Activation of human STING by a molecular glue-like compound.

Stimulator of interferon genes (STING) is a dimeric transmembrane adapter protein that plays a key role in the human innate immune response to infection and has been therapeutically exploited for its antitumor activity. The activation of STING requires its high-order oligomerization, which could be induced by binding of the endogenous ligand, cGAMP, to the cytosolic ligand-binding domain. Here we report the discovery through functional screens of a class of compounds, named NVS-STGs, that activate human STING. Our cryo-EM structures show that NVS-STG2 induces the high-order oligomerization of human STING by binding to a pocket between the transmembrane domains of the neighboring STING dimers, effectively acting as a molecular glue. Our functional assays showed that NVS-STG2 could elicit potent STING-mediated immune responses in cells and antitumor activities in animal models.

Feasibility, Acceptability, and Preliminary Effectiveness of a Sleep Intervention in Adults at Risk for Metabolic Syndrome With Short Sleep Duration.

BACKGROUND: The prevalence of short sleep duration is rising and is linked to chronic comorbidities, such as metabolic syndrome (MetS). Sleep extension interventions in adults with MetS comorbidities and short sleep duration are limited and vary widely in terms of approach and duration. OBJECTIVES: This pilot study aimed to test the feasibility and acceptability of a personalized 12-week systematic sleep time extension intervention on post-intervention sleep outcomes in middle-aged adults at risk for MetS with actigraphy-estimated short sleep duration. METHODS: A single-arm, 12-week, 12-session systematic sleep time extension intervention was delivered weekly via videoconferencing. Feasibility and acceptability were assessed using retention rates and mean sleep diary completions. Sleep was estimated for 14 consecutive days prior to and immediately following the 12-week intervention using wrist actigraphy. Daytime sleepiness was assessed using the Epworth Sleepiness Scale. Paired sample t -tests modeled changes in study outcomes. RESULTS: Study participants ( N = 41) had a mean age of 52 years and were mostly female and White; 86% attended >80% of sessions, and mean sleep diary completion was 6.7 diaries/week. Significant improvements in sleep from pre- to post-intervention included increased total sleep time, earlier sleep onsets, more regular sleep onsets, a higher sleep regularity index, and reduced daytime sleepiness. Extending sleep, as well as improving sleep timing and regularity in middle-aged adults with actigraphy-estimated short sleep duration and at risk for MetS, is feasible and acceptable. DISCUSSION: Behavioral sleep characteristics may be modifiable and present a novel behavioral paradigm for mitigating MetS risk. This pilot study provides a proof of concept for the feasibility, acceptability, and preliminary effectiveness of a systematic sleep time extension for middle-aged adults at risk for MetS with actigraphy-estimated short sleep duration.

A Stem-like Patient-Derived Ovarian Cancer Model of Platinum Resistance Reveals Dissociation of Stemness and Resistance.

To understand chemoresistance in the context of cancer stem cells (CSC), a cisplatin resistance model was developed using a high-grade serous ovarian cancer patient-derived, cisplatin-sensitive sample, PDX4. As a molecular subtype-specific stem-like cell line, PDX4 was selected for its representative features, including its histopathological and BRCA2 mutation status, and exposed to cisplatin in vitro. In the cisplatin-resistant cells, transcriptomics were carried out, and cell morphology, protein expression, and functional status were characterized. Additionally, potential signaling pathways involved in cisplatin resistance were explored. Our findings reveal the presence of distinct molecular signatures and phenotypic changes in cisplatin-resistant PDX4 compared to their sensitive counterparts. Surprisingly, we observed that chemoresistance was not inherently linked with increased stemness. In fact, although resistant cells expressed a combination of EMT and stemness markers, functional assays revealed that they were less proliferative, migratory, and clonogenic-features indicative of an underlying complex mechanism for cell survival. Furthermore, DNA damage tolerance and cellular stress management pathways were enriched. This novel, syngeneic model provides a valuable platform for investigating the underlying mechanisms of cisplatin resistance in a clinically relevant context, contributing to the development of targeted therapies tailored to combat resistance in stem-like ovarian cancer.

Chronic Health Condition Management and School-Based Health Centers in New York: Findings From the 2020 School Health Profiles Survey.

