Community infant safe sleep and breastfeeding promotion and population level-outcomes: A mixed methods study.

PROBLEM: In the U.S., sudden unexpected infant deaths due to accidental suffocation and strangulation in bed are increasing. Though breastfeeding is a protective factor against sudden unexpected infant death, motivations to breastfeed often couple with unsafe infant sleep practices. Racial/ethnic disparities are present in sudden unexpected infant death, accidental suffocation and strangulation in bed, and breastfeeding. BACKGROUND: Promoting infant safe sleep and breastfeeding through community-level initiatives could address disparities in related outcomes. AIM: Investigate the relationship between community-level strategies and associated state-level outcomes for infant safe sleep and breastfeeding. METHODS: We employed an intervention mixed methods framework and exploratory sequential design. The qualitative component entailed a hermeneutical phenomenological framework to analyze key informant interview data from seven U.S. community-level providers participating in a practice improvement initiative. The quantitative component entailed descriptively analyzing infant safe sleep and breastfeeding indicators from the 2019 Pregnancy Risk Assessment Monitoring System and Ohio Pregnancy Assessment Survey. Qualitative and quantitative data were linked through embedded integration. FINDINGS: We identified two mixed insights: gaps in promotion and outcomes, and persistent disparities between infant safe sleep and breastfeeding promotion and outcomes. DISCUSSION: Our findings indicate conversational approaches could improve infant safe sleep and breastfeeding promotion, outcomes, and relative disparities. We find that community collaboration is needed to address organizational capacity limitations in promoting infant safe sleep and breastfeeding. CONCLUSION: Community-level organizations and providers should consider tailoring program offerings and care delivery to include conversational approaches and community collaboration to promote infant safe sleep and breastfeeding and decrease relative disparities in outcomes.

Community-based approaches to infant safe sleep and breastfeeding promotion: a qualitative study.

BACKGROUND: In the U.S., sudden unexpected infant deaths (SUID) due to accidental suffocation and strangulation in bed (ASSB) are increasing, with disparities by race/ethnicity. While breastfeeding is a protective factor against infant mortality, racial/ethnic disparities are present in its uptake, and motivations to breastfeed are also often coupled with non-recommended infant sleep practices that are associated with infant sleep deaths. Combining infant safe sleep (ISS) and breastfeeding promotion on the community level presents opportunities to address racial/ethnic disparities and associated socioeconomic, cultural, and psychosocial influences. METHODS: We completed a descriptive qualitative hermeneutical phenomenology using thematic analysis of focus group data. We examined the phenomenon of community-level providers promoting ISS and breastfeeding in communities vulnerable to ISS and breastfeeding disparities. We asked eighteen informants participating in a national quality improvement collaborative about i.) areas requiring additional support to meet community needs around ISS and breastfeeding, and ii.) recommendations on tools to improve their work promoting ISS and breastfeeding. RESULTS: We identified four themes: i.) education and dissemination, ii.) relationship building and social support, iii.) working with clients' personal circumstances and considerations, and iv.) tools and systems. CONCLUSIONS: Our findings support embedding risk-mitigation approaches in ISS education; relationship building between providers, clients, and peers; and the provision of ISS and breastfeeding supportive material resources with educational opportunities. These findings may be used to inform community-level provider approaches to ISS and breastfeeding promotion.

Maternity Care Clinicians' Experiences Promoting Infant Safe Sleep and Breastfeeding During the COVID-19 Pandemic.

OBJECTIVE: To explore the phenomenon of clinicians' perceptions and experiences of promoting infant safe sleep (ISS) and breastfeeding during the COVID-19 pandemic. DESIGN: Descriptive qualitative hermeneutical phenomenology of key informant interviews conducted as part of a quality improvement initiative. SETTING: Maternity care services of 10 U.S. hospitals from April through September 2020. PARTICIPANTS: Ten hospital teams, including 29 clinicians. INTERVENTION: Participants were part of a national quality improvement intervention focused on promoting ISS and breastfeeding. Participants were asked about challenges and opportunities promoting ISS and breastfeeding during the pandemic. RESULTS: We identified four themes summarizing the experiences and perceptions of clinicians promoting ISS and breastfeeding in the COVID-19 pandemic: Strain on Clinicians Related to Hospital Policies, Coordination, and Capacity; Effects of Isolation for Parentsin Labor and Delivery; ReevaluatingOutpatient Follow-Up Care andSupport; and AdoptingShared Decision-Makingaround ISS andBreastfeeding. CONCLUSIONS: Our results support the need for physical and psychosocial care to reduce crisis-related burnout for clinicians to encourage the continued provision of ISS and breastfeeding education, particularly while navigating capacity constraints. Our findings also suggest that clinicians perceived that parents may require additional support to enhance potentially limited ISS and breastfeeding education. These findings may be used to inform approaches to parental and clinician maternity care support in future public health crises.

