Impact of hypertensive disorders of pregnancy and gestational diabetes mellitus on offspring cardiovascular health in early adolescence.

BACKGROUND: Adverse pregnancy outcomes, including hypertensive disorders of pregnancy and gestational diabetes mellitus, influence maternal cardiovascular health long after pregnancy, but their relationship to offspring cardiovascular health following in-utero exposure remains uncertain. OBJECTIVE: To examine associations of hypertensive disorders of pregnancy or gestational diabetes mellitus with offspring cardiovascular health in early adolescence. STUDY DESIGN: This analysis used data from the prospective Hyperglycemia and Adverse Pregnancy Outcome Study from 2000 to 2006 and the Hyperglycemia and Adverse Pregnancy Outcome Follow-Up Study from 2013 to 2016. This analysis included 3317 mother-child dyads from 10 field centers, comprising 70.8% of Hyperglycemia and Adverse Pregnancy Outcome Follow-Up Study participants. Those with pregestational diabetes and chronic hypertension were excluded. The exposures included having any hypertensive disorders of pregnancy or gestational diabetes mellitus vs not having hypertensive disorders of pregnancy or gestational diabetes mellitus, respectively (reference). The outcome was offspring cardiovascular health when aged 10-14 years, on the basis of 4 metrics: body mass index, blood pressure, total cholesterol level, and glucose level. Each metric was categorized as ideal, intermediate, or poor using a framework provided by the American Heart Association. The primary outcome was defined as having at least 1 cardiovascular health metric that was nonideal vs all ideal (reference), and the second outcome was the number of nonideal cardiovascular health metrics (ie, at least 1 intermediate metric, 1 poor metric, or at least 2 poor metrics vs all ideal [reference]). Modified poisson regression with robust error variance was used and adjusted for covariates at pregnancy enrollment, including field center, parity, age, gestational age, alcohol or tobacco use, child's assigned sex at birth, and child's age at follow-up. RESULTS: Among 3317 maternal-child dyads, the median (interquartile) ages were 30.4 (25.6-33.9) years for pregnant individuals and 11.6 (10.9-12.3) years for children. During pregnancy, 10.4% of individuals developed hypertensive disorders of pregnancy, and 14.6% developed gestational diabetes mellitus. At follow-up, 55.5% of offspring had at least 1 nonideal cardiovascular health metric. In adjusted models, having hypertensive disorders of pregnancy (adjusted risk ratio, 1.14 [95% confidence interval, 1.04-1.25]) or having gestational diabetes mellitus (adjusted risk ratio, 1.10 [95% confidence interval, 1.02-1.19]) was associated with a greater risk that offspring developed less-than-ideal cardiovascular health when aged 10-14 years. The above associations strengthened in magnitude as the severity of adverse cardiovascular health metrics increased (ie, with the outcome measured as ≥1 intermediate, 1 poor, and ≥2 poor adverse metrics), albeit the only statistically significant association was with the "1-poor-metric" exposure. CONCLUSION: In this multinational prospective cohort, pregnant individuals who experienced either hypertensive disorders of pregnancy or gestational diabetes mellitus were at significantly increased risk of having offspring with worse cardiovascular health in early adolescence. Reducing adverse pregnancy outcomes and increasing surveillance with targeted interventions after an adverse pregnancy outcome should be studied as potential avenues to enhance long-term cardiovascular health in the offspring exposed in utero.

Socioeconomic Disadvantage in Pregnancy and Postpartum Risk of Cardiovascular Disease.