School-based health centers (SBHCs) are associated with numerous positive aspects of student health services. Many schools in the United States (US) do not have transparent policies on chronic health condition (CHC) management. Of particular concern is the underreporting of the delivery of health services in U.S. schools concerning CHC management and its relationship with the presence or absence of a SBHC. Data from the 2020 School Health Profiles (SHP) Survey were examined in New York public secondary schools. Specific health services were reviewed, together with the presence or absence of a SBHC, including daily medication administration, stock rescue medication, case management services, community partners, chronic disease-specific education, and assurance that students with CHCs were enrolled in an insurance program. A significantly greater proportion of schools with a SBHC compared with schools without a SBHC provided: (1) daily medication administration (92.9% vs. 86.5%; p < .001), (2) stock or rescue medication (84.9% vs. 77.4%; p < .001), (3) case management services (83.1% vs. 67.2%; p < .001), (4) disease-specific education for families (63.1% vs. 57.2%; p = .022), (5) student and family connection to community health services (84.2% vs. 76.5%; p < .001), and (6) ensured that a protocol existed whereby students with a CHC were enrolled in an insurance plan if eligible (79.6% vs. 66.8%; p < .001). Findings suggest that data on a national scale include essential facts for states to consider concerning school health policies and practices. Additional research should examine the intricacy of elements connected with school-based health care to understand better the care provided to children with CHCs.

Neuroinflammation: A Modifiable Pathway Linking Obesity, Alzheimer's disease, and Depression.

Obesity, depression and Alzheimer's disease (AD) are three major interrelated modern health conditions with complex relationships. Early-life depression may serve as a risk factor for AD, while late-life depression may be a prodrome of AD. Depression affects approximately 23% of obese individuals, and depression itself raises the risk of obesity by 37%. Mid-life obesity independently increases AD risk, while late-life obesity, particularly metabolically healthy obesity, may offer protection against AD pathology. Chronic inflammation serves as a key mechanism linking obesity, AD, and depression, encompassing systemic inflammation from metabolic disturbances, immune dysregulation through the gut microbiome, and direct interactions with amyloid pathology and neuroinflammation. In this review, we explore the biological mechanisms of neuroinflammation in relation to obesity, AD, and depression. We assess the efficacy of therapeutic interventions targeting neuroinflammation and discuss current and future radiological imaging initiatives for studying neuroinflammation. By comprehending the intricate interplay among depression, obesity, and AD, especially the role of neuroinflammation, we can advance our understanding and develop innovative strategies for prevention and treatment.

Study protocol for type II hybrid implementation-effectiveness trial of strategies for depression care task-sharing in community health stations in Vietnam: DEP Project.

BACKGROUND: It is not clear what the most effective implementation strategies are for supporting the enactment and sustainment of depression care services in primary care settings. This type-II Hybrid Implementation-Effectiveness study will compare the effectiveness of three system-level strategies for implementing depression care programs at 36 community health stations (CHSs) across 2 provinces in Vietnam. METHODS: In this cluster-randomized controlled trial, CHSs will be randomly assigned to one of three implementation conditions: (1) Usual Implementation (UI), which consists of training workshops and toolkits; (2) Enhanced Supervision (ES), which includes UI combined with bi-weekly/monthly supervision; and (3) Community-Engaged Learning Collaborative (CELC), which includes all components of ES, combined with bi-monthly province-wide learning collaborative meetings, during which cross-site learning and continuous quality improvement (QI) strategies are implemented to achieve better implementation outcomes. The primary outcome will be measured based on the RE-AIM framework (Reach, Effectiveness, Adoption, Implementation quality, and Maintenance) using indicators on implementation, provider, and client factors. The secondary outcome examines factors associated with barriers and facilitators of quality implementation, while the tertiary outcome evaluates the incremental cost-effectiveness ratio of services provided in the ES and CELC conditions, relative to UI condition for depression care. A total of 1,296 clients receiving depression care at CHSs will be surveyed at baseline and 6-month follow-up to assess mental health and psychosocial outcomes (e.g., depression and anxiety severity, health function, quality of life). Additionally, 180 CHS staff and 180 non-CHS staff will complete pre- and post-training evaluation and surveys at baseline, 6, 12, and 24 months. DISCUSSION: We hypothesize that the additional implementation supports will make mental health service implementation superior in the ES and CELC arms compared to the UI arm. The findings of this project could identify effective implementation models and assess the added value of specific QI strategies for implementing depression care in primary care settings in Vietnam, with implications and recommendations for other low- and middle-income settings. More importantly, this study will provide evidence for key stakeholders and policymakers to consider policies that disseminate, scale up, and advance quality mental health care in Vietnam. TRIAL REGISTRATION: NCT04491045 on Clinicaltrials.gov. Registered July 29, 2020.

