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1.
Contraception ; : 110556, 2024 Aug 14.
Artículo en Inglés | MEDLINE | ID: mdl-39128575

RESUMEN

The Centering Equality, Race, and Cultural Literacy in Family Planning (CERCL-FP) program aims to break racial silence and dismantle structural racism in the field of family planning, by providing racial equity workshops and trainings. OBJECTIVE: The objective of this study was to begin a multi-phased, rigorous evaluation to determine the impact and outcomes of the work of CERCL-FP. STUDY DESIGN: A needs assessment with former graduates and current directors of fellowships in family planning was conducted using qualitative interviews. The focus of these interviews was to determine the ability, readiness, and willingness of the field of family planning to retrofit new curricula grounded in equity, race, and cultural literacy. RESULTS: Nine (N = 9) interviews were completed with seven board certified obstetrician-gynecologists and two board certified family medicine physicians. Three themes were identified: (1) Establishing the Distribution of Work; (2) The Push/Pull of Change from Inside and Outside: Curricula and Faculty Responsibilities; and (3) Reproductive Justice and Fellowships in Family Planning. Despite acknowledging the need to retrofit the field of family planning with content grounded in equity, race, and cultural literacy, there are structural, institutional, and individual level barriers that have limited the adoption of CERCL-FP curricula within family planning curriculum nationwide. CONCLUSION: Findings from this study illuminate multiple barriers that should be considered when expanding foundational knowledge of clinicians and researchers. IMPLICATIONS: Similar to the slow integration of research findings into clinical practice, this study shows that integration of social science and new curricula within the field of family planning faces significant barriers. Strategies to address these barriers are crucial to ensuring successful integration of equity, race, and cultural literacy within family planning.

2.
Physiol Behav ; 284: 114624, 2024 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-38959991

RESUMEN

Angiotensin-II (Ang-II) production is driven by deviations in blood volume and osmolality, and serves the role of regulating blood pressure and fluid intake to maintain cardiovascular and hydromineral homeostasis. These actions are mediated by Ang-II acting on its type 1a receptor (AT1aR) within the central nervous system and periphery. Of relevance, AT1aR are expressed on sensory afferents responsible for conveying cardiovascular information to the nucleus of the solitary tract (NTS). We have previously determined that optical excitation of neurons and vagal afferents within the NTS that express AT1aR (referred to as NTSAT1aR) mimics the perception of increased vascular stretch and induces compensatory responses to restore blood pressure. Here, we test whether NTSAT1aR are also involved in the modulation of water and sodium intake. We directed the light-sensitive excitatory channelrhodopsin-2 (ChR2) or inhibitory halorhodopsin (Halo) to Agtr1a-containing neurons and measured water and sodium chloride (NaCl) intake in the presence and absence of optical stimulation within the NTS during various challenges to fluid homeostasis. Optical perturbation of NTSAT1aR modulates NaCl intake, such that excitation attenuates, whereas inhibition increases intake. This effect is only observed in the water-deprived condition, suggesting that NTSAT1aR are involved in the regulation of sodium intake during an imbalance in both the intracellular and extracellular fluid compartments. Furthermore, optical excitation of NTSAT1aR increases c-Fos expression within oxytocinergic neurons of the paraventricular nucleus of the hypothalamus (PVN), indicating that the regulation of sodium intake by NTSAT1aR may be mediated by oxytocin. Collectively, these results reveal that NTSAT1aR are sufficient and necessary to modulate sodium intake relative to perceived changes in vascular stretch.


Asunto(s)
Neuronas , Receptor de Angiotensina Tipo 1 , Núcleo Solitario , Animales , Núcleo Solitario/metabolismo , Núcleo Solitario/fisiología , Núcleo Solitario/efectos de los fármacos , Receptor de Angiotensina Tipo 1/metabolismo , Neuronas/metabolismo , Neuronas/fisiología , Masculino , Ingestión de Líquidos/fisiología , Ingestión de Líquidos/efectos de los fármacos , Neuronas Aferentes/fisiología , Neuronas Aferentes/metabolismo , Optogenética , Cloruro de Sodio/farmacología
3.
Artículo en Inglés | MEDLINE | ID: mdl-38862844