BACKGROUND: Pregnancy is an educable and actionable life stage to address social determinants of health (SDOH) and lifelong cardiovascular disease (CVD) prevention. But the link between a risk score that combines multiple neighborhood-level social determinants in pregnancy and the risk of long-term CVD remains to be evaluated. OBJECTIVE: To examine whether neighborhood-level socioeconomic disadvantage measured by the Area Deprivation Index (ADI) in early pregnancy is associated with a higher 30-year predicted risk of CVD postpartum, as measured by the Framingham Risk Score. METHODS: An analysis of data from the prospective Nulliparous Pregnancy Outcomes Study-Monitoring Mothers-to-Be (nuMoM2b) Heart Health Study longitudinal cohort. Participant home addresses during early pregnancy were geocoded at the Census-block level. The exposure was neighborhood-level socioeconomic disadvantage using the 2015 ADI by tertile (least deprived [T1], reference; most deprived [T3]) measured in the first trimester. Outcomes were the predicted 30-year risks of atherosclerotic CVD (ASCVD, composite of fatal and non-fatal coronary heart disease and stroke) and total CVD (composite of ASCVD plus coronary insufficiency, angina pectoris, transient ischemic attack, intermittent claudication, and heart failure) using the Framingham Risk Score measured 2-to-7 years after delivery. These outcomes were assessed as continuous measures of absolute estimated risk in increments of 1%, and, secondarily, as categorical measures with high-risk defined as an estimated probability of CVD >10%. Multivariable linear regression and modified Poisson regression models adjusted for baseline age and individual-level social determinants, including health insurance, educational attainment, and household poverty. RESULTS: Among 4,309 nulliparous individuals at baseline, the median age was 27 years (IQR: 23-31) and the median ADI was 43 (IQR: 22-74). At 2-to-7 years postpartum (median: 3.1 years, IQR: 2.5, 3.7), the median 30-year risk of ASCVD was 2.3% (IQR: 1.5, 3.5) and of total CVD was 5.5% (IQR: 3.7, 7.9); 2.2% and 14.3% of individuals had predicted 30-year risk >10%, respectively. Individuals living in the highest ADI tertile had a higher predicted risk of 30-year ASCVD % (adj. ß: 0.41; 95% CI: 0.19, 0.63) compared with those in the lowest tertile; and those living in the top two ADI tertiles had higher absolute risks of 30-year total CVD % (T2: adj. ß: 0.37; 95% CI: 0.03, 0.72; T3: adj. ß: 0.74; 95% CI: 0.36, 1.13). Similarly, individuals living in neighborhoods in the highest ADI tertile were more likely to have a high 30-year predicted risk of ASCVD (aRR: 2.21; 95% CI: 1.21, 4.02) and total CVD ≥10% (aRR: 1.35; 95% CI: 1.08, 1.69). CONCLUSIONS: Neighborhood-level socioeconomic disadvantage in early pregnancy was associated with a higher estimated long-term risk of CVD postpartum. Incorporating aggregated SDOH into existing clinical workflows and future research in pregnancy could reduce disparities in maternal cardiovascular health across the lifespan, and requires further study.

Genome-Wide Analysis of the Oat (Avena sativa) HSP90 Gene Family Reveals Its Identification, Evolution, and Response to Abiotic Stress.

Oats (Avena sativa) are an important cereal crop and cool-season forage worldwide. Heat shock protein 90 (HSP90) is a protein ubiquitously expressed in response to heat stress in almost all plants. To date, the HSP90 gene family has not been comprehensively reported in oats. Herein, we have identified twenty HSP90 genes in oats and elucidated their evolutionary pathways and responses to five abiotic stresses. The gene structure and motif analyses demonstrated consistency across the phylogenetic tree branches, and the groups exhibited relative structural conservation. Additionally, we identified ten pairs of segmentally duplicated genes in oats. Interspecies synteny analysis and orthologous gene identification indicated that oats share a significant number of orthologous genes with their ancestral species; this implies that the expansion of the oat HSP90 gene family may have occurred through oat polyploidization and large fragment duplication. The analysis of cis-acting elements revealed their influential role in the expression pattern of HSP90 genes under abiotic stresses. Analysis of oat gene expression under high-temperature, salt, cadmium (Cd), polyethylene glycol (PEG), and abscisic acid (ABA) stresses demonstrated that most AsHSP90 genes were significantly up-regulated by heat stress, particularly AsHSP90-7, AsHSP90-8, and AsHSP90-9. This study offers new insights into the amplification and evolutionary processes of the AsHSP90 protein, as well as its potential role in response to abiotic stresses. Furthermore, it lays the groundwork for understanding oat adaptation to abiotic stress, contributing to research and applications in plant breeding.

Association of Living in a Food Desert and Poor Periconceptional Diet Quality in a Cohort of Nulliparous Pregnant Individuals.

BACKGROUND: A poor diet can result from adverse social determinants of health and increases the risk of adverse pregnancy outcomes. OBJECTIVE: We aimed to assess, using data from the Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-to-Be prospective cohort, whether nulliparous pregnant individuals who lived in a food desert were more likely to experience poorer periconceptional diet quality compared with those who did not live in a food desert. METHODS: The exposure was living in a food desert based on a spatial overview of food access indicators by income and supermarket access per the Food Access Research Atlas. The outcome was periconceptional diet quality per the Healthy Eating Index (HEI)-2010, analyzed by quartile (Q) from the highest or best (Q4, reference) to the lowest or worst dietary quality (Q1); and secondarily, nonadherence (yes or no) to 12 key aspects of dietary quality. RESULTS: Among 7,956 assessed individuals, 24.9% lived in a food desert. The mean HEI-2010 score was 61.1 of 100 (SD: 12.5). Poorer periconceptional dietary quality was more common among those who lived in a food desert compared with those who did not live in a food desert (Q4: 19.8%, Q3: 23.6%, Q2: 26.5%, and Q1: 30.0% vs. Q4: 26.8%, Q3: 25.8%, Q2: 24.5%, and Q1: 22.9%; overall P < 0.001). Individuals living in a food desert were more likely to report a diet in lower quartiles of the HEI-2010 (i.e., poorer dietary quality) (aOR: 1.34 per quartile; 95% CI: 1.21, 1.49). They were more likely to be nonadherent to recommended standards for 5 adequacy components of the HEI-2010, including fruit, total vegetables, greens and beans, seafood and plant proteins, and fatty acids, and less likely to report excess intake of empty calories. CONCLUSIONS: Nulliparous pregnant individuals living in a food desert were more likely to experience poorer periconceptional diet quality compared with those who did not live in a food desert.