Study Protocol Using Cohort Data and Latent Variable Modeling to Guide Sampling Women With Type 2 Diabetes and Depressive Symptoms.

BACKGROUND: Depression affects one in three women with Type 2 diabetes, and this concurrence significantly increases the risks of diabetes complications, disability, and early mortality. Depression is underrecognized because of wide variation in presentation and the lack of diagnostic biomarkers. Converging evidence suggests inflammation is a shared biological pathway in diabetes and depression. Overlapping epigenetic associations and social determinants of diabetes and depression implicate inflammatory pathways as a common thread. OBJECTIVES: This article describes the protocol and methods for a pilot study aimed to examine associations between depressive symptoms, inflammation, and social determinants of health among women with Type 2 diabetes. METHODS: This is an observational correlational study that leverages existing longitudinal data from the Women's Interagency HIV Study (WIHS), a multicenter cohort of HIV seropositive (66%) and HIV seronegative (33%) women, to inform purposive sampling of members from latent subgroups emergent from a prior retrospective cohort-wide analysis. Local active cohort participants from the Bronx study site are then selected for the study. The WIHS recently merged with the Multicenter Aids Cohort Study (MACS) to form the MACS/WIHS Combined Cohort Study. Latent subgroups represent distinct symptom trajectories resultant from a growth mixture model analysis of biannually collected depressive symptom data. Participants complete surveys (symptom and social determinants) and provide blood samples to analyze plasma levels and DNA methylation of genes that encode for inflammatory markers (CRP, IL-6, TNF-α). Correlation and regression analysis will be used to estimate the effect sizes between depressive symptoms and inflammatory markers, clinical indices (body mass index, hemoglobin A1C, comorbidities), and social determinants of health. RESULTS: The study began in January 2022, and completed data collection is estimated by early 2023. We hypothesize that depressive symptom severity will associate with higher levels of inflammation, clinical indices (e.g., higher hemoglobin A1C), and exposure to specific social determinants of health (e.g., lower income, nutritional insecurity). DISCUSSION: Study findings will provide the basis for future studies aimed at improving outcomes for women with Type 2 diabetes by informing the development and testing of precision health strategies to address and prevent depression in populations most at risk.

Latent Class Analysis of Depressive Symptom Phenotypes Among Black/African American Mothers.

BACKGROUND: Depression is a growing global problem with significant individual and societal costs. Despite their consequences, depressive symptoms are poorly recognized and undertreated because wide variation in symptom presentation limits clinical identification-particularly among African American (AA) women-an understudied population at an increased risk of health inequity. OBJECTIVES: The aims of this study were to explore depressive symptom phenotypes among AA women and examine associations with epigenetic, cardiometabolic, and psychosocial factors. METHODS: This cross-sectional, retrospective analysis included self-reported Black/AA mothers from the Intergenerational Impact of Genetic and Psychological Factors on Blood Pressure study (data collected in 2015-2020). Clinical phenotypes were identified using latent class analysis. Bivariate logistic regression examined epigenetic age, cardiometabolic traits (i.e., body mass index ≥ 30 kg/m 2 , hypertension, or diabetes), and psychosocial variables as predictors of class membership. RESULTS: All participants were Black/AA and predominantly non-Hispanic. Over half of the sample had one or more cardiometabolic traits. Two latent classes were identified (low vs. moderate depressive symptoms). Somatic and self-critical symptoms characterized the moderate symptom class. Higher stress overload scores significantly predicted moderate-symptom class membership. DISCUSSION: In this sample of AA women with increased cardiometabolic burden, increased stress was associated with depressive symptoms that standard screening tools may not capture. Research examining the effect of specific stressors and the efficacy of tools to identify at-risk AA women are urgently needed to address disparities and mental health burdens.

