129 results on '"Miller HE"'
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2. How a concerned family member, friend or member of the public can help someone with gambling problems: a Delphi consensus study.
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Bond, KS, Jorm, AF, Miller, HE, Rodda, SN, Reavley, NJ, Kelly, CM, Kitchener, BA, Bond, KS, Jorm, AF, Miller, HE, Rodda, SN, Reavley, NJ, Kelly, CM, and Kitchener, BA
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BACKGROUND: Gambling is an enjoyable recreational pursuit for many people. However, for some it can lead to significant harms. The Delphi expert consensus method was used to develop guidelines for how a concerned family member, friend or member of the public can recognise the signs of gambling problems and support a person to change their gambling. METHODS: A systematic review of websites, books and journal articles was conducted to develop a questionnaire containing items about the knowledge, skills and actions needed for supporting a person with gambling problems. These items were rated over three rounds by two international expert panels comprising people with a lived experience of gambling problems and professionals who treat people with gambling problems or research gambling problems. RESULTS: A total of 66 experts (34 with lived experience and 32 professionals) rated 412 helping statements according to whether they thought the statements should be included in these guidelines. There were 234 helping statements that were endorsed by at least 80 % of members of both of the expert panels. These endorsed statements were used to develop the guidelines. CONCLUSION: Two groups of experts were able to reach substantial consensus on how someone can recognise the signs of gambling problems and support a person to change.
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- 2016
3. Biorreguladores em feijoeiro cultivado sob dois regimes hídricos
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Miller Henrique Ferreira, Danúbia Aparecida Costa Nobre, and Willian Rodrigues Macedo
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ácido abscísico ,metil jasmonato ,agricultura tropical ,déficit hídrico. ,Agriculture ,Agriculture (General) ,S1-972 ,Veterinary medicine ,SF600-1100 - Abstract
Restrições na disponibilidade hídrica favorecem eventuais danos à cultura do feijoeiro, e o uso de biorreguladores aprimora a sinalização vegetal e potencializa a indução de tolerância ao déficit hídrico. Este estudo objetivou caracterizar alterações fisiológicas, bioquímicas e biométricas em plantas de feijão submetidas à aplicação foliar de biorreguladores sob diferentes regimes hídricos. O ensaio consistiu na aplicação de um controle (água) e três biorreguladores (5 µM de ácido abscísico - ABA; 50 µM de metil jasmonato - MeJA e 5 µM de ABA + 50 µM de MeJA), além de apresentar dois regimes hídricos (60 e 80% da capacidade de campo), num esquema fatorial 4 x 2. Foram analisados: conteúdo de pigmentos fotossintetizantes, trocas gasosas foliares e índices biométricos das plantas de feijoeiro. Com resultado observou-se que o tratamento ABA+MeJA incrementou a concentração de clorofila b, atividades de ascorbato peroxidase (APX) e catalase (CAT), enquanto a taxa fotossintética foi estimulada pela mistura de biorreguladores aos 36 dias após o plantio (DAP), ABA e MeJA, isolados, propiciaram maior taxa fotossintética no feijoeiro aos 34 DAP, enquanto para as variáveis biométricas somente foram influenciadas pelos regimes hídricos, com relação aos mecanismos bioquímicos, constatou-se que o tratamento ABA+MeJA incrementou a atividade das enzimas antioxidantes e melhorou as respostas de trocas gasosas em condição de menor disponibilidade hídrica. Os biorreguladores avaliados nesta pesquisa são benéficos na modulação da fisiologia vegetal em plantas sob estresse hídrico, entretanto o suprimento de água adequado retrata um melhor desenvolvimento das plantas.
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- 2020
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4. INFORMAL DISCUSSION. ENERGY EFFICIENCY.
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MALPAS, R, primary, MILLER, HE, additional, and EASTWOOD, J, additional
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- 1991
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5. INFORMAL DISCUSSION. ENERGY EFFICIENCY.
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EASTWOOD, J, MALPAS, R, and MILLER, HE
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- 1991
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6. Relationship between linguistic and cognitive functioning in children who have sustained traumatic brain injury compared with that seen in non-injured controls.
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Miller HE, Mattys S, McCarter RJ, and Sharples PM
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- 2007
7. Non-verbal and verbal communication in children with severe/moderate traumatic brain injury compared with healthy controls and its relationship to cognitive and psychological functioning.
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Miller HE, Mattys S, McCarter RJ, and Sharples PM
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- 2006
8. Health behaviors and risk factors in those who use complementary and alternative medicine
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Jackson Morgan, Chesney Margaret A, Blackman Marc R, Simile Catherine M, Stussman Barbara J, Barnes Patricia M, Taylor Beth L, Dahlhamer James M, Nahin Richard L, Miller Heather, and McFann Kim K
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Public aspects of medicine ,RA1-1270 - Abstract
Abstract Background Surveys have generally found that individuals more likely to use complementary and alternative medicine are female, live in the western United States, are likely to have a health complaint, and have a higher socioeconomic status than do nonusers. What is not known is the extent to which those who use complementary and alternative medicine also engage in positive health behaviors, such as smoking cessation or increased physical activity and/or exhibit fewer health risk factors such as obesity. This has been identified as a key research question in a recent Institute of Medicine report. In the present study we sought to determine whether the use of complementary and alternative medicine is associated with health behaviors or risk factors known to impact on health status. Methods The current study is a cross-sectional regression analysis using data from the 2002 National Health Interview Survey. Data were collected in-person from 31,044 adults throughout the 50 states and the District of Columbia. Results After controlling for a range of other factors, we found that engaging in leisure-time physical activity, having consumed alcohol in one's life but not being a current heavy drinker, and being a former smoker are independently associated with the use of CAM. Obese individuals are slightly less likely to use CAM than individuals with a healthy body-mass index. No significant associations were observed between receipt of an influenza vaccine and CAM use. Conclusion Those engaging in positive health behaviors and exhibiting fewer health risk factors are more likely to use CAM than those who forgo positive health behaviors or exhibit more health risk factors. The fact that users of CAM tend to pursue generally healthy lifestyles suggests that they may be open to additional recommendations toward optimizing their health.
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- 2007
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9. Relationship between socioeconomic status and cognitive outcome in children with traumatic brain injury compared with non-injured controls.
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Pauldhas D, Miller HE, Cooke H, McCarter RJ, Haworth C, Curran AL, and Sharple PM
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- 2007
10. Relationship between neuroradiological appearances and measures of functional, cognitive, and psychological outcome and health-related quality of life in children with traumatic brain injury.
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Hameed BJ, Miller HE, McCarter RJ, and Sharples PM
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- 2006
11. Mifepristone and misoprostol in California pharmacies after modifications to the Risk Evaluation and Mitigation Strategy Program.
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Beshar I, Miller HE, Kruger S, and Henkel A
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- Humans, California, Female, Health Services Accessibility, United States, Abortion, Induced methods, Abortifacient Agents, Nonsteroidal administration & dosage, United States Food and Drug Administration, Pregnancy, Misoprostol administration & dosage, Mifepristone administration & dosage, Pharmacies, Risk Evaluation and Mitigation
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In January 2023, the Food & Drug Administration modified the Risk Evaluation and Mitigation Strategy program regulating mifepristone to allow direct dispensation from retail pharmacies. In June 2023, we conducted a random, distributive survey of pharmacies in California using secret shopper methodology to investigate the feasibility of accessing mifepristone. One pharmacy had mifepristone immediately available (<24 hours), and misoprostol availability was limited. Accessibility to misoprostol varied by type of pharmacy (p < 0.01), but not by region. Even in a reproductive freedom state, access to mifepristone and misoprostol from outpatient retail pharmacies remains limited., (Copyright © 2024 Elsevier Inc. All rights reserved.)
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- 2024
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12. Clinician care priorities and practices in the fourth trimester: perspective from a California survey.
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Guendelman S, Wang SX, Lahiff M, Lurvey L, and Miller HE
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- Humans, Female, California, Pregnancy, Adult, Surveys and Questionnaires, Postnatal Care standards, Middle Aged, Male, Midwifery, Attitude of Health Personnel, Health Priorities, Obstetrics standards, Practice Patterns, Physicians' statistics & numerical data
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Background: Professional societies such as the American College of Obstetricians and Gynecologists (ACOG) promote the idea that postpartum care is an ongoing process where there is adequate opportunity to provide services and support. Nonetheless, in practice, the guidelines ask clinicians to perform more clinical responsibilities than they might be able to do with limited time and resources., Methods: We conducted an online survey among practicing obstetric clinicians (obstetrician/gynecologists (OB/GYNs), midwives, and family medicine doctors) in California about their priorities and care practices for the first postpartum visit and explored how they prioritize multiple clinical responsibilities within existing time and resources. Between September 2023 and February 2024, 174 out of 229 eligible participants completed the survey, a 76% response rate. From a list of care components, we used descriptive statistics to identify those that were highly prioritized by most clinicians and those that were considered a priority by very few and examined the alignment between prioritized components and recommended care practices., Results: Clinicians were highly invested in the care components that they rated as most important, indicating that they always check these components or assess them when they perceive patient need. Depression and anxiety, breast health/breast feeding issues, vaginal birth complications and family planning counseling were highly ranked components by all clinicians. In contrast, clinicians more often did not assess those care components that infrequently ranked highly among the priority listing, consisting mainly of social drivers of health such as screening and counseling for intimate partner violence, working conditions and food/housing insecurity. In both instances, we found little discordance between priorities and care practices. However, OB/GYNs and midwives differed in some care components that they prioritized highly., Conclusions: While there is growing understanding of how important professional society recommendations are for maternal-infant health, clinicians face barriers completing all recommendations, especially those components related to social drivers of health. However, what the clinicians do prioritize highly, they are likely to perform. Now that Medi-Cal (Medicaid) insurance is available in California for up to 12 months postpartum, there is a need to understand what care clinicians provide and what gaps remain., (© 2024. The Author(s).)
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- 2024
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13. Systematic analysis and characterization of long non-coding RNA genes in inflammatory bowel disease.
