Pregnancy Outcomes of Nifedipine Compared With Labetalol for Oral Treatment of Mild Chronic Hypertension.

OBJECTIVE: To evaluate maternal and neonatal outcomes by type of antihypertensive used in participants of the CHAP (Chronic Hypertension in Pregnancy) trial. METHODS: We conducted a planned secondary analysis of CHAP, an open-label, multicenter, randomized trial of antihypertensive treatment compared with standard care (no treatment unless severe hypertension developed) in pregnant patients with mild chronic hypertension (blood pressure 140-159/90-104 mm Hg before 20 weeks of gestation) and singleton pregnancies. We performed three comparisons based on medications prescribed at enrollment: labetalol compared with standard care, nifedipine compared with standard care, and labetalol compared with nifedipine. Although active compared with standard care groups were randomized, medication assignment within the active treatment group was not random but based on clinician or patient preference. The primary outcome was the occurrence of superimposed preeclampsia with severe features, preterm birth before 35 weeks of gestation, placental abruption, or fetal or neonatal death. The key secondary outcome was small for gestational age (SGA) neonates. We also compared medication adverse effects between groups. Relative risks (RRs) and 95% CIs were estimated with log binomial regression to adjust for confounding. RESULTS: Of 2,292 participants analyzed, 720 (31.4%) received labetalol, 417 (18.2%) received nifedipine, and 1,155 (50.4%) received no treatment. The mean gestational age at enrollment was 10.5±3.7 weeks; nearly half of participants (47.5%) identified as non-Hispanic Black; and 44.5% used aspirin. The primary outcome occurred in 217 (30.1%), 130 (31.2%), and 427 (37.0%) in the labetalol, nifedipine, and standard care groups, respectively. Risk of the primary outcome was lower among those receiving treatment (labetalol use vs standard adjusted RR 0.82, 95% CI, 0.72-0.94; nifedipine use vs standard adjusted RR 0.84, 95% CI, 0.71-0.99), but there was no significant difference in risk when labetalol was compared with nifedipine (adjusted RR 0.98, 95% CI, 0.82-1.18). There were no significant differences in SGA or serious adverse events between participants receiving labetalol and those receiving nifedipine. CONCLUSION: No significant differences in predetermined maternal or neonatal outcomes were detected on the basis of the use of labetalol or nifedipine for treatment of chronic hypertension in pregnancy. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, NCT02299414.

Optimal Timing of Delivery for Pregnant Individuals With Mild Chronic Hypertension.

OBJECTIVE: To investigate the optimal gestational age to deliver pregnant people with chronic hypertension to improve perinatal outcomes. METHODS: We conducted a planned secondary analysis of a randomized controlled trial of chronic hypertension treatment to different blood pressure goals. Participants with term, singleton gestations were included. Those with fetal anomalies and those with a diagnosis of preeclampsia before 37 weeks of gestation were excluded. The primary maternal composite outcome included death, serious morbidity (heart failure, stroke, encephalopathy, myocardial infarction, pulmonary edema, intensive care unit admission, intubation, renal failure), preeclampsia with severe features, hemorrhage requiring blood transfusion, or abruption. The primary neonatal outcome included fetal or neonatal death, respiratory support beyond oxygen mask, Apgar score less than 3 at 5 minutes, neonatal seizures, or suspected sepsis. Secondary outcomes included intrapartum cesarean birth, length of stay, neonatal intensive care unit admission, respiratory distress syndrome (RDS), transient tachypnea of the newborn, and hypoglycemia. Those with a planned delivery were compared with those expectantly managed at each gestational week. Adjusted odds ratios (aORs) with 95% CIs are reported. RESULTS: We included 1,417 participants with mild chronic hypertension; 305 (21.5%) with a new diagnosis in pregnancy and 1,112 (78.5%) with known preexisting hypertension. Groups differed by body mass index (BMI) and preexisting diabetes. In adjusted models, there was no association between planned delivery and the primary maternal or neonatal composite outcome in any gestational age week compared with expectant management. Planned delivery at 37 weeks of gestation was associated with RDS (7.9% vs 3.0%, aOR 2.70, 95% CI, 1.40-5.22), and planned delivery at 37 and 38 weeks was associated with neonatal hypoglycemia (19.4% vs 10.7%, aOR 1.97, 95% CI, 1.27-3.08 in week 37; 14.4% vs 7.7%, aOR 1.82, 95% CI, 1.06-3.10 in week 38). CONCLUSION: Planned delivery in the early-term period compared with expectant management was not associated with a reduction in adverse maternal outcomes. However, it was associated with increased odds of some neonatal complications. Delivery timing for individuals with mild chronic hypertension should weigh maternal and neonatal outcomes in each gestational week but may be optimized by delivery at 39 weeks.