Impact of Co-occurring Cancer-Related and Wound-Specific Symptoms on Functional Performance Among Patients With Advanced Cancer and Malignant Fungating Wounds: An Exploratory, Observational Study.

PURPOSE: The purpose of this study was to examine the impact of co-occurring symptoms in patients with advanced cancer and malignant fungating wounds (MFWs) on palliative and functional performance, and the feasibility of collecting self-reported data in this population. DESIGN: This was an exploratory, observational study. Quantitative surveys and qualitative semistructured interviews using a phenomenological approach were employed. SUBJECTS AND SETTING: The sample comprised 5 adults with advanced breast, oral, and ovarian cancer and MFWs. Participants were recruited from an urban outpatient cancer center, hospice, and wound center located in the Northeastern United States. METHODS: Demographic and clinical characteristics were collected, and self-reported symptom and functional performance data measured. Descriptive statistics, T scores, confidence intervals, and standard deviation were calculated for quantitative data. One-to-one semistructured interviews were conducted by the first author to gain deeper understanding of participants' symptom experience. Qualitative data were analyzed using an iterative and inductive thematic data analysis method to identify major themes. RESULTS: The mean cancer-related and wound-specific symptom occurrence was 17 (SD = 5.56) and 4 (SD = 1.26), respectively. Distressing, extensive co-occurring symptom burdens were experienced by all participants; they also reported poor functional performance and diminished palliative performance. Qualitative findings supported quantitative results. CONCLUSIONS: Findings suggest that co-occurring cancer-related and wound-specific symptoms have incremental and negative impact on functional performance. The use of multiple data collection methods was feasible, including self-reported data in this advanced cancer population.

The Impact of the Early COVID-19 Pandemic on Registered Nurses' Intent to Stay in Nursing.

The COVID-19 pandemic has been difficult for registered nurses. Media reports, most of them anecdotal, have reported upticks in nurse resignations, and plans to resign and/or leave nursing due to COVID-19. This article reports findings from an online anonymous 95-item survey completed by about 1,600 nurses from a New York City metropolitan area health system's (HS) four hospitals and ambulatory care centers about their COVID-19 experience in the spring of 2020, their intent to stay at the HS, and their intent to stay working as a nurse. Conducted early in the pandemic, this survey addresses a major gap in the literature, as there was no timely evaluation of nurses' intent to leave during the "Great Attrition" wave or to stay during the "Great Attraction" trend. Among those nurses completing the survey, 85.7% reported that they planned to work as a nurse one year later and 77.9% reported that they planned to work at the HS one year later. Those nurses who obtained a master's or doctoral degree as their first professional degree in nursing, or had a high level of mastery, were less likely to report an intent to stay at the HS. Those with no children, those who thought the HS was more supportive, and those who thought that registered nurse-medical doctor relations were higher were more likely to intend to stay at the HS. Those nurses who reported worse communication with their nurse manager were less likely to report an intent to stay in nursing. Those who reported lower stress, who were unmarried and had no children were more likely to intend to work as nurses. Our findings on nurses' intent to leave their organization and their intent to leave nursing are much lower than reports in the popular press. Our data were collected early in the pandemic and it may not reflect the accumulated stress nurses experienced from witnessing the death of so many patients.

All-atom simulations of bent liquid crystal dimers: the twist-bend nematic phase and insights into conformational chirality.