RESUMEN

Racism pervades the US criminal legal and family policing systems, particularly impacting cases involving women with a history of a substance use disorder (SUD). Laws criminalizing SUD during pregnancy disproportionately harm Black women, as do family policing policies around family separation. Discrimination within intersecting systems may deter Black pregnant women with a SUD from seeking evidence-based pregnancy and substance use care. This convergent parallel mixed-methods study aimed to illuminate how systemic oppression influenced the lived experiences of Black mothers with a SUD, facing dual involvement in the criminal legal and family policing systems. Using convenience and snowball sampling techniques, we recruited 15 Black mothers who were incarcerated, used substances while pregnant, and had a history with family policing systems. We conducted semi-structured interviews and developed and distributed a scale questionnaire to describe participants' experiences navigating overlapping systems of surveillance and control. Drawing on models of systemic anti-Black racism and sexism and reproductive justice, we assessed participants' experiences of racism and gender-based violence within these oppressive systems. Participants described how intersecting systems of surveillance and control impeded their prenatal care, recovery, and abilities to parent their children in gender and racially specific ways. Although they mostly detailed experiences of interpersonal discriminatory treatment, particularly from custody staff while incarcerated and pregnant, participants highlighted instances of systemic anti-Black gendered racism and obstetric racism while accessing prenatal care and substance use treatment in carceral and community settings. Their narratives emphasize the need for action to measure and address the upstream macro-level systems perpetuating inequities.

4.
J Neurosci ; 44(9)2024 Feb 28.
Artículo en Inglés | MEDLINE | ID: mdl-38242697

RESUMEN

Cardiovascular homeostasis is maintained, in part, by neural signals arising from arterial baroreceptors that apprise the brain of blood volume and pressure. Here, we test whether neurons within the nodose ganglia that express angiotensin type-1a receptors (referred to as NGAT1aR) serve as baroreceptors that differentially influence blood pressure (BP) in male and female mice. Using Agtr1a-Cre mice and Cre-dependent AAVs to direct tdTomato to NGAT1aR, neuroanatomical studies revealed that NGAT1aR receive input from the aortic arch, project to the caudal nucleus of the solitary tract (NTS), and synthesize mechanosensitive ion channels, Piezo1/2 To evaluate the functionality of NGAT1aR, we directed the fluorescent calcium indicator (GCaMP6s) or the light-sensitive channelrhodopsin-2 (ChR2) to Agtr1a-containing neurons. Two-photon intravital imaging in Agtr1a-GCaMP6s mice revealed that NGAT1aR couple their firing to elevated BP, induced by phenylephrine (i.v.). Furthermore, optical excitation of NGAT1aR at their soma or axon terminals within the caudal NTS of Agtr1a-ChR2 mice elicited robust frequency-dependent decreases in BP and heart rate, indicating that NGAT1aR are sufficient to elicit appropriate compensatory responses to vascular mechanosensation. Optical excitation also elicited hypotensive and bradycardic responses in ChR2-expressing mice that were subjected to deoxycorticosterone acetate (DOCA)-salt hypertension; however, the duration of these effects was altered, suggestive of hypertension-induced impairment of the baroreflex. Similarly, increased GCaMP6s fluorescence observed after administration of phenylephrine was delayed in mice subjected to DOCA-salt or chronic delivery of angiotensin II. Collectively, these results reveal the structure and function of NGAT1aR and suggest that such neurons may be exploited to discern and relieve hypertension.


Asunto(s)
Acetato de Desoxicorticosterona , Hipertensión , Proteína Fluorescente Roja , Ratones , Masculino , Femenino , Animales , Acetato de Desoxicorticosterona/farmacología , Núcleo Solitario/fisiología , Células Receptoras Sensoriales , Presión Sanguínea/fisiología , Fenilefrina/farmacología , Canales Iónicos
5.
Matern Child Health J ; 27(Suppl 1): 177-181, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37755582

