Spironolactone Reduces the Risk of Death in Veterans With Heart Failure With Preserved Ejection Fraction.

BACKGROUND: Heart failure with preserved ejection fraction (HFpEF) is a complex syndrome increasing in prevalence and affecting millions worldwide but with limited evidence-based therapies. Results from explanatory clinical trials suggest that spironolactone may help to improve outcomes in patients with HFpEF. We sought to investigate the effectiveness of spironolactone in reducing death and hospitalization outcomes for patients with HFpEF in a real-world setting. METHODS AND RESULTS: We used electronic health records from the US Veterans Affairs (VA) health care system between 2002 and 2012 to identify patients with HFpEF who were followed longitudinally through 2014 using a validated algorithm. Among our HFpEF cohort that is 96% men, 85% White individuals, and aged 74±11 years, 3690 spironolactone users and 49 191 nonusers were identified and followed for a median of 2.9 (interquartile range [IQR], 1.5-2.4) and 3.3 (IQR, 1.6-5.9) years, respectively. We evaluated the effect of spironolactone use on all-cause death and number of days hospitalized per year for heart failure or for any cause by fitting generalized estimating equation-based Poisson and negative binomial models. Crude rates of 10.3 versus 13.5 deaths and 394.0 versus 485.9 days hospitalized were observed per 100 person-years for spironolactone users versus nonusers, respectively. After multivariable adjustment, there was a 21% reduction (95% CI, 13-29; P<0.0001) in rate of all-cause death among spironolactone users compared with nonusers and no statistically significant difference in days hospitalized for all causes or heart failure. CONCLUSIONS: In a real-world national cohort of patients with HFpEF, spironolactone use reduced all-cause death and demonstrated a favorable trend in reducing the burden of hospitalizations.

Stimulus-dependent differences in cortical versus subcortical contributions to visual detection in mice.

The primary visual cortex (V1) and the superior colliculus (SC) both occupy stations early in the processing of visual information. They have long been thought to perform distinct functions, with the V1 supporting the perception of visual features and the SC regulating orienting to visual inputs. However, growing evidence suggests that the SC supports the perception of many of the same visual features traditionally associated with the V1. To distinguish V1 and SC contributions to visual processing, it is critical to determine whether both areas causally contribute to the detection of specific visual stimuli. Here, mice reported changes in visual contrast or luminance near their perceptual threshold while white noise patterns of optogenetic stimulation were delivered to V1 or SC inhibitory neurons. We then performed a reverse correlation analysis on the optogenetic stimuli to estimate a neuronal-behavioral kernel (NBK), a moment-to-moment estimate of the impact of V1 or SC inhibition on stimulus detection. We show that the earliest moments of stimulus-evoked activity in the SC are critical for the detection of both luminance and contrast changes. Strikingly, there was a robust stimulus-aligned modulation in the V1 contrast-detection NBK but no sign of a comparable modulation for luminance detection. The data suggest that behavioral detection of visual contrast depends on both V1 and SC spiking, whereas mice preferentially use SC activity to detect changes in luminance. Electrophysiological recordings showed that neurons in both the SC and V1 responded strongly to both visual stimulus types, while the reverse correlation analysis reveals when these neuronal signals actually contribute to visually guided behaviors.

Elevated fear states facilitate ventral hippocampal engagement of basolateral amygdala neuronal activity.

Fear memory formation and retention rely on the activation of distributed neural circuits. The basolateral amygdala (BLA) and ventral hippocampus (VH) in particular are two regions that support contextual fear memory processes and share reciprocal connections. The VH → BLA pathway is critical for increases in fear after initial learning, in both fear renewal following extinction learning and during fear generalization. This raises the possibility that functional changes in VH projections to the BLA support increases in learned fear. In line with this, fear can also be increased with alterations to the original content of the memory via reconsolidation, as in fear elevation procedures. However, very little is known about the functional changes in the VH → BLA pathway supporting reconsolidation-related increases in fear. In this study, we used in vivo extracellular electrophysiology to examine the functional neuronal changes within the BLA and in the VH → BLA pathway as a result of fear elevation and standard fear retrieval procedures. Elevated fear expression was accompanied by higher BLA spontaneous firing compared to a standard fear retrieval condition. Across a range of stimulation frequencies, we also found that VH stimulation evoked higher BLA firing following fear elevation compared to standard retrieval. These results suggest that fear elevation is associated with an increased capacity of the VH to drive neuronal activity in the BLA, highlighting a potential circuit involved in strengthening existing fear memories.

