Evaluating the implementation of Nuevo Amanecer-II in rural community settings using mixed methods and equity frameworks.

BACKGROUND: The 10-week Nuevo Amanecer-II intervention, tested through a randomized controlled trial, reduced anxiety and improved stress management skills among Spanish-speaking Latina breast cancer survivors. This paper describes the implementation and equity evaluation outcomes of the Nuevo Amanecer-II intervention delivered in three California rural communities. METHODS: Using implementation and equity frameworks, concurrent convergent mixed methods were applied to evaluate implementation (feasibility, fidelity, acceptability, adoption, appropriateness, and sustainability) and equity (shared power and capacity building) outcomes. Quantitative data were collected using tracking forms, fidelity rating forms, and program evaluation surveys; qualitative data were collected using semi-structured in-depth interviews. Respondents included community-based organization (CBO) administrators, recruiters, compañeras (interventionists), and program participants. RESULTS: Of 76 women randomized to the intervention, 65 (86%) completed at least 7 of 10 sessions. Participants' knowledge (85% correct of 7 questions) and skills mastery were high (85% able to correctly perform 14 skills). Mean fidelity ratings across compañeras ranged from 3.8 (modeled skills) to 5.0 (used supportive/caring communication); 1-5 scale. The program was rated as very good/excellent by 90% of participants. Participants and compañeras suggested including family members; compañeras suggested expanding content on managing thoughts and mood and healthy living and having access to participant's survivorship care plan to tailor breast cancer information. CBOs adopted the program because it aligned with their priority populations and mission. Building on CBOs' knowledge, resources, and infrastructure, implementation success was due to shared power, learning, responsibility, and co-ownership, resulting in a co-created tailored program for community and organizational contexts. Building intervention capacity prior to implementation, providing funding, and ongoing technical support to CBOs were vital for fidelity and enhancement of recruiter and compañera professional skills. Two of three CBOs created plans for program sustainability beyond the clinical trial; all administrators discussed the need for new funding sources to sustain the program as delivered. CONCLUSIONS: Building on community assets and using equitable participatory research processes were central to the successful implementation of a peer-delivered psychosocial intervention in three rural communities among Spanish-speaking Latinas with breast cancer.

Cortisol levels in rural Latina breast cancer survivors participating in a peer-delivered cognitive-behavioral stress management intervention: The Nuevo Amanecer-II RCT.

Background: Compared to their White counterparts, Latina breast cancer survivors have poorer survival rates and health-related quality of life, and higher rates of depression and anxiety which may be a result of chronic stress. Chronic stress impacts the hypothalamic-pituitary-adrenal (HPA) axis, resulting in cortisol dysregulation which may be associated with breast cancer survival. However, cortisol levels and cortisol profiles of Latina breast cancer survivors are poorly characterized due to their underrepresentation in biomedical research. Objective: The objective of this study was to describe cortisol levels and patterns of cortisol secretions in rural Latina breast cancer survivors participating in an RCT study of Nuevo Amanecer-II, an evidence-based peer-delivered cognitive behavioral stress management intervention. Methods: Participant-centered recruitment and collection strategies were used to obtain biospecimens for cortisol analysis. Nine saliva samples (3/day for 3 days) and a hair sample were obtained at baseline and 6-months (3-months post-intervention). We describe cortisol levels and profiles, explore correlations of biomarkers with self-report measures of stress and psychological distress, and compare women who received the intervention with a delayed intervention group on biomarkers of stress. Mean hair cortisol concentration (HCC) was used to assess chronic stress. Based on daily measures of cortisol (awakening, 30 min post-awakening, and bedtime), we calculated three summary measures of the dynamic nature of the cortisol awakening response (CAR): 1) the CAR slope, 2) whether CAR demonstrates a percent change ≥40, and 3) total daily cortisol output (AUCg). Linear and log-binomial regression, accounting for multiple samples per participant, were used to compare cortisol measures at 6-month follow-up by treatment arm. Results: Participants (n = 103) were from two rural California communities; 76 provided at least one saliva sample at baseline and follow-up and were included in the analysis. At baseline, mean age was 57 years, mean years since diagnosis was 2 years, 76% had a high school education or less, and 34% reported financial hardship. The overall median CAR slope was 0.10, and median cortisol AUCg (in thousands) was 11.34 (range = 0.93, 36.66). Mean hair cortisol concentration was 1751.6 pg/mg (SD = 1148.6). Forty-two percent of samples had a ≥40% change in CAR. We found no statistically significant correlations between the cortisol measures and self-reported measures of stress and psychological distress. At follow-up, no differences were seen in HCC (mean difference between intervention and control: -0.11, 95% CI -0.48, 0.25), CAR slope (0.001, 95% CI -0.005, 0.008), cortisol AUCg (-0.15, 95% CI -0.42, 0.13), or ≥40% change in CAR (prevalence ratio 0.87, 95% CI 0.42, 1.77) between treatment arms. Conclusion: Our findings of flattened cortisol profiles among more than half of the sample suggest potential HPA-axis dysregulation among rural Spanish-speaking Latina breast cancer survivors that merits further study due to its implications for long-term survival. Trial registration: http://www.ClinicalTrials.gov identifier NCT02931552.