RESUMEN

BACKGROUND: Many pregnant and parenting people with substance use disorders (SUD) refrain from seeking perinatal care or treatment for their SUD for fear of being treated poorly by health care providers and/or triggering a child welfare investigation. For those who do seek treatment, there are relatively few clinicians willing and able to prescribe medications for opioid use disorder (MOUD) to pregnant people. Both stigma and lack of access to treatment put many pregnant and parenting people at risk. Drug-related deaths contribute significantly to U.S. maternal mortality rates, with people at especially high risk of drug overdose in the months following delivery. METHODS: The Foundation for Opioid Response Efforts (FORE) is a national philanthropy focused on finding and fostering solutions to the opioid crisis. We draw lessons from our grantees' efforts to expand access to substance use treatment and recovery supports for pregnant and parenting people. RESULTS: To build systems of care that ensure more pregnant people get timely perinatal care, we need to expand training for perinatal providers on how to provide OUD treatment, clarify child welfare reporting rules, and engage and support trusted organizations and community-based services. CONCLUSIONS: In addition to changes to our systems of SUD treatment and recovery, we need greater philanthropic investment in efforts to combat the public health crisis of substance use and overdose among pregnant and parenting people. Private funders have the leeway to act quickly, take risks, and demonstrate the effectiveness of new approaches, building the case for investment of public resources in such initiatives.


Asunto(s)
Miedo , Trastornos Relacionados con Opioides , Niño , Femenino , Embarazo , Humanos , Analgésicos Opioides , Protección a la Infancia , Salud de la Familia , Trastornos Relacionados con Opioides/terapia
6.
bioRxiv ; 2023 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-37425814

RESUMEN

Interoception broadly refers to awareness of one's internal milieu. Vagal sensory afferents monitor the internal milieu and maintain homeostasis by engaging brain circuits that alter physiology and behavior. While the importance of the body-to-brain communication that underlies interoception is implicit, the vagal afferents and corresponding brain circuits that shape perception of the viscera are largely unknown. Here, we use mice to parse neural circuits subserving interoception of the heart and gut. We determine vagal sensory afferents expressing the oxytocin receptor, hereafter referred to as NDGOxtr, send projections to the aortic arch or stomach and duodenum with molecular and structural features indicative of mechanosensation. Chemogenetic excitation of NDGOxtr significantly decreases food and water consumption, and remarkably, produces a torpor-like phenotype characterized by reductions in cardiac output, body temperature, and energy expenditure. Chemogenetic excitation of NDGOxtr also creates patterns of brain activity associated with augmented hypothalamic-pituitary-adrenal axis activity and behavioral indices of vigilance. Recurrent excitation of NDGOxtr suppresses food intake and lowers body mass, indicating that mechanosensation of the heart and gut can exert enduring effects on energy balance. These findings suggest that the sensation of vascular stretch and gastrointestinal distention may have profound effects on whole body metabolism and mental health.

7.
Ann Fam Med ; 21(3): 227-233, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37019478

RESUMEN

PURPOSE: We undertook a study to assess whether presence of community support persons (CSPs), with no hospital affiliation or alignment, mitigates acts of obstetric racism during hospitalization for labor, birth, and immediate postpartum care. METHODS: We conducted a cross-sectional cohort study, measuring 3 domains of obstetric racism as defined for, by, and with Black birthing people: humanity (violation of safety and accountability, autonomy, communication and information exchange, and empathy); kinship (denial or disruption of community and familial bonds that support Black birthing people); and racism in the form of anti-Black racism and misogynoir (weaponization of societal stereotypes and scripts in service provision that reproduce gendered anti-Black racism in the hospital). We used a novel, validated instrument, the Patient-Reported Experience Measure of Obstetric Racism (the PREM-OB Scale suite), and linear regression analysis to determine the association between CSP presence during hospital births and obstetric racism. RESULTS: Analyses were based on 806 Black birthing people, 720 (89.3%) of whom had at least 1 CSP present throughout their labor, birth, and immediate postpartum care. The presence of CSPs was associated with fewer acts of obstetric racism across all 3 domains, with statistically significant reductions in scores in the CSP group of one-third to two-third SD units relative to the no-CSP group. CONCLUSIONS: Our findings suggest that CSPs may be an effective way to reduce obstetric racism as part of quality improvement initiatives, emphasizing the need for democratizing the birthing experience and birth space, and incorporating community members as a way to promote the safety of Black birthing people in hospital settings.Annals "Online First" article.