Association between Individual versus Community-level Social Vulnerability and Neonatal Opioid Withdrawal Syndrome among Pregnant Individuals Receiving Buprenorphine for Opioid Use Disorder.

OBJECTIVE: Individual patient-level measures of adverse social determinants of health are associated with neonatal opioid withdrawal syndrome (NOWS), but the relative impact of community-level adverse social determinants of health remains to be defined. We examined the association between community-level social vulnerability and NOWS among pregnant individuals receiving buprenorphine for opioid use disorder. STUDY DESIGN: We conducted a secondary analysis of an established cohort of pregnant individuals and their infants participating in a multidisciplinary prenatal/addiction care program from 2013 to 2021. Addresses were geocoded using ArcGIS and linked at the census tract to the Centers for Disease Control and Prevention 2018 Social Vulnerability Index (SVI), incorporating 15 census variables. The primary exposure was the SVI as a composite measure of community-level social vulnerability, and secondarily, individual scores for four thematic domains (socioeconomic status, household composition and disability, minority status and language, and housing type and transportation). The primary outcome was a clinical diagnosis of NOWS defined as withdrawal requiring pharmacological treatment following buprenorphine exposure. RESULTS: Among 703 pregnant individuals receiving buprenorphine, 39.8% (280/703) of infants were diagnosed with NOWS. Among our patinets, those who were nulliparous, had post-traumatic stress disorder, a term birth (≥ 37 weeks) and had a male infant were more likely to have an infant diagnosed with NOWS. Individuals with and without an infant diagnosed with NOWS had similarly high community-level social vulnerability per composite SVI scores (mean [standard deviation]: 0.6 [0.4-0.7] vs. 0.6 [0.4-0.7], p = 0.2]. In adjusted analyses, SVI, as a composite measure as well as the four domains, was not associated with NOWS diagnosis. CONCLUSION: Among pregnant persons receiving buprenorphine enrolled in a multidisciplinary prenatal and addition care program, while individual risk factors that measure adverse social determinants of health were associated with an NOWS diagnosis in the infant, community-level social vulnerability as measured by the SVI was not associated with the outcome. KEY POINTS: · Community-level SVI was not associated with neonatal opioid use disorder.. · Certain individual risk factors were identified as being associated with NOWS.. · Homogeneity of composite SVI scores may have led to lack of significant findings..

Patient Priorities, Decisional Comfort, and Satisfaction with Metformin versus Insulin for the Treatment of Gestational Diabetes Mellitus.

OBJECTIVE: We compared patient priorities, decisional comfort, and satisfaction with treating gestational diabetes mellitus (GDM) with metformin versus insulin among pregnant individuals with GDM requiring pharmacotherapy. STUDY DESIGN: We conducted a cross-sectional study of patients' perspectives about GDM pharmacotherapy in an integrated prenatal and diabetes care program from October 19, 2022, to August 24, 2023. The exposure was metformin versus insulin as the initial medication decision. Outcomes included standardized measures of patient priorities, decisional comfort, and satisfaction about their medication decision. RESULTS: Among 144 assessed individuals, 60.4% were prescribed metformin and 39.6% were prescribed insulin. Minoritized individuals were more likely to receive metformin compared with non-Hispanic White individuals (34.9 vs. 17.5%; p = 0.03). Individuals who were willing to participate in a GDM pharmacotherapy clinical trial were more likely to receive insulin than those who were unwilling (30.4 vs. 19.5%; p = 0.02). Individuals receiving metformin were more likely to report prioritizing avoiding injections (62.4 vs. 19.3%; adjusted odds ratio [aOR]: 2.83; 95% confidence interval [CI]: 1.10-7.31), wanting to take a medication no more than twice daily (56.0 vs. 30.4%; aOR: 3.67; 95% CI: 1.56-8.67), and believing that both medications can equally prevent adverse pregnancy outcomes (70.9 vs. 52.6%; aOR: 2.67; 95% CI: 1.19-6.03). Conversely, they were less likely to report prioritizing a medication that crosses the placenta (39.1 vs. 82.5%; aOR: 0.09; 95% CI: 0.03-0.25) and needing supplemental insulin to achieve glycemic control (21.2 vs. 47.4%; aOR: 0.36; 95% CI: 0.15-0.90). Individuals reported similarly high (mean score > 80%) levels of decisional comfort, personal satisfaction with medication decision-making, and satisfaction about their conversation with their provider about their medication decision with metformin and insulin (p ≥ 0.05 for all). CONCLUSION: Individuals with GDM requiring pharmacotherapy reported high levels of decision comfort and satisfaction with both metformin and insulin, although they expressed different priorities in medication decision-making. These results can inform future patient-centered GDM treatment strategies. KEY POINTS: · Pregnant individuals with GDM requiring pharmacotherapy expressed a high level of decisional comfort and satisfaction with medication decision making.. · Individuals placed different priorities on deciding to take metformin versus insulin.. · These results can inform interventions aimed at delivering person-centered diabetes care in pregnancy that integrates patient autonomy and knowledge about treatment options..