Perceived general, mental, and physical health of Latinos in the United States following adoption of immigrant-inclusive state-level driver's license policies: a time-series analysis.

BACKGROUND: In the United States (U.S.), several states have laws that allow individuals to obtain driver's licenses regardless of their immigration status. Possession of a driver's license can improve an individual's access to social programs, healthcare services, and employment opportunities, which could lead to improvements in perceived mental and physical health among Latinos living in the U.S. METHODS: Using Behavioral Risk Factor Surveillance System data (2011-2019) for Latinos living in the U.S. overall (immigration status was not available), we compared the average number of self-reported perceived poor mental and physical health days/month, and general health status (single-item measures) before (January 2011-June 2013) and after implementation (July 2015-December 2019) of immigrant-inclusive license policies using interrupted time-series analyses and segmented linear regression, and a control group of states in which such policies were not implemented. We also compared the average number of adults reporting any perceived poor mental or physical health days (≥ 1 day/month) using a similar approach. RESULTS: One hundred twenty-three thousand eight hundred seven Latino adults were included; 66,805 lived in states that adopted immigrant-inclusive license policies. After implementation, average number of perceived poor physical health days significantly decreased from 4.30 to 3.80 days/month (immediate change = -0.64, 95% CI = -1.10 to -0.19). The proportion reporting ≥ 1 perceived poor physical and mental health day significantly decreased from 41 to 34% (OR = 0.89, 95% CI = 0.80-1.00) and from 40 to 33% (OR = 0.84, 95% CI = 0.74-0.94), respectively. CONCLUSIONS: Among all Latinos living in the U.S., immigrant-inclusive license policies were associated with fewer perceived poor physical health days per month and fewer adults experiencing poor physical and mental health. Because anti-immigrant policies can harm Latino communities regardless of immigration status and further widen health inequities, implementing state policies that do not restrict access to driver licenses based on immigrant status documentation could help address upstream drivers of such inequities.

COVID-19-Related Discrimination Among Racial/Ethnic Minorities and Other Marginalized Communities in the United States.