Asunto(s)
Trabajo de Parto , Racismo , Embarazo , Femenino , Humanos , Racismo/prevención & control , Estudios Transversales , Apoyo Comunitario , Parto Obstétrico
9.
Clin Obstet Gynecol ; 65(3): 663-675, 2022 09 01.
Artículo en Inglés | MEDLINE | ID: mdl-35723647

RESUMEN

Optimizing postpartum care highlights the need for care coordination, enhancement, and expansion of health care services after childbirth. Yet the prioritization of disease surveillance, management, and mitigation during birth and beyond within the American College of Obstetrics and Gynecology facilitates the medicalization and pathologization of Black bodies, voices, and power. Thus, we offer the Building and Bridging Black Futures Beyond Birth Model: A 12-Step Black Woman-Person First Approach, as a more humane and holistic model of culturally affirming and clinically responsive care. Destigmatizing and democratizing care bridges the gap between intent and impact in postpartum care optimization, particularly for Black women, girls, and gender expansive people and their communities.


Asunto(s)
Ginecología , Obstetricia , Parto Obstétrico , Femenino , Humanos , Atención Posnatal , Embarazo
10.
Womens Health Rep (New Rochelle) ; 3(1): 476-482, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35651994

RESUMEN

Objective: The objective of this study was to explore clinician perceptions of how racism affects Black women's pregnancy experiences, perinatal care, and birth outcomes. Materials and Methods: We conducted 25 semi-structured interviews with perinatal care clinicians practicing in the San Francisco Bay Area (January to March 2019) who serve racially diverse women. Participants were primarily recruited through "Dear Perinatal Care Provider" email correspondences sent through department listservs. Culturally concordant, qualitatively trained research assistants conducted all interviews in person. The interviews ranged from 30 to 60 minutes and were audio-recorded and professionally transcribed verbatim. We used the constant comparative method consistent with grounded theory to analyze data. Results: Most participants were obstetrician/gynecologists (n = 11, 44%) or certified nurse midwives (n = 8, 32%), had worked in their current role for 1 to 5 years (n = 10, 40%), and identified as white (n = 16, 64%). Three themes emerged from the interviews: provision of inequitable care (e.g., I had a woman who had a massive complication during her labor course and felt like she wasn't being treated seriously); surveillance of Black women and families (e.g., A urine tox screen on the Black baby even though it was not indicated, and they didn't do it on the white baby when, in fact, it was indicated); and structural care issues (e.g., the history of medical racial experimentation). Conclusion: Clinicians' views about how racism is currently operating and negatively impacting Black women's care experiences, health outcomes, and well-being in medical institutions will be used to develop a racial equity training for perinatal care clinicians in collaboration with Black women and clinicians.

11.
Appetite ; 175: 106054, 2022 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-35447163

RESUMEN

Maintaining homeostasis while navigating one's environment involves accurately assessing and interacting with external stimuli while remaining consciously in tune with internal signals such as hunger and thirst. Both atypical social interactions and unhealthy eating patterns emerge as a result of dysregulation in factors that mediate the prioritization and attention to salient stimuli. Oxytocin is an evolutionarily conserved peptide that regulates attention to exteroceptive and interoceptive stimuli in a social environment by functioning in the brain as a modulatory neuropeptide to control social behavior, but also in the periphery as a hormone acting at oxytocin receptors (Oxtr) expressed in the heart, gut, and peripheral ganglia. Specialized sensory afferent nerve endings of Oxtr-expressing nodose ganglia cells transmit cardiometabolic signals via the Vagus nerve to integrative regions in the brain that also express Oxtr(s). These brain regions are influenced by vagal sensory pathways and coordinate with external events such as those demanding attention to social stimuli, thus the sensations related to cardiometabolic function and social interactions are influenced by oxytocin signaling. This review investigates the literature supporting the idea that oxytocin mediates the interoception of cardiovascular and gastrointestinal systems, and that the modulation of this awareness likewise influences social cognition. These concepts are then considered in relation to Autism Spectrum Disorder, exploring how atypical social behavior is comorbid with cardiometabolic dysfunction.

