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Polycystic ovary syndrome (PCOS) is the leading cause of anovulatory infertility in women of reproductive age, and obesity can increase the severity and development of the PCOS phenotype. Prenatal testosterone (T) treatment between gestational days 30-90 advanced puberty and disrupted the reproductive and metabolic phenotype in female sheep, recapitulating attributes of women with PCOS, with postnatal obesity amplifying its severity. On the other hand, prenatal T treatment from gestational days 60-90 led to a much milder phenotype. We hypothesized that reproductive neuroendocrine defects programmed by prenatal T treatment between gestational days 60-90 are amplified by postnatal obesity in sheep. Suffolk ewes received T propionate (T; 100 mg) or corn oil (C; vehicle) twice weekly from gestational days 60-90. At 5 months of age, T lambs were assigned to either a maintenance (100% of NRC requirements) or overfed (130% NRC) diet and C lambs were fed the maintenance diet. We compared the timing of puberty (n = 15/group) determined by twice weekly measurement of progesterone concentrations, estradiol positive feedback responsiveness (n = 8/group) determined by assessing LH secretion in response to exogenous estradiol, periovulatory LH dynamics during the second breeding season (n = 8/group) following synchronization with two injections of PGF2α, and progesterone negative feedback (n = 8/group) determined by characterizing LH pulses during the mid-luteal phase between C, T-maintenance and T-overfed groups. Our findings indicate that postnatal obesity: 1) exacerbated reproductive defects and further deteriorated reproductive cyclicity during the second breeding season (adulthood); 2) did not amplify the impairment in estradiol positive feedback in delaying the timing and amplitude of the LH surge, although it reduced the total amount of LH secreted during the preovulatory LH surge; 3) amplified the reduced responsiveness to progesterone negative feedback manifested as an increase in LH pulse amplitude and peak. These observations, in addition to supporting our previous findings that prenatal T treatment results in reproductive neuroendocrine dysfunction and periovulatory disruptions, provide evidence that these neuroendocrine defects programmed between gestational days 60-90 are amplified by postnatal obesity in female sheep.
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Oncogene amplification on extrachromosomal DNA (ecDNA) is a pervasive driver event in cancer, yet our understanding of how ecDNA forms is limited. Here, we couple a CRISPR-based method for ecDNA induction with extensive characterization of newly formed ecDNA to examine their biogenesis. We find that DNA circularization is efficient, irrespective of 3D genome context, with formation of 800kb, 1 Mb, and 1.8 Mb ecDNAs reaching or exceeding 15%. We show non-homologous end joining and microhomology-mediated end joining both contribute to ecDNA formation, while inhibition of DNA-PKcs and ATM have opposing impacts on ecDNA formation. EcDNA and the corresponding chromosomal excision scar can form at significantly different rates and respond differently to DNA-PKcs and ATM inhibition. Taken together, our results support a model of ecDNA formation in which double strand break ends dissociate from their legitimate ligation partners prior to joining of illegitimate ends to form the ecDNA and excision scar.
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Extrachromosomal DNA (ecDNA) is a central mechanism for focal oncogene amplification in cancer, occurring in approximately 15% of early-stage cancers and 30% of late-stage cancers. EcDNAs drive tumor formation, evolution, and drug resistance by dynamically modulating oncogene copy-number and rewiring gene-regulatory networks. Elucidating the genomic architecture of ecDNA amplifications is critical for understanding tumor pathology and developing more effective therapies. Paired-end short-read (Illumina) sequencing and mapping have been utilized to represent ecDNA amplifications using a breakpoint graph, where the inferred architecture of ecDNA is encoded as a cycle in the graph. Traversals of breakpoint graph have been used to successfully predict ecDNA presence in cancer samples. However, short-read technologies are intrinsically limited in the identification of breakpoints, phasing together of complex rearrangements and internal duplications, and deconvolution of cell-to-cell heterogeneity of ecDNA structures. Long-read technologies, such as from Oxford Nanopore Technologies, have the potential to improve inference as the longer reads are better at mapping structural variants and are more likely to span rearranged or duplicated regions. Here, we propose CoRAL (Complete Reconstruction of Amplifications with Long reads), for reconstructing ecDNA architectures using long-read data. CoRAL reconstructs likely cyclic architectures using quadratic programming that simultaneously optimizes parsimony of reconstruction, explained copy number, and consistency of long-read mapping. CoRAL substantially improves reconstructions in extensive simulations and 10 datasets from previously-characterized cell lines as compared to previous short and long-read based tools. As long-read usage becomes wide-spread, we anticipate that CoRAL will be a valuable tool for profiling the landscape and evolution of focal amplifications in tumors.