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Velissari R, Ilieva M, Dao J, Miller HE, Madsen JH, Gorodkin J, Aikawa M, Ishii H, and Uchida S
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- Humans, Colitis, Ulcerative genetics, Crohn Disease genetics, Transcriptome genetics, RNA, Long Noncoding genetics, Inflammatory Bowel Diseases genetics
- Abstract
The cases of inflammatory bowel disease (IBD) are increasing rapidly around the world. Due to the multifactorial causes of IBD, there is an urgent need to understand the pathogenesis of IBD. As such, the usage of high-throughput techniques to profile genetic mutations, microbiome environments, transcriptome and proteome (e.g. lipidome) is increasing to understand the molecular changes associated with IBD, including two major etiologies of IBD: Crohn disease (CD) and ulcerative colitis (UC). In the case of transcriptome data, RNA sequencing (RNA-seq) technique is used frequently. However, only protein-coding genes are analyzed, leaving behind all other RNAs, including non-coding RNAs (ncRNAs) to be unexplored. Among these ncRNAs, long non-coding RNAs (lncRNAs) may hold keys to understand the pathogenesis of IBD as lncRNAs are expressed in a cell/tissue-specific manner and dysregulated in a disease, such as IBD. However, it is rare that RNA-seq data are analyzed for lncRNAs. To fill this gap in knowledge, we re-analyzed RNA-seq data of CD and UC patients compared with the healthy donors to dissect the expression profiles of lncRNA genes. As inflammation plays key roles in the pathogenesis of IBD, we conducted loss-of-function experiments to provide functional data of IBD-specific lncRNA, lung cancer associated transcript 1 (LUCAT1), in an in vitro model of macrophage polarization. To further facilitate the lncRNA research in IBD, we built a web database, IBDB (https://ibd-db.shinyapps.io/IBDB/), to provide a one-stop-shop for expression profiling of protein-coding and lncRNA genes in IBD patients compared with healthy donors., (© The Author(s) 2023. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)
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- 2024
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14. Racial and Ethnic Disparities in Cervical Insufficiency, Cervical Cerclage, and Preterm Birth.
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Miller HE, Mayo JA, Reddy RA, Leonard SA, Lee HC, Suharwardy S, and Lyell DJ
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Background: The frequency of cervical insufficiency differs among the major racial and ethnic groups, with limited data specific to Asian American and Native Hawaiian/Pacific Islander (AANHPI) subpopulations. We assessed cervical insufficiency diagnoses and related outcomes across 10 racial and ethnic groups, including disaggregated AANHPI subgroups, in a large population-based cohort. Study Design: We performed a retrospective cohort study of all singleton births between 20-42 weeks' gestation in California from 2007 to 2018. Logistic regression models were performed to estimate the odds of cervical insufficiency and, among people with cervical insufficiency, the odds of cerclage and preterm birth according to self-reported race and ethnicity. Results: Among 5,114,470 births, 38,605 (0.8%) had a diagnosis code for cervical insufficiency. Compared with non-Hispanic White people, non-Hispanic Black people had the highest odds of cervical insufficiency (adjusted odds ratio [aOR] 3.07; 95% confidence interval [CI], 2.97, 3.18), for cerclage placement and higher odds for preterm birth. Disaggregating AANHPI subgroups showed that Indian people had the highest odds (aOR 1.94; 95% CI, 1.82, 2.07) of cervical insufficiency and had significantly higher odds of cerclage without increased odds of preterm birth; Southeast Asian people had the highest odds of preterm birth. Conclusion: Within a large, diverse population-based cohort, non-Hispanic Black people experienced the highest rates of cervical insufficiency, and among those with cervical insufficiency, had among the highest rates of cerclage and preterm birth. Among AANHPI subgroups specifically, Indian people had the highest rates of cervical insufficiency and cerclage placement, without increased rates of preterm birth; Southeast Asian people had the highest rates of preterm birth, without increased rates of cerclage. Disaggregating AANHPI subgroups identifies important differences in obstetric risk factors and outcomes.
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- 2024
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15. Physical activity among pregnant inpatients and outpatients and associations with anxiety.
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Panelli DM, Miller HE, Simpson SL, Hurtado J, Shu CH, Boncompagni AC, Chueh J, Carvalho B, Sultan P, Aghaeepour N, and Druzin ML
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- Humans, Female, Pregnancy, Adult, Prospective Studies, Young Adult, Inpatients psychology, Inpatients statistics & numerical data, Outpatients statistics & numerical data, Adolescent, Middle Aged, Pregnancy Complications psychology, Anxiety, Exercise psychology
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Objective: Physical activity is linked to lower anxiety, but little is known about the association during pregnancy. This is especially important for antepartum inpatients, who are known to have increased anxiety yet may not be able to achieve target levels of physical activity during hospitalization. We compared physical activity metrics between pregnant inpatients and outpatients and explored correlations with anxiety., Materials and Methods: This was a prospective cohort between 2021 and 2022 of pregnant people aged 18-55 years carrying singleton gestations ≥ 16 weeks. Three exposure groups were matched for gestational age: 1) outpatients from general obstetric clinics; 2) outpatients from high-risk Maternal-Fetal Medicine obstetric clinics; and 3) antepartum inpatients. Participants wore Actigraph GT9X Link accelerometer watches for up to 7 days to measure physical activity. The primary outcome was mean daily step count. Secondary outcomes were metabolic equivalent tasks (METs), hourly kilocalories (kcals), moderate to vigorous physical activity (MVPA) bursts, and anxiety (State-Trait Anxiety Inventory [STAI]). Step counts were compared using multivariable generalized estimating equations adjusting for maternal age, body-mass index, and insurance type as a socioeconomic construct, accounting for within-group clustering by gestational age. Spearman correlations were used to correlate anxiety scores with step counts., Results: 58 participants were analyzed. Compared to outpatients, inpatients had significantly lower mean daily steps (primary outcome, adjusted beta -2185, 95 % confidence interval [CI] -3146, -1224, p < 0.01), METs (adjusted beta -0.18, 95 % CI -0.23, -0.13, p < 0.01), MVPAs (adjusted beta -38.2, 95 % CI -52.3, -24.1, p < 0.01), and kcals (adjusted beta -222.9, 95 % CI -438.0, -7.8, p = 0.04). Over the course of the week, steps progressively decreased for inpatients (p-interaction 0.01) but not for either of the outpatient groups. Among the entire cohort, lower step counts correlated with higher anxiety scores (r = 0.30, p = 0.02)., Conclusion: We present antenatal population norms and variance for step counts, metabolic equivalent tasks, moderate to vigorous physical activity bursts, and kcals, as well as correlations with anxiety. Antepartum inpatients had significantly lower physical activity than outpatients, and lower step counts correlated with higher anxiety levels. These results highlight the need for physical activity interventions, particularly for hospitalized pregnant people., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)
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- 2024
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16. Evaluation of Sleep in Pregnant Inpatients Compared With Outpatients.
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Panelli DM, Miller HE, Simpson SL, Hurtado J, Shu CH, Boncompagni AC, Chueh J, Barwick F, Carvalho B, Sultan P, Aghaeepour N, and Druzin ML
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- Humans, Female, Pregnancy, Adult, Prospective Studies, Young Adult, Pregnancy Complications, Adolescent, Sleep Initiation and Maintenance Disorders, Middle Aged, Sleep physiology, Hospitalization statistics & numerical data, Actigraphy, Outpatients statistics & numerical data, Inpatients statistics & numerical data
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Objective: To evaluate whether antepartum hospitalization was associated with differences in sleep duration or disrupted sleep patterns., Methods: This was a prospective cohort study with enrollment of pregnant people aged 18-55 years with singleton gestations at 16 weeks of gestation or more between 2021 and 2022. Each enrolled antepartum patient was matched by gestational age to outpatients recruited from obstetric clinics at the same institution. Participants responded to the ISI (Insomnia Severity Index) and wore actigraph accelerometer watches for up to 7 days. The primary outcome was total sleep duration per 24 hours. Secondary outcomes included sleep efficiency (time asleep/time in bed), ISI score, clinical insomnia (ISI score higher than 15), short sleep duration (less than 300 minutes/24 hours), wakefulness after sleep onset, number of awakenings, and sleep fragmentation index. Outcomes were evaluated with multivariable generalized estimating equations adjusted for body mass index (BMI), sleep aid use, and insurance type, accounting for gestational age correlations. An interaction term assessed the joint effects of time and inpatient status., Results: Overall 58 participants were included: 18 inpatients and 40 outpatients. Inpatients had significantly lower total sleep duration than outpatients (mean 4.4 hours [SD 1.6 hours] inpatient vs 5.2 hours [SD 1.5 hours] outpatient, adjusted β=-1.1, 95% CI, -1.8 to -0.3, P =.01). Awakenings (10.1 inpatient vs 13.8, P =.01) and wakefulness after sleep onset (28.3 inpatient vs 35.5 outpatient, P =.03) were lower among inpatients. There were no differences in the other sleep outcomes, and no interaction was detected for time in the study and inpatient status. Inpatients were more likely to use sleep aids (39.9% vs 12.5%, P =.03)., Conclusion: Hospitalized pregnant patients slept about 1 hour/day less than outpatients. Fewer awakenings and reduced wakefulness after sleep onset among inpatients may reflect increased use of sleep aids in hospitalized patients., Competing Interests: Financial Disclosure The authors did not report any potential conflicts of interest., (Copyright © 2024 by the American College of Obstetricians and Gynecologists. Published by Wolters Kluwer Health, Inc. All rights reserved.)
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- 2024
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17. Vascular health years after a hypertensive disorder of pregnancy: The EPOCH study.
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Miller HE, Tierney S, Stefanick ML, Mayo JA, Sedan O, Rosas LG, Melbye M, Boyd HA, Stevenson DK, Shaw GM, Winn VD, and Hlatky MA
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- Humans, Female, Pregnancy, Adult, Blood Pressure physiology, Risk Factors, Atherosclerosis physiopathology, Atherosclerosis epidemiology, Atherosclerosis diagnosis, Atherosclerosis complications, Pulse Wave Analysis, Carotid Arteries diagnostic imaging, Carotid Arteries physiopathology, Pre-Eclampsia physiopathology, Pre-Eclampsia epidemiology, Pre-Eclampsia diagnosis, Case-Control Studies, Endothelium, Vascular physiopathology, Carotid Intima-Media Thickness, Hypertension, Pregnancy-Induced physiopathology, Hypertension, Pregnancy-Induced epidemiology, Vascular Stiffness physiology
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Background: Preeclampsia is associated with a two-fold increase in a woman's lifetime risk of developing atherosclerotic cardiovascular disease (ASCVD), but the reasons for this association are uncertain. The objective of this study was to examine the associations between vascular health and a hypertensive disorder of pregnancy among women ≥ 2 years postpartum., Methods: Pre-menopausal women with a history of either a hypertensive disorder of pregnancy (cases: preeclampsia or gestational hypertension) or a normotensive pregnancy (controls) were enrolled. Participants were assessed for standard ASCVD risk factors and underwent vascular testing, including measurements of blood pressure, endothelial function, and carotid artery ultrasound. The primary outcomes were blood pressure, ASCVD risk, reactive hyperemia index measured by EndoPAT and carotid intima-medial thickness. The secondary outcomes were augmentation index normalized to 75 beats per minute and pulse wave amplitude measured by EndoPAT, and carotid elastic modulus and carotid beta-stiffness measured by carotid ultrasound., Results: Participants had a mean age of 40.7 years and were 5.7 years since their last pregnancy. In bivariate analyses, cases (N = 68) were more likely than controls (N = 71) to have hypertension (18% vs 4%, P = .034), higher calculated ASCVD risk (0.6 vs 0.4, P = .02), higher blood pressures (systolic: 118.5 vs 111.6 mm Hg, P = .0004; diastolic: 75.2 vs 69.8 mm Hg, P = .0004), and higher augmentation index values (7.7 vs 2.3, P = .03). They did not, however, differ significantly in carotid intima-media thickness (0.5 vs 0.5, P = .29) or reactive hyperemia index (2.1 vs 2.1, P = .93), nor in pulse wave amplitude (416 vs 326, P = .11), carotid elastic modulus (445 vs 426, P = .36), or carotid beta stiffness (2.8 vs 2.8, P = .86)., Conclusion: Women with a prior hypertensive disorder of pregnancy had higher ASCVD risk and blood pressures several years postpartum, but did not have more endothelial dysfunction or subclinical atherosclerosis., Competing Interests: Conflict of Interest Dr. Melbye is a co-founder of Mirvie, Inc. Drs Shaw and Stevenson are co-inventors on a patent application submitted by the Chan Zuckerberg Biohub and Stanford University that covers noninvasive early prediction of preeclampsia and monitoring maternal organ health over pregnancy (US Patent and Trademark Office application numbers 63/159,400, filed on March 10, 2021, and 63/276,467, filed on November 5, 2021). The remaining authors have no relationships with industry relevant to this manuscript., (Copyright © 2024 Elsevier Inc. All rights reserved.)