Objectives. To determine the prevalence of COVID-19-related discrimination among major US racial/ethnic groups and estimate associations between discrimination, race/ethnicity, and other sociodemographic characteristics. Methods. We conducted a nationally representative online survey of 5500 American Indian/Alaska Native, Asian, Black/African American, Hawaiian/Pacific Islander, Latino (English and Spanish speaking), White, and multiracial adults from December 2020 to February 2021. Associations between sociodemographic characteristics and COVID-19-related discrimination were estimated via multinomial logistic regression. Results. A total of 22.1% of the participants reported experiencing discriminatory behaviors, and 42.7% reported that people acted afraid of them. All racial/ethnic minorities were more likely than White adults to experience COVID-19-related discrimination, with Asian and American Indian/Alaska Native adults being most likely to experience such discrimination (discriminatory behaviors: adjusted odd ratio [AOR] = 2.59; 95% confidence interval [CI] = 1.73, 3.89; and AOR = 2.67; 95% CI = 1.76, 4.04; people acting afraid: AOR = 1.54; 95% CI = 1.15, 2.07; and AOR = 1.84; 95% CI = 1.34, 2.51). Limited English proficiency, lower education, lower income, and residing in a big city or the East South Central census division also increased the prevalence of discrimination. Conclusions. COVID-19-related discrimination is common, and it appears that the pandemic has exacerbated preexisting resentment against racial/ethnic minorities and marginalized communities. Efforts are needed to minimize and discredit racially driven language and discrimination around COVID-19 and future epidemics. (Am J Public Health. 2022;112(3):453-466. https://doi.org/10.2105/AJPH.2021.306594).

Racial/ethnic disparities in intent to obtain a COVID-19 vaccine: A nationally representative United States survey.

Black, Latino, Pacific Islander, and American Indian/Alaska Native adults are more likely than White adults to experience SARS-CoV-2-related infections, hospitalizations, and mortality. We assessed intent to be vaccinated and concerns among 7 U.S. racial/ethnic groups (1,000 Black/African American, 500 American Indian/Alaska Native, 1,000 Asian, 1,000 Latino (500 English- and 500 Spanish-speaking), 500 Pacific Islander, 500 multiracial, and 1,000 White adults) in a cross-sectional online survey conducted December 2020-February 2021, weighted to be nationally representative within groups. Intent to be vaccinated was ascertained with: "If a COVID-19 vaccine becomes available, how likely are you to get vaccinated?" (not at all/slightly/moderately/very/extremely likely). Respondents identified which concerns would keep them from being vaccinated: cost, not knowing where, safety, effectiveness, side-effects, and other. Multinomial logistic regression models assessed associations of race/ethnicity with odds of being extremely/very/moderately, slightly likely to be vaccinated (ref = not at all), controlling for demographics and health. Overall, 30% were extremely likely, 22% not at all likely, and 48% unsure. Compared to White respondents, American Indian/Alaska Native (Adjusted Odds Ratio (AOR) = 0.66, 95% CI, 0.47-0.92) and Black/African American (AOR = 0.54, 95% CI, 0.41-0.72) respondents were less likely, and Asian (AOR = 2.21, 95% CI, 1.61-3.02) and Spanish-speaking Latino respondents (AOR = 3.74, 95% CI, 2.51-5.55) were more likely to report being extremely likely to be vaccinated. Side-effects (52%) and safety (45%) were overriding concerns. Intent and vaccination rates are changing rapidly; these results constitute a comprehensive baseline for ongoing vaccination efforts among U.S. racial and ethnic groups.

Hemolytic Membrane Vesicles of Group B Streptococcus Promote Infection.

BACKGROUND: Group B streptococci (GBS) are ß-hemolytic, Gram-positive bacteria associated with fetal injury, preterm birth, spontaneous abortion, and neonatal infections. A key factor promoting GBS virulence is the ß-hemolysin/cytolysin, a pigmented ornithine rhamnolipid (also known as granadaene) associated with the bacterial surface. METHODS: A previous study indicated that GBS produce small structures known as membrane vesicles (MVs), which contain virulence-associated proteins. In this study, we show that GBS MVs are pigmented and hemolytic, indicating that granadaene is functionally active in MVs. RESULTS: In addition, MVs from hyperhemolytic GBS induced greater cell death of neutrophils, T cells, and B cells compared with MVs from isogenic nonhemolytic GBS, implicating MVs as a potential mechanism for granadaene-mediated virulence. Finally, hemolytic MVs reduced oxidative killing of GBS and aggravated morbidity and mortality of neonatal mice infected with GBS. CONCLUSIONS: These studies, taken together, reveal a novel mechanism by which GBS deploy a crucial virulence factor to promote bacterial dissemination and pathogenesis.