Financial responsibility, financial context, and ambulatory blood pressure in early middle-aged African-American women.

BACKGROUND: African-American women have excess rates of elevated blood pressure (BP) and hypertension compared to women of all other racial/ethnic backgrounds. Several researchers have speculated that race and gender-related socioeconomic status (SES) stressors might play a role. OBJECTIVE: To examine the association between a novel SES-related stressor highly salient among African-American women, financial responsibility for one's household, and 48-h ambulatory BP. We further examined whether aspects related to African-American women's financial context (e.g., single parenthood, household income, marital status) played a role. METHODS: Participants were N = 345 employed, healthy African-American women aged 30-46 from diverse SES backgrounds who underwent 48-h ambulatory BP monitoring. Linear regression analyses were conducted to examine associations between self-reported financial responsibility and daytime and nighttime BP, adjusting for age, SES and other sociodemographics, cardiovascular risk factors, financial strain and depressive symptoms. Interactions between financial responsibility and single parenthood, household income, and marital/partnered status were tested. RESULTS: In age-adjusted analyses, reporting financial responsibility was associated with higher daytime systolic (ß = 4.42, S.E. = 1.36, p = 0.0013), and diastolic (ß = 2.82, S.E. = 0.98, p = 0.004) BP. Associations persisted in fully adjusted models. Significant associations were also observed for nighttime systolic and diastolic BP. There were no significant interactions with single parenthood, household income, nor marital/partnered status. CONCLUSION: Having primary responsibility for one's household may be an important driver of BP in early middle-aged African-American women, independent of SES, financial strain, and across a range of financial contexts. Future studies examining prospective associations are needed, and policy interventions targeting structural factors contributing to financial responsibility in African-American women may be warranted.

The association between Superwoman schema and subjective sleep quality among Black women.

OBJECTIVES: Similar to women overall, Black women are socialized to be communal and "self-sacrificing," but unlike women from other racial/ethnic backgrounds, Black women are also socialized to be "strong" and "invulnerable." This phenomenon is labeled Superwoman schema. This study examined associations between Superwoman schema endorsement and subjective sleep quality. METHODS: Participants included 405 Black women (ages 30-46). Superwoman schema was measured using a 35-item scale capturing five dimensions: obligation to present strength, suppress emotions, resistance to vulnerability, motivation to succeed, and obligation to help others. Superwoman schema overall and the five dimensions/subscales were analyzed. The Pittsburgh Sleep Quality Index (PSQI) was used to investigate overall subjective sleep quality (range: 0-19), poor sleep quality (PSQI >5), and specific sleep domains (eg, sleep duration, sleep disturbances). We fit linear and binary logistic regression models, adjusting for health-related and sociodemographic factors. RESULTS: Superwoman schema dimension obligation to help others was associated with lower overall subjective sleep quality (ß: .81, 95%CI=0.29, 1.32) and poor sleep quality (OR: 1.55, 95%CI=1.10, 2.19), as well as bad subjective sleep quality (OR: 1.76, 95%CI=1.18, 2.66), sleep disturbances (ß: .73, 95%CI =0.07, 1.41), and daytime sleepiness (OR: 2.01, 95%CI=1.25, 3.26). Suppress emotions (OR: 1.41, 95%CI=1.01, 1.99) was associated with poor subjective sleep quality. Superwoman schema overall was associated with daytime sleepiness (OR: 2.01, 95%CI=1.06, 3.82). CONCLUSION: Superwoman schema endorsement, especially obligation to help others and suppress emotions, may be important psychosocial risk factors for Black women's sleep health.

Female Genital Schistosomiasis Lesion Resolution Post-Treatment with Praziquantel in Zambian Adults.

We evaluated changes in female genital schistosomiasis (FGS) 6 to 12 months after praziquantel treatment among 43 adult Zambian women. Most women (60%) experienced decreased FGS severity and 23% experienced complete lesion resolution. This is the first study to demonstrate a meaningful effect of praziquantel treatment of FGS in adult women.

Temporal weighting of cortical and subcortical spikes reveals stimulus dependent differences in their contributions to behavior.