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- 2024
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18. Associations between anxiety, sleep, and blood pressure parameters in pregnancy: a prospective pilot cohort study.
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Miller HE, Simpson SL, Hurtado J, Boncompagni A, Chueh J, Shu CH, Barwick F, Leonard SA, Carvalho B, Sultan P, Aghaeepour N, Druzin M, and Panelli DM
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- Humans, Female, Pregnancy, Pilot Projects, Prospective Studies, Adult, Sleep physiology, Pregnancy Complications psychology, Surveys and Questionnaires, Actigraphy, Anxiety, Blood Pressure physiology, Sleep Initiation and Maintenance Disorders psychology, Sleep Initiation and Maintenance Disorders epidemiology
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Background: The potential effect modification of sleep on the relationship between anxiety and elevated blood pressure (BP) in pregnancy is understudied. We evaluated the relationship between anxiety, insomnia, and short sleep duration, as well as any interaction effects between these variables, on BP during pregnancy., Methods: This was a prospective pilot cohort of pregnant people between 23 to 36 weeks' gestation at a single institution between 2021 and 2022. Standardized questionnaires were used to measure clinical insomnia and anxiety. Objective sleep duration was measured using a wrist-worn actigraphy device. Primary outcomes were systolic (SBP), diastolic (DBP), and mean (MAP) non-invasive BP measurements. Separate sequential multivariable linear regression models fit with generalized estimating equations (GEE) were used to separately assess associations between anxiety (independent variable) and each BP parameter (dependent variables), after adjusting for potential confounders (Model 1). Additional analyses were conducted adding insomnia and the interaction between anxiety and insomnia as independent variables (Model 2), and adding short sleep duration and the interaction between anxiety and short sleep duration as independent variables (Model 3), to evaluate any moderating effects on BP parameters., Results: Among the 60 participants who completed the study, 15 (25%) screened positive for anxiety, 11 (18%) had subjective insomnia, and 34 (59%) had objective short sleep duration. In Model 1, increased anxiety was not associated with increases in any BP parameters. When subjective insomnia was included in Model 2, increased DBP and MAP was significantly associated with anxiety (DBP: β 6.1, p = 0.01, MAP: β 6.2 p < 0.01). When short sleep was included in Model 3, all BP parameters were significantly associated with anxiety (SBP: β 9.6, p = 0.01, DBP: β 8.1, p < 0.001, and MAP: β 8.8, p < 0.001). No moderating effects were detected between insomnia and anxiety (p interactions: SBP 0.80, DBP 0.60, MAP 0.32) or between short sleep duration and anxiety (p interactions: SBP 0.12, DBP 0.24, MAP 0.13) on BP., Conclusions: When including either subjective insomnia or objective short sleep duration, pregnant people with anxiety had 5.1-9.6 mmHg higher SBP, 6.1-8.1 mmHg higher DBP, and 6.2-8.8 mmHg higher MAP than people without anxiety., (© 2024. The Author(s).)
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- 2024
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19. Mental health conditions and contraception: current landscape, reproductive health and obstetric outcomes, and clinical guidance.
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Miller HE, Kruger SL, and Panelli DM
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- Pregnancy, Female, Humans, Adult, Contraception adverse effects, Reproduction, Contraceptives, Oral, Hormonal adverse effects, Reproductive Health, Mental Health
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Purpose of Review: This review presents the epidemiology of mental health conditions among reproductive aged people, common adverse reproductive outcomes, the hormonal profile of contraception and its relationship with psychiatric outcomes, and updated information for clinicians providing contraceptive counselling for this population., Recent Findings: There is variability among contraceptive behaviours and patterns across those who have mental health conditions, impacting reproductive, psychiatric, and perinatal outcomes. The endocrinology of hormonal contraceptives is well understood, however, the impacts of steroidal hormones on mental health outcomes continue to be less understood. Overall, hormonal contraceptives are safe to use among those with mental health conditions, and among those using selective serotonin reuptake inhibitors and serotonin norepinephrine reuptake inhibitors. Additional considerations are needed when prescribing contraception among people who may be at risk of poor adherence, who use certain classes of antidepressants, antipsychotics, antiepileptics, and who are <6 weeks postpartum., Summary: Barriers to effective contraceptive use should be addressed and myths on negative psychiatric impacts of hormonal contraceptives should be dispelled. Healthcare clinicians should seek out opportunities to become proficient in contraception counselling to improve health outcomes among people with mental health conditions., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)
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- 2024
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20. A Case of an Obstructed Delivery by a Large, Lower Uterine Segment Fibroid Interlocked with a Fetal Mentum.
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Miller SE, Miller HE, Waldrop AR, Karakash SD, and Shaw KA
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Uterine leiomyomata are associated with many pregnancy complications and will likely become increasingly common as the average age of childbearing increases. We describe a case of an obstructed delivery by a large fibroid. A 37-year-old G2P1001 with a 10-cm anterior, lower uterine segment fibroid presented for labor induction. Labor was complicated by arrest of descent due to suspected obstruction of the fetal body by the fibroid after descent of the fetal head, and delivery during cesarean section was complicated by apparent interlocking of the fetal mentum with the fibroid. Large, anterior lower uterine segment fibroids have the potential to obstruct delivery of the fetal head or of the fetal body, and these patients should be counseled regarding the potential for complications via both vaginal and cesarean deliveries., Competing Interests: Conflict of Interest None declared., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. ( https://creativecommons.org/licenses/by-nc-nd/4.0/ ).)
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- 2024
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21. Prior Cesarean Birth and Risk of Uterine Rupture in Second-Trimester Medication Abortions Using Mifepristone and Misoprostol: A Systematic Review and Meta-analysis.
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Henkel A, Miller HE, Zhang J, Lyell DJ, and Shaw KA
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- Humans, Female, Pregnancy, Abortifacient Agents, Nonsteroidal adverse effects, Abortifacient Agents, Nonsteroidal administration & dosage, Abortifacient Agents, Steroidal adverse effects, Abortifacient Agents, Steroidal administration & dosage, Mifepristone adverse effects, Mifepristone administration & dosage, Misoprostol adverse effects, Misoprostol administration & dosage, Uterine Rupture etiology, Pregnancy Trimester, Second, Abortion, Induced adverse effects, Cesarean Section
- Abstract
Objective: To assess the risk difference of uterine rupture when using current mifepristone and misoprostol regimens for second-trimester abortion among individuals with prior cesarean birth compared with those without prior cesarean birth., Data Sources: We searched the terms second trimester, induction, mifepristone, and abortion in PubMed, EMBASE, POPLINE, ClinicalTrials.gov , and Cochrane Library from inception until December 2022., Methods of Study Selection: We included randomized trials and observational studies including a mixed cohort, with and without uterine scar, of individuals at 14-28 weeks of gestation who used mifepristone and misoprostol to end a pregnancy or to manage a fetal death. We excluded case reports, narrative reviews, and studies not published in English. Two reviewers independently screened studies., Tabulation, Integration, and Results: Absolute risks with binomial CIs were calculated from pooled data. Using R software, we estimated total risk difference by the Mantel-Haenszel random-effects method without continuity correction. For studies with zero events, a continuity correction of 0.5 was applied for individual risk differences and plotted graphically with forest plots. Statistical heterogeneity was assessed with Higgins I2 statistics. Funnel plot assessed for publication bias. Of 198 articles identified, 22 met the inclusion criteria: seven randomized trials (n=923) and 15 observational studies (n=6,195). Uterine rupture risk with prior cesarean birth was 1.1% (10/874) (95% CI 0.6-2.1) and without prior cesarean birth was 0.01% (2/6,244) (95% CI 0.0-0.12). The risk difference was 1.23% (95% CI 0.46-2.00, I2 =0%). Of the 12 reported uterine ruptures, three resulted in hysterectomy., Conclusion: Uterine rupture with mifepristone and misoprostol use during second-trimester induction abortion is rare, with the risk increased to 1% in individuals with prior cesarean birth., Systematic Review Registration: PROSPERO, CRD42022302626., (Copyright © 2023 by the American College of Obstetricians and Gynecologists. Published by Wolters Kluwer Health, Inc. All rights reserved.)
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- 2023
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22. Do Not Cut Off Your Tail: A Mega-Analysis of Responses to Auditory Perturbation Experiments.
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Miller HE, Kearney E, Nieto-Castañón A, Falsini R, Abur D, Acosta A, Chao SC, Dahl KL, Franken M, Heller Murray ES, Mollaei F, Niziolek CA, Parrell B, Perrachione T, Smith DJ, Stepp CE, Tomassi N, and Guenther FH
- Subjects
- Humans, Aged, Feedback, Sensory physiology, Speech physiology, Parkinson Disease
- Abstract
Purpose: The practice of removing "following" responses from speech perturbation analyses is increasingly common, despite no clear evidence as to whether these responses represent a unique response type. This study aimed to determine if the distribution of responses to auditory perturbation paradigms represents a bimodal distribution, consisting of two distinct response types, or a unimodal distribution., Method: This mega-analysis pooled data from 22 previous studies to examine the distribution and magnitude of responses to auditory perturbations across four tasks: adaptive pitch, adaptive formant, reflexive pitch, and reflexive formant. Data included at least 150 unique participants for each task, with studies comprising younger adult, older adult, and Parkinson's disease populations. A Silverman's unimodality test followed by a smoothed bootstrap resampling technique was performed for each task to evaluate the number of modes in each distribution. Wilcoxon signed-ranks tests were also performed for each distribution to confirm significant compensation in response to the perturbation., Results: Modality analyses were not significant ( p > .05) for any group or task, indicating unimodal distributions. Our analyses also confirmed compensatory reflexive responses to pitch and formant perturbations across all groups, as well as adaptive responses to sustained formant perturbations. However, analyses of sustained pitch perturbations only revealed evidence of adaptation in studies with younger adults., Conclusion: The demonstration of a clear unimodal distribution across all tasks suggests that following responses do not represent a distinct response pattern, but rather the tail of a unimodal distribution., Supplemental Material: https://doi.org/10.23641/asha.24282676.
