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OBJECTIVE: Understanding and quantifying biases when designing and implementing actionable approaches to increase fairness and inclusion is critical for artificial intelligence (AI) in biomedical applications. METHODS: In this Special Communication, we discuss how bias is introduced at different stages of the development and use of AI applications in biomedical sciences and health care. We describe various AI applications and their implications for fairness and inclusion in sections on 1) Bias in Data Source Landscapes, 2) Algorithmic Fairness, 3) Uncertainty in AI Predictions, 4) Explainable AI for Fairness and Equity, and 5) Sociological/Ethnographic Issues in Data and Results Representation. RESULTS: We provide recommendations to address biases when developing and using AI in clinical applications. CONCLUSION: These recommendations can be applied to informatics research and practice to foster more equitable and inclusive health care systems and research discoveries.
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BACKGROUND: Offspring of hypertensive disorders of pregnancy are at an increased risk of developing neurodevelopmental and neurobehavioral disorders compared to offspring from non-affected pregnancies. Using rodent models of Preeclampsia (PreE; new onset of hypertension after 20 weeks gestation) and HELLP (hemolysis, elevated liver enzymes, and low platelets), we studied the behavioral outcome of their offspring in adolescence. METHODS: A subset of dams received Orencia, a T-cell activation inhibitor, as T cells have been associated with the induction of hypertension and inflammation during pregnancy. We hypothesized that offspring from hypertensive dams would experience adverse behavioral outcomes in social, cognitive, locomotor, and anxiety tests, and offspring from dams treated with Orencia would demonstrate less adverse behaviors. RESULTS: Male offspring of PreE + Orencia dams (p < 0.05) and female offspring from HELLP + Orencia dams (p < 0.05) spent more time playing compared to normal pregnant offspring. All offspring from hypertensive and Orencia-treated dams performed worse on the Barnes Maze test compared to normal pregnant. We also measured adult (postnatal day > 60) myelin basic protein (MBP) and NeuN expression in both the prefrontal cortex and hippocampus. In the hippocampus and prefrontal cortex, there was no difference in expression of either MBP or NeuN in all groups regardless of sex. CONCLUSION: The results from this study suggest that offspring of hypertensive disorders of pregnancy have behavioral changes, specifically cognitive differences. This study has shown that there is a sex dependent difference in offspring neurobehavioral development, influenced in part by the type of hypertensive disorder of pregnancy, and alterations in the maternal immune system.
Children of pregnancies that are complicated by hypertensive disorders of pregnancy (HDP) such as Preeclampsia and HELLP (hemolysis, elevated liver enzymes, and low platelets) syndrome have an increased risk of having behavioral deficits and changes in brain development. Both Preeclampsia and HELLP have been shown to activate the immune and inflammation systems in the body of the mother. In this study, we used offspring of rat models of Preeclampsia and HELLP to study their behavior including anxiety-like behaviors and memory deficits. We also compared offspring of rat models of Preeclampsia and HELLP that were given Orencia, which minimizes immune responses by blocking the activation of T cells. We also studied two regions of the brain (prefrontal cortex and hippocampus) to measure two proteins (myelin basic protein (MBP) and NeuN) involved in brain function. Our study found that offspring from dams that were treated with Orencia during pregnancy with HDP had sex differences in time playing. All offspring, regardless of the HDP dam being treated with or without Orencia, had evidence of spatial learning deficits. When sexes and groups were compared there was no difference in MBP or NeuN expression in the prefrontal cortex or hippocampus.