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This paper presents statistical shape models of the four fingers of the hand, with an emphasis on anatomic analysis of the proximal and distal interphalangeal joints. A multi-body statistical shape modelling pipeline was implemented on an exemplar training dataset of computed tomography (CT) scans of 10 right hands (5F:5M, 27-37 years, free from disease or injury) imaged at 0.3 mm resolution, segmented, meshed and aligned. Model generated included pose neutralisation to remove joint angle variation during imaging. Repositioning was successful; no joint flexion variation was observed in the resulting model. The first principal component (PC) of morphological variation represented phalanx size in all fingers. Subsequent PCs showed variation in position along the palmar-dorsal axis, and bone breadth: length ratio. Finally, the models were interrogated to provide gross measures of bone lengths and joint spaces. These models have been published for open use to support wider community efforts in hand biomechanical analysis, providing bony anatomy descriptions whilst preserving the security of the underlying imaging data and privacy of the participants. The model describes a small, homogeneous population, and assumptions cannot be made about how it represents individuals outside the training dataset. However, it supplements anthropometric datasets with additional shape information, and may be useful for investigating factors such as joint morphology and design of hand-interfacing devices and products. The model has been shared as an open-source repository ( https://github.com/abel-research/OpenHands ), and we encourage the community to use and contribute to it.
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OBJECTIVES: This study aimed to determine whether family poverty over the early childhood, adolescent, and adult periods of the life course independently predicts experiences of intimate partner violence (IPV) in adulthood. STUDY DESIGN: This was a birth cohort study in Brisbane, Australia, with pregnant women recruited at their first booking-in visit and their children, followed up to 30 and 40 years of age. METHODS: Family income was obtained from the mother when the child was 6 months, 5 and 14 years of age. Offspring reported their own family income at 21, 30, and 40 years of age. The offspring completed the Composite Abuse Scale at 30 and 40 years. Adjusted logistic regression models are used to predict experiences of IPV at 30 (n = 2157) and 40 (n = 1438) years. RESULTS: The findings at 30 and 40 years of age are consistent. Only poverty experienced concurrently with the assessment of IPV is strongly associated. At the 40-year follow-up, family poverty predicts higher ratios of all four forms of IPV; severe combined abuse (odds ratio [OR] = 2.24, 95% confidence interval [CI] = 1.24, 4.05), physical abuse (OR = 3.37, 95% CI = 1.95, 5.82), emotional abuse (OR = 2.09, 95% CI = 2.58, 8.57) and harassment (OR = 4.70, 95% CI = 2.58, 8.57). CONCLUSION: Concurrent family poverty is strongly and consistently associated with patterns of IPV. These associations are for cross-sectionally collected data with the prospectively collected data not replicating these findings. Although it is not possible to identify a specific causal pathway, the findings suggest that the immediate consequences of poverty are strongly associated with IPV. Programmes that address poverty reduction provide the best prospect for reducing societal levels of IPV.
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Violência por Parceiro Íntimo , Pobreza , Humanos , Violência por Parceiro Íntimo/estatística & dados numéricos , Violência por Parceiro Íntimo/psicologia , Pobreza/estatística & dados numéricos , Feminino , Adulto , Adolescente , Masculino , Adulto Jovem , Pré-Escolar , Austrália , Lactente , Estudos de Coortes , Criança , Gravidez , Coorte de Nascimento , Fatores de RiscoRESUMO
The current exploratory study examines the impact of the rapid acceleration of telehealth during the COVID-19 pandemic from the perspective of healthcare providers. Understanding provider perspectives, particularly in terms of adaptations made during this critical time, is a useful lens into service innovation in times of crisis and can help elucidate successful strategies for continuing the use of telehealth during the postpandemic period. Fourteen providers from 11 different service agencies in a southeastern state were interviewed. Findings identified three themes: (1) dynamic adaptations enacted by healthcare providers at the onset of the pandemic, such as hybrid services, rapid innovations in workflow, collective decision making among providers, and outreach to educate patients; (2) the relaxation of policies by regulators/insurers, focused most often on reimbursement of services; and (3) how patient engagement was impacted via telehealth, including openness to telehealth, more family-level accessibility, and reduced no-show rates. Implications for social workers include heightened professional training on telehealth as well as increasing the critical role that social workers serve in educating providers and patients on telehealth.
