No evidence for causal effects of C-reactive protein (CRP) on chronic pain conditions: a Mendelian randomization study.

Objective: We conducted a Mendelian randomization (MR) study to examine causal associations of C-reactive protein (CRP) with (1) spinal pain; (2) extent of multisite chronic pain; and (3) chronic widespread musculoskeletal pain. Design: Two-sample MR study. Setting/Subjects: We used summary statistics from publicly available genome-wide association studies (GWAS) conducted in multiple cohorts and biobanks. Genetic instrumental variables were taken from an exposure GWAS of CRP (n=204,402). Outcome GWASs examined spinal pain (n=1,028,947), extent of multisite chronic pain defined as the number of locations with chronic pain (n=387,649), and chronic widespread pain (n=249,843). Methods: We examined MR evidence for causal associations using inverse-variance weighted (IVW) analysis and sensitivity analyses using other methods. We calculated odds ratios (ORs), 95% confidence intervals (95% CIs), and p-values, using a Bonferroni correction (p<0.0166) to account for 3 primary comparisons. Results: Greater serum CRP (mg/L) was not significantly causally associated with spinal pain (OR=1.04, 95% CI 1.00-1.08; p=0.07) in IVW analysis. Greater serum CRP also showed no significant causal association with extent of multisite chronic pain in IVW analysis (beta coefficient= 0.014, standard error=0.011; p=0.19). CRP also showed no significant causal association with chronic widespread pain in IVW analysis (OR=1.00, 95% CI 1.00-1.00; p=0.75). All secondary and sensitivity analyses also showed no significant associations. Conclusions: This MR study found no causal association of CRP on spinal pain, the extent of chronic pain, or chronic widespread pain. Future studies examining mechanistic biomarkers for pain conditions should consider other candidates besides CRP.

Using a Programme Science approach to substantially reduce the risk of HIV transmission and acquisition in sex transactions among female sex workers in Zimbabwe.

INTRODUCTION: We used a Programme Science platform, to generate evidence to support the implementation of programmes for sex workers in Africa. Female sex workers are estimated to make up 1.6% (1.3%-1.8%) of the population of women aged 15-49 years in Zimbabwe. We highlight how programme science can be used to help distinguish between when, where and with whom programmes need to be implemented and discuss two case studies that exemplify implementing better (Case study 1 (1 June 2019-30 June 2021) Optimizing implementation of a risk differentiated microplanning intervention) and implementing differently (Case study 2 (1 October 2016-30 September 2022) Reorientating implementation of DREAMS for young women selling sex). METHODS: Zimbabwe's nationally scaled programme for sex workers was established in 2009 in partnership with sex workers to provide comprehensive services for sex workers and generate evidence for programme design, implementation and scale up. Since inception, comprehensive data have been collected from all sex workers seeking services. As the scope of service provision has expanded so has the scope of data collection and analysis. At enrolment, sex workers are assigned an alphanumeric unique identifier which links consultations within and across programme sites. We conduct descriptive analyses of the Key Population (KP) programme data to guide programme implementation and redesign, embedding programmatic qualitative enquiry as required. RESULTS: Two case studies describing different approaches to programme optimization are presented. In the first, an optimization exercise was used to strengthen programme implementation ensuring that the KP programme got back on track after SARS-COV-2. In the second, an in-depth review of research and programme data led to a re-orientation of the DREAMS programme to ensure that young women at the highest risk of HIV acquisition were enrolled and had access to DREAMS social support interventions in turn strengthening their uptake of HIV prevention. CONCLUSIONS: Optimizing and sustaining HIV care and treatment programmes requires effective delivery with sufficient scale and intensity for population impact. Our programme science approach guided the scale up of the KP programme in Zimbabwe, providing evidence to support strategy, implementation and ongoing management, and importantly helping us distinguish between when we needed to just implement, implement better or implement differently.

Programme science methodologies and practices that address "FURRIE" challenges: examples from the field.

INTRODUCTION: "Programme science" deploys scientific methods to address questions that are a priority to support the impact of public health programmes. As such, programme science responds to the challenges of making such studies: (1) feasible to undertake, (2) useful, (3) rigorous, (4) real-world-relevant, (5) informative, and undertaken by (6) equitable partnerships. The acronym "FURRIE" is proposed to describe this set of six challenges. This paper discusses selected HIV/STI (sexually transmitted infection) programme science case studies to illustrate how programme science rises to the FURRIE challenges. DISCUSSION: One way in which programme science is made more feasible is through the analysis and interpretation of data collected through service delivery. For some questions, these data can be augmented through methods that reach potential clients of services who have not accessed services or been lost to follow-up. Process evaluation can enhance the usefulness of programme science by studying implementation processes, programme-client interactions and contextual factors. Ensuring rigour by limiting bias and confounding in the real-world context of programme science studies requires methodological innovation. Striving for scientific rigour can also have the unintended consequence of creating a gap between what happens in a study, and what happens in the "real-world." Community-led monitoring is one approach to grounding data collection in the real-world experience of clients. Evaluating complex, context-specific strategies to strengthen health outcomes in a way that is informative for other settings requires clear specification of the intervention packages that are planned and delivered in practice. Programme science provides a model for equitable partnership through co-leadership between programmes, researchers and the communities they serve. CONCLUSIONS: Programme science addresses the FURRIE challenges, thereby improving programme impact and ultimately health outcomes and health equity. The adoption and adaptation of the types of novel programme science approaches showcased here should be promoted within and beyond the HIV/STI field.

HIV incidence among women engaging in sex work in sub-Saharan Africa: a systematic review and meta-analysis.