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- 2023
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23. A comparison of structural morphometry in children and adults with persistent developmental stuttering.
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Miller HE, Garnett EO, Heller Murray ES, Nieto-Castañón A, Tourville JA, Chang SE, and Guenther FH
- Abstract
This cross-sectional study aimed to differentiate earlier occurring neuroanatomical differences that may reflect core deficits in stuttering versus changes associated with a longer duration of stuttering by analysing structural morphometry in a large sample of children and adults who stutter and age-matched controls. Whole-brain T
1 -weighted structural scans were obtained from 166 individuals who stutter (74 children, 92 adults; ages 3-58) and 191 controls (92 children, 99 adults; ages 3-53) from eight prior studies in our laboratories. Mean size and gyrification measures were extracted using FreeSurfer software for each cortical region of interest. FreeSurfer software was also used to generate subcortical volumes for regions in the automatic subcortical segmentation. For cortical analyses, separate ANOVA analyses of size (surface area, cortical thickness) and gyrification (local gyrification index) measures were conducted to test for a main effect of diagnosis (stuttering, control) and the interaction of diagnosis-group with age-group (children, adults) across cortical regions. Cortical analyses were first conducted across a set of regions that comprise the speech network and then in a second whole-brain analysis. Next, separate ANOVA analyses of volume were conducted across subcortical regions in each hemisphere. False discovery rate corrections were applied for all analyses. Additionally, we tested for correlations between structural morphometry and stuttering severity. Analyses revealed thinner cortex in children who stutter compared with controls in several key speech-planning regions, with significant correlations between cortical thickness and stuttering severity. These differences in cortical size were not present in adults who stutter, who instead showed reduced gyrification in the right inferior frontal gyrus. Findings suggest that early cortical anomalies in key speech planning regions may be associated with stuttering onset. Persistent stuttering into adulthood may result from network-level dysfunction instead of focal differences in cortical morphometry. Adults who stutter may also have a more heterogeneous neural presentation than children who stutter due to their unique lived experiences., Competing Interests: The authors report no competing interests., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Guarantors of Brain.)- Published
- 2023
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24. Abortion Bans and Resource Utilization for Congenital Heart Disease: A Decision Analysis.
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Miller HE, Fraz F, Zhang J, Henkel A, Leonard SA, Maskatia SA, El-Sayed YY, and Blumenfeld YJ
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- Pregnancy, Infant, Newborn, Child, Female, United States epidemiology, Humans, Gestational Age, Decision Support Techniques, Abortion, Legal, Abortion, Induced, Heart Defects, Congenital surgery, Abortion, Spontaneous, Perinatal Death
- Abstract
Objective: To investigate the implications of potential national abortion ban scenarios on the incidence of neonatal single-ventricle cardiac defects., Methods: A decision tree model was developed to predict the incidence of neonatal single-ventricle cardiac defects and related outcomes in the United States under four theoretical national abortion bans: 1) abortion restrictions in existence immediately before the June 2022 Dobbs v Jackson Women's Health Organization Supreme Court decision, 2) 20 weeks of gestation, 3) 13 weeks of gestation, and 4) a complete abortion ban. The model included incidence of live births of neonates with single-ventricle cardiac defects, neonatal heart surgery (including heart transplant and extracorporeal membrane oxygenation [ECMO]), and neonatal death. Cohort size was based on national pregnancy incidence and different algorithm decision point probabilities were aggregated from the existing literature. Monte Carlo simulations were conducted with 10,000 iterations per model., Results: In the scenario before the Dobbs decision, an estimated 6,369,000 annual pregnancies in the United States resulted in 1,006 annual cases of single-ventricle cardiac defects. Under a complete abortion ban, the model predicted a 53.7% increase in single-ventricle cardiac defects, or an additional 9 cases per 100,000 live births. This increase would result in an additional 531 neonatal heart surgeries, 16 heart transplants, 77 ECMO utilizations, and 102 neonatal deaths annually. More restrictive gestational age-based bans are predicted to confer increases in cases of neonatal single-ventricle cardiac defects and related adverse outcomes as well., Conclusion: Universal abortion bans are estimated to increase the incidence of neonatal single-ventricle cardiac defects, associated morbidity, and resource utilization. States considering limiting abortion should consider the implications on the resources required to care for increasing number of children that will be born with significant and complex medical needs, including those with congenital heart disease., Competing Interests: Financial Disclosure The authors did not report any potential conflicts of interest., (Copyright © 2023 by the American College of Obstetricians and Gynecologists. Published by Wolters Kluwer Health, Inc. All rights reserved.)
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- 2023
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25. Exploration and analysis of R-loop mapping data with RLBase.
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Miller HE, Montemayor D, Li J, Levy SA, Pawar R, Hartono S, Sharma K, Frost B, Chedin F, and Bishop AJR
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- DNA genetics, DNA chemistry, Hybridization, Genetic, Nucleic Acid Hybridization, RNA genetics, RNA chemistry, R-Loop Structures, Databases, Genetic
- Abstract
R-loops are three-stranded nucleic acid structures formed from the hybridization of RNA and DNA. In 2012, Ginno et al. introduced the first R-loop mapping method. Since that time, dozens of R-loop mapping studies have been conducted, yielding hundreds of publicly available datasets. Current R-loop databases provide only limited access to these data. Moreover, no web tools for analyzing user-supplied R-loop datasets have yet been described. In our recent work, we reprocessed 810 R-loop mapping samples, building the largest R-loop data resource to date. We also defined R-loop consensus regions and developed a framework for R-loop data analysis. Now, we introduce RLBase, a user-friendly database that provides the capability to (i) explore hundreds of public R-loop mapping datasets, (ii) explore R-loop consensus regions, (iii) analyze user-supplied data and (iv) download standardized and reprocessed datasets. RLBase is directly accessible via the following URL: https://gccri.bishop-lab.uthscsa.edu/shiny/rlbase/., (© The Author(s) 2022. Published by Oxford University Press on behalf of Nucleic Acids Research.)
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- 2023
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26. Influence of fiber type and carbohydrase supplementation on nutrient digestibility, energy and nitrogen balance, and physiology of sows at mid and late gestation.
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Crome TA, Giesemann MA, Miller HE, and Petry AL
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- Pregnancy, Swine, Animals, Female, Digestion physiology, Nutrients, Dietary Fiber metabolism, Nitrogen metabolism, Animal Feed analysis, Dietary Supplements, Diet veterinary
- Abstract
Carbohydrase supplementation in grow-finish pig diets improves energy, nutrient digestibility, and gastrointestinal function, but their efficacy in gestation diets is understudied. The experimental objective was to evaluate the efficacy of a multicarbohydrase to improve digestion, energetics, and various physiological functions in gestating sows fed soluble and insoluble fiber diets. On day 28 of gestation, 36 sows (186 ± 4.6 kg body weight), blocked by parity, were randomly assigned to a 2 × 2 factorial arrangement of dietary treatments (n = 9). Factors included fiber type of insoluble (IF; 20% dried distiller grains with solubles) or soluble fiber (SF; 20% sugar beet pulp) and with (+) or without (-) enzyme (0.05%, Rovabio Advance P10; Adisseo, Antony, France). Diets were fed from days 28 to 109 of gestation at a feeding level of 2.1 kg (SID-Lys 11 g/d and 4.5 net energy-Mcal/d). Two separate 9-d metabolism periods were conducted on days 50 to 59 (mid) and 99 to 108 (late) of gestation. During each period, days 1 to 3 served as an adaptation period, days 4 to 7 total urine and feces were collected (96-h) and followed by a 48-h lactulose-mannitol study. Serum and plasma were collected on days 50 and 99. Data were analyzed as repeated records using a linear mixed model with block as a random effect and fiber type, enzyme, and period and their interactions as fixed effects. Sows fed SF+ had increased serum IL-1ra (Fiber × Enzyme P = 0.035), and IL-2 (Fiber × Enzyme P = 0.042). In the presence of IF, multicarbohydrases increased serum lipopolysaccharide-binding protein, but not when supplemented with SF (Fiber × Enzyme P = 0.028). Circulating IL-8 and TNF-α were decreased in sows fed multicarbohydrases (P < 0.05). Multicarbohydrase supplementation increased the apparent total tract digestibility (ATTD) of gross energy (GE), dry matter, and neutral detergent fiber by 2.8%, 3.4%, and 8.3%, respectively (P < 0.05). Compared to IF-, the ATTD of hemicellulose was 5.3% greater in sows fed IF+ but did not differ from SF- and SF+ (Fiber × Enzyme P = 0.037). Sows fed IF+ had the greatest ATTD of insoluble dietary fiber (Fiber × Enzyme P = 0.011). Sows fed multicarbohydrases excreted less energy in their urine (519 vs. 469 GE kcal/d; Enzyme P = 0.033) and in their feces (985 vs. 900 GE kcal/d; Enzyme P = 0.003). This resulted in an improvement in both digestible energy (Enzyme P < 0.01) and metabolizable energy (Enzyme P = 0.041), irrespective of fiber type. In conclusion, multicarbohydrase supplementation increased the digestibility and energetic contribution of fiber, irrespective of adaptation time or fiber type, but modulation of inflammatory responses was unique to dietary fiber type., (© The Author(s) 2023. Published by Oxford University Press on behalf of the American Society of Animal Science.)
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- 2023
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27. RLSuite: An Integrative R-Loop Bioinformatics Framework.
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Miller HE, Montemayor D, Levy S, Sharma K, Frost B, and Bishop AJR
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We recently described the development of a database of 810 R-loop mapping datasets and used this data to conduct a meta-analysis of R-loops. R-loops are three-stranded nucleic acid structures containing RNA:DNA hybrids and we were able to verify that 30% of expressed genes have an associated R-loop in a location conserved manner.. Moreover, intergenic R-loops map to enhancers, super enhancers and with TAD domain boundaries. This work demonstrated that R-loop mapping via high-throughput sequencing can reveal novel insight into R-loop biology, however the analysis and quality control of these data is a non-trivial task for which few bioinformatic tools exist. Herein we describe RLSuite, an integrative R-loop bioinformatics framework for pre-processing, quality control, and downstream analysis of R-loop mapping data. RLSuite enables users to compare their data to hundreds of public datasets and generate a user-friendly analysis report for sharing with non-bioinformatician colleagues. Taken together, RLSuite is a novel analysis framework that should greatly benefit the emerging R-loop bioinformatics community in a rapidly expanding aspect of epigenetic control that is still poorly understood., Competing Interests: Competing interests None declared.