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COVID-19 , Pessoal de Saúde , SARS-CoV-2 , Telemedicina , Humanos , COVID-19/epidemiologia , Pessoal de Saúde/psicologia , Pandemias , Feminino , Entrevistas como Assunto , Masculino , Pesquisa Qualitativa , Acessibilidade aos Serviços de SaúdeRESUMO
Extrachromosomal DNA (ecDNA) is a central mechanism for focal oncogene amplification in cancer, occurring in approximately 15% of early stage cancers and 30% of late-stage cancers. EcDNAs drive tumor formation, evolution, and drug resistance by dynamically modulating oncogene copy-number and rewiring gene-regulatory networks. Elucidating the genomic architecture of ecDNA amplifications is critical for understanding tumor pathology and developing more effective therapies. Paired-end short-read (Illumina) sequencing and mapping have been utilized to represent ecDNA amplifications using a breakpoint graph, where the inferred architecture of ecDNA is encoded as a cycle in the graph. Traversals of breakpoint graph have been used to successfully predict ecDNA presence in cancer samples. However, short-read technologies are intrinsically limited in the identification of breakpoints, phasing together of complex rearrangements and internal duplications, and deconvolution of cell-to-cell heterogeneity of ecDNA structures. Long-read technologies, such as from Oxford Nanopore Technologies, have the potential to improve inference as the longer reads are better at mapping structural variants and are more likely to span rearranged or duplicated regions. Here, we propose CoRAL (Complete Reconstruction of Amplifications with Long reads), for reconstructing ecDNA architectures using long-read data. CoRAL reconstructs likely cyclic architectures using quadratic programming that simultaneously optimizes parsimony of reconstruction, explained copy number, and consistency of long-read mapping. CoRAL substantially improves reconstructions in extensive simulations and 9 datasets from previously-characterized cell-lines as compared to previous short-read-based tools. As long-read usage becomes wide-spread, we anticipate that CoRAL will be a valuable tool for profiling the landscape and evolution of focal amplifications in tumors.
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PURPOSE: To evaluate the domain match (truth) and feasibility of candidate instruments assessing flare in knee and hip osteoarthritis (OA) according to the identified domains. MATERIAL AND METHODS: From a literature review (575 papers), instruments were selected and evaluated using the truth and feasibility elements of the OMERACT Filter 2.2. These were evaluated by 26 experts, including patients, in two Delphi survey rounds. The final selection was obtained by a vote. RESULTS: 44 instruments were identified. In Delphi Round 1, five instruments were selected. In Round 2, all instruments obtained at least 75 % in terms of content match with the endorsed domains and feasibility. In the final selection, the Flare-OA questionnaire obtained 100 % favorable votes. CONCLUSION: Through consensus of the working group, the Flare-OA questionnaire was selected as the best candidate instrument to move into a full assessment of its measurement properties using the OMERACT Filter 2.2.
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Osteoartrite do Quadril , Humanos , Osteoartrite do Quadril/diagnóstico , Estudos de Viabilidade , Articulação do Joelho , ConsensoRESUMO
Invasive primary Candida surgical site infections (IP-SSIs) are a common complication of liver transplantation, and targeted antifungal prophylaxis is an efficient strategy to limit their occurrence. We performed a retrospective single-center cohort study among adult single liver transplant recipients at Duke University Hospital in the period between 1 January 2015 and 31 December 2020. The study aimed to determine the rate of Candida IP-SSI according to the peri-transplant antifungal prophylaxis received. Of 470 adult single liver transplant recipients, 53 (11.3%) received micafungin prophylaxis, 100 (21.3%) received fluconazole prophylaxis, and 317 (67.4%) did not receive systemic antifungal prophylaxis in the peri-transplant period. Ten Candida IP-SSIs occurred among 5 of 53 (9.4%) micafungin recipients, 1 of 100 (1.0%) fluconazole recipients, and 4 of 317 (1.3%) recipients who did not receive antifungal prophylaxis. Our study highlights the limitations of antifungal prophylaxis in preventing invasive Candida IP-SSI after liver transplant surgery. We hypothesize that pathogen, host, and pharmacokinetic-related factors contributed to the occurrence of Candida IP-SSI despite antifungal prophylaxis. Our study reinforces the need for a risk-based, multi-pronged approach to fungal prevention, including targeted antifungal administration in patients with risks for invasive candidiasis and close monitoring, especially among patients with surgically complex procedures, with timely control of surgical leaks.