Lipid analogs reveal features critical for hemolysis and diminish granadaene mediated Group B Streptococcus infection.

Although certain microbial lipids are toxins, the structural features important for cytotoxicity remain unknown. Increased functional understanding is essential for developing therapeutics against toxic microbial lipids. Group B Streptococci (GBS) are bacteria associated with preterm births, stillbirths, and severe infections in neonates and adults. GBS produce a pigmented, cytotoxic lipid, known as granadaene. Despite its importance to all manifestations of GBS disease, studies towards understanding granadaene's toxic activity are hindered by its instability and insolubility in purified form. Here, we report the synthesis and screening of lipid derivatives inspired by granadaene, which reveal features central to toxin function, namely the polyene chain length. Furthermore, we show that vaccination with a non-toxic synthetic analog confers the production of antibodies that inhibit granadaene-mediated hemolysis ex vivo and diminish GBS infection in vivo. This work provides unique structural and functional insight into granadaene and a strategy to mitigate GBS infection, which will be relevant to other toxic lipids encoded by human pathogens.

Group B streptococcus exploits vaginal epithelial exfoliation for ascending infection.

Thirteen percent of pregnancies result in preterm birth or stillbirth, accounting for fifteen million preterm births and three and a half million deaths annually. A significant cause of these adverse pregnancy outcomes is in utero infection by vaginal microorganisms. To establish an in utero infection, vaginal microbes enter the uterus by ascending infection; however, the mechanisms by which this occurs are unknown. Using both in vitro and murine models of vaginal colonization and ascending infection, we demonstrate how a vaginal microbe, group B streptococcus (GBS), which is frequently associated with adverse pregnancy outcomes, uses vaginal exfoliation for ascending infection. GBS induces vaginal epithelial exfoliation by activation of integrin and ß-catenin signaling. However, exfoliation did not diminish GBS vaginal colonization as reported for other vaginal microbes. Rather, vaginal exfoliation increased bacterial dissemination and ascending GBS infection, and abrogation of exfoliation reduced ascending infection and improved pregnancy outcomes. Thus, for some vaginal bacteria, exfoliation promotes ascending infection rather than preventing colonization. Our study provides insight into mechanisms of ascending infection by vaginal microbes.

Congenital Zika virus infection as a silent pathology with loss of neurogenic output in the fetal brain.

Zika virus (ZIKV) is a flavivirus with teratogenic effects on fetal brain, but the spectrum of ZIKV-induced brain injury is unknown, particularly when ultrasound imaging is normal. In a pregnant pigtail macaque (Macaca nemestrina) model of ZIKV infection, we demonstrate that ZIKV-induced injury to fetal brain is substantial, even in the absence of microcephaly, and may be challenging to detect in a clinical setting. A common and subtle injury pattern was identified, including (i) periventricular T2-hyperintense foci and loss of fetal noncortical brain volume, (ii) injury to the ependymal epithelium with underlying gliosis and (iii) loss of late fetal neuronal progenitor cells in the subventricular zone (temporal cortex) and subgranular zone (dentate gyrus, hippocampus) with dysmorphic granule neuron patterning. Attenuation of fetal neurogenic output demonstrates potentially considerable teratogenic effects of congenital ZIKV infection even without microcephaly. Our findings suggest that all children exposed to ZIKV in utero should receive long-term monitoring for neurocognitive deficits, regardless of head size at birth.

Human Cervical Mucus Plugs Exhibit Insufficiencies in Antimicrobial Activity Towards Group B Streptococcus.