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- 2023
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28. Optimizing postpartum contraception for high-risk obstetric patients.
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Miller HE, Darmawan KF, and Henkel A
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- Humans, Infant, Newborn, Female, Pregnancy, Pandemics, Contraception, Postpartum Period, Contraception Behavior, Premature Birth prevention & control, COVID-19 epidemiology, COVID-19 prevention & control
- Abstract
Purpose of Review: This review will focus on those who are at greatest risk of maternal and neonatal morbidity from a subsequent unplanned or short interval pregnancy and the interventions to increase contraceptive uptake in the postpartum period., Recent Findings: Populations at highest risk of maternal or neonatal morbidity - those with a history of preterm birth or those with complex medical conditions - are also those at the highest risk for unintended pregnancies attributed to low-efficacy contraceptive failure/ noncontraceptive use, and many are discharged from birth hospitalization without understanding the importance of birth spacing related to their high-risk pregnancies. Current innovative strategies to improve postpartum contraception access and uptake among high-risk populations include utilizing the antenatal period to initiate contraception counseling, developing multidisciplinary teams, and incorporating multimedia-based educational tools. However, ongoing challenges that continue to pose barriers to contraception access include racial and economic disparities and the restructuring of obstetric care during the COVID-19 pandemic., Summary: Preventing an unintended short interval pregnancy by providing contraception in the postpartum period is one of the most modifiable risk factors for those at highest risk of subsequent maternal or neonatal morbidity and therefore should be prioritized by clinicians, hospitals, and insurance coverage., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)
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- 2022
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29. The endogenous Coxiella burnetii plasmid encodes a functional toxin-antitoxin system.
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Wachter S, Cockrell DC, Miller HE, Virtaneva K, Kanakabandi K, Darwitz B, Heinzen RA, and Beare PA
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- Animals, Chlorocebus aethiops, Vero Cells, Plasmids genetics, Virulence, Coxiella burnetii genetics, Coxiella burnetii metabolism, Toxin-Antitoxin Systems genetics
- Abstract
Coxiella burnetii is the causative agent of Q fever. All C. burnetii isolates encode either an autonomously replicating plasmid (QpH1, QpDG, QpRS, or QpDV) or QpRS-like chromosomally integrated plasmid sequences. The role of the ORFs present in these sequences is unknown. Here, the role of the ORFs encoded on QpH1 was investigated. Using a new C. burnetii shuttle vector (pB-TyrB-QpH1ori), we cured the C. burnetii Nine Mile Phase II strain of QpH1. The ΔQpH1 strain grew normally in axenic media but had a significant growth defect in Vero cells, indicating QpH1 was important for C. burnetii virulence. We developed an inducible CRISPR interference system to examine the role of individual QpH1 plasmid genes. CRISPRi of cbuA0027 resulted in significant growth defects in axenic media and THP-1 cells. The cbuA0028/cbuA0027 operon encodes CBUA0028 (ToxP) and CBUA0027 (AntitoxP), which are homologous to the HigB2 toxin and HigA2 antitoxin, respectively, from Vibrio cholerae. Consistent with toxin-antitoxin systems, overexpression of toxP resulted in a severe intracellular growth defect that was rescued by co-expression of antitoxP. ToxP inhibited protein translation. AntitoxP bound the toxP promoter (PtoxP) and ToxP, with the resulting complex binding also PtoxP. In summary, our data indicate that C. burnetii maintains an autonomously replicating plasmid because of a plasmid-based toxin-antitoxin system., (Published 2022. This article is a U.S. Government work and is in the public domain in the USA. Molecular Microbiology published by John Wiley & Sons Ltd.)
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- 2022
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30. Addressing postpartum contraception practices utilizing a multidisciplinary Pregnancy Heart Team approach.
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Miller HE, Do SC, Cruz G, Panelli DM, Leonard SA, Girsen A, Lee CJ, Khandelwal A, Shaw KA, and Bianco K
- Abstract
Background: Cardiovascular disease has emerged as the leading cause of maternal morbidity and mortality, making planned pregnancy, and thereby reliable contraception among people with cardiovascular disease, vital., Objective: This study aimed to compare postpartum contraceptive practices among people with cardiovascular disease (cardiac cohort) cared for by a Pregnancy Heart Team to people with other chronic comorbidities (high-risk cohort), and people without comorbidities (low-risk cohort). We hypothesized that the Pregnancy Heart Team influenced baseline contraception counseling and practices among those with cardiovascular disease., Study Design: This was a retrospective cohort study comparing postpartum contraceptive practices between a cardiac cohort who received care by a multidisciplinary team between 2012 and 2020 and high-risk and low-risk cohorts delivering at a single academic center between 2016 and 2019. We investigated presence of a contraceptive plan (at birthing admission, discharge, and postpartum visit) and uptake of reliable contraception by 8 weeks postpartum., Results: We included 1464 people: 189 with cardiovascular disease, 197 with other chronic comorbidities, and 1078 low-risk people. At birth hospitalization admission, reliable contraception was planned among 42% of the cardiac cohort, 40% of the high-risk cohort, and 31% of the low-risk cohort, with similar distributions at the time of discharge and at 8 weeks postpartum. Compared with the cardiac cohort, by 8 weeks postpartum, the high-risk cohort had similar odds of using highly reliable forms of contraception (39% vs 36%; adjusted odds ratio, 0.78; 95% confidence interval, 0.50-1.21) and similar odds of having a plan to use the most reliable forms of contraception (intrauterine device, implant, bilateral tubal ligation) at the time of birthing admission (42% vs 40%; adjusted odds ratio, 0.78; 95% confidence interval, 0.50-1.22), discharge (47% vs 45%; adjusted odds ratio, 0.95; 95% confidence interval, 0.61-1.48), and postpartum visit (35% vs 29%; adjusted odds ratio, 0.76; 95% confidence interval, 0.49-1.17). The low-risk cohort had lower odds of using a reliable form of contraception (39% vs 27%; adjusted odds ratio, 0.53; 95% confidence interval, 0.37-0.75) and was less likely to have a plan for reliable contraception at the time of birthing admission (42% vs 31%; adjusted odds ratio, 0.54; 95% confidence interval, 0.38-0.76), discharge (47% vs 33%; adjusted odds ratio, 0.58; 95% confidence interval, 0.4-0.82), and postpartum visit (35% vs 21%; adjusted odds ratio, 0.50; 95% confidence interval, 0.35-0.71)., Conclusion: People with cardiovascular disease cared for by a Pregnancy Heart Team had higher odds of reliable postpartum contraception planning and uptake compared with a low-risk cohort and similar odds compared with a high-risk cohort. Pregnancy could serve as a critical period for contraception counseling and family planning among people with cardiovascular disease. A multidisciplinary team should be used to address postpartum contraception as a modifiable risk factor to reduce maternal morbidity and mortality among those with cardiovascular disease., (© 2022 The Authors.)
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- 2022
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31. Impact of water flow rate on finishing pig performance.
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Miller HE, McClellan K, Perez-Palencia JY, Samuel RS, Levesque CL, and Thaler RC
- Abstract
A survey of 23 South Dakota pork producers in 2019 reported that 68% of the waterers in finishing barns had water flow rates above the recommended rate of 500-1,000 mL/min. The objective of the two studies was to determine the impact of water flow rate on finishing pig performance in the summer months. Study 1 used a total of 396 pigs in two groups in a 77-day trial (35.0 to 104.3 kg BW) with 6 pigs/pen and 1 cup waterer/pen. Study 2, conducted in a commercial style barn, used a total of 1,227 pigs in an 84-day trial (60.9 to 117.4 kg BW) with 26 pigs/pen and 2 cup waters/pen. Pens were assigned to one of three water flow rates (high, medium, low) based on the 3-hole settings of the water nipples (2.0, 1.0, and 0.8 mm; n = 22 and 16 pens/treatment for Study 1 and 2, respectively). Room temperature, outside temperature and relative humidity were recorded daily for both studies. In Study 1, water disappearance was recorded daily, and individual pen water flow rates were recorded every two weeks. At every diet phase change (26 ± 2.6 days), feed disappearance and individual pig body weights were recorded. Water flow rates averaged 1856 ± 188, 906 ± 214, 508 ± 100 mL/min for high, medium, and low flow settings, respectively. In Study 2, individual pen water flow rate, water disappearance, BW, and feed disappearance were recorded every two weeks. Water flow rates averaged 1115 ± 98, 906 ± 209, and 605 ± 203 mL/min for high, medium, and low flow settings, respectively. In both studies, there were no differences in final BW, cumulative ADG, or G:F. Due to the variability of water flow rate within a setting, data was further analyzed using regression with flow rate as the independent variable. Apart from average daily water disappearance (adj. R
2 = 0.87), there was a low relationship between pig performance and water flow rate (adj. R2 < 0.09). The low R2 values associated with pig performance and the high association with water disappearance suggests that water flow rate above current recommendations has little impact on finishing pig performance but does contribute to water wastage and its associated costs., (© The Author(s) 2022. Published by Oxford University Press on behalf of the American Society of Animal Science.)- Published
- 2022
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32. Quality-controlled R-loop meta-analysis reveals the characteristics of R-loop consensus regions.
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Miller HE, Montemayor D, Abdul J, Vines A, Levy SA, Hartono SR, Sharma K, Frost B, Chédin F, and Bishop AJR
- Subjects
- Consensus, DNA chemistry, Nucleic Acid Hybridization, R-Loop Structures, RNA chemistry, RNA genetics
- Abstract
R-loops are three-stranded nucleic acid structures formed from the hybridization of RNA and DNA. While the pathological consequences of R-loops have been well-studied to date, the locations, classes, and dynamics of physiological R-loops remain poorly understood. R-loop mapping studies provide insight into R-loop dynamics, but their findings are challenging to generalize. This is due to the narrow biological scope of individual studies, the limitations of each mapping modality, and, in some cases, poor data quality. In this study, we reprocessed 810 R-loop mapping datasets from a wide array of biological conditions and mapping modalities. From this data resource, we developed an accurate R-loop data quality control method, and we reveal the extent of poor-quality data within previously published studies. We then identified a set of high-confidence R-loop mapping samples and used them to define consensus R-loop sites called 'R-loop regions' (RL regions). In the process, we identified a stark divergence between RL regions detected by S9.6 and dRNH-based mapping methods, particularly with respect to R-loop size, location, and colocalization with RNA binding factors. Taken together, this work provides a much-needed method to assess R-loop data quality and offers novel context regarding the differences between dRNH- and S9.6-based R-loop mapping approaches., (© The Author(s) 2022. Published by Oxford University Press on behalf of Nucleic Acids Research.)
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- 2022
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33. Systematic Analysis of Long Non-Coding RNA Genes in Nonalcoholic Fatty Liver Disease.