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Síndrome HELLP , Hipertensão Induzida pela Gravidez , Pré-Eclâmpsia , Gravidez , Humanos , Masculino , Feminino , Abatacepte , HipocampoRESUMO
BACKGROUND: Patient portals play an increasingly critical role in engaging patients in their health care. They have the potential to significantly impact the health of those living with chronic diseases, such as HIV, for whom consistent care engagement is both critical and complex. OBJECTIVE: The primary aim was to examine the longitudinal relationships between individual portal tool use and health-related outcomes in patients living with HIV. DESIGN: Retrospective cohort study using electronic health record data to examine the relationship between patient portal tool use and key HIV-specific, health-related outcomes in patients engaged in care in the Veterans Health Administration (VA) through the application of marginal structural models. PARTICIPANTS: A national sample of patients living with HIV (PLWH) active in VA care who were registered to use the VA's patient portal, My HealtheVet (MHV; n = 18,390) between 10/1/2012 and 4/1/2017. MAIN MEASURES: The MHV tools examined were prescription refill (including prescription refill of an antiretroviral (ART) medication and any medication), secure messaging, view appointments, and view labs. Primary outcomes were viral load test receipt, viral load suppression, and ART medication adherence (measured as proportion of days covered). KEY RESULTS: The use of prescription refill for any medication or for ART was positively associated with ART adherence. Secure messaging was positively associated with ART adherence but not with viral load test receipt or viral load suppression. The use of view appointments was positively associated with ART adherence and viral load test receipt but not viral load suppression. The use of view labs was positively associated with viral load suppression but not ART adherence or viral load test receipt. CONCLUSIONS: These findings highlight the valuable role patient portals may play in improving health-related outcomes among PLWH and have implications for patients living with other types of chronic disease.
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Fármacos Anti-HIV , Infecções por HIV , Portais do Paciente , Comportamento de Utilização de Ferramentas , Humanos , Fármacos Anti-HIV/uso terapêutico , Estudos Retrospectivos , Carga Viral , Infecções por HIV/tratamento farmacológico , Adesão à MedicaçãoRESUMO
INTRODUCTION: The Veterans Health Administration (VHA) distributes video-enabled tablets to individuals with barriers to accessing care. Data suggests that many tablets are under-used. We surveyed Veterans who received a tablet to identify barriers that are associated with lower use, and evaluated the impact of a telephone-based orientation call on reported barriers and future video use. METHODS: We used a national survey to assess for the presence of 13 barriers to accessing video-based care, and then calculated the prevalence of the barriers stratified by video care utilization in the 6 months after survey administration. We used multivariable modeling to examine the association between each barrier and video-based care use and evaluated whether a telephone-based orientation modified this association. RESULTS: The most prevalent patient-reported barriers to video-based care were not knowing how to schedule a visit, prior video care being rescheduled/canceled, and past problems using video care. Following adjustment, individuals who reported vision or hearing difficulties and those who reported that video care does not provide high-quality care had a 19% and 12% lower probability of future video care use, respectively. Individuals who reported no interest in video care, or did not know how to schedule a video care visit, had an 11% and 10% lower probability of being a video care user, respectively. A telephone-based orientation following device receipt did not improve the probability of being a video care user. DISCUSSION: Barriers to engaging in virtual care persist despite access to video-enabled devices. Targeted interventions beyond telephone-based orientation are needed to facilitate adoption and engagement in video visits.
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Telemedicina , Veteranos , Humanos , Saúde dos Veteranos , Inquéritos e Questionários , ComprimidosRESUMO
INTRODUCTION: This is the first North American clinical evidence for MV140, a novel bacterial sublingual vaccine, developed for prevention of recurrent urinary tract infection (UTI) in women. METHODS: Female subjects with ≥3 documented UTIs/year underwent three-month vaccination treatment, nine-month efficacy period, and optional three-month followup (total 15 months). Primary outcome was no clinically diagnosed UTI following vaccination (UTI-free rate). Secondary outcomes included absolute, mean, and median overall reduction in UTI compared to pre-vaccination, quality of life, global response assessment, patient satisfaction, microbiology, and safety. RESULTS: Sixty-seven subjects (mean age 56 years, range 18-80) were enrolled; 64 completed the vaccination period and at least one post-vaccination assessment. Prior to vaccination, subjects reported a mean 6.8 UTIs/year. The UTI-free rate for the nine-month efficacy period was 40.6%. Compared to the infection rate in the year prior to vaccination, the reduction was 75.3% for the nine-month efficacy period post-vaccination. At 12-month followup, 80.3% reported that they were moderately/markedly improved; 58.1% were mostly satisfied, pleased, or delighted, while mean quality of life score improved by 1.5 points. Fourteen of the adverse events in nine subjects were potentially related to the vaccine - all mild and resolved by three months. None of the 13 serious adverse events were related to vaccine. CONCLUSIONS: This first-in-North-America, prospective case series with the sublingual vaccine, MV140, adds further clinical evidence to its safety and effectiveness in reducing recurrent UTIs in women.