The primary visual cortex (V1) and the superior colliculus (SC) both occupy stations early in the processing of visual information. They have long been thought to perform distinct functions, with V1 supporting perception of visual features and the SC regulating orienting to visual inputs. However, growing evidence suggests that the SC supports perception of many of the same visual features traditionally associated with V1. To distinguish V1 and SC contributions to visual processing, it is critical to determine whether both areas causally contribute to perception of specific visual stimuli. Here, mice reported changes in visual contrast or luminance near perceptual threshold while we presented white noise patterns of optogenetic stimulation to V1 or SC inhibitory neurons. We then performed a reverse correlation analysis on the optogenetic stimuli to estimate a neuronal-behavioral kernel (NBK), a moment-to-moment estimate of the impact of V1 or SC inhibition on stimulus detection. We show that the earliest moments of stimulus-evoked activity in SC are critical for detection of both luminance or contrast changes. Strikingly, there was a robust stimulus-aligned modulation in the V1 contrast-detection NBK, but no sign of a comparable modulation for luminance detection. The data suggest that perception of visual contrast depends on both V1 and SC spiking, whereas mice preferentially use SC activity to detect changes in luminance. Electrophysiological recordings showed that neurons in both SC and V1 responded strongly to both visual stimulus types, while the reverse correlation analysis reveals when these neuronal signals actually contribute to visually-guided behaviors.

Network stressors, personal stressors, and ambulatory blood pressure in African-American women-Does superwoman schema play a role?

OBJECTIVE: Life stressors have been linked to cardiovascular risk; however, studies typically focus on stressors that directly impact the individual, that is, personal stressors. Research suggests that women, particularly African-American women, may be more vulnerable to network stressors that involve family members and friends-potentially due to norms around needing to be a "Superwoman." Yet few studies have examined these phenomena. METHOD: We examined associations between network, versus personal, stressors, and elevated blood pressure (BP) in N = 392 African-American women aged 30-46. Questionnaire-assessed negative life events were classified into upsetting network or personal stressors. BP was assessed in clinic and via 48-hr ambulatory monitoring. Linear and logistic regression models examined associations between type of stressors and 48-hr daytime and nighttime systolic BP (SBP) and diastolic BP (DBP), and sustained hypertension after adjusting for relevant covariates. Interactions with questionnaire-assessed superwoman schema (SWS) were tested in exploratory analyses. RESULTS: In age and sociodemographic-adjusted models, network stressors were significantly associated with daytime SBP, ß (SE) = 2.01 (0.51), p ≤ .0001, and DBP, ß (SE) = 1.59 (0.37), p ≤ .0001, but personal stressors were not (p values > .10). Associations persisted after adjustment for cardiovascular and psychosocial risk factors. Patterns were similar for nighttime BP and sustained hypertension. There were no interactions with SWS. CONCLUSIONS: Network, but not personal, stressors were associated with elevated rates of daytime SBP and DBP, as well as sustained hypertension in African-American women, irrespective of SWS endorsement. Future research is needed to determine whether stress-management interventions focused on network stressors might impact BP in this high-risk population. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Use of "Strengthening Our Vows" Video Intervention to Encourage Negotiated Explicit Sexual Agreements in Zambian Heterosexual HIV Seroconcordant-Negative Couples.

Negotiating sexual agreements in combination with couples' voluntary HIV counseling and testing (CVCT) may help further reduce HIV transmission in Zambian concordant HIV-negative couples (CNC). Though CVCT has been shown to reduce HIV transmission in CNC by 47%, approximately half of residual infections occur in this group. We developed a "Strengthening Our Vows" video session to foster communication and negotiation of explicit sexual agreements to reduce concurrent sexual exposures and prevent HIV transmission to the spouse due to unprotected, extramarital sex. CNC were recruited through CVCT services at five clinics in Lusaka and Ndola in 2016. Enrolled CNC attending the facilitated group video sessions were encouraged to discuss sexual agreements at home and return 1-2 weeks later for follow-up assessment. One-fourth of the 580 CNC returning reported a history of extramarital partners and/or a sexually transmitted infection (STI) prior to enrollment. More than 95% reported a friendly, supportive 15-60 min negotiation culminating in an agreement to remain monogamous or disclose sexual contacts and use condoms together until a repeat HIV test 30 days after an outside sexual exposure. Two-thirds of participants identified at least one threat to adherence of their agreements including alcohol use, financial pressures, travel, discord in the home, and post-partum or menstrual abstinence. CNC negotiated explicit sexual agreements to avoid exposure to HIV through concurrent partnerships and protect the spouse in the event of an outside sexual contact. Open communication was a consistent theme to facilitate mutual protective efforts. Long-term follow-up of HIV/STI incidence is ongoing to assess the impact of these agreements.Trial registration This sub-study is part of a trial retrospectively registered on ClinicalTrials.gov (Identifier: NCT02744586) on April 20, 2016.