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Ilieva M, Dao J, Miller HE, Madsen JH, Bishop AJR, Kauppinen S, and Uchida S
- Abstract
The largest solid organ in humans, the liver, performs a variety of functions to sustain life. When damaged, cells in the liver can regenerate themselves to maintain normal liver physiology. However, some damage is beyond repair, which necessitates liver transplantation. Increasing rates of obesity, Western diets (i.e., rich in processed carbohydrates and saturated fats), and cardiometabolic diseases are interlinked to liver diseases, including non-alcoholic fatty liver disease (NAFLD), which is a collective term to describe the excess accumulation of fat in the liver of people who drink little to no alcohol. Alarmingly, the prevalence of NAFLD extends to 25% of the world population, which calls for the urgent need to understand the disease mechanism of NAFLD. Here, we performed secondary analyses of published RNA sequencing (RNA-seq) data of NAFLD patients compared to healthy and obese individuals to identify long non-coding RNAs (lncRNAs) that may underly the disease mechanism of NAFLD. Similar to protein-coding genes, many lncRNAs are dysregulated in NAFLD patients compared to healthy and obese individuals, suggesting that understanding the functions of dysregulated lncRNAs may shed light on the pathology of NAFLD. To demonstrate the functional importance of lncRNAs in the liver, loss-of-function experiments were performed for one NAFLD-related lncRNA, LINC01639 , which showed that it is involved in the regulation of genes related to apoptosis, TNF/TGF, cytokine signaling, and growth factors as well as genes upregulated in NAFLD. Since there is no lncRNA database focused on the liver, especially NAFLD, we built a web database, LiverDB, to further facilitate functional and mechanistic studies of hepatic lncRNAs.
- Published
- 2022
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34. Development and characterization of a mass cytometry panel for detecting the effect of acute doxorubicin exposure on murine cardiac nonmyocytes.
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Iskra BS, Davis L, Miller HE, Chiu YC, Bishop AJR, Chen Y, and Aune GJ
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- Animals, Antibiotics, Antineoplastic toxicity, Doxorubicin toxicity, Heart, Mice, Myocytes, Cardiac, Cardiotoxicity, Endothelial Cells pathology
- Abstract
Childhood cancer survivors (CCSs) face lifelong side effects related to their treatment with chemotherapy. Anthracycline agents, such as doxorubicin (DOX), are important in the treatment of childhood cancers but are associated with cardiotoxicity. Cardiac toxicities represent a significant source of chronic disability that cancer survivors face; despite this, the chronic cardiotoxicity phenotype and how it relates to acute toxicity remains poorly defined. To address this critical knowledge gap, we studied the acute effect of DOX on murine cardiac nonmyocytes in vivo. Determination of the acute cellular effects of DOX on nonmyocytes, a cell pool with finite replicative capacity, provides a basis for understanding the pathogenesis of the chronic heart disease that CCSs face. To investigate the acute cellular effects of DOX, we present single-cell RNA sequencing (scRNAseq) data from homeostatic cardiac nonmyocytes and compare it with preexisting datasets, as well as a novel CyTOF datasets. SCANPY, a python-based single-cell analysis, was used to assess the heterogeneity of cells detected in scRNAseq and CyTOF. To further assist in CyTOF data annotation, joint analyses of scRNAseq and CyTOF data using an artificial neural network known as sparse autoencoder for clustering, imputation, and embedding (SAUCIE) are performed. Lastly, the panel is tested on a mouse model of acute DOX exposure at two time points (24 and 72 h) after the last dose of doxorubicin and examined with joint clustering. In sum, we report the first ever CyTOF study of cardiac nonmyocytes and characterize the effect of acute DOX exposure with scRNAseq and CyTOF. NEW & NOTEWORTHY We describe the first mass cytometry studies of murine cardiac nonmyocytes. The mass cytometry panel is compared with single-cell RNA sequencing data. Homeostatic cardiac nonmyocytes are characterized by mass cytometry to identify and quantify four major cell populations: endothelial cells, fibroblasts, leukocytes, and pericytes. The single-cell acute nonmyocyte response to doxorubicin is studied at 24 and 72 h after doxorubicin exposure given daily for 5 days at a dose of 4 mg/kg/day.
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- 2022
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35. Uterine atony.
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Miller HE and Ansari JR
- Subjects
- Female, Humans, Oxytocin therapeutic use, Pregnancy, Misoprostol therapeutic use, Oxytocics therapeutic use, Postpartum Hemorrhage etiology, Postpartum Hemorrhage prevention & control, Uterine Inertia chemically induced, Uterine Inertia drug therapy
- Abstract
Purpose of Review: Postpartum hemorrhage (PPH) is the leading preventable cause of maternal morbidity and mortality worldwide. Uterine atony is identified as the underlying etiology in up to 80% of PPH. This serves as a contemporary review of the epidemiology, risk factors, pathophysiology, and treatment of uterine atony., Recent Findings: Rates of postpartum hemorrhage continue to rise worldwide with the largest fraction attributed to uterine atony. A simple 0-10 numerical rating score for uterine tone was recently validated for use during cesarean delivery and may allow for more standardized assessment in clinical and research settings. The optimal prophylactic dose of oxytocin differs depending on the patient population, but less than 5 units and as low as a fraction of one unit is needed for PPH prevention, with an increased requirements within that range for cesarean birth, those on magnesium, and advanced maternal age. Carbetocin is an appropriate alternative to oxytocin. Misoprostol shows limited to no efficacy for uterine atony in recent studies. Several uncontrolled case studies demonstrate novel mechanical and surgical interventions for treating uterine atony., Summary: There is a critical, unmet need for contemporary, controlled studies to address the increasing threat of atonic PPH., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)
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- 2022
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36. Current Status of Epitranscriptomic Marks Affecting lncRNA Structures and Functions.
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Miller HE, Ilieva M, Bishop AJR, and Uchida S
- Abstract
Long non-coding RNAs (lncRNAs) belong to a class of non-protein-coding RNAs with their lengths longer than 200 nucleotides. Most of the mammalian genome is transcribed as RNA, yet only a small percent of the transcribed RNA corresponds to exons of protein-coding genes. Thus, the number of lncRNAs is predicted to be several times higher than that of protein-coding genes. Because of sheer number of lncRNAs, it is often difficult to elucidate the functions of all lncRNAs, especially those arising from their relationship to their binding partners, such as DNA, RNA, and proteins. Due to their binding to other macromolecules, it has become evident that the structures of lncRNAs influence their functions. In this regard, the recent development of epitranscriptomics (the field of study to investigate RNA modifications) has become important to further elucidate the structures and functions of lncRNAs. In this review, the current status of lncRNA structures and functions influenced by epitranscriptomic marks is discussed.
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- 2022
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37. FibroDB: Expression Analysis of Protein-Coding and Long Non-Coding RNA Genes in Fibrosis.
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Ilieva M, Miller HE, Agarwal A, Paulus GK, Madsen JH, Bishop AJR, Kauppinen S, and Uchida S
- Abstract
Most long non-coding RNAs (lncRNAs) are expressed at lower levels than protein-coding genes and their expression is often restricted to specific cell types, certain time points during development, and various stress and disease conditions, respectively. To revisit this long-held concept, we focused on fibroblasts, a common cell type in various organs and tissues. Using fibroblasts and changes in their expression profiles during fibrosis as a model system, we show that the overall expression level of lncRNA genes is significantly lower than that of protein-coding genes. Furthermore, we identified lncRNA genes whose expression is upregulated during fibrosis. Using dermal fibroblasts as a model, we performed loss-of-function experiments and show that the knockdown of the lncRNAs LINC00622 and LINC01711 result in gene expression changes associated with cellular and inflammatory responses, respectively. Since there are no lncRNA databases focused on fibroblasts and fibrosis, we built a web application, FibroDB, to further promote functional and mechanistic studies of fibrotic lncRNAs.
- Published
- 2022
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38. Clinical factors associated with a positive postpartum depression screen in people with cardiac disease during pregnancy.
- Author
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Panelli DM, Sherwin EB, Lee CJ, Leonard SA, Miller SE, Miller HE, Tolani AT, Hoover V, Ansari JR, Khandelwal A, and Bianco K
- Abstract
Background: While people with cardiac disease are known to be at increased lifetime risk of depression, little is known about postpartum depression rates in this population. Describing rates of positive postpartum depression screens and identifying risk factors that are unique to cardiac patients may help inform risk reduction strategies., Methods: This retrospective cohort study included pregnant patients with congenital and/or acquired cardiac disease who delivered at a single institution between 2014 and 2020. The primary outcome was a positive postpartum depression screen, defined as Edinburgh Postpartum Depression Score (EPDS) ≥10. Potential exposures were selected a priori and compared between patients with and without a positive postpartum depression screen using Wilcoxon rank-sum and Fisher's exact tests. Secondary outcomes were responses to a longitudinal follow-up survey sent to English-speaking patients evaluating cardiac status, mental health, and infant development., Results: Of 126 eligible cardiac patients, 23 (18.3%) had a positive postpartum depression screen. Patients with a positive postpartum depression screen were more likely to have had antepartum anticoagulation with heparin or enoxaparin (56.5% versus 26.2%, p=0.007), blood transfusion during delivery (8.7% versus 0%, p=0.032), and maternal-infant separation postpartum (52.2% versus 28.2%, p=0.047) compared to patients with a negative screen. Among 29 patients with a positive screen who responded to the follow up survey, 50% reported being formally diagnosed with anxiety or depression and 33.3% reported child development problems., Conclusions: Our results highlight the importance of screening for postpartum depression in patients with cardiac disease, especially those requiring antepartum anticoagulation or maternal-infant separation postpartum., Competing Interests: Conflict of Interest The authors declare that they have no conflict of interest.
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- 2022
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39. Improvements in Speech of Children with Apraxia: The Efficacy of Treatment for Establishing Motor Program Organization (TEMPO SM ).
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Miller HE, Ballard KJ, Campbell J, Smith M, Plante AS, Aytur SA, and Robin DA
- Subjects
- Child, Child, Preschool, Cyclic N-Oxides, Humans, Speech Disorders, Speech Therapy, Apraxias, Speech
- Abstract
Purpose : This study investigated the efficacy of Treatment for Establishing Motor Program Organization (TEMPO
SM ) in childhood apraxia of speech (CAS). Method: A mixed between- and within-participant design with multiple baselines across participants and behaviors was used to examine acquisition, generalization, and maintenance of skills. TEMPOSM was administered in four one-hour sessions a week over a four-week period for eleven participants (ages 5 to 8), allocated to either an immediate treatment group or a wait-list control group. Acoustic and perceptual variables were measured at baseline, immediate post-treatment, and one-month post-treatment. Results: Children demonstrated significant improvements in specific acoustic measures of segmentation and lexical stress, as well as perceptual measures of fluency, lexical stress, and speech-sound accuracy. Treatment and generalization effects were maintained one-month post-treatment with generalization to untreated stimuli. Conclusion: TEMPOSM was efficacious in improving segmental and suprasegmental impairments in the speech of children with CAS.- Published
- 2021
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40. The impact of the COVID-19 pandemic on postpartum contraception planning.