Mean Arterial Pressure and Neonatal Outcomes in Pregnancies Complicated by Mild Chronic Hypertension.

OBJECTIVE: To estimate the association between mean arterial pressure during pregnancy and neonatal outcomes in participants with chronic hypertension using data from the CHAP (Chronic Hypertension and Pregnancy) trial. METHODS: A secondary analysis of the CHAP trial, an open-label, multicenter randomized trial of antihypertensive treatment in pregnancy, was conducted. The CHAP trial enrolled participants with mild chronic hypertension (blood pressure [BP] 140-159/90-104 mm Hg) and singleton pregnancies less than 23 weeks of gestation, randomizing them to active treatment (maintained on antihypertensive therapy with a goal BP below 140/90 mm Hg) or standard treatment (control; antihypertensives withheld unless BP reached 160 mm Hg systolic BP or higher or 105 mm Hg diastolic BP or higher). We used logistic regression to measure the strength of association between mean arterial pressure (average and highest across study visits) and to select neonatal outcomes. Unadjusted and adjusted odds ratios (per 1-unit increase in millimeters of mercury) of the primary neonatal composite outcome (bronchopulmonary dysplasia, retinopathy of prematurity, necrotizing enterocolitis, or intraventricular hemorrhage grade 3 or 4) and individual secondary outcomes (neonatal intensive care unit admission [NICU], low birth weight [LBW] below 2,500 g, and small for gestational age [SGA]) were calculated. RESULTS: A total of 2,284 participants were included: 1,155 active and 1,129 control. Adjusted models controlling for randomization group demonstrated that increasing average mean arterial pressure per millimeter of mercury was associated with an increase in each neonatal outcome examined except NEC, specifically neonatal composite (adjusted odds ratio [aOR] 1.12, 95% CI, 1.09-1.16), NICU admission (aOR 1.07, 95% CI, 1.06-1.08), LBW (aOR 1.12, 95% CI, 1.11-1.14), SGA below the fifth percentile (aOR 1.03, 95% CI, 1.01-1.06), and SGA below the 10th percentile (aOR 1.02, 95% CI, 1.01-1.04). Models using the highest mean arterial pressure as opposed to average mean arterial pressure also demonstrated consistent associations. CONCLUSION: Increasing mean arterial pressure was positively associated with most adverse neonatal outcomes except NEC. Given that the relationship between mean arterial pressure and adverse pregnancy outcomes may not be consistent at all mean arterial pressure levels, future work should attempt to further elucidate whether there is an absolute threshold or relative change in mean arterial pressure at which fetal benefits are optimized along with maternal benefits. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov , NCT02299414.

Evidence of SARS-CoV-2 convergent evolution in immunosuppressed patients treated with antiviral therapies.

BACKGROUND: The factors contributing to the accelerated convergent evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are not fully understood. Unraveling the contribution of viral replication in immunocompromised patients is important for the early detection of novel mutations and developing approaches to limit COVID-19. METHODS: We deep sequenced SARS-CoV-2 RNA from 192 patients (64% hospitalized, 39% immunosuppressed) and compared the viral genetic diversity within the patient groups of different immunity and hospitalization status. Serial sampling of 14 patients was evaluated for viral evolution in response to antiviral treatments. RESULTS: We identified hospitalized and immunosuppressed patients with significantly higher levels of viral genetic diversity and variability. Further evaluation of serial samples revealed accumulated mutations associated with escape from neutralizing antibodies in a subset of the immunosuppressed patients treated with antiviral therapies. Interestingly, the accumulated viral mutations that arose in this early Omicron wave, which were not common in the patient viral lineages, represent convergent mutations that are prevalent in the later Omicron sublineages, including the XBB, BA.2.86.1 and its descendent JN sublineages. CONCLUSIONS: Our results illustrate the importance of identifying convergent mutations generated during antiviral therapy in immunosuppressed patients, as they may contribute to the future evolutionary landscape of SARS-CoV-2. Our study also provides evidence of a correlation between SARS-CoV-2 convergent mutations and specific antiviral treatments. Evaluating high-confidence genomes from distinct waves in the pandemic with detailed patient metadata allows for discerning of convergent mutations that contribute to the ongoing evolution of SARS-CoV-2.