The liquid crystal dimer 1,7-bis-4-(4'-cyanobiphenyl)heptane (CB7CB) is known to exhibit a nematic-nematic phase transition, with the lower temperature phase identified as the twist-bend nematic (NTB) phase. Despite the achiral nature of the mesogen, the NTB phase demonstrates emergent chirality through the spontaneous formation of a helical structure. We present extensive molecular dynamics simulations of CB7CB using an all-atom force field. The NTB phase is observed in this model and, upon heating, shows phase transitions into the nematic (N) and isotropic phases. The simulated NTB phase returns a pitch of 8.35 nm and a conical tilt angle of 29°. Analysis of the bend angle between the mesogenic units reveals an average angle of 127°, which is invariant to the simulated phase. We have calculated distributions of the chirality order parameter, χ, for the ensemble of conformers in the NTB and N phases. These distributions elucidate that CB7CB is statistically achiral but can adopt chiral conformers with no preference for a specific handedness. Furthermore, there is no change in the extent of conformational chirality between the NTB and N phases. Using single-molecule stochastic dynamics simulations in the gas phase, we study the dimer series CBnCB (where n = 6, 7, 8 or 9) and CBX(CH2)5YCB (where X/Y = CH2, O or S) in terms of the bend angle and conformational chirality. We confirm that the bent molecular shape determines the ability of a dimer to exhibit the NTB phase rather than its potential to assume chiral conformers; as |χ|max increases with the spacer length, but the even-membered dimers have a linear shape in contrast to the bent nature of dimers with spacers of odd parity. For CBX(CH2)5YCB, it is found that |χ|max increases as the bend angle of the dimer decreases, while the flexibility of the dimers remains unchanged through the series.

Determinants of never-treated status in rural versus urban contexts for individuals with schizophrenia in a population-based study in China.

BACKGROUND: A goal of China's 2012 National Mental Health Law is to improve access to services and decrease urban versus rural disparities in services. However, pre-reform data is needed for objective evaluation of these reforms' effectiveness. Accordingly, this study compares the pre-reform utilization of medical services for the treatment of schizophrenia in rural and urban communities in China. METHODS: In a large community-based study in four provinces representing 12% of China's population conducted from 2001 to 2005, we identified 326 individuals with schizophrenia (78 never treated). Comparing those living in urban (n = 86) versus rural (n = 240) contexts, we used adjusted Poisson regression models to assess the relationship of 'never treated' status with family-level factors (marital status, family income, and number of co-resident family members) and illness severity factors (age of onset, symptom severity and functional impairment). RESULTS: Despite similar impairments due to symptoms, rural patients were less likely to have received intensive mental health services (i.e., use psychiatric inpatient services), and appeared more likely to be 'never treated' or to only have received outpatient care. Among rural patients, only having more than four co-resident family members was independently associated with 'never-treated' status (RR = 0.34; 95% CI, 0.12-0.94; p = 0.039). Among urban patients, only older age of onset was independently associated with 'never-treated' status (RR = 1.06; 95% CI 1.02-1.10, p = 0.003). CONCLUSIONS: Identifying differential drivers of service utilization in urban and rural communities is needed before implementing policies to improve the utilization and equity of services and to define metrics of program success.

Multimorbidity patterns in adult day health center clients with dementia: a latent class analysis.

BACKGROUND: Persons living with dementia (PLWD) in adult day centers (ADCs) represent a complex and vulnerable population whose well-being is at risk based on numerous factors. Greater knowledge of the interaction between dementia, chronic conditions, and social determinants of health would enable ADCs to identify and target the use of their resources to better support clients in need of in-depth intervention. The purpose of this paper is to (a) classify PLWD in ADCs according to their level of medical complexity and (b) identify the demographic, functional, and clinical characteristics of those with the highest degree of medical complexity. METHODS: This was a secondary data analysis of 3052 clients with a dementia diagnosis from 53 ADCs across the state of California between 2012 and 2019. The most common diagnosis codes were organized into 28 disease categories to enable a latent class analysis (LCA). Chi-square test, analysis of variance (ANOVA), and Kruskal-Wallis tests were conducted to examine differences among latent classes with respect to clinical and functional characteristics. RESULTS: An optimal 4-class solution was chosen to reflect chronic conditions among PLWD: high medical complexity, moderate medical complexity, low medical complexity, and no medical complexity. Those in the high medical complexity were taking an average of 12.72 (+/- 6.52) medications and attending the ADC an average of 3.98 days (+/- 1.31) per week-values that exceeded any other class. They also experienced hospitalizations more than any other group (19.0%) and met requirements for the nursing facility level of care (77.4%). In addition, the group experienced the greatest frequency of bladder (57.5%) and bowel (15.7%) incontinence. CONCLUSIONS: Our results illustrate a high degree of medical complexity among PLWD in ADCs. A majority of PLWD not only have multimorbidity but are socially disadvantaged. Our results demonstrate that a comprehensive multidisciplinary approach that involves community partners such as ADCs is critically needed that addresses functional decline, loneliness, social isolation, and multimorbidity which can negatively impact PLWD.