Single-cell analysis reveals prognostic fibroblast subpopulations linked to molecular and immunological subtypes of lung cancer.

Fibroblasts are poorly characterised cells that variably impact tumour progression. Here, we use single cell RNA-sequencing, multiplexed immunohistochemistry and digital cytometry (CIBERSORTx) to identify and characterise three major fibroblast subpopulations in human non-small cell lung cancer: adventitial, alveolar and myofibroblasts. Alveolar and adventitial fibroblasts (enriched in control tissue samples) localise to discrete spatial niches in histologically normal lung tissue and indicate improved overall survival rates when present in lung adenocarcinomas (LUAD). Trajectory inference identifies three phases of control tissue fibroblast activation, leading to myofibroblast enrichment in tumour samples: initial upregulation of inflammatory cytokines, followed by stress-response signalling and ultimately increased expression of fibrillar collagens. Myofibroblasts correlate with poor overall survival rates in LUAD, associated with loss of epithelial differentiation, TP53 mutations, proximal molecular subtypes and myeloid cell recruitment. In squamous carcinomas myofibroblasts were not prognostic despite being transcriptomically equivalent. These findings have important implications for developing fibroblast-targeting strategies for cancer therapy.

Monitoring of Adverse Events in Recipients of the 2-Dose Ebola Vaccine Regimen of Ad26.ZEBOV Followed by MVA-BN-Filo in the UMURINZI Ebola Vaccination Campaign.

BACKGROUND: From 2019 to 2021, Rwandan residents of the border with the Democratic Republic of the Congo were offered the Ad26.ZEBOV (adenovirus type 26 vector vaccine encoding Ebola virus glycoprotein) and MVA-BN-Filo (modified vaccinia virus Ankara vector vaccine, encoding glycoproteins from Ebola, Sudan, Marburg, and nucleoprotein from Tai Forest viruses) Ebola vaccine regimen. METHODS: Nonpregnant persons aged ≥2 years were eligible. Unsolicited adverse events (UAEs) were reported through phone calls or visits, and serious adverse events (SAEs) were recorded per International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use guidelines. RESULTS: Following Ad26.ZEBOV, UAEs were reported by 0.68% of 216 113 vaccinees and were more common in younger children (aged 2-8 years, 1.2%) compared with older children (aged 9-17 years, 0.4%) and adults (aged ≥18 years, 0.7%). Fever and headache were the most reported symptoms. All 17 SAEs related to vaccine were in children aged 2-8 years (10 postvaccination febrile convulsions ± gastroenteritis and 7 fever and/or gastroenteritis). The incidence of febrile seizures was 8 of 26 062 (0.031%) prior to initiation of routine acetaminophen in December 2020 and 2 of 15 897 (0.013%) thereafter. Nonobstetric SAEs were similar in males and females. All 20 deaths were unrelated to vaccination. Young girls and adult women with UAEs were less likely to receive the second dose than those without UAEs. Seven unrelated SAEs occurred in 203 267 MVA-BN-Filo recipients. CONCLUSIONS: Postvaccination febrile convulsions in young children were rare but not previously described after Ad26.ZEBOV and were reduced with routine acetaminophen. The regimen was otherwise safe and well-tolerated.

Extreme racism-related events and poor sleep in African-American women.

RATIONALE: Much of the research linking racism-related stressors to poor health has focused on fairly non-violent forms of racism that directly impact individuals under study. Exposure to particularly extreme and/or violent racist events are increasingly visible via smartphone recordings and social media, with consistent anecdotal reports of the effects of seeing and hearing about these events on sleep among minorities who racially identify with the victims. OBJECTIVE: This study examines whether exposure to direct and vicarious racism-related events (RREs), including more extreme events, are associated with sleep quality. Additionally, we examine effects of less and more violent direct RREs and vicarious RREs witnessed in person and via social media. METHODS: Among 422 African-American women, we assessed exposure to RREs using a modified version of the Race-Related Events Scale and assessed sleep quality using the Pittsburgh Sleep Quality Index (PSQI). Linear regression analyses were used to model continuous global sleep. RESULTS: Direct (ß = 0.24 [95% CI: 0.13, 0.35]) RREs were associated with worse continuous global sleep quality scores in analyses adjusted for sociodemographics and risk factors for poor sleep. More violent direct RREs (ß = 0.59 [95% CI: 0.30, 0.89]) had stronger associations with poor sleep quality than less violent direct RREs (ß = 0.25 [95% CI: 0.11, 0.40]). Vicarious RREs overall (ß = 0.04 [95% CI: 0.14, 0.21]) and those witnessed via social media (ß = -0.07 [95% CI: 0.29, 0.14]) were not associated with global sleep quality; conversely, vicarious RREs witnessed in person were (ß = 0.52 [95% CI: 0.21, 0.83]). CONCLUSION: Extreme, direct experiences of racism, particularly those that are violent in nature, are associated with poor sleep quality. However, extreme vicarious experiences are not-- unless witnessed in person.