Parents Report Positive Changes in Parental Feeding Practices 12 Months After Intervention.

OBJECTIVE: Determine self-reported parental feeding behavior changes and perspectives on parental feeding intervention at 12-month follow-up. METHODS: Telephone focus groups using a 2 × 2 design (English/Spanish × in-class or online) with Expanded Food and Nutrition Education Program participants (n = 37) with children 2-8 years and high exposure to the Food, Feeding, and Your Family intervention (7 lessons). Researchers (n = 3) independently identified themes. RESULTS: Parental behavior changes that (1) positively influenced children's diets, (2) involved children in food-related activities, (3) eased stressful situations around food, (4) led to healthier food choices, and (5) saved money when food shopping. Commonly implemented practices included establishing structured mealtime routines, introducing new foods multiple times, and encouraging children's eating competence. Online participants noted materials were easily accessible via text messages. CONCLUSIONS AND IMPLICATIONS: Incorporating parental feeding content (in-class or online) into nutrition education interventions, such as the Expanded Food and Nutrition Education Program, supports developing positive parental feeding behaviors in families with low income.

Using Mobile Technology for Family-Based Prevention in Families with Low Incomes: Lessons from a Randomized Controlled Trial of a Childhood Obesity Prevention Program.

Researchers are increasingly using web-based technologies to deliver family-based, prevention programming. Few studies have examined the success of such approaches for families with low incomes. The purpose of this study was to describe the level of in-class and online engagement in a childhood obesity prevention program for parents with low incomes, to examine the demographic correlates of parent engagement, and to examine dosage effects on parental feeding outcomes as a function of online exposure. All participants attended in-class nutrition education classes (Eating Smart · Being Active) as part of the Expanded Food and Nutrition Education Program (EFNEP) in Colorado and Washington State (classes were offered in English and Spanish). Participants in this analysis were 168 parents from a larger cluster randomized controlled trial who had been randomly assigned to also receive a newly developed, mobile-based version of an efficacious, feeding-focused, childhood obesity prevention program. Results showed that despite high levels of in-person attendance (70%), participants only accessed 47% of the videos (online content). Older parents and parents of girls showed higher levels of in-person attendance; currently employed parents showed lower levels. Online engagement varied as a function of ethnicity and acculturation: non-Hispanic parents accessed the most videos, low-acculturated Hispanic parents accessed the second most, and highly acculturated Hispanic parents accessed the least. In contrast, low-acculturated Hispanic parents showed the highest in-person attendance. For all but one outcome, significant online program effects were found only for parents who accessed at least half of the videos. Implications for mobile-based, family-based prevention programs for parents with low incomes are considered.ClinicalTrials.gov Identifier: NCT03170700; Registration Date: March 08, 2017.

24-Hour Dietary Recall in the Expanded Food and Nutrition Education Program: Perspective of the Program Coordinator.

The purpose of this study was to determine how the 24-hour dietary recall (24HDR) is administered and how the Expanded Food and Nutrition Education Program (EFNEP) peer educators and other staff are trained on the data collection and entry process, from the EFNEP coordinators' perspectives. This cross-sectional, quantitative study utilized an online survey to collect information from EFNEP coordinators representing 61 of 76 EFNEP programs. While 56% of the programs collected the 24HDR data starting with the first thing eaten the previous day, 49% of them started collecting data at the time of class, going backwards. Most programs, i.e., 72%, reported using a multiple-pass method; however, only one-third of them reported using the standard five-pass method. Almost all programs, i.e., 97%, reported one peer educator collecting data from a group of 2-12 clients. All programs reported collecting the 24HDR data in a group setting, with about one-third of the programs also collecting data one-on-one. Most programs, i.e., 57%, reported spending ≤4 h on the initial training of staff in how to collect 24HDR data, and 54% of them reported that the peer educators entered the data themselves. This study found that the methods used to collect answers, train the staff, and enter the 24HDR data varied across EFNEP programs and that there is a need to standardize or revise the collection of 24HDR data.