Postpartum sedentary behaviour and pelvic floor support: A prospective cohort study.

We evaluated the association between sedentary time and pelvic floor support in primiparas delivered vaginally. The 532 participants (29.2 ± 4.9 years) wore wrist accelerometers 6 months postpartum to assess sedentary time, light physical activity (LPA) and moderate to vigorous physical activity (MVPA). We assessed pelvic floor support 1 year postpartum, considered worse if vaginal walls or apex prolapsed to or beyond the hymen. We used multivariable isotemporal substitution analyses to determine the prevalence of worse support when replacing sedentary time with equal time spent in either LPA or MVPA. In 1 year, 9.4% demonstrated worse pelvic floor support. Decreasing sedentary time by 30 min/day with a concomitant increase in MVPA, controlling for LPA, was associated with increased prevalence of worse support (PR 1.43 (95% CI 1.15, 1.77), P < 0.01). Decreasing the sedentary time by 30 min/day with a concomitant increase in LPA, controlling for MVPA, was not significant (PR 0.89 (95% CI 0.80, 0.99), P = 0.04, > pre-set alpha of 0.02). Increasing MVPA while decreasing LPA, controlling for sedentary time, also increased the prevalence of worse support (PR 1.66 (95% CI 1.28, 2.16), P < 0.001). In conclusion, decreasing sedentary time increased the prevalence of worse pelvic floor support when replaced by MVPA, but not LPA.

Association of initial COVID-19 vaccine hesitancy with subsequent vaccination among pregnant and postpartum individuals.

OBJECTIVE: To examine the association between initial COVID-19 vaccine hesitancy and subsequent vaccination among pregnant and postpartum individuals. DESIGN: Prospective cohort. SETTING: A Midwestern tertiary-care academic medical center. Individuals completed a baseline vaccine hesitancy assessment from 22 March 2021 to 2 April 2021, with subsequent ascertainment of vaccination status at 3-6 months follow-up. METHODS: We used multivariable Poisson regression to estimate the relative risk of vaccination by baseline vaccine hesitancy status, and then characteristics associated with vaccination. MAIN OUTCOME MEASURES: Self-report of COVID-19 vaccination, and secondarily, consideration of COVID-19 vaccination among those not vaccinated. RESULTS: Of 456 individuals (93% pregnant, 7% postpartum) initially surveyed, 290 individuals (64%; 23% pregnant, 77% postpartum) provided subsequent vaccination status (median = 17 weeks). Of these 290 individuals, 40% (116/290) reported COVID-19 vaccine hesitancy upon enrolment, of whom 52% reported subsequent vaccination at follow-up. Few individuals transitioned during the study period from vaccine hesitant to vaccinated (10%); in comparison, 80% of those who were not vaccine hesitant were vaccinated at follow-up (aRR 0.19, 95% CI 0.11-0.33). Among those who remained unvaccinated at follow-up, 38% who were vaccine hesitant at baseline were considering vaccination, compared with 71% who were not vaccine hesitant (aRR 0.48, 95% CI 0.33-0.67). Individuals who were older, parous, employed and of higher educational attainment were more likely to be vaccinated, and those who identified as non-Hispanic black, were Medicaid beneficiaries, and were still pregnant at follow-up were less likely to be vaccinated. CONCLUSIONS: COVID-19 vaccine hesitancy persisted over time in the peripartum period, and few individuals who reported hesitancy at baseline were later vaccinated. Interventions that address vaccine hesitancy in pregnancy are needed.

Variations of a group coaching intervention to support early-career biomedical researchers in Grant proposal development: a pragmatic, four-arm, group-randomized trial.

BACKGROUND: Funded grant proposals provide biomedical researchers with the resources needed to build their research programs, support trainees, and advance public health. Studies using National Institutes of Health (NIH) data have found that investigators from underrepresented groups in the biomedical workforce are awarded NIH research grants at disproportionately lower rates. Grant writing training initiatives are available, but there is a dearth of rigorous research to determine the effectiveness of such interventions and to discern their essential features. METHODS: This 2 × 2, unblinded, group-randomized study compares the effectiveness of variations of an NIH-focused, grant writing, group coaching intervention for biomedical postdoctoral fellows and early-career faculty. The key study outcomes are proposal submission rates and funding rates. Participants, drawn from across the United States, are enrolled as dyads with a self-selected scientific advisor in their content area, then placed into coaching groups led by senior NIH-funded investigators who are trained in the intervention's coaching practices. Target enrollment is 72 coaching groups of 4-5 dyads each. Groups are randomized to one of four intervention arms that differ on two factors: [1] duration of coaching support (regular dose = 5 months of group coaching, versus extended dose = regular dose plus an additional 18 months of one-on-one coaching); and [2] mode of engaging scientific advisors with the regular dose group coaching process (unstructured versus structured engagement). Intervention variations were informed by programs previously offered by the NIH National Research Mentoring Network. Participant data are collected via written surveys (baseline and 6, 12, 18, and 24 months after start of the regular dose) and semi-structured interviews (end of regular dose and 24 months). Quantitative analyses will be intention-to-treat, using a 2-sided test of equality of the effects of each factor. An inductive, constant comparison analysis of interview transcripts will be used to identify contextual factors -- associated with individual participants, their engagement with the coaching intervention, and their institutional setting - that influence intervention effectiveness. DISCUSSION: Results of this study will provide an empirical basis for a readily translatable coaching approach to supporting the essential grant writing activities of faculty, fellows, and other research trainees, including those from underrepresented groups.