Molecular elucidation of drug-induced abnormal assemblies of the hepatitis B virus capsid protein by solid-state NMR.

Hepatitis B virus (HBV) capsid assembly modulators (CAMs) represent a recent class of anti-HBV antivirals. CAMs disturb proper nucleocapsid assembly, by inducing formation of either aberrant assemblies (CAM-A) or of apparently normal but genome-less empty capsids (CAM-E). Classical structural approaches have revealed the CAM binding sites on the capsid protein (Cp), but conformational information on the CAM-induced off-path aberrant assemblies is lacking. Here we show that solid-state NMR can provide such information, including for wild-type full-length Cp183, and we find that in these assemblies, the asymmetric unit comprises a single Cp molecule rather than the four quasi-equivalent conformers typical for the icosahedral T = 4 symmetry of the normal HBV capsids. Furthermore, while in contrast to truncated Cp149, full-length Cp183 assemblies appear, on the mesoscopic level, unaffected by CAM-A, NMR reveals that on the molecular level, Cp183 assemblies are equally aberrant. Finally, we use a eukaryotic cell-free system to reveal how CAMs modulate capsid-RNA interactions and capsid phosphorylation. Our results establish a structural view on assembly modulation of the HBV capsid, and they provide a rationale for recently observed differences between in-cell versus in vitro capsid assembly modulation.

Effects of household and participant characteristics on personal exposure and kitchen concentration of fine particulate matter and black carbon in rural Honduras.

Traditional cooking with solid fuels (biomass, animal dung, charcoals, coal) creates household air pollution that leads to millions of premature deaths and disability worldwide each year. Exposure to household air pollution is highest in low- and middle-income countries. Using data from a stepped-wedge randomized controlled trial of a cookstove intervention among 230 households in Honduras, we analyzed the impact of household and personal variables on repeated 24-h measurements of fine particulate matter (PM2.5) and black carbon (BC) exposure. Six measurements were collected approximately six-months apart over the course of the three-year study. Multivariable mixed models explained 37% of variation in personal PM2.5 exposure and 49% of variation in kitchen PM2.5 concentrations. Additionally, multivariable models explained 37% and 47% of variation in personal and kitchen BC concentrations, respectively. Stove type, season, presence of electricity, primary stove location, kitchen enclosure type, stove use time, and presence of kerosene for lighting were all associated with differences in geometric mean exposures. Stove type explained the most variability of the included variables. In future studies of household air pollution, tracking the cooking behaviors and daily activities of participants, including outdoor exposures, may explain exposure variation beyond the household and personal variables considered here.

Racial And Ethnic Inequities In Children's Neighborhoods: Evidence From The New Child Opportunity Index 2.0.

Neighborhoods influence children's health, so it is important to have measures of children's neighborhood environments. Using the Child Opportunity Index 2.0, a composite metric of the neighborhood conditions that children experience today across the US, we present new evidence of vast geographic and racial/ethnic inequities in neighborhood conditions in the 100 largest metropolitan areas in the US. Child Opportunity Scores range from 20 in Fresno, California, to 83 in Madison, Wisconsin. However, more than 90 percent of the variation in neighborhood opportunity happens within metropolitan areas. In 35 percent of these areas the Child Opportunity Gap (the difference between Child Opportunity Scores in very low- and very high-opportunity neighborhoods) is higher than across the entire national neighborhood distribution. Nationally, the Child Opportunity Score for White children (73) is much higher than for Black (24) and Hispanic (33) children. To improve children's health and well-being, the health sector must move beyond a focus on treating disease or modifying individual behavior to a broader focus on neighborhood conditions. This will require the health sector to both implement place-based interventions and collaborate with other sectors such as housing to execute mobility-based interventions.

Understanding ER+ Breast Cancer Dormancy Using Bioinspired Synthetic Matrices for Long-Term 3D Culture and Insights into Late Recurrence.