12.
Front Physiol ; 13: 841078, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35399269

RESUMEN

The brain maintains cardiovascular homeostasis, in part, via the arterial baroreflex which senses changes in blood pressure (BP) at the level of the aortic arch. Sensory afferents innervating the aortic arch employ baroreceptors to convert stretch exerted on the arterial wall into action potentials carried by the vagus nerve to second order neurons residing within the nucleus of the solitary tract (NTS). Although the baroreflex was described more than 80 years ago, the specific molecular, structural, and functional phenotype of the baroreceptors remain uncharacterized. This is due to the lack of tools that provide the genetic and target organ specificity that is required to selectively characterize baroreceptor afferents. Here, we use a novel approach to selectively target baroreceptors. Male mice on a C57BL/6J background were anesthetized with isoflurane, intubated, and artificially ventilated. Following sternotomy, the aortic arch was exposed, and a retrograde adeno-associated virus was applied to the aortic arch to direct the expression of channelrhoropsin-2 (ChR2) and/or tdTomato (tdTom) to sensory afferents presumably functioning as baroreceptors. Consistent with the structural characteristics of arterial baroreceptors, robust tdTom expression was observed in nerve endings surrounding the aortic arch, within the fibers of the aortic depressor and vagus nerves, cell bodies of the nodose ganglia (NDG), and neural projections to the caudal NTS (cNTS). Additionally, the tdTom labeled cell bodies within the NDG also expressed mRNAs coding for the mechanically gated ion channels, PIEZO-1 and PIEZO-2. In vitro electrophysiology revealed that pulses of blue light evoked excitatory post-synaptic currents in a subset of neurons within the cNTS, suggesting a functional connection between the labeled aortic arch sensory afferents and second order neurons. Finally, the in vivo optogenetic stimulation of the cell bodies of the baroreceptor expressing afferents in the NDG produced robust depressor responses. Together, these results establish a novel approach for selectively targeting sensory neurons innervating the aortic arch. This approach may be used to investigate arterial baroreceptors structurally and functionally, and to assess their role in the etiology or reversal of cardiovascular disease.

13.
Birth ; 49(3): 514-525, 2022 09.
Artículo en Inglés | MEDLINE | ID: mdl-35301757

RESUMEN

BACKGROUND: Perinatal quality improvement lacks valid tools to measure adverse hospital experiences disproportionately impacting Black mothers and birthing people. Measuring and mitigating harm requires using a framework that centers the lived experiences of Black birthing people in evaluating inequitable care, namely, obstetric racism. We sought to develop a valid patient-reported experience measure (PREM) of Obstetric Racism© in hospital-based intrapartum care designed for, by, and with Black women as patient, community, and content experts. METHODS: PROMIS© instrument development standards adapted with cultural rigor methodology. Phase 1 included item pool generation, modified Delphi method, and cognitive interviews. Phase 2 evaluated the item pool using factor analysis and item response theory. RESULTS: Items were identified or written to cover 7 previously identified theoretical domains. 806 Black mothers and birthing people completed the pilot test. Factor analysis concluded a 3 factor structure with good fit indices (CFI = 0.931-0.977, RMSEA = 0.087-0.10, R2  > .3, residual correlation < 0.15). All items in each factor fit the IRT model and were able to be calibrated. Factor 1, "Humanity," had 31 items measuring experiences of safety and accountability, autonomy, communication, and empathy. A 12-item short form was created to ease respondent burden. Factor 2, "Racism," had 12 items measuring experiences of neglect and mistreatment. Factor 3, "Kinship," had 7 items measuring hospital denial and disruption of relationships between Black mothers and their child or support system. CONCLUSIONS: The PREM-OB Scale™ suite is a valid tool to characterize and quantify obstetric racism for use in perinatal improvement initiatives.


Asunto(s)
Racismo , Femenino , Humanos , Medición de Resultados Informados por el Paciente , Psicometría/métodos , Encuestas y Cuestionarios
14.
BJOG ; 129(10): 1704-1711, 2022 09.
Artículo en Inglés | MEDLINE | ID: mdl-35133077