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Candidíase Invasiva , Candidíase , Transplante de Fígado , Adulto , Humanos , Antifúngicos/uso terapêutico , Fluconazol/uso terapêutico , Transplante de Fígado/efeitos adversos , Micafungina/uso terapêutico , Estudos Retrospectivos , Estudos de Coortes , Infecção da Ferida Cirúrgica/prevenção & controle , Infecção da Ferida Cirúrgica/tratamento farmacológico , Candidíase Invasiva/tratamento farmacológico , Candidíase Invasiva/prevenção & controle , CandidaRESUMO
Objective: As part of the first phase of the OARSI Early-stage Symptomatic Knee Osteoarthritis (EsSKOA) initiative, we explored the first symptoms and experiences recalled by individuals with knee osteoarthritis (OA). Design: This qualitative study, informed by qualitative description, was a secondary analysis of focus groups (n â= â17 groups) and one-on-one interviews (n â= â3) conducted in 91 individuals living with knee OA as part of an international study to better understand the OA pain experience. In each focus group or interview, participants were asked to describe their first symptoms of knee OA. We inductively coded these transcripts and conducted thematic analysis. Results: Mean age of participants was 70 years (range 47-92) and 68 â% were female. We developed four overarching themes: Insidious and Episodic Onset, Diverse Early Symptoms, Must be Something Else, and Adjustments. Participants described the gradual and intermittent way in which symptoms of knee OA developed over many years; many could not identify a specific starting point. Participants described diverse initial knee symptoms, including activity-exacerbated joint pain, stiffness and crepitus. Most participants dismissed early symptoms or rationalized their presence, employing various strategies to enable continued participation in recreational and daily activities. Few sought medical attention until physical functioning was demonstrably impacted. Conclusions: The earliest symptoms of knee OA are frequently insidious in onset, episodic and present long before individuals present to health professionals. These results highlight challenges to identifying people with knee OA early and support the development of specific classification criteria for EsSKOA to capture individuals at an early stage.
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Absolute gamma-ray emission intensities for 36 characteristic gamma rays from the decay of 224Ra, 212Pb, and their progeny were determined by measuring sources calibrated for activity by means of primary methods based on well-defined high-purity germanium (HPGe) detectors at both NIST and NPL. Results from the two laboratories agree with recent data evaluations, except for gamma rays with low emission intensities. The decay schemes have been re-balanced based on the new results. In addition, the half-life for 212Pb was measured using several HPGe detectors, ionization chambers, and a well-type NaI(Tl) detector.
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Oncogene amplification on extrachromosomal DNA (ecDNA) is a pervasive driver event in cancer, yet our understanding of how ecDNA forms is limited. Here, we couple a CRISPR-based method for induction of ecDNA with extensive characterization of newly formed ecDNA to examine ecDNA biogenesis. We find that DNA circularization is efficient, irrespective of 3D genome context, with formation of a 1 Mb and 1.8 Mb ecDNA both reaching 15%. We show non-homologous end joining and microhomology mediated end joining both contribute to ecDNA formation, while inhibition of DNA-PKcs and ATM have opposing impacts on ecDNA formation. EcDNA and the corresponding chromosomal excision scar form at significantly different rates and respond differently to DNA-PKcs and ATM inhibition. Taken together, our results support a model of ecDNA formation in which double strand break ends dissociate from their legitimate ligation partners prior to joining of illegitimate ends to form the ecDNA and excision scar.
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Circular extrachromosomal DNA (ecDNA) in patient tumors is an important driver of oncogenic gene expression, evolution of drug resistance and poor patient outcomes. Applying computational methods for the detection and reconstruction of ecDNA across a retrospective cohort of 481 medulloblastoma tumors from 465 patients, we identify circular ecDNA in 82 patients (18%). Patients with ecDNA-positive medulloblastoma were more than twice as likely to relapse and three times as likely to die within 5 years of diagnosis. A subset of tumors harbored multiple ecDNA lineages, each containing distinct amplified oncogenes. Multimodal sequencing, imaging and CRISPR inhibition experiments in medulloblastoma models reveal intratumoral heterogeneity of ecDNA copy number per cell and frequent putative 'enhancer rewiring' events on ecDNA. This study reveals the frequency and diversity of ecDNA in medulloblastoma, stratified into molecular subgroups, and suggests copy number heterogeneity and enhancer rewiring as oncogenic features of ecDNA.