Preterm birth is a leading cause of neonatal mortality and lacks an effective therapy. Ascending microbial infections from the lower genital tract lead to infection of the placenta, amniotic fluid, and fetus causing preterm birth or stillbirth. Directly in the path of an ascending infection is the cervical mucus plug (CMP), a dense mucoid structure in the cervical canal with potential antimicrobial properties. In this study, we aimed to define the components of CMP responsible for antimicrobial activity against a common lower genital tract organism associated with preterm birth and stillbirths, namely, group B streptococcus (GBS). Using a quantitative proteomic approach, we identified antimicrobial factors in CMPs that were collected from healthy human pregnancies. However, we noted that the concentration of antimicrobial peptides present in the human CMPs were insufficient to directly kill GBS, and antimicrobial activity, when observed, was due to antibiotics retained in the CMPs. Despite this insufficiency, CMP proteins were able to activate leukocytes in whole blood resulting in increased rates of bacterial killing, suggesting a role for the CMP in enhancing complement-mediated killing or leukocyte activation. This study provides new insight into how the human CMP may limit ascending bacterial infection.

Group B Streptococcus circumvents neutrophils and neutrophil extracellular traps during amniotic cavity invasion and preterm labor.

Preterm birth is a leading cause of neonatal morbidity and mortality. Although microbial invasion of the amniotic cavity (MIAC) is associated with the majority of early preterm births, the temporal events that occur during MIAC and preterm labor are not known. Group B Streptococci (GBS) are ß-hemolytic, gram-positive bacteria, which commonly colonize the vagina but have been recovered from the amniotic fluid in preterm birth cases. To understand temporal events that occur during MIAC, we utilized a unique chronically catheterized nonhuman primate model that closely emulates human pregnancy. This model allows monitoring of uterine contractions, timing of MIAC and immune responses during pregnancy-associated infections. Here, we show that adverse outcomes such as preterm labor, MIAC, and fetal sepsis were observed more frequently during infection with hemolytic GBS when compared to nonhemolytic GBS. Although MIAC was associated with systematic progression in chorioamnionitis beginning with chorionic vasculitis and progressing to neutrophilic infiltration, the ability of the GBS hemolytic pigment toxin to induce neutrophil cell death and subvert killing by neutrophil extracellular traps (NETs) in placental membranes in vivo facilitated MIAC and fetal injury. Furthermore, compared to maternal neutrophils, fetal neutrophils exhibit decreased neutrophil elastase activity and impaired phagocytic functions to GBS. Collectively, our studies demonstrate how a unique bacterial hemolytic lipid toxin enables GBS to circumvent neutrophils and NETs in placental membranes to induce fetal injury and preterm labor.

Mast cell degranulation by a hemolytic lipid toxin decreases GBS colonization and infection.

Ascending infection of microbes from the lower genital tract into the amniotic cavity increases the risk of preterm birth, stillbirth, and newborn infections. Host defenses that are critical for preventing ascending microbial infection are not completely understood. Group B Streptococcus (GBS) are Gram-positive bacteria that frequently colonize the lower genital tract of healthy women but cause severe infections during pregnancy, leading to preterm birth, stillbirth, or early-onset newborn infections. We recently described that the GBS pigment is hemolytic, and increased pigment expression promotes GBS penetration of human placenta. Here, we show that the GBS hemolytic pigment/lipid toxin and hyperpigmented GBS strains induce mast cell degranulation, leading to the release of preformed and proinflammatory mediators. Mast cell-deficient mice exhibit enhanced bacterial burden, decreased neutrophil mobilization, and decreased immune responses during systemic GBS infection. In a vaginal colonization model, hyperpigmented GBS strains showed increased persistence in mast cell-deficient mice compared to mast cell-proficient mice. Consistent with these observations, fewer rectovaginal GBS isolates from women in their third trimester of pregnancy were hyperpigmented/hyperhemolytic. Our work represents the first example of a bacterial hemolytic lipid that induces mast cell degranulation and emphasizes the role of mast cells in limiting genital colonization by hyperpigmented GBS.