Public health communication in Canada during the COVID-19 pandemic.

OBJECTIVES: Communication is central to the implementation and effectiveness of public health measures. Informed by theories of good governance, COVID-19 pandemic public health messaging in 3 Canadian provinces is assessed for its potential to encourage or undermine public trust and adherence. METHODS: This study employed a mixed-methods constant comparative approach to triangulate epidemiological COVID-19 data and qualitative data from news releases, press briefings, and key informant interviews. Communications were analyzed from January 2020 to October 2021 in Nova Scotia, Ontario, and Alberta. Interview data came from 34 semi-structured key informant interviews with public health actors across Canada. Team-based coding and thematic analysis were conducted to analyze communications and interview transcripts. RESULTS: Four main themes emerged as integral to good communication: transparency, promptness, clarity, and engagement of diverse communities. Our data indicate that a lack of transparency surrounding evidence and public health decision-making, delays in public health communications, unclear and inconsistent terminology and activities within and across jurisdictions, and communications that did not consider or engage diverse communities' perspectives may have decreased the effectiveness of public health communications and adherence to public health measures throughout the COVID-19 pandemic. CONCLUSION: This study suggests that increased federal guidance with wider jurisdictional collaboration backed by transparent evidence could improve the effectiveness of communication practices by instilling public trust and adherence with public health measures. Effective communication should be transparent, supported by reliable evidence, prompt, clear, consistent, and sensitive to diverse values. Improved communication training, established engagement infrastructure, and increased collaborations and diversity of decision-makers and communicators are recommended.

RéSUMé: OBJECTIFS: La communication est centrale à l'implantation et au succès des mesures de santé publique. À partir des théories de bonne gouvernance, les messages de santé publique sur la COVID-19 de trois provinces canadiennes ont été analysés afin d'évaluer si ces messages renforçaient ou diminuaient la confiance et l'adhésion de la population. MéTHODES: Cette étude utilise une approche comparative constante et des méthodes mixtes pour trianguler des données épidémiologiques sur la COVID-19 avec des données qualitatives provenant de communiqués de presse, de conférences de presse et d'entretiens avec des informateurs clés. Les communications ont été analysées entre janvier 2020 et octobre 2021 en Nouvelle-Écosse, Ontario et Alberta. Les données proviennent également de 34 entretiens semi-dirigés avec des acteurs de santé publique à travers le Canada. Une codification en équipe et une analyse de contenu thématique ont été réalisées pour analyser les communications et les verbatim des entretiens. RéSULTATS: Quatre thèmes principaux sont apparus comme faisant partie intégrante d'une bonne communication : la transparence, la rapidité, la clarté et l'engagement des diverses communautés. Nos données indiquent qu'un manque de transparence en ce qui a trait aux données probantes et aux processus de prise de décision en santé publique, que les retards dans les stratégies de communication de santé publique, qu'une terminologie et des activités incohérentes et inconsistantes dans les provinces et entre elles, ainsi que des communications qui ne tenaient pas compte des points de vue ou qui n'incluaient pas les diverses communautés, ont pu réduire l'efficacité des communications et l'adhésion aux mesures de santé publique tout au long de la pandémie de COVID-19. CONCLUSION: Cette étude suggère que des lignes directrices nationales et une collaboration accrue entre les provinces et les territoires soutenues par des données probantes transparentes pourraient améliorer l'efficacité des communications en suscitant la confiance du public et l'adhésion aux mesures de santé publique. Une communication efficace doit être transparente, appuyée sur des données probantes fiables, rapide, claire, cohérente et sensible aux différentes valeurs. Il est recommandé d'améliorer la formation en communication, d'établir une infrastructure pour accroître l'engagement, et de soutenir la collaboration et la diversité des décideurs et des communicateurs.

A mixed-methods study of factors influencing postpartum intrauterine device uptake after family planning counseling among women in Kigali, Rwanda.