Associations of insomnia symptoms with sociodemographic, clinical, and lifestyle factors in persons with HF: Health and retirement study.

Insomnia symptoms are very common in persons with heart failure (HF). However, many of the correlates and predictors of insomnia symptoms in this population remain unclear. The purpose of this study is to investigate the associations of sociodemographic, clinical, and lifestyle factors with insomnia symptoms in persons with HF. A theoretical framework was adapted from the neurocognitive model of chronic insomnia to guide the study. Data from the health and retirement study were used for the analysis. Parametric and nonparametric bivariate and multivariate analyses were conducted to investigate these associations. Age, depressive symptoms, comorbidity, dyspnea, pain, and smoking had significant bivariate associations with all insomnia symptoms. Race, Hispanic ethnicity, marital status, household income, poverty, and physical activity were associated with difficulty initiating sleep (DIS) and early morning awakening (EMA). Female sex, education, and alcohol consumption had a significant bivariate association with DIS. Sleep-disordered breathing and body mass index were significantly associated with EMA. Multivariate analysis suggested that depressive symptoms, comorbidity, dyspnea, and pain had independent associations with each insomnia symptom. Age explained DIS and difficulty maintaining sleep, and significant interaction effects between age and physical activity on DIS and EMA were revealed. Results suggest that insomnia symptoms are associated with several sociodemographic, clinical, and lifestyle factors. Age below 70 years, depressive symptoms, comorbidity, dyspnea, and pain might be considered as a phenotype to identify persons with HF who are at increased risk for insomnia symptoms.

Combined Race and Gender Trend Disparities in Depressive Symptoms among U.S. High School Students: 1999-2019.

In 2019, over 3.2 million adolescents in the U.S. reported depressive symptoms-a number that continues to increase annually. Not only can depression negatively impact an adolescent's academic performance, social development, and cognitive function, but it is also the most common condition associated with suicide. Previous studies have reported prevalence rates and statistical trends by either gender or race. We conducted an in-depth analysis of the current racial and gender trend disparities in adolescent depressive symptoms by examining linear and quadratic trends from the Youth Behavior Risk Survey (N = 158,601) over two decades (1999-2019), stratified by gender and race subgroups, both separately and combined. This novel quantitative method allows for a more nuanced approach when exploring social and cultural influences on adolescent depressive symptoms. We found a significant difference in the prevalence of depressive symptoms between males and females among Black, Hispanic, and multiracial adolescents in each separate year of pooled data. However, an increased prevalence trend over the 20-year period was only seen among the females of these three racial categories. White and Asian female adolescents also exhibited a statistical increase in prevalence of depressive symptoms over time. The only group of males with a significant trend increase over time were White adolescents. Understanding the intersection of gender and race in adolescent depressive symptoms trends enhances evidence for nurses and other healthcare professionals when developing and implementing targeted, effective prevention and intervention measures.

Gender-equitable caregiver attitudes and education and safety of adolescent girls in South Kivu, DRC: A secondary analysis from a randomized controlled trial.