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BACKGROUND: Concerns around opioid safety for patients living with chronic pain have led to a growing number of collaborative and multimodal pain care initiatives. A major challenge in these efforts has been identifying and engaging patients on high-risk opioid regimens in a timely manner. OBJECTIVES: In this clinical informatics case report, we describe the development and implementation of a web-based tool to support providers as they implement an integrated pain support clinical initiative at primary care clinics across three health care systems. METHODS: The tool identifies patients on risky opioid medication regimens and generates autopopulated patient outreach letters. It contains three core functions that: (1) identify patients prescribed high-dose opioids or coprescribed opioids and benzodiazepines, (2) generate automated letters for patients with an upcoming primary care appointment, and (3) allow clinic staff to write back to a database to track outreach and referrals. Qualitative stakeholder feedback was gathered through interviews and user testing to assess perceived usefulness and ease of use of the tool. RESULTS: Over a 24-month period, the tool identified 1,125 patients prescribed risky medication regimens and generated 1,315 total letters as some patients became reeligible. Stakeholder feedback revealed that the tool was useful to quickly find patients on risky medication regimens and efficient in generating prepopulated letters that could be mailed in large batches. Additional feedback led to iterative refinements and improved system capabilities that varied across clinics. CONCLUSION: Deploying clinical informatics tools that prioritize, engage, and track high-risk patient populations supports reduction of risky medication regimens. Such tools can reduce workload burden on busy primary care staff, particularly during implementation studies, and enhance patient-centered care through the use of direct-to-consumer outreach.
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Analgésicos Opioides , Dor Crônica , Humanos , Analgésicos Opioides/uso terapêutico , Assistência Centrada no PacienteRESUMO
The binding of viral RNA to RIG-I-like receptors triggers the formation of mitochondrial antiviral signaling (MAVS) protein aggregates critical for interferon (IFN) expression. Several rotavirus strains have been shown to suppress IFN expression by inducing MAVS degradation. Relying on transient expression assays, previous studies reached different conclusions regarding the identity of the rotavirus protein responsible for MAVS degradation, suggesting it was an activity of the rotavirus capping enzyme VP3 or the interferon antagonist NSP1. Here, we have used recombinant SA11 rotaviruses to identify the endogenous viral protein responsible for MAVS degradation and to analyze how the attack on MAVS impacts IFN expression. The recombinant viruses included those expressing modified VP3 or NSP1 proteins deficient in the ability to induce the degradation of MAVS or interferon regulatory factor-3 (IRF3), or both. With these viruses, we determined that VP3 directs the proteasomal degradation of MAVS but plays no role in IRF3 degradation. Moreover, NSP1 was determined to induce IRF3 degradation but to have no impact on MAVS degradation. Analysis of rotavirus-infected cells indicated that IRF3 degradation was more efficient than MAVS degradation and that NSP1 was primarily responsible for suppressing IFN expression in infected cells. However, VP3-mediated MAVS degradation contributed to IFN suppression in cells that failed to produce functional NSP1, pointing to a subsidiary role for VP3 in the IFN antagonist activity of NSP1. Thus, VP3 is a multifunctional protein with several activities that counter anti-rotavirus innate immune responses, including capping of viral (+)RNAs, hydrolysis of the RNase L 2-5A (2'-5' oligoadenylate) signaling molecule, and proteasomal degradation of MAVS. IMPORTANCE Rotavirus is an enteric RNA virus that causes severe dehydrating gastroenteritis in infants and young children through infection of enterocytes in the small intestine. Timely clearance of the virus demands a robust innate immune response by cells associated with the small intestine, including the expression of interferon (IFN). Previous studies have shown that some rotavirus strains suppress the production of interferon, by inducing the degradation of mitochondrial antiviral signaling (MAVS) protein and interferon regulatory factor-3 (IRF3). In this study, we have used reverse genetics to generate recombinant rotaviruses expressing compromised forms of VP3 or NSP1, or both, to explore the function of these viral proteins in the degradation of MAVS and IRF3. Our results demonstrate that VP3 is responsible for MAVS depletion in rotavirus-infected cells, and through this activity, helps to suppress IFN production. Thus, VP3 functions to support the activity of rotavirus NSP1, the major interferon antagonist of the virus.