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Neoplasias Cerebelares , Meduloblastoma , Neoplasias , Humanos , DNA Circular , Meduloblastoma/genética , Estudos Retrospectivos , Neoplasias/genética , Oncogenes , Neoplasias Cerebelares/genéticaRESUMO
Pharmacological interventions for treating posttraumatic stress disorder in Canadian Armed Forces (CAF) members and Veterans often achieve modest results. The field of pharmacogenetics, or the study of how genes influence an individual's response to different medications, offers insight into how prior knowledge of gene-drug interactions may potentially improve the trial-and-error process of drug selection in pharmacotherapy, thereby improving treatment effects and remission rates. Given the relative recency of pharmacogenetics testing and sparse research in military samples, we used pharmacogenetics testing in a small pilot group (n=23) of CAF members and Veterans who were already engaged in pharmacotherapy for a service-related mental health condition to better understand the associated opportunities and challenges of pharmacogenetics testing in this population. Our preliminary evaluation involved: (1) reporting the prevalence of pharmacogenetics testing 'bin' status according to participants' reports ('green', 'yellow' or 'red'; intending to signal 'go', 'caution' or 'stop', regarding the potential for gene-drug interactions); (2) calculating the percentage of currently prescribed psychotropic medications that were assessed and included in the reports; (3) evaluating whether prescribers used pharmacogenetics testing information according to clinical notes and (4) collecting informal feedback from participating psychiatrists. While pharmacogenetics testing appeared to provide valuable information for a number of clients, a major limitation was the number of commonly prescribed medications not included in the reports.
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The chromosomal theory of inheritance has dominated human genetics, including cancer genetics. Genes on the same chromosome segregate together while genes on different chromosomes assort independently, providing a fundamental tenet of Mendelian inheritance. Extrachromosomal DNA (ecDNA) is a frequent event in cancer that drives oncogene amplification, dysregulated gene expression and intratumoral heterogeneity, including through random segregation during cell division. Distinct ecDNA sequences, herein termed ecDNA species, can co-exist to facilitate intermolecular cooperation in cancer cells. However, how multiple ecDNA species within a tumor cell are assorted and maintained across somatic cell generations to drive cancer cell evolution is not known. Here we show that cooperative ecDNA species can be coordinately inherited through mitotic co-segregation. Imaging and single-cell analyses show that multiple ecDNAs encoding distinct oncogenes co-occur and are correlated in copy number in human cancer cells. EcDNA species are coordinately segregated asymmetrically during mitosis, resulting in daughter cells with simultaneous copy number gains in multiple ecDNA species prior to any selection. Computational modeling reveals the quantitative principles of ecDNA co-segregation and co-selection, predicting their observed distributions in cancer cells. Finally, we show that coordinated inheritance of ecDNAs enables co-amplification of specialized ecDNAs containing only enhancer elements and guides therapeutic strategies to jointly deplete cooperating ecDNA oncogenes. Coordinated inheritance of ecDNAs confers stability to oncogene cooperation and novel gene regulatory circuits, allowing winning combinations of epigenetic states to be transmitted across cell generations.
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Extrachromosomal DNAs (ecDNAs) are common in cancer, but many questions about their origin, structural dynamics and impact on intratumor heterogeneity are still unresolved. Here we describe single-cell extrachromosomal circular DNA and transcriptome sequencing (scEC&T-seq), a method for parallel sequencing of circular DNAs and full-length mRNA from single cells. By applying scEC&T-seq to cancer cells, we describe intercellular differences in ecDNA content while investigating their structural heterogeneity and transcriptional impact. Oncogene-containing ecDNAs were clonally present in cancer cells and drove intercellular oncogene expression differences. In contrast, other small circular DNAs were exclusive to individual cells, indicating differences in their selection and propagation. Intercellular differences in ecDNA structure pointed to circular recombination as a mechanism of ecDNA evolution. These results demonstrate scEC&T-seq as an approach to systematically characterize both small and large circular DNA in cancer cells, which will facilitate the analysis of these DNA elements in cancer and beyond.