Anti-inflammatory effects of paeoniflorin caused by regulation of the hif1a/miR-210/caspase1/GSDMD signaling pathway in astrocytes: a novel strategy for hypoxia-induced brain injury in rats.

Context: Hypoxia-induced injury is a classic symptom of obstructive sleep apnea hypopnea syndrome (OSAHS), which is a risk factor of various diseases, such as hypertension, heart failure and stroke. However, there is no effective therapy for hypoxia-induced injury or OSAHS due to the elusive mechanism involved.Objective: This study aimed to assess the effects of paeoniflorin on hypoxia-induced injury and explore the underlying mechanism.Materials and methods: Hypoxic models of SD rats and CTX-TNA2 cells were used to assess the effect of paeoniflorin, and the expressions of hif1a, miR-210, caspase1 and GSDMD were detected using western blots and RT-PCR. Plasmid transfection was performed to explore the role of miR-210 in the effect of paeoniflorin.Results: Firstly, we confirmed that hypoxia induced severe neuronal injury and an enhancement of inflammation in the rat brain, with elevated expression of caspase1, IL1b and IL18. In addition, the results showed an activation of astrocytes and an increased level of pyroptosis under hypoxic conditions, which suggested a critical role of pyroptosis in hypoxiainduced injury of the brain. Furthermore, we found that compared with the controls, paeoniflorin treatment improved hypoxia-induced pyroptosis in astrocytes. Moreover, we detected the activation of hif1a/miR-210 signaling in the effects of paeoniflorin on astrocytes. As expected, the expression of hif1a and miR-210 was significantly upregulated in astrocytes when exposed to hypoxia, while paeoniflorin treatment reversed these enhancements. After transfection of miR-210 mimics, the attenuation of pyroptosis induced by paeoniflorin was suppressed, which was accompanied by an increase of ROS levels, as well as LDH release, indicating a critical role of miR-210 in pyroptosis in astrocytes.Conclusions: Our findings demonstrated that paeoniflorin improved hypoxia-induced pyroptosis in astrocytes via depressing hif1a/miR-210/caspase1/GSDMD signaling, providing robust evidence for the treatment of hypoxic injury and OSAHS.HighlightsHypoxia induces severe injury and inflammatory response in the rat brain;Hypoxia enhanced pyroptotic level and led to an activation of astrocytes.;Paeoniflorin alleviates hypoxia-induced pyroptosis in astrocytes;Transfection of miR-210 mimics suppressed the effects of paeoniflorin on hypoxia-induced pyroptosis in astrocytes.

Losartan protects against intermittent hypoxia-induced peritubular capillary loss by modulating the renal renin-angiotensin system and angiogenesis factors.

Obstructive sleep apnea is characterized by chronic intermittent hypoxia (CIH), which is a risk factor for renal peritubular capillary (PTC) loss, and angiotensin II receptor blockers can alleviate PTC loss. However, the mechanism by which losartan (an angiotensin II receptor blocker) reduces CIH-induced PTC loss and attenuates kidney damage is still unknown. Thus, in this study, we examined the protective effects of losartan against CIH-induced PTC loss and explored the underlying mechanisms in rat CIH model. The immunohistochemical staining of CD34 and morphological examination showed that CIH reduced PTC density and damaged tubular epithelial cells. Immunohistochemistry, enzyme-linked immunosorbent assay (ELISA), real-time quantitative PCR, and western blot analysis results revealed that CIH increased the expression of hypoxia inducible factor-1α (HIF-1α), angiotensin II (Ang II), angiotensin II type 1 receptor (AT1R), pro-angiogenesis factor vascular endothelial growth factor (VEGF), and anti-angiogenesis factor thrombospondin-1 (TSP-1) in the renal cortex of rats. CIH may up-regulate VEGF expression and simultaneously increase TSP-1 production. By histopathological, immunohistochemistry, ELISA, RT-qPCR, and western blot analysis, we found that the expressions of renal renin-angiotensin system (RAS), HIF-1α, VEGF, and TSP-1 were decreased, and PTC loss and tubular epithelial cell injury were attenuated with losartan treatment. Losartan ameliorated CIH-induced PTC loss by modulating renal RAS to improve the crosstalk between endothelial cells and tubular epithelial cells and subsequently regulate the balance of angiogenesis factors. Our study provided novel insights into the mechanisms of CIH-induced kidney damage and indicated that losartan could be a potential therapeutic agent for renal protection by alleviating CIH-induced PTC loss.