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Objectives: Health-related chatbots have demonstrated early promise for improving self-management behaviors but have seldomly been utilized for hypertension. This research focused on the design, development, and usability evaluation of a chatbot for hypertension self-management, called "Medicagent." Materials and Methods: A user-centered design process was used to iteratively design and develop a text-based chatbot using Google Cloud's Dialogflow natural language understanding platform. Then, usability testing sessions were conducted among patients with hypertension. Each session was comprised of: (1) background questionnaires, (2) 10 representative tasks within Medicagent, (3) System Usability Scale (SUS) questionnaire, and (4) a brief semi-structured interview. Sessions were video and audio recorded using Zoom. Qualitative and quantitative analyses were used to assess effectiveness, efficiency, and satisfaction of the chatbot. Results: Participants (n = 10) completed nearly all tasks (98%, 98/100) and spent an average of 18 min (SD = 10 min) interacting with Medicagent. Only 11 (8.6%) utterances were not successfully mapped to an intent. Medicagent achieved a mean SUS score of 78.8/100, which demonstrated acceptable usability. Several participants had difficulties navigating the conversational interface without menu and back buttons, felt additional information would be useful for redirection when utterances were not recognized, and desired a health professional persona within the chatbot. Discussion: The text-based chatbot was viewed favorably for assisting with blood pressure and medication-related tasks and had good usability. Conclusion: Flexibility of interaction styles, handling unrecognized utterances gracefully, and having a credible persona were highlighted as design components that may further enrich the user experience of chatbots for hypertension self-management.
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Rates of pregnancy-related acute kidney injury (PR-AKI) have increased in the U.S over the past two decades, but how PR-AKI affects the blood-brain barrier (BBB) is understudied. AKI is associated with increased amounts of uremic toxins, like indoxyl sulfate (I.S), whose chronic administration leads to BBB and cognitive changes. This study's objective was to determine if (1) PR-AKI increases I.S and (2) if administration of I.S during pregnancy elicits renal injury and/or increases BBB permeability. From gestational day (GD) 11 to GD19, Sprague Dawley rats were given either 100 or 200 mg/kg body-weight dose of I.S. PR-AKI was induced on GD18 via 45 min bilateral renal ischemic reperfusion surgery. On GD18, metabolic cage metrics and metabolic waste was collected and on GD19 blood pressure, and BBB permeability (by Evan's Blue infusion) were measured. I.S and creatinine were measured in both urine and circulation, respectively. One-way ANOVA or student t-tests were performed using GraphPad Prism with a p < 0.05 significance. I.S and PR-AKI led to oliguria. I.S administration led to increased BBB permeability compared to normal pregnant and PR-AKI animals. These results suggest that I.S administration during pregnancy leads to increased BBB permeability and evidence of renal injury comparable to PR-AKI animals.
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Injúria Renal Aguda , Barreira Hematoencefálica , Ratos , Gravidez , Animais , Feminino , Barreira Hematoencefálica/metabolismo , Ratos Sprague-Dawley , Indicã/metabolismo , Rim/metabolismo , PermeabilidadeRESUMO
Rapid development and adoption of natural language processing (NLP) techniques has led to a multitude of exciting and innovative societal and health care applications. These advancements have also generated concerns around perpetuation of historical injustices and that these tools lack cultural considerations. While traditional health care NLP techniques typically include clinical subject matter experts to extract health information or aid in interpretation, few NLP tools involve community stakeholders with lived experiences. In this perspective paper, we draw upon the field of community-based participatory research, which gathers input from community members for development of public health interventions, to identify and examine ways to equitably involve communities in developing health care NLP tools. To realize the potential of community-based NLP (CBNLP), research and development teams must thoughtfully consider mechanisms and resources needed to effectively collaborate with community members for maximal societal and ethical impact of NLP-based tools.