RESUMEN

OBJECTIVE: Evaluate the risk of preterm (<37 weeks) or early term birth (37 or 38 weeks) by body mass index (BMI) in a propensity score-matched sample. DESIGN: Retrospective cohort analysis. SETTING: California, USA. POPULATION: Singleton live births from 2011-2017. METHODS: Propensity scores were calculated for BMI groups using maternal factors. A referent sample of women with a BMI between 18.5 and <25.0 kg/m2 was selected using exact propensity score matching. Risk ratios for preterm and early term birth were calculated. MAIN OUTCOME MEASURES: Early birth. RESULTS: Women with a BMI <18.5 kg/m2 were at elevated risk of birth of 28-31 weeks (relative risk [RR] 1.2, 95% CI 1.1-1.4), 32-36 weeks (RR 1.3, 95% CI 1.2-1.3), and 37 or 38 weeks (RR 1.1, 95% CI 1.1-1.1). Women with BMI ≥25.0 kg/m2 were at 1.2-1.4-times higher risk of a birth <28 weeks and were at reduced risk of a birth between 32 and 36 weeks (RR 0.8-0.9) and birth during the 37th or 38th week (RR 0.9). CONCLUSION: Women with a BMI <18.5 kg/m2 were at elevated risk of a preterm or early term birth. Women with BMI ≥25.0 kg/m2 were at elevated risk of a birth <28 weeks. Propensity score-matched women with BMI ≥30.0 kg/m2 were at decreased risk of a spontaneous preterm birth with intact membranes between 32 and 36 weeks, supporting the complexity of BMI as a risk factor for preterm birth. TWEETABLE ABSTRACT: Propensity score-matched women with BMI ≥30 kg/m2 were at decreased risk of a late spontaneous preterm birth.


Asunto(s)
Nacimiento Prematuro , Índice de Masa Corporal , Estudios de Cohortes , Femenino , Edad Gestacional , Humanos , Recién Nacido , Nacimiento Prematuro/epidemiología , Nacimiento Prematuro/etiología , Puntaje de Propensión , Estudios Retrospectivos , Factores de Riesgo
15.
Cardiovasc Res ; 118(3): 883-896, 2022 02 21.
Artículo en Inglés | MEDLINE | ID: mdl-33723600

RESUMEN

AIMS: These studies evaluate whether angiotensin type-2 receptors (AT2Rs) that are expressed on γ-aminobutyric acid (GABA) neurons in the nucleus of the solitary tract (NTS) represent a novel endogenous blood pressure-lowering mechanism. METHODS AND RESULTS: Experiments combined advanced genetic and neuroanatomical techniques, pharmacology, electrophysiology, and optogenetics in mice to define the structure and cardiovascular-related function of NTS neurons that contain AT2R. Using mice with Cre-recombinase directed to the AT2R gene, we discovered that optogenetic stimulation of AT2R-expressing neurons in the NTS increases GABA release and blood pressure. To evaluate the role of the receptor, per se, in cardiovascular regulation, we chronically delivered C21, a selective AT2R agonist, into the brains of normotensive mice and found that central AT2R activation reduces GABA-related gene expression and blunts the pressor responses induced by optogenetic excitation of NTS AT2R neurons. Next, using in situ hybridization, we found that the levels of Agtr2 mRNAs in GABAergic NTS neurons rise during experimentally induced hypertension, and we hypothesized that this increased expression may be exploited to ameliorate the disease. Consistent with this, final experiments revealed that central administration of C21 attenuates hypertension, an effect that is abolished in mice lacking AT2R in GABAergic NTS neurons. CONCLUSION: These studies unveil novel hindbrain circuits that maintain arterial blood pressure, and reveal a specific population of AT2R that can be engaged to alleviate hypertension. The implication is that these discrete receptors may serve as an access point for activating an endogenous depressor circuit.


Asunto(s)
Hipertensión , Receptor de Angiotensina Tipo 2/metabolismo , Núcleo Solitario , Animales , Hipertensión/genética , Hipertensión/metabolismo , Imidazoles , Ratones , Neuronas/metabolismo , Núcleo Solitario/metabolismo , Sulfonamidas , Tiofenos
16.
Front Pharmacol ; 12: 773455, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34776984