Identification of two novel epitopes targeting glycoprotein E of pseudorabies virus using monoclonal antibodies.

Pseudorabies virus (PRV), the agent of pseudorabies, has raised considerable attention since 2011 due to the outbreak of emerging PRV variants in China. In the present study, we obtained two monoclonal antibodies (mAbs) known as 2E5 and 5C3 against the glycoprotein E (gE) of a PRV variant (JS-2012 strain). The two mAbs reacted with wild PRV but not the vaccine strain (gE-deleted virus). The 2E5 was located in 161RLRRE165, which was conserved in almost of all PRV strains, while 5C3 in 148EMGIGDY154 was different from almost of all genotype I PRV, in which the 149th amino acid is methionine (M) instead of arginine (R). The two epitopes peptides located in the hydrophilic region and reacted with positive sera against genotype II PRV (JS-2012), which suggests they were likely dominant B-cell epitopes. Furthermore, the mutant peptide 148ERGIGDY154 (genotype I) did not react with the mAb 5C3 or positive sera against genotype II PRV (JS-2012). In conclusion, both mAb 2E5 and 5C3 could be used to identify wild PRV strains from vaccine strains, and mAb 5C3 and the epitope peptide of 5C3 might be used for epidemiological investigation to distinguish genotype II from genotype I PRV.

Comparative genomic analyses of a virulent pseudorabies virus and a series of its in vitro passaged strains.

BACKGROUND: Pseudorabies virus (PRV) of the family Herpesviridae is the causative agent of Aujeszky's disease. Attenuation of PRV by serial passaging in vitro is a well-established method; however, the dynamic variations occurring on viral genome during this process have not been characterized. METHODS: Genome sequencing and comparative genomic analyses of a virulent pseudorabies virus and a series of its plaque-purified strains via serial passaging in vitro were performed, and the properties in vitro and in vivo of which were further characterized. RESULTS: Compared to the parental virus, replication in vitro was enhanced in the highly passaged F50, F91, and F120. In contrast, lethality in mice decreased gradually with passage number. Genome sequencing of F50, F91, and F120 showed deletion of a large fragment containing gE, which is likely related to their attenuation. In addition, single nucleotide variations were identified in many genes of F50, F91, and F120. In-frame and frameshift indels were also detected in specific genes of passaged strains. Particularly frameshift mutations were observed in highly passaged strains, resulting in a truncated but overexpressed pUL46. CONCLUSION: During attenuation of PRV by serial passaging in Vero cells, dynamic variation patterns including a large deletion, single nucleotide variations, small in-frame indels, and also frameshifts mutations successively emerged, contributing to evolution of the viral population and enabling the gradual attenuation of the virus. These data provide clues to better understand PRV attenuation during passaging.

Generation and characterization of UL41 null pseudorabies virus variant in vitro and in vivo.

BACKGROUND: The alphaherpesvirus virion host shutoff (vhs) gene, UL41, can induce degradation of host mRNAs and shut off host protein synthesis. The roles of vhs in HSV-1 and HSV-2 have been studied extensively in previous studies, however, relatively little is known about the vhs protein of PRV. METHODS: A novel method combining CRISPR/Cas9 and Gibson assembly was developed to generate UL41 null PRV variant. The properties of UL41 null PRV in vitro and in vivo were further characterized. And the vhs activity of UL41 protein of PRV variant was evaluated by luciferase assay, Western-blot and RT-qPCR. RESULTS: Gibson assembly based on homologous recombination can accomplish one-step insertion of viral DNA fragments into donor plasmids efficiently (> 80%). Cas9/gRNA further largely enhanced the efficiency of homologous recombination. Using this method we were able to rapidly generate the UL41 null and revertant viruses of PRV variant. Compared to wild type (JS-2012), the UL41 null virus showed significantly smaller plaques and lower titers in Vero cells and impaired lethality and neuroinvasion in mice. Further the UL41 protein from different PRV strains exhibited unequal vhs activity in vitro, which of JS-2012 showed significantly weaker vhs activity than that of European-American strains. In addition UL41 null virus can also significantly decrease the expression of host genes during the early period of infection, which suggests other viral factors may be also involved in host shutoff. CONCLUSIONS: CRISPR/Cas9 combined with Gibson assembly efficiently generated UL41 null PRV. Compared to wild type, UL41 null PRV showed impaired both replication capability in vitro and neuroinvasion in vivo. Further UL41 protein of PRV variant showed significantly weaker vhs activity than that of PRV SC (European-American-like strain), suggesting the deficiency of vhs activity by the PRV variant UL41 protein.

Night-time sleep duration and postpartum weight retention in primiparous women.