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Pesquisa Participativa Baseada na Comunidade , Processamento de Linguagem Natural , HumanosRESUMO
BACKGROUND: Chlorate is an effective herbicide, but also a byproduct of chlorinating agents used to disinfect water, which is one of the reasons why it is regularly found in food. Perchlorate is a ubiquitous contaminant, which is naturally occurring in the environment but also released from anthropogenic sources such as the industrial use of certain natural fertilizers. Chlorate affects the hematological system, and perchlorate the thyroid. OBJECTIVE: Implement and validate a simple and robust analytical method for the accurate determination of chlorate and perchlorate in baby food, infant and adult formulas, and ingredients thereof, which is suited for its application in routine environments where a broad variety of food commodities must be analyzed simultaneously. METHOD: Typically, analytes are extracted with a mixture of water, acidified methanol, and dichloromethane. Optionally, for dairy products and byproducts, extraction can be performed with water, acidified methanol, and EDTA, followed by two steps of cleanup (freezing out and dispersive solid-phase extraction with C18 in acetonitrile). Quantitative determination is carried out by isotopic dilution liquid chromatography tandem mass spectrometry (LC-MS/MS). RESULTS: The method was single-laboratory validated in five Nestlé Quality Assurance Centers (NQACs) in a comprehensive range of representative matrixes of different categories such as baby foods, infant/adult formulas, and ingredients, with results generally in agreement with the acceptance criteria of the Standard Method Performance Requirement (SMPR®) 2021.001 defined by AOAC INTERNATIONAL, in terms of representative matrixes validated, LOQs, trueness, and precision.The data generated during validation show that the method proposed is simple, accurate and robust enough to be implemented and applied in routine environments. CONCLUSION: The data generated during validation show that the method proposed is simple, accurate and robust enough to be implemented and applied in routine environments. HIGHLIGHTS: The AOAC Expert Review Panel approved the present method as AOAC Official First Action 2022.06.
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Cloratos , Espectrometria de Massas em Tandem , Humanos , Lactente , Adulto , Cromatografia Líquida/métodos , Cloratos/análise , Percloratos/análise , Metanol , Fórmulas Infantis/análise , Água , Cromatografia Líquida de Alta PressãoRESUMO
To enable the monitoring of a wide scope of per- and polyfluoroalkyl substances (PFAS) in the ng/kg level in foodstuffs, an LC-MS/MS method comprising 57 analytes was developed and validated in seven different matrices (milk powder, milk-based infant formula, meat-based baby food puree, fish and fish oil, fresh egg, and soluble coffee). The analytical approach was based on an acetonitrile:water extraction followed by solid phase extraction clean-up with subsequent quantification of the extracted analytes either by isotope dilution (55 compounds) or by standard addition (2 compounds) mass spectrometry. The validation criteria followed the guidance document for the analysis of PFAS issued by the European Union Reference Laboratory for Halogenated Persistent Organic Pollutants. The lowest limits of quantification (LOQs) for the four recently regulated compounds (L-PFOS, PFOA, PFNA, L-PFHxS) were set at 0.010 µg/kg in baby and infant foods (as sold) but also in dairy ingredients. Exception was for PFOA in milk powder due to too large variability in the repeatability. Applicability of the method was further demonstrated in 37 commodity check matrices. Overall validation data demonstrated the robustness of the method for most of the compounds and the LOQs achieved were low enough to ensure compliance with Commission Regulation EU 2022/2388 but also to support future collection of occurrence data in ng/kg level in food.
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Fluorocarbonos , Espectrometria de Massas em Tandem , Animais , Cromatografia Líquida , Pós/análise , Leite/química , Fórmulas Infantis/análise , Fluorocarbonos/análiseRESUMO
Smartphone devices capable of monitoring users' health, physiology, activity, and environment revolutionize care delivery, medical research, and remote patient monitoring. Such devices, laden with clinical-grade sensors and cloud connectivity, allow clinicians, researchers, and patients to monitor health longitudinally, passively, and persistently, shifting the paradigm of care and research from low-resolution, intermittent, and discrete to one of persistent, continuous, and high resolution. The collection, transmission, and storage of sensitive health data using mobile devices presents unique challenges that serve as significant barriers to entry for care providers and researchers alike. Compliance with standards like HIPAA and GDPR requires unique skills and practices. These requirements make off-the-shelf technologies insufficient for use in the digital health space. As a result, budget, timeline, talent, and resource constraints are the largest barriers to new digital technologies. The CardinalKit platform is an open-source project addressing these challenges by focusing on reducing these barriers and accelerating the innovation, adoption, and use of digital health technologies. CardinalKit provides a mobile template application and web dashboard to enable an interoperable foundation for developing digital health applications. We demonstrate the applicability of CardinalKit to a wide variety of digital health applications across 18 innovative digital health prototypes.