RESUMEN

Mutations in N-methyl-d-aspartate receptors (NMDAR) subunits have been implicated in a growing number of human neurodevelopmental disorders. Previously, a de novo mutation in GRIN2A, encoding the GluN2A subunit, was identified in a patient with severe epilepsy and developmental delay. This missense mutation, which leads to GluN2A-P552R, produces significant dendrotoxicity in transfected rodent cortical neurons, as evidenced by pronounced dendritic blebbing. This injurious process can be prevented by treatment with the NMDA antagonist memantine. Given the increasing use of FDA approved NMDA antagonists to treat patients with GRIN mutations, who may have seizures refractory to traditional anti-epileptic drugs, we investigated whether additional NMDA antagonists were effective in attenuating neurotoxicity associated with GluN2A-P552R expression. Intriguingly, we found that while treatment with memantine can effectively block GluN2A-P552R-mediated dendrotoxicity, treatment with ketamine does not, despite the fact that both drugs work as open NMDAR channel blockers. Interestingly, we found that neurons expressing GluN2A-P552R were more vulnerable to an excitotoxic insult-an effect that, in this case, could be equally rescued by both memantine and ketamine. These findings suggest that GluN2A-P552R induced dendrotoxicity and increased vulnerability to excitotoxic stress are mediated through two distinct mechanisms. The differences between memantine and ketamine in halting GluN2A-P552R dendrotoxicity could not be explained by NMDA antagonist induced changes in MAP or Src kinase activation, previously shown to participate in NMDA-induced excitotoxicity. Our findings strongly suggest that not all NMDA antagonists may be of equal clinical utility in treating GRIN2A-mediated neurological disorders, despite a shared mechanism of action.

17.
Lancet Reg Health Am ; 2: 100027, 2021 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-34642685

RESUMEN

INTRODUCTION: Our understanding of the association between coronavirus disease 19 (COVID-19) and preterm or early term birth among racially and ethnically diverse populations and people with chronic medical conditions is limited. METHODS: We determined the association between COVID-19 and preterm (PTB) birth among live births documented by California Vital Statistics birth certificates between July 2020 and January 2021 (n=240,147). We used best obstetric estimate of gestational age to classify births as very preterm (VPTB, <32 weeks), PTB (< 37 weeks), early term (37 and 38 weeks), and term (39-44 weeks), as each confer independent risks to infant health and development. Separately, we calculated the joint effects of COVID-19 diagnosis, hypertension, diabetes, and obesity on PTB and VPTB. FINDINGS: COVID-19 diagnoses on birth certificates increased for all racial/ethnic groups between July 2020 and January 2021 and were highest for American Indian/Alaska Native (12.9%), Native Hawaiian/Pacific Islander (11.4%), and Latinx (10.3%) birthing people. COVID-19 diagnosis was associated with an increased risk of VPTB (aRR 1.6, 95% CI [1.4, 1.9]), PTB (aRR 1.4, 95% CI [1.3, 1.4]), and early term birth (aRR 1.1, 95% CI [1.1, 1.2]). There was no effect modification of the overall association by race/ethnicity or insurance status. COVID-19 diagnosis was associated with elevated risk of PTB in people with hypertension, diabetes, and/or obesity. INTERPRETATION: In a large population-based study, COVID-19 diagnosis increased the risk of VPTB, PTB, and early term birth, particularly among people with medical comorbidities. Considering increased circulation of COVID-19 variants, preventative measures, including vaccination, should be prioritized for birthing persons. FUNDING: UCSF-Kaiser Department of Research Building Interdisciplinary Research Careers in Women's Health Program (BIRCWH) National Institute of Child Health and Human Development (NICHD) and the Office of Research on Women's Health (ORWH) [K12 HD052163] and the California Preterm Birth Initiative, funded by Marc and Lynn Benioff.