BACKGROUND: Adolescent girls face myriad threats to their well-being and safety as a result of gender-inequitable attitudes and norms, and these risks are often exacerbated during humanitarian emergencies. While humanitarian actors have begun to address caregivers' behaviors and gender attitudes as an approach to support and meet the needs of adolescent girls, best practices for working with caregivers to improve adolescent girls' well-being in these settings have yet to be identified. METHODS AND FINDINGS: This study uses panel data from a program evaluation to analyze associations between changes in gender-equitable attitudes among caregivers and changes in schooling and violence victimization for girls ages 10 to 14 years old in the Democratic Republic of the Congo (DRC). Participants were recruited in May 2015 for baseline (May to July 2015) and endline (August to October 2016) data collection. Baseline and endline data for both caregivers and girls were available for 732 girls. The average ages of adolescents and caregivers were 12 and 40.7, respectively, and 92% of caregivers were female. The predictor of interest was the change in caregivers' gender-equitable attitudes between the 2 points in time, where attitudes were measured using 10 underlying survey questions. The primary outcomes of interest were dichotomous and included improvement in schooling participation and declines in physical, sexual, and emotional violence and feeling uncared for. Logistic regression was used to estimate the association between changes in caregivers' attitudes and 5 outcomes of interest and revealed that an increase in a caregiver's gender-equitable attitude score was associated with significantly greater odds of a girl experiencing an improvement in schooling participation (aOR = 1.08, CI [1.005, 1.154], p = 0.036) and of a girl experiencing a marginal decline in physical violence victimization (aOR = 1.07, CI [0.989, 1.158], p = 0.092). Analyses also revealed that older girls had lower odds of experiencing an improvement in schooling participation (aOR = 0.77, CI [0.686, 0.861], p < 0.001), physical violence (aOR = 0.86, CI [0.757, 0.984], p = 0.028), sexual violence (aOR = 0.86, CI [0.743, 1.003], p = 0.055), or emotional violence (aOR = 0.98, CI [0.849, 1.105], p = 0.005). Important limitations in this study include the self-reported nature of outcomes, use of single questionnaire items to construct the outcome variables, and potential self-selection bias. CONCLUSIONS: Results suggest that supporting caregivers to increase gender equitable attitudes may be associated with benefits in dual outcomes of education and safety for adolescent girls in eastern DRC. Further research is needed to better understand how to induce a shift in these attitudes in multisectoral programming. TRIAL REGISTRATION: NCT02384642.

Comparison of social cognition using an adapted Chinese version of the Reading the Mind in the Eyes Test in drug-naive and regularly medicated individuals with chronic schizophrenia and healthy controls in rural China.

BACKGROUND: Social cognition has not previously been assessed in treatment-naive patients with chronic schizophrenia, in patients over 60 years of age, or in patients with less than 5 years of schooling. METHODS: We revised a commonly used measure of social cognition, the Reading the Mind in the Eyes Test (RMET), by expanding the instructions, using both self-completion and interviewer-completion versions (for illiterate respondents), and classifying each test administration as 'successfully completed' or 'incomplete'. The revised instrument (RMET-CV-R) was administered to 233 treatment-naive patients with chronic schizophrenia (UT), 154 treated controls with chronic schizophrenia (TC), and 259 healthy controls (HC) from rural communities in China. RESULTS: In bivariate and multivariate analyses, successful completion rates and RMET-CV-R scores (percent correct judgments about emotion exhibited in 70 presented slides) were highest in HC, intermediate in TC, and lowest in UT (adjusted completion rates, 97.0, 72.4, and 49.9%, respectively; adjusted RMET-CV-R scores, 45.4, 38.5, and 34.6%, respectively; all p < 0.02). Stratified analyses by the method of administration (self-completed v. interviewer-completed) and by education and age ('educated-younger' v. 'undereducated-older') show the same relationship between groups (i.e. NC>TC>UT), though not all differences remain statistically significant. CONCLUSIONS: We find poorer social cognition in treatment-naive than in treated patients with chronic schizophrenia. The discriminant validity of RMET-CV-R in undereducated, older patients demonstrates the feasibility of administering revised versions of RMET to patients who may otherwise be considered ineligible due to education or age by changing the method of test administration and carefully assessing respondents' ability to complete the task successfully.

Atomistic simulation studies of ionic cyanine dyes: self-assembly and aggregate formation in aqueous solution.