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A novel method was implemented in the Interprofessional education (IPE) program, which incorporated a Simulated-Avatar© case presentation preceding the virtual breakout segments. Simulated real-time clinical interactions replaced the in-person encounters, leading to the translation of the participants' basic science knowledge of pathophysiology and pharmacology (P&P) into effective treatment of the patient-avatar's condition.
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With the numerous advances and broad applications of mobile health (mHealth), establishing concrete data sharing, privacy, and governance strategies at national (or regional) levels is essential to protect individual privacy and data usage. This article applies the recent Health Data Governance Principles to provide a guiding framework for low- and middle-income countries (LMICs) to create a comprehensive mHealth data governance strategy. We provide three objectives: (1) establish data rights and ownership to promote equitable benefits from health data, (2) protect people through building trust and addressing patients' concerns, and (3) promote health value by enhancing health systems and services. We also recommend actions for realizing each objective to guide LMICs based on their unique mHealth data ecosystems. These objectives require adopting a regulatory framework for data rights and protection, building trust for data sharing, and enhancing interoperability to use new datasets in advancing healthcare services and innovation.
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Privacidade , Telemedicina , Humanos , Países em Desenvolvimento , Promoção da Saúde , Ecossistema , Disseminação de InformaçãoRESUMO
Objective: Understanding the current state of real-world Fast Healthcare Interoperability Resources (FHIR) applications (apps) will benefit biomedical research and clinical care and facilitate advancement of the standard. This study aimed to provide a preliminary assessment of these apps' clinical, technical, and implementation characteristics. Materials and Methods: We searched public repositories for potentially eligible FHIR apps and surveyed app implementers and other stakeholders. Results: Of the 112 apps surveyed, most focused on clinical care (74) or research (45); were implemented across multiple sites (56); and used SMART-on-FHIR (55) and FHIR version R4 (69). Apps were primarily stand-alone web-based (67) or electronic health record (EHR)-embedded (51), although 49 were not listed in an EHR app gallery. Discussion: Though limited in scope, our results show FHIR apps encompass various domains and characteristics. Conclusion: As FHIR use expands, this study-one of the first to characterize FHIR apps at large-highlights the need for systematic, comprehensive methods to assess their characteristics.
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OBJECTIVE: Examine whether distribution of tablets to patients with access barriers influences their adoption and use of patient portals. MATERIALS AND METHODS: This retrospective cohort study included Veterans Affairs (VA) patients (n = 28â659) who received a VA-issued tablet between November 1, 2020 and April 30, 2021. Tablets included an app for VA's My HealtheVet (MHV) portal. Veterans were grouped into 3 MHV baseline user types (non-users, inactive users, and active users) based on MHV registration status and feature use pre-tablet receipt. Three multivariable models were estimated to examine the factors predicting (1) MHV registration among non-users, (2) any MHV feature use among inactive users, and (3) more MHV use among active users post-tablet receipt. Differences in feature use during the 6 months pre-/post-tablet were examined with McNemar chi-squared tests of proportions. RESULTS: In the 6 months post-tablet, 1298 (8%) non-users registered for MHV, 525 (24%) inactive users used at least one MHV feature, and 4234 (46%) active users increased feature use. Across veteran characteristics, there were differences in registration and feature use post-tablet, particularly among older adults and those without prior use of video visits (P < .01). Among active users, use of all features increased during the 6 months post-tablet, with the greatest differences in viewing prescription refills and scheduling appointments (P < .01). CONCLUSION: Providing patients who experience barriers to in-person care with a portal-enabled device supports engagement in health information and management tasks. Additional strategies are needed to promote registration and digital inclusion among inactive and non-users of portals.