INTRODUCTION: Rwanda has high unmet need for family planning (FP), especially in the postpartum period when women are advised to space pregnancies at least two years for improved maternal-child health. Despite interest in the copper intrauterine device (IUD), a highly cost-effective method, access and uptake remain low. This study aimed to determine factors associated with postpartum IUD (PPIUD) uptake after postpartum family planning (PPFP) counseling as well as provider perceptions of facilitators and barriers to clients' PPIUD uptake. METHODS: Postpartum women who received PPFP counseling and were less than 6 weeks postpartum were recruited for a case-control study in Kigali, Rwanda in 2018. We recruited n = 74 women who had accepted and n = 91 women who had declined the PPIUD. Multivariate logistic regression analyses evaluated associations between women's socio-demographics, FP knowledge and decision-making, and the outcome of PPIUD uptake. Six focus groups (FGs) were conducted with FP providers (n = 24) and community health workers (n = 17) trained to deliver PPFP counseling to assess perceptions of PPFP counseling and facilitators and barriers to PPIUD uptake. FG discussions were recorded, translated, and analyzed for themes. RESULTS: Factors associated (P<0.1) with PPIUD uptake included citing its non-hormonal nature, effectiveness, and duration of protection against pregnancy as advantages. Exclusive male partner control over FP decisions (relative to women's control or joint decision-making) was associated with non-use. Overall, limited knowledge about some aspects of the PPIUD persisted among clients even after counseling. Provider FGs highlighted client concerns, inconsistent FP messaging, and lack of male partner involvement as factors influencing non-use. CONCLUSIONS: Knowledge of the IUD and its benefits was associated with PPIUD uptake. There is need to refine PPFP counseling messages to address remaining knowledge gaps and concerns. Additionally, male partner involvement in FP counseling and decisions with their partners could be a key strategy to increase both PPIUD and FP uptake in Rwanda.

Extreme racism-related events and poor sleep in African-American women.

RATIONALE: Much of the research linking racism-related stressors to poor health has focused on fairly non-violent forms of racism that directly impact individuals under study. Exposure to particularly extreme and/or violent racist events are increasingly visible via smartphone recordings and social media, with consistent anecdotal reports of the effects of seeing and hearing about these events on sleep among minorities who racially identify with the victims. OBJECTIVE: This study examines whether exposure to direct and vicarious racism-related events (RREs), including more extreme events, are associated with sleep quality. Additionally, we examine effects of less and more violent direct RREs and vicarious RREs witnessed in person and via social media. METHODS: Among 422 African-American women, we assessed exposure to RREs using a modified version of the Race-Related Events Scale and assessed sleep quality using the Pittsburgh Sleep Quality Index (PSQI). Linear regression analyses were used to model continuous global sleep. RESULTS: Direct (ß = 0.24 [95% CI: 0.13, 0.35]) RREs were associated with worse continuous global sleep quality scores in analyses adjusted for sociodemographics and risk factors for poor sleep. More violent direct RREs (ß = 0.59 [95% CI: 0.30, 0.89]) had stronger associations with poor sleep quality than less violent direct RREs (ß = 0.25 [95% CI: 0.11, 0.40]). Vicarious RREs overall (ß = 0.04 [95% CI: 0.14, 0.21]) and those witnessed via social media (ß = -0.07 [95% CI: 0.29, 0.14]) were not associated with global sleep quality; conversely, vicarious RREs witnessed in person were (ß = 0.52 [95% CI: 0.21, 0.83]). CONCLUSION: Extreme, direct experiences of racism, particularly those that are violent in nature, are associated with poor sleep quality. However, extreme vicarious experiences are not-- unless witnessed in person.

Synthesis, Mesomorphism, Photophysics, and Device Properties of Liquid-Crystalline Pincer Complexes of Gold(III) Containing Semiperfluorinated Chains.