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Miller HE, Henkel A, Leonard SA, Miller SE, Tran L, Bianco K, and Shaw KA
- Subjects
- Adult, Contraception, Female, Humans, Infant, Newborn, Pandemics, Postpartum Period, Pregnancy, Retrospective Studies, SARS-CoV-2, COVID-19, Maternal Health Services
- Abstract
Objective: The COVID-19 pandemic necessitated rapid adjustment of obstetrical delivery models including fewer antenatal appointments and increased use of telehealth. We hypothesized that an increase in telemedicine and a decrease in antepartum visits owing to the COVID-19 pandemic led to a decreased proportion of people with a postpartum contraception plan at the time of the birth-hospitalization admission and a reduced uptake of top-tier forms of contraception at birth-hospitalization admission and discharge, and the routine postpartum visit, which has otherwise been increasing in recent years.
1 , 2 STUDY DESIGN: A retrospective cohort study comparing a randomly selected sample of people giving birth at a large, tertiary referral center during a regional "shelter in place" order, March 16, 2020, to July 31, 2020, with a previously abstracted random sample of people delivering between November 1, 2017, and April 30, 2018, was conducted. This study was reviewed and approved by the Stanford University Institutional Review Board before its initiation. The study was powered to detect a 10% difference in the proportion of those arriving at birth-hospitalization with a contraceptive plan (power 80%, alpha 0.05). The final sample size included 586 people (318 in the pre-COVID cohort and 268 in the COVID cohort). Multivariable modified Poisson regression model was used to estimate the relative risk of arriving at birth-hospitalization with a contraceptive plan in pre-COVID vs COVID cohorts, adjusting for age, parity, insurance status, and delivery mode. Secondary outcomes included tier of contraception plan at admission, discharge, and 6 weeks postpartum (classified by World Health Organization Tiered-Effectiveness3 ), attendance at postpartum visit, and whether the postpartum visit was conducted via telehealth. Tiered effectiveness was used for this study's purposes because it was hypothesized that telehealth would mostly affect the provision of top-tier forms of contraception that require in-person initiation. Fisher exact test was used to compare the secondary outcomes., Results: For the 2 cohorts, the median age was 32 years (range, 17-48 years) and median parity was 1 (range, 0-6). The majority (78%) had private insurance and most commonly identified as non-Hispanic White (38%) and Asian (36%). Baseline demographics did not differ between the cohorts. At birth-hospitalization admission, a smaller proportion of people had a postpartum contraceptive plan in the COVID cohort than in the pre-COVID cohort (73.9% vs 99.4%, adjusted risk ratio, 0.87; 95% confidence interval, 0.84-0.91, P<.001). A smaller proportion of people had a plan for top-tier contraception among the COVID cohort compared with the pre-COVID cohort at both admission and discharge (46.0% vs 71.0%, P<.01 and 31.0% vs 37.9%, P=.05) (Figure). More than 80% of the people attended a routine postpartum visit in both cohorts (P=.30) with 17.7% being telehealth visits in the COVID cohort compared with telehealth not being offered pre-COVID. Among those who attended their postpartum visit, the proportion discharged with a plan for interval top-tier contraception that was fulfilled was high in both groups (76.3% pre-COVID vs 71.2% post-COVID, P=.56)., Conclusion: The study found a significant decrease in people arriving at birth-hospitalization with a contraception plan in the months following a COVID-19 "shelter in place" order when compared with the pre-COVID cohort. It is suspected that changes in the obstetrical service models indirectly deprioritized the most effective forms of postpartum contraception because sterilization requires a signed consent before birth-hospitalization and postplacental intrauterine devices require consent before delivery.4 , 5 Current state legislation requiring in-person signature to consent for federally funded sterilization remains a barrier. We found that fewer individuals left with top-tier contraception than with plan on admission, especially within the COVID cohort. In addition to clinical contraindications that arise during labor, which preclude placement of an intrauterine device in the postpartum setting, many patients requested an expedited discharge during the peak of the COVID-19 pandemic. As the prenatal care model continues, this transition to adopt virtual visits, reduce visit schedules, and expedite postpartum discharge, actualizing patients' contraceptive plans is increasingly more dependent on early inpatient provision. Maternity care providers should consider initiating postpartum contraception counseling and completing mandatory consents earlier in the antenatal period. This study is inherently limited by its retrospective nature of review and additional qualitative studies may better characterize this trend in contraceptive uptake. In the meantime, obstetrical care providers should carefully evaluate institutional barriers to postpartum contraception during this movement to telehealth., (Copyright © 2021 Elsevier Inc. All rights reserved.)- Published
- 2021
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41. Correlation AnalyzeR: functional predictions from gene co-expression correlations.
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Miller HE and Bishop AJR
- Subjects
- Computational Biology, Databases, Factual, Gene Expression, Phenotype, Gene Expression Profiling, Software
- Abstract
Background: Co-expression correlations provide the ability to predict gene functionality within specific biological contexts, such as different tissue and disease conditions. However, current gene co-expression databases generally do not consider biological context. In addition, these tools often implement a limited range of unsophisticated analysis approaches, diminishing their utility for exploring gene functionality and gene relationships. Furthermore, they typically do not provide the summary visualizations necessary to communicate these results, posing a significant barrier to their utilization by biologists without computational skills., Results: We present Correlation AnalyzeR, a user-friendly web interface for exploring co-expression correlations and predicting gene functions, gene-gene relationships, and gene set topology. Correlation AnalyzeR provides flexible access to its database of tissue and disease-specific (cancer vs normal) genome-wide co-expression correlations, and it also implements a suite of sophisticated computational tools for generating functional predictions with user-friendly visualizations. In the usage example provided here, we explore the role of BRCA1-NRF2 interplay in the context of bone cancer, demonstrating how Correlation AnalyzeR can be effectively implemented to generate and support novel hypotheses., Conclusions: Correlation AnalyzeR facilitates the exploration of poorly characterized genes and gene relationships to reveal novel biological insights. The database and all analysis methods can be accessed as a web application at https://gccri.bishop-lab.uthscsa.edu/correlation-analyzer/ and as a standalone R package at https://github.com/Bishop-Laboratory/correlationAnalyzeR .
- Published
- 2021
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42. Neural substrates of verbal repetition deficits in primary progressive aphasia.
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Miller HE, Cordella C, Collins JA, Ezzo R, Quimby M, Hochberg D, Tourville JA, Dickerson BC, and Guenther FH
- Abstract
In this cross-sectional study, we examined the relationship between cortical thickness and performance on several verbal repetition tasks in a cohort of patients with primary progressive aphasia in order to test predictions generated by theoretical accounts of phonological working memory that predict phonological content buffers in left posterior inferior frontal sulcus and supramarginal gyrus. Cortical surfaces were reconstructed from magnetic resonance imaging scans from 42 participants diagnosed with primary progressive aphasia. Cortical thickness was measured in a set of anatomical regions spanning the entire cerebral cortex. Correlation analyses were performed between cortical thickness and average score across three phonological working memory-related tasks: the Repetition sub-test from the Western Aphasia Battery, a forward digit span task, and a backward digit span task. Significant correlations were found between average working memory score across tasks and cortical thickness in left supramarginal gyrus and left posterior inferior frontal sulcus, in support of prior theoretical accounts of phonological working memory. Exploratory whole-brain correlation analyses performed for each of the three behavioural tasks individually revealed a distinct set of positively correlated regions for each task. Comparison of cortical thickness measures from different primary progressive aphasia sub-types to cortical thickness in age-matched controls further revealed unique patterns of atrophy in the different subtypes., (© The Author(s) (2021). Published by Oxford University Press on behalf of the Guarantors of Brain.)
- Published
- 2021
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43. Modelling speech motor programming and apraxia of speech in the DIVA/GODIVA neurocomputational framework.
- Author
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Miller HE and Guenther FH
- Abstract
Background: The Directions Into Velocities of Articulators (DIVA) model and its partner, the Gradient Order DIVA (GODIVA) model, provide neurobiologically grounded, computational accounts of speech motor control and motor sequencing, with applications for the study and treatment of neurological motor speech disorders., Aims: In this review, we provide an overview of the DIVA and GODIVA models and how they explain the interface between phonological and motor planning systems to build on previous models and provide a mechanistic accounting of apraxia of speech (AOS), a disorder of speech motor programming., Main Contribution: Combined, the DIVA and GODIVA models account for both the segmental and suprasegmental features that define AOS via damage to (i) a speech sound map, hypothesized to reside in left ventral premotor cortex, (ii) a phonological content buffer hypothesized to reside in left posterior inferior frontal sulcus, and/or (iii) the axonal projections between these regions. This account is in line with a large body of behavioural work, and it unifies several prior theoretical accounts of AOS., Conclusions: The DIVA and GODIVA models provide an integrated framework for the generation and testing of both behavioural and neuroimaging hypotheses about the underlying neural mechanisms responsible for motor programming in typical speakers and in speakers with AOS.
- Published
- 2021
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44. Placenta Accreta Spectrum Among Women With Twin Gestations.
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Miller HE, Leonard SA, Fox KA, Carusi DA, and Lyell DJ
- Subjects
- Adult, California epidemiology, Female, Humans, Placenta Accreta etiology, Pregnancy, Retrospective Studies, Risk Factors, Placenta Accreta epidemiology, Pregnancy, Twin statistics & numerical data
- Abstract
Objective: To assess whether placenta accreta spectrum occurs more frequently among women with twin gestations compared with singleton gestations., Methods: All live births in California from 2016 to 2017 were identified from previously linked records of birth certificates and birth hospitalization discharges. The primary outcome was placenta accreta spectrum (which includes placenta accreta, increta, and percreta), identified using International Classification of Diseases, Tenth Revision, Clinical Modification codes (O43.2x) for placenta accreta, increta, and percreta. We analyzed the association between twin gestation and placenta accreta spectrum by using multivariable logistic regression and assessed whether our findings were replicated by using a previously validated International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM)-based approach., Results: Among 918,452 live births, 1,126 were diagnosed with placenta accreta spectrum. The prevalence of placenta accreta spectrum was 11.8 per 10,000 among singleton pregnancies and 41.6 per 10,000 among twin pregnancies. In the unadjusted regression analysis, twin pregnancy was associated with higher relative risk of placenta accreta spectrum (RR 3.41, 95% CI 2.57-4.52). After adjusting the regression model for maternal age, previous cesarean birth, and sociodemographic factors, the association held with higher relative risk of placenta accreta spectrum (aRR 2.96, 95% CI 2.23-3.93). Women with twin compared with singleton gestations with placenta accreta spectrum were less likely to have placenta previa. When assessed using ICD-9-CM codes, placenta accreta spectrum was similarly more prevalent among twins than singletons, with an increase in the relative risk of placenta accreta spectrum (aRR 2.45, 95% CI 2.33-3.25)., Conclusion: Twin gestation conferred an increased risk for placenta accreta spectrum independent of measured risk factors, which may contribute to increased maternal morbidity in twin gestation compared with singleton gestation. Clinicians should be aware of the increased risk for placenta accreta spectrum in twin gestation and should consider it during ultrasonographic screening., Competing Interests: Financial Disclosure Stephanie A. Leonard reports receiving funding from Stanford University (internal department funds). Karin A. Fox reports that money was paid to her institution from the NICHD (RO1 Vascular MRI in Placenta Accreta) and SMFM (Banner Health-Critical Care OB Course honorarium). Money was paid to her from Wolters Kluwer (UpToDate authorship honorarium) and Symposia Medicus (lecture honorarium paid to me [ongoing]; Billion to One [past], grant paid to institution). Daniela A. Carusi reports receiving funding from Wolters Kluwer and The Hess Foundation. Deirdre J. Lyell reports receiving funding from Bloomlife (stock options for consultancy), Wolters Kluwer (UpToDate authorship honorarium), SMFM (Banner Health-Critical Care OB Course honorarium), and she is a stockholder in ZenFlow (privately held medical device company). Hayley E. Miller did not report any potential conflicts of interest., (Copyright © 2020 by the American College of Obstetricians and Gynecologists. Published by Wolters Kluwer Health, Inc. All rights reserved.)
