understanding of the long-term cardiovascular risks associated with GDM.
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Diabète gestationnel , Femelle , Grossesse , Humains , Obésité/complications , Troisième trimestre de grossesse , Coeur , Adénosine triphosphateRÉSUMÉ
SCOPE: During pregnancy, mother-to-fetus transfer of nutrients is mediated by the placenta; sub-optimal placental development and/or function results in fetal growth restriction (FGR), and the attendant risk of stillbirth, neurodevelopmental delay, and non-communicable diseases in adulthood. A maternal diet high in fruit and vegetables lowers the risk of FGR but the association cannot be explained fully by known macro- and micronutrients. METHODS AND RESULTS: This study investigates if dietary-derived extracellular vesicles (EVs) can regulate placental function. The study characterizes the microRNA and protein cargo of EVs isolated from watermelon, show they are actively internalized by human intestinal epithelial cells in vitro, use mass spectrometry to demonstrate that they alter the intestinal secretome and bioinformatic analyses to predict the likely affected pathways in cells/tissues distal to gut. Application of the watermelon EV-modified intestinal secretome to human placental trophoblast cells and ex vivo tissue explants affects the trophoblast proteome and key aspects of trophoblast behavior, including migration and syncytialization. CONCLUSION: Dietary-derived plant EVs can modify intestinal communication with distal tissues, including the placenta. Harnessing the beneficial properties of dietary-derived plant EVs and/or exploiting their potential as natural delivery agents may provide new ways to improve placental function and reduce rates of FGR.