Conducting 24-Hour Dietary Recalls in Group Settings with Adults Having Low-Income: Perspectives of EFNEP Peer Educators.

The Expanded Food and Nutrition Education Program (EFNEP) is a federally funded program that teaches nutrition education to adults and youth with low-income. EFNEP is funded throughout the United States including federal territories. The purpose of EFNEP is to provide nutrition education. Evaluation for adult programs includes pre/post surveys and pre/post 24-h diet recalls (24HDR). A validated standard of dietary measures, 24HDR are useful when collected as designed: one-on-one by a trained professional. In EFNEP, 24HDR are collected in group settings by EFNEP peer educators who often have not received a college degree or any formal education in nutrition. The purpose of this study was to explore attitudes and behaviors of EFNEP peer educators regarding how they collect diet recalls in a group setting, their perceptions of how adult participants feel about the recalls, and the benefits and challenges of using recalls. Online interviews were conducted with EFNEP peer educators across the U.S. Peer educators recognized the importance of collecting the recall data but identified several challenges such as time, resources, and participant reluctance to complete the recall. Program evaluation through methods like the 24HDR is important to measure outcomes and inform program improvements but also needs to include how evaluation can benefit participants and minimize data collection burden. Future research needs to examine the validity of collecting recalls in a group setting compared to other measures of diet quality.

Perinatal Outcomes Associated With Management of Stage 1 Hypertension.

OBJECTIVE: To evaluate the association between maternal blood pressure (BP) below 130/80 mm Hg compared with 130-139/80-89 mm Hg and pregnancy outcomes. METHODS: We conducted a planned secondary analysis of CHAP (Chronic Hypertension and Pregnancy), an open label, multicenter, randomized controlled trial. Participants with mean BP below 140/90 mm Hg were grouped as below 130/80 mm Hg compared with 130-139/80-89 mm Hg by averaging postrandomization clinic BP throughout pregnancy. The primary composite outcome was preeclampsia with severe features, indicated preterm birth before 35 weeks of gestation, placental abruption, or fetal or neonatal death. The secondary outcome was small for gestational age (SGA). RESULTS: Of 2,408 patients in CHAP, 2,096 met study criteria; 1,328 had mean BP 130-139/80-89 mm Hg and 768 had mean BP below 130/80 mm Hg. Participants with mean BP below 130/80 mm Hg were more likely to be older, on antihypertensive medication, in the active treatment arm, and to have lower BP at enrollment. Mean clinic BP below 130/80 mm Hg was associated with lower frequency of the primary outcome (16.0% vs 35.8%, adjusted relative risk 0.45; 95% CI 0.38-0.54) as well as lower risk of severe preeclampsia and indicated birth before 35 weeks of gestation. There was no association with SGA. CONCLUSION: In pregnant patients with mild chronic hypertension, mean BP below 130/80 mm Hg was associated with improved pregnancy outcomes without increased risk of SGA. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov , NCT02299414.

Breastfeeding initiation and duration among people with mild chronic hypertension: a secondary analysis of the Chronic Hypertension and Pregnancy trial.