- Published
- 2021
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45. Integration of memory content in adults and children: Developmental differences in task conditions and functional consequences.
- Author
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Bauer PJ, Cronin-Golomb LM, Porter BM, Jaganjac A, and Miller HE
- Abstract
How separate yet related episodes of experience are associated in memory is a major question in cognitive science and cognitive neuroscience. Adults and children both integrate content acquired in separate episodes, yet they may do so under different task conditions. Neuroimaging studies suggest that adults integrate the contents of separate memory traces at encoding and thus without an explicit prompt; behavioral studies suggest that children do so only when specifically prompted. In the present research, we developed a novel paradigm to test integration of memory content using eye-gaze in an indirect (unprompted) test and self-derivation of new factual knowledge based on related facts in direct (open-ended and forced-choice) tests. To permit use of color images to accompany the stimuli, we developed a procedure for equating color images on 23 low-level properties that otherwise might control eye-gaze behavior. We used the paradigm with adults (Experiment 1) and 7- to 9-year-old children (Experiment 2). Both groups succeeded on the direct tests. Among adults, unprompted integration of memory content (in the indirect test) was apparent and supported open-ended self-derivation (in the direct test). Across trials, children did not show evidence of unprompted integration of memory content and performance during the unprompted indirect test did not support open-ended self-derivation; longer looking to target versus foil images during the indirect test was related to direct test performance under forced-choice conditions, however. The patterns indicate that adults and children engage the process of integration of memory content under different task conditions, and that when integration processes take place without an explicit prompt they have different functional consequences for adults and children. (PsycInfo Database Record (c) 2020 APA, all rights reserved).
- Published
- 2020
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46. Speech and Gesture Production Provide Unique Insights Into Young Children's Spatial Reasoning.
- Author
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Miller HE, Andrews CA, and Simmering VR
- Subjects
- Child, Child, Preschool, Female, Humans, Male, Child Development physiology, Gestures, Language, Space Perception physiology, Speech physiology, Thinking physiology
- Abstract
This study took a novel approach to understanding the role of language in spatial development by combining approaches from spatial language and gesture research. It analyzed forty-three 4.5- to 6-year-old's speech and gesture production during explanations of reasoning behind performance on Spatial Analogies and Children's Mental Transformation Tasks. Results showed that speech and gesture relevant for solving the trials (disambiguating correct choices) predicted spatial performance when controlling for age, gender, and spatial words and gestures produced. Children performed the spatial tasks well if they produced relevant information either verbally through speech or nonverbally through gesture. These results highlight the importance of not only focusing on concepts children can reference but also on how such concepts are used in spatial tasks., (© 2020 Society for Research in Child Development.)
- Published
- 2020
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47. Drainage, irrigation and fibrinolytic therapy (DRIFT) for posthaemorrhagic ventricular dilatation: 10-year follow-up of a randomised controlled trial.
- Author
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Luyt K, Jary SL, Lea CL, Young GJ, Odd DE, Miller HE, Kmita G, Williams C, Blair PS, Hollingworth W, Morgan M, Smith-Collins AP, Walker-Cox S, Aquilina K, Pople I, and Whitelaw AG
- Subjects
- Cerebral Intraventricular Hemorrhage complications, Child, Child Behavior, Child, Preschool, Dilatation, Pathologic, Drainage methods, Female, Follow-Up Studies, Heart Ventricles physiopathology, Humans, Infant, Infant, Newborn, Infant, Premature, Male, Spinal Puncture, Therapeutic Irrigation methods, Thrombolytic Therapy methods, Visual Acuity, Cerebral Intraventricular Hemorrhage therapy, Cognitive Dysfunction prevention & control, Infant, Premature, Diseases therapy
- Abstract
Background: Progressive ventricular dilatation after intraventricular haemorrhage (IVH) in preterm infants has a very high risk of severe disability and death. Drainage, irrigation and fibrinolytic therapy (DRIFT), in a randomised controlled trial (RCT), reduced severe cognitive impairment at 2 years., Objective: To assess if the cognitive advantage of DRIFT seen at 2 years persisted until school age., Participants: The RCT conducted in four centres recruited 77 preterm infants with IVH and progressive ventricular enlargement over specified measurements. Follow-up was at 10 years of age., Intervention: Intraventricular injection of a fibrinolytic followed by continuous lavage, until the drainage was clear, and standard care consisting of control of expansion by lumbar punctures and if expansion persisted via a ventricular access device., Primary Outcome: Cognitive quotient (CQ), derived from the British Ability Scales and Bayley III Scales, and survival without severe cognitive disability., Results: Of the 77 children randomised, 12 died, 2 could not be traced, 10 did not respond and 1 declined at 10-year follow-up. 28 in the DRIFT group and 24 in the standard treatment group were assessed by examiners blinded to the intervention. The mean CQ score was 69.3 (SD=30.1) in the DRIFT group and 53.7 (SD=35.7) in the standard treatment group (unadjusted p=0.1; adjusted p=0.01, after adjustment for the prespecified variables sex, birth weight and IVH grade). Survival without severe cognitive disability was 66% in the DRIFT group and 35% in the standard treatment group (unadjusted p=0.019; adjusted p=0.003)., Conclusion: DRIFT is the first intervention for posthaemorrhagic ventricular dilatation to objectively demonstrate sustained cognitive improvement., Trial Registration Number: ISRCTN80286058., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY. Published by BMJ.)
- Published
- 2020
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48. Pathogenic Tau Causes a Toxic Depletion of Nuclear Calcium.
- Author
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Mahoney R, Ochoa Thomas E, Ramirez P, Miller HE, Beckmann A, Zuniga G, Dobrowolski R, and Frost B
- Subjects
- Alzheimer Disease genetics, Alzheimer Disease metabolism, Alzheimer Disease pathology, Animals, Animals, Genetically Modified, Brain metabolism, Cyclic AMP Response Element-Binding Protein metabolism, Drosophila melanogaster genetics, Drosophila melanogaster metabolism, Gene Expression Profiling, Gene Expression Regulation, Induced Pluripotent Stem Cells metabolism, Membrane Potentials, Neurons metabolism, Neurotoxins toxicity, Calcium metabolism, Cell Nucleus metabolism, tau Proteins metabolism
- Abstract
Synaptic activity-induced calcium (Ca
2+ ) influx and subsequent propagation into the nucleus is a major way in which synapses communicate with the nucleus to regulate transcriptional programs important for activity-dependent survival and memory formation. Nuclear Ca2+ shapes the transcriptome by regulating cyclic AMP (cAMP) response element-binding protein (CREB). Here, we utilize a Drosophila model of tauopathy and induced pluripotent stem cell (iPSC)-derived neurons from humans with Alzheimer's disease to study the effects of pathogenic tau, a pathological hallmark of Alzheimer's disease and related tauopathies, on nuclear Ca2+ . We find that pathogenic tau depletes nuclear Ca2+ and CREB to drive neuronal death, that CREB-regulated genes are over-represented among differentially expressed genes in tau transgenic Drosophila, and that activation of big potassium (BK) channels elevates nuclear Ca2+ and suppresses tau-induced neurotoxicity. Our studies identify nuclear Ca2+ depletion as a mechanism contributing to tau-induced neurotoxicity, adding an important dimension to the calcium hypothesis of Alzheimer's disease., Competing Interests: Declaration of Interests The authors declare no competing interests., (Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.)- Published
- 2020
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49. Cohesin SA1 and SA2 are RNA binding proteins that localize to RNA containing regions on DNA.
- Author
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Pan H, Jin M, Ghadiyaram A, Kaur P, Miller HE, Ta HM, Liu M, Fan Y, Mahn C, Gorthi A, You C, Piehler J, Riehn R, Bishop AJR, Tao YJ, and Wang H
- Subjects
- Binding Sites, DNA metabolism, RNA metabolism, Cohesins, Cell Cycle Proteins metabolism, Chromosomal Proteins, Non-Histone metabolism, R-Loop Structures, RNA-Binding Proteins metabolism
- Abstract
Cohesin SA1 (STAG1) and SA2 (STAG2) are key components of the cohesin complex. Previous studies have highlighted the unique contributions by SA1 and SA2 to 3D chromatin organization, DNA replication fork progression, and DNA double-strand break (DSB) repair. Recently, we discovered that cohesin SA1 and SA2 are DNA binding proteins. Given the recently discovered link between SA2 and RNA-mediated biological pathways, we investigated whether or not SA1 and SA2 directly bind to RNA using a combination of bulk biochemical assays and single-molecule techniques, including atomic force microscopy (AFM) and the DNA tightrope assay. We discovered that both SA1 and SA2 bind to various RNA containing substrates, including ssRNA, dsRNA, RNA:DNA hybrids, and R-loops. Importantly, both SA1 and SA2 localize to regions on dsDNA that contain RNA. We directly compared the SA1/SA2 binding and R-loops sites extracted from Chromatin Immunoprecipitation sequencing (ChIP-seq) and DNA-RNA Immunoprecipitation sequencing (DRIP-Seq) data sets, respectively. This analysis revealed that SA1 and SA2 binding sites overlap significantly with R-loops. The majority of R-loop-localized SA1 and SA2 are also sites where other subunits of the cohesin complex bind. These results provide a new direction for future investigation of the diverse biological functions of SA1 and SA2., (© The Author(s) 2020. Published by Oxford University Press on behalf of Nucleic Acids Research.)
- Published
- 2020
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50. Connect the Dots-May 2020.
- Author
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Miller HE, Gentile ND, Holton SM, and Chescheir NC
- Published
- 2020
- Full Text
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