Cyanine dyes are known to form large-scale aggregates of various morphologies via spontaneous self-assembly in aqueous solution, akin to chromonic liquid crystals. Atomistic molecular dynamics simulations have been performed on four cyanine dyes: pseudoisocyanine chloride (PIC), pinacyanol chloride (PCYN), 5,5',6,6'-tetrachloro-1,1',3,3'-tetraethylbenzimidazolylcarbocyanine chloride (TTBC) and 1,1'-disulfopropyl-3,3'-diethyl-5,5',6,6'-tetrachloro-benzimidazolylcarbocyanine sodium salt (BIC). Simulations employed an optimised general AMBER force field and demonstrate the organisation of the dyes into stacked structures at dilute concentrations. The thermodynamics of self-assembly was studied by calculating potentials of mean force for n-mers (n = 2, 3 or 4), from which the free energies of association are determined. We report binding free energies in the range of 8 to 15kBT for dimerisation, concordant with typical values for ionic chromonics (7 to 14kBT), and examine the enthalpic and entropic contributions to the aggregation process. The self-assembly of these dyes yields two distinct classes of structures. We observe the formation of H-aggregate stacks for PCYN, with further complexity in these assemblies for PIC; where the aggregates contain shift and Y junction defects. TTBC and BIC associate into a J-aggregate sheet structure of unimolecular thickness, and is composed of a brickwork arrangement between molecules. These sheet structures are characteristic of the smectic chromonic mesophase, and such assemblies provide a route to the emergence of nanoscale tubular architectures.

Latent Class Analysis of Symptom Burden Among Seriously Ill Adults at the End of Life.

BACKGROUND: Serious illness is characterized by high symptom burden that negatively affects quality of life (QOL). Although palliative care research has highlighted symptom burden in seriously ill adults with cancer, symptom burden among those with noncancer serious illness and multiple chronic conditions has been understudied. Latent class analysis is a statistical method that can be used to better understand the relationship between severity of symptom burden and covariates, such as the presence of multiple chronic conditions. Although latent class analysis has been used to highlight subgroups of seriously ill adults with cancer based on symptom clusters, none have incorporated multiple chronic conditions. OBJECTIVES: The objectives of this study were to (a) describe the demographic and baseline characteristics of seriously ill adults at the end of life in a palliative care cohort, (b) identify latent subgroups of seriously ill individuals based on severity of symptom burden, and (c) examine variables associated with latent subgroup membership, such as QOL, functional status, and the presence of multiple chronic conditions. METHODS: A secondary data analysis of a palliative care clinical trial was conducted. The latent class analysis was based on the Edmonton Symptom Assessment System, which measures nine symptoms on a scale of 0-10 (e.g., pain, fatigue, nausea, depression, anxiousness, drowsiness, appetite, well-being, and shortness of breath). Clinically significant cut-points for symptom severity were used to categorize each symptom item in addition to a categorized total score. RESULTS: Three latent subgroups were identified (e.g., low, moderate, and high symptom burden). Lower overall QOL was associated with membership in the moderate and high symptom burden subgroups. Multiple chronic conditions were associated with statistically significant membership in the high symptom burden latent subgroup. Older adults between 65 and 74 years had a lower likelihood of moderate or high symptom burden subgroup membership compared to the low symptom burden class. DISCUSSION: Lower QOL was associated with high symptom burden. Multiple chronic conditions were associated with high symptom burden, which underlines the clinical complexity of serious illness. Palliative care at the end of life for seriously ill adults with high symptom burden must account for the presence of multiple chronic conditions.

Insomnia and Insomnia Symptoms in Persons With Heart Failure: An Integrative Review.

BACKGROUND/OBJECTIVE: Insomnia and insomnia symptoms are highly prevalent in persons with heart failure (HF), and they are associated with several untoward outcomes. The purpose of this integrative review is to describe the correlates, predictors, and outcomes of insomnia and insomnia symptoms in persons with HF. METHODS: Using integrative review methods, an extensive electronic search of 5 databases was conducted for the period of 2000-2019. Sixteen studies were identified that met the inclusion criteria for review and investigated insomnia or insomnia symptoms in HF. RESULTS: Various sociodemographic factors, chronic comorbidities, clinical factors, and cognitive-behavioral factors are correlates and predictors of insomnia and insomnia symptoms in persons with HF. Depression, fatigue, daytime sleepiness, poor self-reported physical functioning, decreased exercise capacity, cardiac events, and poor health-related quality of life are significant outcomes of insomnia and insomnia symptoms in persons with HF. The associations of insomnia and insomnia symptoms with age, sex, sleep-disordered breathing, and cognition were not consistent across all studies. CONCLUSION: Larger studies with diverse age and race groups as well as longitudinal studies and designs that test mediation effects are needed to disentangle complex relationships between insomnia and insomnia symptoms and several of their potential predictors and correlates in HF.