BACKGROUND: Increased duration of breastfeeding improves maternal cardiovascular health and may be especially beneficial in high-risk populations, such as those with chronic hypertension. Others have shown that individuals with hypertension are less likely to breastfeed, and there has been limited research aimed at supporting breastfeeding goals in this population. The impact of perinatal blood pressure control on breastfeeding outcomes among people with chronic hypertension is unknown. OBJECTIVE: This study aimed to evaluate whether breastfeeding initiation and short-term duration assessed at the postpartum clinic visit differed according to perinatal blood pressure treatment strategy (targeting blood pressure <140/90 mm Hg vs reserving antihypertensive treatment for blood pressure ≥160/105 mm Hg). STUDY DESIGN: We performed a secondary analysis of the Chronic Hypertension and Pregnancy trial. This was an open-label, multicenter, randomized trial where pregnant participants with mild chronic hypertension were randomized to receive antihypertensive medications with goal blood pressure <140/90 mm Hg (active treatment) or deferred treatment until blood pressure ≥160/105 mm Hg (control). The primary outcome was initiation and duration of breastfeeding, assessed at the postpartum clinic visit. We performed bivariate analyses and log-binomial and cumulative logit regression models, adjusting models for variables that were unbalanced in bivariate analyses. We performed additional analyses to explore the relationship between breastfeeding duration and blood pressure measurements at the postpartum visit. RESULTS: Of the 2408 participants from the Chronic Hypertension and Pregnancy trial, 1444 (60%) attended the postpartum study visit and provided breastfeeding information. Participants in the active treatment group had different body mass index class distribution and earlier gestational age at enrollment, and (by design) were more often discharged on antihypertensives. Breastfeeding outcomes did not differ significantly by treatment group. In the active and control treatment groups, 563 (77.5%) and 561 (78.1%) initiated breastfeeding, and mean durations of breastfeeding were 6.5±2.3 and 6.3±2.1 weeks, respectively. The probability of ever breastfeeding (adjusted relative risk, 0.99; 95% confidence interval, 0.93-1.05), current breastfeeding at postpartum visit (adjusted relative risk, 1.01; 95% confidence interval, 0.94-1.10), and weeks of breastfeeding (adjusted odds ratio, 0.87; 95% confidence interval, 0.68-1.12) did not differ by treatment group. Increased duration (≥2 vs <2 weeks) of breastfeeding was associated with slightly lower blood pressure measurements at the postpartum visit, but these differences were not significant in adjusted models. CONCLUSION: In a secondary analysis of the cohort of Chronic Hypertension and Pregnancy trial participants who attended the postpartum study visit and provided breastfeeding information (60% of original trial participants), breastfeeding outcomes did not differ significantly by treatment group. This suggests that maintaining goal blood pressure <140/90 mm Hg throughout the perinatal period is associated with neither harm nor benefit for short-term breastfeeding goals. Further study is needed to understand long-term breastfeeding outcomes among individuals with chronic hypertension and how to support this population in achieving their breastfeeding goals.

SARS-CoV-2 nonstructural protein 6 from Alpha to Omicron: evolution of a transmembrane protein.

We recently reported that mutations in both the spike glycoprotein and nonstructural protein 6 (nsp6) were associated with attenuation of the SARS-CoV-2 Omicron BA.1 variant. While mutations in spike allow evasion of neutralizing antibodies and promote specific modes of viral entry, the role of nsp6 mutations in pathogenesis is less clear. Nsp6 is essential for modifying the endoplasmic reticulum and generating double-membrane vesicles, the site of viral RNA replication. To investigate the evolution of nsp6, we evaluated 91,596 high-confidence human SARS-CoV-2 whole-genome sequences across 19 variants and lineages. While nsp6 of early variants of concern, such as Alpha, Beta, and Gamma, carried a triple amino acid deletion (106-108, termed ΔSGF), the Delta, Epsilon, and Mu lineages retained the ancestral nsp6 sequence. For nsp6 in the emerging Omicron variants, we report a transition from an amino acid 105-107 ΔLSG deletion in BA.1 to increased dominance of the ΔSGF in BA.2 and subsequent lineages. Our findings indicate that deletion within nsp6 was independently selected in multiple lineages of SARS-CoV-2, both early and late in the pandemic. Analysis of SARS-CoV-2-related coronaviruses in bats and pangolins revealed nsp6 sequences similar to the ancestral SARS-CoV-2 virus, indicating that the deletion in nsp6 may be an adaptation to replication in humans. Analysis of nsp6 sequences from multiple coronaviruses predicts a multipass transmembrane protein with a conserved C-terminal domain. Monitoring and evaluating changes in nsp6 and other nonstructural proteins will contribute to our understanding of factors associated with the attenuation of pandemic coronaviruses. IMPORTANCE There is an ongoing need to evaluate genetic changes in SARS-CoV-2 for effects on transmission and pathogenesis. We recently reported an unexpected role for replicase component nsp6, in addition to changes in spike, in the attenuation of Omicron BA.1. In this commentary, we document a triple-amino-acid deletion in a predicted lumenal domain of nsp6 that was found in multiple, independent variants of SARS-CoV-2, including all recent Omicron lineages. Furthermore, we modeled the predicted structure of nsp6, implicating a multipass transmembrane architecture as conserved in members of the Coronaviridae family. This information can guide future studies investigating the role of nsp6 in the pathogenesis of existing and emerging coronaviruses.