Objectives: Approximately 75% of women weigh more at 1-year postpartum than pre-pregnancy. More than 47% retain >10 lbs at 1-year postpartum, which is associated with adverse health outcomes for mother and child. Disturbed sleep may contribute to risk of postpartum weight retention (PWR) as short sleep duration is associated with increased risk of obesity. Thus, we investigated whether night-time sleep duration is associated with risk for excessive PWR. We also explored night-time sleep duration and change in postpartum waist circumference. Methods: This is an ancillary analysis from a prospective cohort study. Participants were healthy primiparous adults with a singleton birth. Excessive PWR at 1-year postpartum was defined as ≥7% of pre-pregnancy weight. Log-binomial and linear regression assessed associations between night-time sleep duration at 6 months postpartum and PWR at 1-year postpartum. Linear regression assessed the association between night-time sleep duration and change in postpartum waist circumference. Results: Mean age of participants (N = 467) was 29.51 (SD ±â€…4.78) years. Night-time sleep duration by actigraphy or self-report was not associated with risk for excessive PWR (risk ratio 0.96, [95%CI 0.87-1.06]; risk ratio 0.95 [95%CI 0.83-1.07], respectively) or change in waist circumference. Conclusion: Night-time sleep duration at 6 months postpartum was not associated with PWR at 1-year postpartum. Mixed findings among our results and previous research could be due to our focus on night-time sleep, and differences in sleep measurement methods and timeframes across studies. More comprehensively assessing sleep, including multiple sleep dimensions, may help advance our understanding of potential links between sleep and PWR. Trial Registration: The parent study, Motherhood and Pelvic Health (MAP Study), is registered at https://clinicaltrials.gov/ct2/show/NCT02512016, NCT02512016.

A cross-sectional and population-based study from primary care on post-COVID-19 conditions in non-hospitalized patients.

BACKGROUND: Current research on post-COVID-19 conditions (PCC) has focused on hospitalized COVID-19 patients, and often lacks a comparison group. This study assessed the prevalence of PCC in non-hospitalized COVID-19 primary care patients compared to primary care patients not diagnosed with COVID-19. METHODS: This cross-sectional, population-based study (n = 2539) analyzed and compared the prevalence of PCC in patients with a positive COVID-19 test (n = 1410) and patients with a negative COVID-19 test (n = 1129) never hospitalized for COVID-19 related conditions. Participants were identified using electronic health records and completed an electronic questionnaire, available in English and Spanish, including 54 potential post COVID-19 symptoms. Logistic regression was conducted to assess the association of PCC with COVID-19. RESULTS: Post-COVID-19 conditions are prevalent in both groups, and significantly more prevalent in patients with COVID-19. Strong significant differences exist for the twenty most reported conditions, except for anxiety. Common conditions are fatigue (59.5% (COVID-19 positive) vs. 41.3% (COVID-19 negative); OR 2.15 [1.79-2.60]), difficulty sleeping (52.1% (positive) vs. 41.9% (negative); OR 1.42 [1.18-1.71]) and concentration problems (50.6% (positive) vs 28.5% (negative); OR 2.64 [2.17-3.22]). Similar disparities in prevalence are also observed after comparing two groups (positive vs. negative) by age, sex, time since testing, and race/ethnicity. CONCLUSIONS: PCC is highly prevalent in non-hospitalized COVID-19 patients in primary care. However, it is important to note that PCC strongly overlaps with common health symptoms seen in primary care, including fatigue, difficulty sleeping, and headaches, which makes the diagnosis of PCC in primary care even more challenging.

Research on post-COVID-19 conditions (PCC), also known as Long COVID, has often involved hospitalized COVID-19 patients. However, many patients with COVID-19 were not hospitalized, therefore how commonly the condition affects individuals attending primary care services is not accounted for. Here, we assessed non-hospitalized primary care patients with and without COVID-19. Our results demonstrate that PCC is highly common among primary care patients with COVID-19 and often presents as fatigue, difficulty sleeping, and concentration problems. As these symptoms overlap with other non-COVID-related conditions, it is challenging to accurately diagnose PCC. This calls for improved diagnostics and management of PCC in primary care settings, which is often the first point of contact with the healthcare systems for many patients.

Community-level social determinants of health and pregestational and gestational diabetes.