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Neoplasias , Transcriptoma , Humanos , Transcriptoma/genética , DNA , Neoplasias/genética , Oncogenes , DNA Circular/genéticaRESUMO
Conducting comprehensive but efficient literature searches for complex evidence syntheses involves selecting databases that will retrieve the greatest number of relevant results on the question. Lack of a comprehensive single database on allied health educational topics challenges those seeking such literature. In this study, six participants contributed research questions on instructional methods and materials for allied health patients, caregivers, and future health professionals. Two health sciences librarians created search strategies for these questions and searched eleven databases. Both the librarians and the six participants evaluated the search results using a rubric based on PICO to assess extent of alignment between the librarians' and requestors' relevance judgments. Intervention, Outcome, and Assessment Method constituted the most frequent bases for assessments of relevance by both librarians and participants. The librarians were more restrictive in all of their assessments except in a preliminary search yielding twelve citations without abstracts. The study's results could be used to identify effective techniques for reference interviewing, selecting databases, and weeding search results.
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Bibliotecários , Medicina , Humanos , Pessoal de SaúdeRESUMO
Recombinant adeno-associated viral vectors (rAAVs) are among the most commonly used vehicles for in vivo based gene therapies. However, it is hard to predict which AAV capsid will provide the most robust expression in human subjects due to the observed discordance in vector-mediated transduction between species. In our study, we use a primate specific capsid, AAV-LK03, to demonstrate that the limitation of this capsid towards transduction of mouse cells is unrelated to cell entry and nuclear transport but rather due to depleted histone H3 chemical modifications related to active transcription, namely H3K4me3 and H3K27ac, on the vector DNA itself. A single-amino acid insertion into the AAV-LK03 capsid enables efficient transduction and the accumulation of active-related epigenetic marks on the vector chromatin in mouse without compromising transduction efficiency in human cells. Our study suggests that the capsid protein itself is involved in driving the epigenetic status of the vector genome, most likely during the process of uncoating. Programming viral chromatin states by capsid design may enable facile DNA transduction between vector and host species and ultimately lead to rational selection of AAV capsids for use in humans.
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Proteínas do Capsídeo , Capsídeo , Humanos , Camundongos , Animais , Capsídeo/metabolismo , Proteínas do Capsídeo/genética , Proteínas do Capsídeo/metabolismo , Transdução Genética , Dependovirus/metabolismo , Vetores Genéticos/genética , Cromatina/genética , Cromatina/metabolismo , Epigênese GenéticaRESUMO
OBJECTIVE: Preeclampsia is a leading cause of pregnancy-related deaths. Up to 60% of maternal deaths associated with preeclampsia may be prevented. Clinical trials have shown that low-dose aspirin reduces preeclampsia up to 30% among women at increased risk. Since 2014, multiple professional societies and the U.S. Preventive Services Task Force have released guidelines on the use of low-dose aspirin to reduce the risk of preeclampsia. We aimed to evaluate physician's knowledge and practices surrounding low-dose aspirin for preeclampsia risk reduction. STUDY DESIGN: We distributed an anonymous electronic survey to licensed physicians in the Rio Grande Valley of Texas who provide prenatal care, including general obstetrician-gynecologists, maternal fetal medicine subspecialists, and family medicine physicians. The survey consisted of 20 items assessing demographics, provider practices, and knowledge on the use of low-dose aspirin for preeclampsia risk reduction. RESULTS: We received 48 surveys with a response rate of 55%. More than 90% of physicians reported recommending low-dose aspirin for preeclampsia risk reduction, of which 98% correctly identified the dose. Of the physicians recommending aspirin, 83% initiate dosing between 12 and 16 weeks, but only 52% continue it until the day of delivery. Nearly 80% of respondents identified that one high-risk factor for preeclampsia is an indication for prophylaxis, but only 56% identified that two or more moderate risk factors should prompt aspirin recommendation. CONCLUSION: Despite clear professional guidelines, physicians demonstrated gaps in knowledge and differences in practices. Enhancing screening tools to assess patient's risk of developing preeclampsia and tailored medical education on moderate risk factors are needed to identify patients who may benefit from this intervention. Increasing the use of aspirin in patients at risk is critical given the benefits of low-dose aspirin in the reduction of poor maternal and neonatal outcomes related to preeclampsia. KEY POINTS: · Low-dose aspirin reduces preeclampsia in patients up to 30%.. · Physicians have gaps in knowledge despite guidelines.. · Following guidelines reduces poor outcomes associated with preeclampsia..