Gold(III) complexes of C∧N∧C-coordinating 2,6-diphenylpyridine pincer ligands with arylacetylide co-ligands are known triplet emitters at room temperature. We have reported previously that by functionalizing both the pincer ligand and the phenylacetylene with alkoxy chains, liquid crystallinity may be induced, with the complexes showing columnar mesophases. We now report new derivatives in which the phenylacetylene incorporates one, two, or three 1H,1H,2H,2H-perfluoroalkyl chains. In terms of intermolecular interactions, solution 1H NMR experiments suggest that the semiperfluoroalkyl chains promote a parallel, head-to-head arrangement of neighboring molecules relative to one another, rather than the anti-parallel, head-to-tail orientation found for the all-hydrocarbon materials. In terms of the liquid crystal properties, the complexes show columnar phases, with the addition of the more rigid fluorocarbon chains leading to a stabilization of both the crystal and liquid crystal mesophases. Mesophase temperature ranges were also wider. Interestingly, the amphiphilic nature of these complexes is evident through the observation of a frustrated columnar nematic phase between a Colr and a Colh phase, an observation recently reported in detail for one compound (Liq. Cryst., 2022, doi: 10.1080/02678292.2021.1991017). While calculation shows that, despite the "electronic insulation" provided by the dimethylene spacer group in the semiperfluoroalkyl chains, a small hypsochromic shift in one component of the absorption band is anticipated, experimentally this effect is not observed in the overall absorption envelope. Complexes with substituents in the 3,3',4,4'-positions of the phenyl rings of the pincer ligand once more show higher-luminescence quantum yields than the analogues with substituents in the 4,4'-positions only, associated with the lower-energy-emissive state in the former. However, in contrast to the observations with all-hydrocarbon analogues, the luminescence quantum yield of the complexes with 3,3',4,4'-substitution on the pincer increases as the number of semiperfluoroalkyl chains on the phenylacetylide increases, from 20% (one chain) to 34% (three chains). External quantum efficiencies in fabricated OLED devices are, however, low, attributed to the poor dispersion in the host materials on account of the fluorinated chains.

Social Determinants of Health Associated With Patient Portal Use in Pediatric Diabetes.

OBJECTIVES: Social determinants of health (SDOH) are associated with type 1 diabetes (T1D) outcomes. Patient portal (PP) use can improve care quality. Therefore, equitable PP access is essential. Associations between SDOH and PP access have not been reported in pediatric T1D. The purpose of this study was to determine whether PP access and use are associated with SDOH in pediatric T1D. METHODS: This work was a cross-sectional study of patients <18 years of age with T1D who were seen in a diabetes clinic at a tertiary care centre between April 1, 2020, and March 31, 2021. Patient postal code, PP activation status and use, and characteristics were collected from electronic health records on April 1, 2021. SDOH were assessed using patient postal code linked to the Ontario Marginalization Index (ON-Marg) to determine quintile score across 4 dimensions of deprivation. Statistical analysis tested for an association between PP activation status and ON-Marg quintile. RESULTS: Data were obtained for 634 patients with a mean age of 12.8±3.8 years; 53% were male and mean glycated hemoglobin was 8.4±2.0%. In the last year, 334 patients (53%) were PP active and 332 (52%) used the PP. The odds of inactive PP status were higher for those with the highest degree of material deprivation (odds ratio [OR], 2.91; 95% confidence interval [CI], 1.62 to 5.36) and residential instability (OR, 3.49; 95% CI, 1.86 to 6.70). PP activation status was not associated with dependency or ethnic concentration. CONCLUSIONS: In our pediatric T1D population, inactive PP status is associated with greater material deprivation and residential instability. How these factors impact PP activation and how to improve equitable access requires further study.

Safety, reactogenicity, and immunogenicity of a 2-dose Ebola vaccine regimen of Ad26.ZEBOV followed by MVA-BN-Filo in healthy adult pregnant women: study protocol for a phase 3 open-label randomized controlled trial.

BACKGROUND: Risks to mother and fetus following Ebola virus infection are very high. Evaluation of safety and immunogenicity of non-replicating Ebola vaccine candidates is a priority for use in pregnant women. This is the protocol for a randomized, open-label, single-center phase 3 clinical trial of the safety, reactogenicity, and immunogenicity of the 2-dose Ebola vaccine regimen in healthy adult pregnant women. This 2-dose regimen has been shown to be safe, judged effective, and approved in non-pregnant populations. METHODS: A total of 2000 adult (≥ 18 years of age) pregnant women will be enrolled from antenatal care facilities in Western Rwanda and randomized (1:1) to receive the 2-dose Ebola vaccine regimen (Ad26.ZEBOV, MVA-BN-Filo (group A)) or control (unvaccinated pregnant women (group B)). The primary objectives are to (1) assess adverse maternal/fetal outcomes in randomized pregnant women up to 1.5 months after delivery and (2) assess adverse neonatal/infant outcomes in neonates/infants born to randomized women up to 3.5 months after birth. The frequency and relatedness of all serious adverse events in women and newborns from randomization or birth, respectively, until study end will be reported. The reactogenicity and unsolicited adverse events of the 2-dose Ebola vaccine regimen in all vaccinated pregnant women (group A) will be reported. We will also assess the immunogenicity of the 2-dose Ebola vaccine regimen in 150 pregnant women who are anticipated to receive both vaccine doses within the course of their pregnancy (a subset of the 1000 pregnant vaccinated women from group A) compared to 150 non-pregnant women vaccinated after delivery (a subset of group B). The persistence of maternal antibodies in 75 infants born to women from the group A subset will be assessed. Exploratory analyses include assessment of acceptability of the 2-dose Ebola vaccine regimen among group A and assessment of maternal antibodies in breast milk in 50 women from group A and 10 controls (women from group B prior to vaccination). DISCUSSION: This study is intended to support a label variation to relax restrictions on use in pregnant women, a vulnerable population with high medical need. TRIAL REGISTRATION: Clinicaltrials.gov NCT04556526 . September 21, 2020.