18.
Drug Alcohol Depend ; 227: 108998, 2021 10 01.
Artículo en Inglés | MEDLINE | ID: mdl-34482037

RESUMEN

BACKGROUND: As cannabis legalization spreads, so do concerns about potential harms from use during pregnancy. Legalization may facilitate improved patient-provider interactions about cannabis use. Yet little is known about pregnant people's discussions of cannabis use with healthcare providers in an environment where recreational cannabis is legal. METHODS: In May-August 2019, we conducted semi-structured in-depth interviews with 33 pregnant or postpartum people in California who used cannabis during pregnancy, and explored their discussions with healthcare providers about their cannabis use. We audio-recorded and transcribed interviews, and conducted thematic analysis using inductive and deductive methods. RESULTS: Participants were diverse by age, race/ethnicity, and socio-economic position. Most reported daily cannabis use, both before and during pregnancy. Most participants did not disclose their cannabis use to their prenatal care providers, due to fears of being reported to child protective services (CPS), or fears of provider judgment. Participants reported that few providers initiated any discussions about cannabis use in pregnancy with them; some participants interpreted this omission as tacit endorsement of cannabis use in pregnancy. When participants and providers did discuss cannabis use in pregnancy, participants heard a wide range of sometimes-conflicting health messages, as well as some legal threats. CONCLUSIONS: This study documents notable deficits in patient-provider interactions about cannabis. Pregnant patients' fears of being reported to CPS and separated from their children for cannabis use persist despite cannabis legalization. Providers' role as potential reporters to CPS appears to pose a significant barrier to comprehensive, compassionate counseling and education on cannabis use in pregnancy.


Asunto(s)
Cannabis , Alucinógenos , Niño , Humanos , Legislación de Medicamentos , Periodo Posparto , Embarazo , Atención Prenatal
19.
J Perinatol ; 41(12): 2736-2741, 2021 12.
Artículo en Inglés | MEDLINE | ID: mdl-34282261

RESUMEN

OBJECTIVE: Examine the risk of adverse perinatal outcomes among the United States (US)-born and foreign-born Black women in California. STUDY DESIGN: The study comprised all singleton live births to Black women in California between 2011 and 2017. We defined maternal nativity as US-born or foreign-born. Using Poisson regression, we computed risk ratios (RR) and 95% confidence intervals (CI) for three adverse perinatal outcomes: preterm birth, small for gestational age deliveries, and infant mortality. RESULTS: Rates of adverse perinatal outcomes were significantly higher among US-born Black women. In adjusted models, US-born Black women experienced an increased risk of preterm birth (RR 1.51, 95% CI 1.39, 1.65) and small for gestational age deliveries (RR 1.52, 95% CI 1.41, 1.64), compared to foreign-born Black women. CONCLUSIONS: Future studies should consider experiences of racism across the life course when exploring heterogeneity in the risk of adverse perinatal outcomes by nativity among Black women in the US.


Asunto(s)
Nacimiento Prematuro , Población Negra , Femenino , Retardo del Crecimiento Fetal , Humanos , Lactante , Mortalidad Infantil , Recién Nacido , Recién Nacido Pequeño para la Edad Gestacional , Embarazo , Nacimiento Prematuro/epidemiología , Estados Unidos
20.
Neuropsychopharmacology ; 46(11): 1958-1968, 2021 10.
Artículo en Inglés | MEDLINE | ID: mdl-34040156

RESUMEN

The oxytocin (OXT) system has been strongly implicated in the regulation of social behaviour and anxiety, potentially contributing to the aetiology of a wide range of neuropathologies. Birth by Caesarean-section (C-section) results in alterations in microbiota diversity in early-life, alterations in brain development and has recently been associated with long-term social and anxiety-like behaviour deficits. In this study, we assessed whether OXT intervention in the early postnatal period could reverse C-section-mediated effects on behaviour, and physiology in early life and adulthood. Following C-section or per vaginum birth, pups were administered with OXT (0.2 or 2 µg/20 µl; s.c.) or saline daily from postnatal days 1-5. We demonstrate that early postnatal OXT treatment has long-lasting effects reversing many of the effects of C-section on mouse behaviour and physiology. In early-life, high-dose OXT administration attenuated C-section-mediated maternal attachment impairments. In adulthood, low-dose OXT restored social memory deficits, some aspects of anxiety-like behaviour, and improved gastrointestinal transit. Furthermore, as a consequence of OXT intervention in early life, OXT plasma levels were increased in adulthood, and dysregulation of the immune response in C-section animals was attenuated by both doses of OXT treatment. These findings indicate that there is an early developmental window sensitive to manipulations of the OXT system that can prevent lifelong behavioural and physiological impairments associated with mode of birth.


Asunto(s)
Oxitocina , Receptores de Oxitocina , Animales , Ansiedad/tratamiento farmacológico , Ansiedad/etiología , Cesárea , Femenino , Ratones , Embarazo , Conducta Social
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