Cell culture systems for isolation of SARS-CoV-2 clinical isolates and generation of recombinant virus.

A simple and robust cell culture system is essential for generating authentic SARS-CoV-2 stocks for evaluation of viral pathogenicity, screening of antiviral compounds, and preparation of inactivated vaccines. Evidence suggests that Vero E6, a cell line commonly used in the field to grow SARS-CoV-2, does not support efficient propagation of new viral variants and triggers rapid cell culture adaptation of the virus. We generated a panel of 17 human cell lines overexpressing SARS-CoV-2 entry factors and tested their ability to support viral infection. Two cell lines, Caco-2/AT and HuH-6/AT, demonstrated exceptional susceptibility, yielding highly concentrated virus stocks. Notably, these cell lines were more sensitive than Vero E6 cells in recovering SARS-CoV-2 from clinical specimens. Further, Caco-2/AT cells provided a robust platform for producing genetically reliable recombinant SARS-CoV-2 through a reverse genetics system. These cellular models are a valuable tool for the study of SARS-CoV-2 and its continuously emerging variants.

Continent-wide declines in shallow reef life over a decade of ocean warming.

Human society is dependent on nature1,2, but whether our ecological foundations are at risk remains unknown in the absence of systematic monitoring of species' populations3. Knowledge of species fluctuations is particularly inadequate in the marine realm4. Here we assess the population trends of 1,057 common shallow reef species from multiple phyla at 1,636 sites around Australia over the past decade. Most populations decreased over this period, including many tropical fishes, temperate invertebrates (particularly echinoderms) and southwestern Australian macroalgae, whereas coral populations remained relatively stable. Population declines typically followed heatwave years, when local water temperatures were more than 0.5 °C above temperatures in 2008. Following heatwaves5,6, species abundances generally tended to decline near warm range edges, and increase near cool range edges. More than 30% of shallow invertebrate species in cool latitudes exhibited high extinction risk, with rapidly declining populations trapped by deep ocean barriers, preventing poleward retreat as temperatures rise. Greater conservation effort is needed to safeguard temperate marine ecosystems, which are disproportionately threatened and include species with deep evolutionary roots. Fundamental among such efforts, and broader societal needs to efficiently adapt to interacting anthropogenic and natural pressures, is greatly expanded monitoring of species' population trends7,8.

Analysis of Plasmablasts From Children With Kawasaki Disease Reveals Evidence of a Convergent Antibody Response to a Specific Protein Epitope.

BACKGROUND: Kawasaki disease (KD) is a febrile illness of young childhood that can result in coronary artery aneurysms and death. Coronavirus disease 2019 (COVID-19) mitigation strategies resulted in a marked decrease in KD cases worldwide, supporting a transmissible respiratory agent as the cause. We previously reported a peptide epitope recognized by monoclonal antibodies (MAbs) derived from clonally expanded peripheral blood plasmablasts from 3 of 11 KD children, suggesting a common disease trigger in a subset of patients with KD. METHODS: We performed amino acid substitution scans to develop modified peptides with improved recognition by KD MAbs. We prepared additional MAbs from KD peripheral blood plasmablasts and assessed MAb characteristics that were associated with binding to the modified peptides. RESULTS: We report a modified peptide epitope that is recognized by 20 MAbs from 11 of 12 KD patients. These MAbs predominantly use heavy chain VH3-74; two-thirds of VH3-74 plasmablasts from these patients recognize the epitope. The MAbs were nonidentical between patients but share a common complementarity-determining region 3 (CDR3) motif. CONCLUSIONS: These results demonstrate a convergent VH3-74 plasmablast response to a specific protein antigen in children with KD, supporting one predominant causative agent in the etiopathogenesis of the illness.