Implementation and evaluation of a large-scale postpartum family planning program in Rwanda: study protocol for a clinic-randomized controlled trial.

BACKGROUND: Though the Rwandan Ministry of Health (MOH) prioritizes the scale-up of postpartum family planning (PPFP) programs, uptake and sustainability of PPFP services in Rwanda are low. Furthermore, highly effective long-acting reversible contraceptive method use (LARC), key in effective PPFP programs, is specifically low in Rwanda. We previously pilot tested a supply-demand intervention which significantly increased the use of postpartum LARC (PPLARC) in Rwandan government clinics. In this protocol, we use an implementation science framework to test whether our intervention is adaptable to large-scale implementation, cost-effective, and sustainable. METHODS: In a type 2 effectiveness-implementation hybrid study, we will evaluate the impact of our PPFP intervention on postpartum LARC (PPLARC) uptake in a clinic-randomized trial in 12 high-volume health facilities in Kigali, Rwanda. We will evaluate this hybrid study using the RE-AIM framework. The independent effectiveness of each PPFP demand creation strategy on PPLARC uptake among antenatal clinic attendees who later deliver in a study facility will be estimated. To assess sustainability, we will assess the intervention adoption, implementation, and maintenance. Finally, we will evaluate intervention cost-effectiveness and develop a national costed implementation plan. DISCUSSION: Adaptability and sustainability within government facilities are critical aspects of our proposal, and the MOH and other local stakeholders will be engaged from the outset. We expect to deliver PPFP counseling to over 21,000 women/couples during the project period. We hypothesize that the intervention will significantly increase the number of stakeholders engaged, PPFP providers and promoters trained, couples/clients receiving information about PPFP, and PPLARC uptake comparing intervention versus standard of care. We expect PPFP client satisfaction will be high. Finally, we also hypothesize that the intervention will be cost-saving relative to the standard of care. This intervention could dramatically reduce unintended pregnancy and abortion, as well as improve maternal and newborn health. Our PPFP implementation model is designed to be replicable and expandable to other countries in the region which similarly have a high unmet need for PPFP. TRIAL REGISTRATION: ClinicalTrials.gov NCT05056545 . Registered on 31 March 2022.

Measles immunity gap among reproductive-age women participating in a simulated HIV vaccine efficacy trial in Zambia.

Measles is a vaccine-preventable viral disease whose vaccination coverage remains low in Zambia, where the target group for vaccination is children aged 9 to 18 months. In addition to inadequate measles vaccination coverage among children, few studies address potential resultant immunity gaps among adults. We analyzed data from a simulated HIV vaccine efficacy trial (SiVET) conducted from 2015-2017 among adult Zambian women of childbearing age to determine measles antibody seroprevalence before and after vaccination with the measles, mumps and rubella (MMR) vaccine. We used MMR vaccine as a substitute for an experimental HIV vaccine as part of a simulation exercise to prepare for an HIV vaccine efficacy trial. We found that 75% of women had measles antibodies prior to receiving MMR, which increased to 98% after vaccination. In contrast, mumps and rubella antibody prevalence was high before (93% and 97%, respectively) and after (99% and 100%, respectively) vaccination. The low baseline measles seropositivity suggests an immunity gap among women of childbearing age. We recommend that measles vaccination programs target women of childbearing age, who can pass antibodies on to neonates. Moreover, administering the MMR vaccine to clinical trial candidates could prevent measles, mumps or rubella-related adverse events during actual trials.