Late recurrences of breast cancer are hypothesized to originate from disseminated tumor cells that re-activate after a long period of dormancy, ≥5 years for estrogen-receptor positive (ER+) tumors. An outstanding question remains as to what the key microenvironment interactions are that regulate this complex process, and well-defined human model systems are needed for probing this. Here, a robust, bioinspired 3D ER+ dormancy culture model is established and utilized to probe the effects of matrix properties for common sites of late recurrence on breast cancer cell dormancy. Formation of dormant micrometastases over several weeks is examined for ER+ cells (T47D, BT474), where the timing of entry into dormancy versus persistent growth depends on matrix composition and cell type. In contrast, triple negative cells (MDA-MB-231), associated with early recurrence, are not observed to undergo long-term dormancy. Bioinformatic analyses quantitatively support an increased "dormancy score" gene signature for ER+ cells (T47D) and reveal differential expression of genes associated with different biological processes based on matrix composition. Further, these analyses support a link between dormancy and autophagy, a potential survival mechanism. This robust model system will allow systematic investigations of other cell-microenvironment interactions in dormancy and evaluation of therapeutics for preventing late recurrence.

Rate-based approach for controlling the mechanical properties of 'thiol-ene' hydrogels formed with visible light.

The mechanical properties of synthetic hydrogels traditionally have been controlled with the concentration, molecular weight, or stoichiometry of the macromolecular building blocks used for hydrogel formation. Recently, the rate of formation has been recognized as an important and effective handle for controlling the mechanical properties of these water-swollen polymer networks, owing to differences in network heterogeneity (e.g., defects) that arise based on the rate of gelation. Building upon this, in this work, we investigate a rate-based approach for controlling mechanical properties of hydrogels both initially and temporally with light. Specifically, synthetic hydrogels are formed with visible light-initiated thiol-ene 'click' chemistry (PEG-8-norbornene, dithiol linker, LAP photoinitiator with LED lamp centered at 455 nm), using irradiation conditions to control the rate of formation and the mechanical properties of the resulting hydrogels. Further, defects within these hydrogels were subsequently exploited for temporal modulation of mechanical properties with a secondary cure using low doses of long wavelength UV light (365 nm). The elasticity of the hydrogel, as measured with Young's and shear moduli, was observed to increase with increasing light intensity and concentration of photoinitiator used for hydrogel formation. In situ measurements of end group conversion during hydrogel formation with magic angle spinning (MAS 1H NMR) correlated with these mechanical properties measurements, suggesting that both dangling end groups and looping contribute to the observed mechanical properties. Dangling end groups provide reactive handles for temporal stiffening of hydrogels with a secondary UV-initiated thiol-ene polymerization, where an increase in Young's modulus by a factor of ~ 2.5x was observed. These studies demonstrate how the rate of photopolymerization can be tuned with irradiation wavelength, intensity, and time to control the properties of synthetic hydrogels, which may prove useful in a variety of applications from coatings to biomaterials for controlled cell culture and regenerative medicine.

Proliferation, behavior, and differentiation of osteoblasts on surfaces of different microroughness.

OBJECTIVES: Titanium surface roughness is recognized as an important parameter influencing osseointegration. However, studies concerning the effect of well-defined surface topographies of titanium surfaces on osteoblasts have been limited in scope. In the present study we have investigated how Ti surfaces of different micrometer-scale roughness influence proliferation, migration, and differentiation of osteoblasts in-vitro. METHODS: Titanium replicas with surface roughnesses (Ra) of approximately 0, 1, 2, and 4µm were produced and MG-63 osteoblasts were cultured on these surfaces for up to 5 days. The effect of surface micrometer-scale roughness on proliferation, migration in time-lapse microscopy experiments, as well as the expression of alkaline phosphatase, osteocalcin, vascular-endothelial growth factor (VEGF), osteoprotegerin (OPG), and receptor activator of nuclear factor kappa-B ligand (RANKL) were investigated. RESULTS: Proliferation of MG-63 cells was found to decrease gradually with increasing surface roughness. However, the highest expression of alkaline phosphatase, osteocalcin and VEGF was observed on surfaces with Ra values of approximately 1 and 2µm. Further increase in surface roughness resulted in decreased expression of all investigated parameters. The cell migration speed measured in time-lapse microscopy experiments was significantly lower on surfaces with a Ra value of about 4µm, compared to those with lower roughness. No significant effect of surface roughness on the expression of OPG and RANKL was observed. SIGNIFICANCE: Thus, surfaces with intermediate Ra roughness values of 1-2µm seem to be optimal for osteoblast differentiation. Neither proliferation nor differentiation of osteoblasts appears to be supported by surfaces with higher or lower Ra values.

Patterning gradients.

Surface-chemical and -morphological gradients can be extremely useful in cell-biological research as high-throughput screening tools-for example, exposing a given set of cells to many different surface conditions at once, under identical ambient conditions, in order to monitor cell behavior such as proliferation or specific gene expression. They can also be used to investigate the effects of gradients themselves on cell behavior, such as migration. A number of simple, reliable techniques for both chemical- and morphological-gradient fabrication have been developed in our laboratories and are described in detail in the following.