BACKGROUND: Individual adverse social determinants of health are associated with increased risk of diabetes in pregnancy, but the relative influence of neighborhood or community-level social determinants of health is unknown. OBJECTIVE: This study aimed to determine whether living in neighborhoods with greater socioeconomic disadvantage, food deserts, or less walkability was associated with having pregestational diabetes and developing gestational diabetes. STUDY DESIGN: We conducted a secondary analysis of the prospective Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-To-Be. Home addresses in the first trimester were geocoded at the census tract level. The exposures (modeled separately) were the following 3 neighborhood-level measures of adverse social determinants of health: (1) socioeconomic disadvantage, defined by the Area Deprivation Index and measured in tertiles from the lowest tertile (ie, least disadvantage [T1]) to the highest (ie, most disadvantage [T3]); (2) food desert, defined by the United States Department of Agriculture Food Access Research Atlas (yes/no by low income and low access criteria); and (3) less walkability, defined by the Environmental Protection Agency National Walkability Index (most walkable score [15.26-20.0] vs less walkable score [<15.26]). Multinomial logistic regression was used to model the odds of gestational diabetes or pregestational diabetes relative to no diabetes as the reference, adjusted for age at delivery, chronic hypertension, Medicaid insurance status, and low household income (<130% of the US poverty level). RESULTS: Among the 9155 assessed individuals, the mean Area Deprivation Index score was 39.0 (interquartile range, 19.0-71.0), 37.0% lived in a food desert, and 41.0% lived in a less walkable neighborhood. The frequency of pregestational and gestational diabetes diagnosis was 1.5% and 4.2%, respectively. Individuals living in a community in the highest tertile of socioeconomic disadvantage had increased odds of entering pregnancy with pregestational diabetes compared with those in the lowest tertile (T3 vs T1: 2.6% vs 0.8%; adjusted odds ratio, 2.52; 95% confidence interval, 1.41-4.48). Individuals living in a food desert (4.8% vs 4.0%; adjusted odds ratio, 1.37; 95% confidence interval, 1.06-1.77) and in a less walkable neighborhood (4.4% vs 3.8%; adjusted odds ratio, 1.33; 95% confidence interval, 1.04-1.71) had increased odds of gestational diabetes. There was no significant association between living in a food desert or a less walkable neighborhood and pregestational diabetes, or between socioeconomic disadvantage and gestational diabetes. CONCLUSION: Nulliparous individuals living in a neighborhood with higher socioeconomic disadvantage were at increased odds of entering pregnancy with pregestational diabetes, and those living in a food desert or a less walkable neighborhood were at increased odds of developing gestational diabetes, after controlling for known covariates.

Adverse Pregnancy Outcomes and Predicted 30-Year Risk of Maternal Cardiovascular Disease 2-7 Years After Delivery.

OBJECTIVE: To determine whether adverse pregnancy outcomes are associated with a higher predicted 30-year risk of atherosclerotic cardiovascular disease (CVD; ie, coronary artery disease or stroke). METHODS: This was a secondary analysis of the prospective Nulliparous Pregnancy Outcomes Study-Monitoring Mothers-to-Be Heart Health Study longitudinal cohort. The exposures were adverse pregnancy outcomes during the first pregnancy (ie, gestational diabetes mellitus [GDM], hypertensive disorder of pregnancy, preterm birth, and small- and large-for-gestational-age [SGA, LGA] birth weight) modeled individually and secondarily as the cumulative number of adverse pregnancy outcomes (ie, none, one, two or more). The outcome was the 30-year risk of atherosclerotic CVD predicted with the Framingham Risk Score assessed at 2-7 years after delivery. Risk was measured both continuously in increments of 1% and categorically, with high predicted risk defined as a predicted risk of atherosclerotic CVD of 10% or more. Linear regression and modified Poisson models were adjusted for baseline covariates. RESULTS: Among 4,273 individuals who were assessed at a median of 3.1 years after delivery (interquartile range 2.5-3.7), the median predicted 30-year atherosclerotic CVD risk was 2.2% (interquartile range 1.4-3.4), and 1.8% had high predicted risk. Individuals with GDM (least mean square 5.93 vs 4.19, adjusted ß=1.45, 95% CI, 1.14-1.75), hypertensive disorder of pregnancy (4.95 vs 4.22, adjusted ß=0.49, 95% CI, 0.31-0.68), and preterm birth (4.81 vs 4.27, adjusted ß=0.47, 95% CI, 0.24-0.70) were more likely to have a higher absolute risk of atherosclerotic CVD. Similarly, individuals with GDM (8.7% vs 1.4%, adjusted risk ratio [RR] 2.02, 95% CI, 1.14-3.59), hypertensive disorder of pregnancy (4.4% vs 1.4%, adjusted RR 1.91, 95% CI, 1.17-3.13), and preterm birth (5.0% vs 1.5%, adjusted RR 2.26, 95% CI, 1.30-3.93) were more likely to have a high predicted risk of atherosclerotic CVD. A greater number of adverse pregnancy outcomes within the first birth was associated with progressively greater risks, including per 1% atherosclerotic CVD risk (one adverse pregnancy outcome: 4.86 vs 4.09, adjusted ß=0.59, 95% CI, 0.43-0.75; two or more adverse pregnancy outcomes: 5.51 vs 4.09, adjusted ß=1.16, 95% CI, 0.82-1.50), and a high predicted risk of atherosclerotic CVD (one adverse pregnancy outcome: 3.8% vs 1.0%, adjusted RR 2.33, 95% CI, 1.40-3.88; two or more adverse pregnancy outcomes: 8.7 vs 1.0%, RR 3.43, 95% CI, 1.74-6.74). Small and large for gestational age were not consistently associated with a higher atherosclerotic CVD risk. CONCLUSION: Individuals who experienced adverse pregnancy outcomes in their first birth were more likely to have a higher predicted 30-year risk of CVD measured at 2-7 years after delivery. The magnitude of risk was higher with a greater number of adverse pregnancy outcomes experienced.