Booster course of antenatal corticosteroids after preterm prelabor rupture of membranes: a double-blind randomized trial.

BACKGROUND: Preterm prelabor rupture of membranes is a leading cause of preterm birth and is responsible for 18% to 20% of perinatal deaths in the United States. An initial course of antenatal corticosteroids has been shown to reduce morbidity and mortality in patients with preterm prelabor rupture of membranes. For patients who remain undelivered for 7 days or more after the initial course of antenatal corticosteroids, it is uncertain whether a booster course of antenatal corticosteroids reduces neonatal morbidity or increases the infection risk. The American College of Obstetricians and Gynecologists has concluded that the current evidence is insufficient to make a recommendation. OBJECTIVE: This study aimed to evaluate if a single booster course of antenatal corticosteroids improves neonatal outcomes after preterm prelabor rupture of membranes. STUDY DESIGN: We conducted a multicenter, placebo-controlled randomized clinical trial. The inclusion criteria were preterm prelabor rupture of membranes, gestational age of 24.0 to 32.9 weeks, singleton, initial antenatal corticosteroid course administered at least 7 days before randomization, and planned expectant management. Consenting patients were randomized in gestational age blocks to either receive booster antenatal corticosteroids (12 mg betamethasone every 24 hours for 2 days) or a saline placebo. The primary outcome was composite neonatal morbidity or death. A sample size of 194 patients was calculated to yield 80% power at P<.05 to detect a reduction in primary outcome from 60% in placebo group to 40% in antenatal corticosteroids group. RESULTS: From April 2016 through August 2022, 194 patients consented and were randomized (47% of 411 eligible patients). Intent-to-treat analysis was performed on 192 patients (2 placebo patients left hospital, outcomes unknown). The groups had similar baseline characteristics. The primary outcome occurred in 64% of patients who received booster antenatal corticosteroids vs in 66% of patients who received the placebo (odds ratio, 0.82; 95% confidence interval, 0.43-1.57; gestational age-stratified Cochran-Mantel-Haenszel test). Individual components of the primary outcome and secondary neonatal and maternal outcomes were not significantly different between the antenatal corticosteroids and placebo groups. Specifically, chorioamnionitis (22% vs 20%), postpartum endometritis (1% vs 2%), wound infections (2% vs 0%), and proven neonatal sepsis (5% vs 3%) were not different between the groups. CONCLUSION: A booster course of antenatal corticosteroids at least 7 days after the first antenatal corticosteroids course in patients with preterm prelabor rupture of membranes did not improve neonatal morbidity or any other outcome in this adequately-powered, double-blind randomized clinical trial. Booster antenatal corticosteroids did not increase maternal or neonatal infection.

Spike and nsp6 are key determinants of SARS-CoV-2 Omicron BA.1 attenuation.

The SARS-CoV-2 Omicron variant is more immune evasive and less virulent than other major viral variants that have so far been recognized1-12. The Omicron spike (S) protein, which has an unusually large number of mutations, is considered to be the main driver of these phenotypes. Here we generated chimeric recombinant SARS-CoV-2 encoding the S gene of Omicron (BA.1 lineage) in the backbone of an ancestral SARS-CoV-2 isolate, and compared this virus with the naturally circulating Omicron variant. The Omicron S-bearing virus robustly escaped vaccine-induced humoral immunity, mainly owing to mutations in the receptor-binding motif; however, unlike naturally occurring Omicron, it efficiently replicated in cell lines and primary-like distal lung cells. Similarly, in K18-hACE2 mice, although virus bearing Omicron S caused less severe disease than the ancestral virus, its virulence was not attenuated to the level of Omicron. Further investigation showed that mutating non-structural protein 6 (nsp6) in addition to the S protein was sufficient to recapitulate the attenuated phenotype of Omicron. This indicates that although the vaccine escape of Omicron is driven by mutations in S, the pathogenicity of Omicron is determined by mutations both in and outside of the S protein.

Short-Term Efficacy of a Childhood Obesity Prevention Program Designed to Pair Feeding Content With Nutrition Education.