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Portais do Paciente , Veteranos , Humanos , Idoso , Estudos Retrospectivos , ComprimidosRESUMO
Mental health disorders such as anxiety and/or depression are the most common mental health disorders seen among reproductive aged women and can increase during pregnancy. Many sociodemographic risk factors have been associated with anxiety and/or depression in pregnancy, which can lead to adverse maternal and infant outcomes including the risk of a hypertensive pregnancy. The current study prospectively examined self-reported anxiety, depression and stress in pregnant women without a history of fetal loss or mood disorders beginning at 20-26 weeks. At each study visit, circulating immune factors associated with perinatal mood disorders were measured in blood samples that were collected. A total of 65 women were eligible for data analysis, 26 of which had hypertensive pregnancies. There was not a significant difference in self-reported depression, anxiety or stress between hypertensive disorders of pregnancy and normotensive women. Black women were more likely to have a hypertensive pregnancy and develop a perinatal mood disorder compared to non-black women. Both the inflammatory cytokines interleukin-17 and tumor necrosis factor-alpha were increased in patients with perinatal mood disorders. However, additional research is needed in a larger sample to truly understand the relationship between these factors along with the underlying etiologies and the associated outcomes.
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PURPOSE OF REVIEW: It is well established that controlled immune activation and balance is critical for women's reproductive health and successful pregnancy outcomes. Research in recent decades in both clinical and animal studies has demonstrated that aberrant immune activation and inflammation play a role in the development and progression of women's reproductive health and pregnancy-related disorders. Inflammasomes are multi-protein cytoplasmic complexes that mediate immune activation. In this review, we summarize current knowledge on the role of inflammasome activation in pregnancy-related disorders. RECENT FINDINGS: Increased activation of inflammasome is associated with multiple women's health reproductive disorders and pregnancy-associated disorders, including preeclampsia (PreE). Inflammasome activation is also associated with the novel coronavirus disease 2019 (COVID-19) disease caused by the SARS-Cov-2 virus. We and others have observed a positive association between increased PreE incidences with the onset of the COVID-19 pandemic. Here, we present our recent data indicating increased inflammasome activation, represented by caspase-1 activity, in women with COVID-19 and PreE compared to normotensive pregnant women COVID-19. The role of inflammation in pregnancy-related disorders is an area of intense research interest. With the onset of the COVID-19 pandemic and the associated increase in PreE observed clinically, there is a greater need to identify mechanisms of pathophysiology and targets to treat this maternal disorder. Inflammasome activation is associated with PreE and COVID-19 infection and may hold therapeutic potential to improve outcomes associated with PreE and curb the morbidity attributed to PreE.
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COVID-19 , Hipertensão , Pré-Eclâmpsia , Complicações na Gravidez , Animais , Feminino , Humanos , Inflamassomos , Inflamação , Proteína 3 que Contém Domínio de Pirina da Família NLR , Pandemias , Gravidez , SARS-CoV-2RESUMO
BACKGROUND: Hypertensive disorders of pregnancy, such as Preeclampsia (PreE) and HELLP (hemolysis, elevated liver enzyme, low platelet) syndrome, affects approximately 5-10% of pregnancies and increases the risk of women developing disorders, such as anxiety or depression, in the postpartum period. Using preclinical rodent models, we set out to determine whether rats with a history of PreE or HELLP had evidence of anxiety, depression or cognitive impairment and whether immune suppression during pregnancy prevented these changes in mood and/or cognition. METHODS: Timed-pregnant rats were infused with sFlt-1 and/or sEng to induce PreE or HELLP beginning on gestational day 12. After delivery, a battery of validated behavioral assays was used to assess post-partum depression, anxiety and learning. RESULTS: There was no negative effect on maternal pup interaction due to PreE or HELLP; however, hypertensive dams spent more time immobile in the forced swim test (p < 0.0001). Hypertensive dams also spent less time in the open area of the open field (p = 0.001). There were no significant changes in recognition memory (p = 0.08); however, spatial learning was impaired in hypertensive dams (p = 0.003). Immobility time in the forced swim test was positively correlated with increased circulating S100B (p = 0.04), while increased time spent in the outer zones of the open field was negatively correlated with BDNF levels (p < 0.0001). CONCLUSION: The results from this study suggest that hypertensive pregnancy disorders are associated with depression, anxiety and learning impairments in the post-partum period.