Background: Family-based programs show considerable promise in preventing overweight and obesity in young children. However, dissemination is difficult because significant participant and staff involvement is required. This study examined the short-term efficacy of adding parental feeding content to a widely-used nutrition education curriculum for families in low-resourced communities comparing the influence of two delivery methods (in-class and online) on parents' feeding knowledge, practices, and styles. Methods: In this cluster randomized controlled trial, parents of 2- to 8-year-old children enrolled in the EFNEP (Expanded Food and Nutrition Education Program) in Colorado and Washington were randomly assigned to: in-class nutrition education only, in-class nutrition education with in-class feeding content, or in-class nutrition education with online feeding content. Data from the 382 participants who completed both pretest and posttest assessments are reported in this study. Results: Multilevel analyses showed empirical support for the influence of the program on parents' feeding knowledge, practices, and styles. Online and in-class methods were equally effective in delivering feeding content in low-resourced communities. Consistent effects were seen across the two delivery methods for encouraging children to try new foods (p < 0.05), use of child-centered feeding practices (i.e., greater responsiveness, p < 0.05), child involvement in food preparation (p < 0.05), and understanding the number of presentations often necessary for child acceptance of a new food (p < 0.001). Location and language differences were seen across some constructs. Conclusions: This study demonstrates the efficacy of in-class and online approaches to feeding highlighting the program's positive effects on promoting healthy feeding behaviors for parents of children in low-resourced families. ClinicalTrials.gov Identifier: NCT03170700.

Development of EFNEP and SNAP-Ed Core Competencies in the Land-Grant University System.

This report describes the development and revision of core competencies for the Expanded Food and Nutrition Education Program and Supplemental Nutrition Assistance Program-Education program leaders, supervisors, and paraprofessional educators across the land-grant university system. The developing curriculum methodologies were used to engage panels of exemplary employees and an advisory panel of program leaders. A crosswalk examined key documents, and a gap analysis explored the competencies of similar professions. The resulting job duties and tasks reflect cultural, environmental, and educational trends. The core competencies are critical for writing job descriptions, guiding hiring, evaluating performance, and providing initial and ongoing training for the Expanded Food and Nutrition Education Program and Supplemental Nutrition Assistance Program-Education.

Role of spike in the pathogenic and antigenic behavior of SARS-CoV-2 BA.1 Omicron.

The recently identified, globally predominant SARS-CoV-2 Omicron variant (BA.1) is highly transmissible, even in fully vaccinated individuals, and causes attenuated disease compared with other major viral variants recognized to date. The Omicron spike (S) protein, with an unusually large number of mutations, is considered the major driver of these phenotypes. We generated chimeric recombinant SARS-CoV-2 encoding the S gene of Omicron in the backbone of an ancestral SARS-CoV-2 isolate and compared this virus with the naturally circulating Omicron variant. The Omicron S-bearing virus robustly escapes vaccine-induced humoral immunity, mainly due to mutations in the receptor binding motif (RBM), yet unlike naturally occurring Omicron, efficiently replicates in cell lines and primary-like distal lung cells. In K18-hACE2 mice, while Omicron causes mild, non-fatal infection, the Omicron S-carrying virus inflicts severe disease with a mortality rate of 80%. This indicates that while the vaccine escape of Omicron is defined by mutations in S, major determinants of viral pathogenicity reside outside of S.

Reduction of Catheter-Associated Urinary Tract Infections: A Multidisciplinary Approach to Driving Change.

Despite the many advancements in infection prevention, catheter-associated urinary tract infections (CAUTI) continue to be problematic for many hospitals. The large urban teaching hospital featured in this article developed a team that consisted of a registered nurse quality Lean coach, bedside nurses from each inpatient nursing unit, physicians, an infection prevention specialist nurse, an education specialist nurse, and members of the quality department to study this matter. The team focused on understanding current practice related to the use and duration of indwelling urinary catheters. It was discovered that while some indwelling urinary catheters were justified, others could have been avoided altogether or removed earlier. Multifaceted measures were instituted at this hospital to decrease indwelling urinary catheter days and reduce CAUTI rates. The team's journey to successfully decreasing indwelling urinary catheter days by 19.79% and CAUTI rates by 38% is highlighted.