BACKGROUND: Women who engage in sex work in sub-Saharan Africa have a high risk of acquiring HIV infection. HIV incidence has declined among all women in sub-Saharan Africa, but trends among women who engage in sex work are poorly characterised. We synthesised data on HIV incidence among women who engage in sex work in sub-Saharan Africa and compared these with the total female population to understand relative incidence and trends over time. METHODS: We searched MEDLINE, Embase, Global Health, and Google Scholar from Jan 1, 1990, to Feb 28, 2024, and grey literature for studies that reported empirical estimates of HIV incidence among women who engage in sex work in any sub-Saharan Africa country. We calculated incidence rate ratios (IRRs) compared with total female population incidence estimates matched for age, district, and year, did a meta-analysis of IRRs, and used a continuous mixed-effects model to estimate changes in IRR over time. FINDINGS: From 32 studies done between 1985 and 2020, 2194 new HIV infections were observed among women who engage in sex work over 51 490 person-years. Median HIV incidence was 4·3 per 100 person years (IQR 2·8-7·0 per 100 person-years). Incidence among women who engage in sex work was eight times higher than matched total population women (IRR 7·8 [95% CI 5·1-11·8]), with larger relative difference in western and central Africa (19·9 [9·6-41·0]) than in eastern and southern Africa (4·9 [3·4-7·1]). There was no evidence that IRRs changed over time (IRR per 5 years: 0·9 [0·7-1·2]). INTERPRETATION: Across sub-Saharan Africa, HIV incidence among women who engage in sex work remains disproportionately high compared with the total female population. However, constant relative incidence over time indicates HIV incidence among women who engage in sex work has declined at a similar rate. Location-specific data for women who engage in sex work incidence are sparse, but improved surveillance and standardisation of incidence measurement approaches could fill these gaps. Sustained and enhanced HIV prevention for women who engage in sex work is crucial to address continuing inequalities and ensure declines in new HIV infections. FUNDING: Bill & Melinda Gates Foundation, UK Research and Innovation, National Institutes of Health. TRANSLATION: For the French translation of the abstract see Supplementary Materials section.

Consensus-building to improve implementation of NICE guidance on planning for end-of-life treatment and care: a mixed-methods study.

BACKGROUND: Despite the availability of guidance for the provision of good end-of-life care, there are significant variations across the UK in its delivery. This study sought to identify the influences on end-of-life treatment and care planning across several areas where deficiencies in evidence-based practice have been identified, and to develop consensus among healthcare providers and users for recommendations on how to address these deficits. METHODS: An online survey (106 responses), qualitative interviews (55 participants) and a consensus-building exercise (475 participants in the initial round) were undertaken. Participants included people approaching the end of life, people important to them, and health and care practitioners who help people plan for the end of life or provide end-of-life care. Recruitment was via online methods, including social media and online newsletters of relevant charities and professional organisations. Thematic analysis using the framework method was used to analyse qualitative data. Synthesis of qualitative and quantitative data led to the development of statements regarding recommendations for advancing implementation of good practice. A two-stage consensus-building exercise asked respondents first to rate these statements and then to rate and rank further sub-recommendations in three areas. RESULTS: Results from the consensus building exercise confirmed that end-of-life care planning conversations are to be welcomed and encouraged, and that the priority should be to have the conversation (which could be initiated by a range of professionals, or people planning end-of-life care themselves), rather than to wait for an ideal time to have it. Further rounds identified specific components of a standardised record of end-of-life treatment and care preferences that should be prioritised, specific health and care staff that should be empowered through training in advanced communication, and aspects of communication most important to include in training for healthcare professionals. CONCLUSIONS: Our study has identified opportunities for action to improve end-of-life treatment and care by combining multiple stakeholder perspectives and building consensus among them: the resulting recommendations have sufficient granularity to be implemented and evaluated. They are of relevance to policy makers, those who train healthcare professionals, and those looking after patients approaching the end of life.

Parkinson's Disease Progression and Exposure to Contaminated Water at Camp Lejeune.

BACKGROUND: We recently reported an increased risk of Parkinson's disease (PD) in service members who resided at Marine Base Camp Lejeune, North Carolina, when water supplies were contaminated with trichloroethylene and other volatile organic compounds (VOCs). Prior studies suggest that environmental exposures may affect PD phenotype or progression, but this has not been reported for VOCs. OBJECTIVE: The objective of this study was to test whether PD progression is faster in individuals exposed to VOCs in water at Camp Lejeune. METHODS: A cohort of 172,128 marines residing at Camp Lejeune between 1975 and 1985 was previously assembled. We identified individuals with PD in Veterans Health Administration and Medicare databases between 2000 and 2021. Using estimates derived by the US Agency for Toxic Substances and Disease Registry, we classified individuals as exposed or unexposed to VOCs in residential water. We used Kaplan-Meier and Cox regression models to test differences between exposed and unexposed groups in the time from PD diagnosis until psychosis, fracture, fall, or death. RESULTS: Among 270 persons with PD, 177 (65.6%) were exposed to VOCs in residential water. Median cumulative exposure was 4970 µg/L-months, >50-fold the permissible level. Time until psychosis, fracture, and fall were all shorter in the exposed group, with adjusted hazard ratios (HRs) exceeding 2: psychosis HR, 2.19 (95% confidence interval [CI]: 0.99-4.83); fracture HR, 2.44 (95% CI: 0.91-6.55); and fall HR, 2.64 (95% CI: 0.97-7.21). A significant dose response was observed for time to fall (P trend, 0.032). No differences were observed for time until death. CONCLUSIONS: PD progression may be faster in persons exposed to trichloroethylene and other VOCs in water decades earlier. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.

A mixed-methods analysis of provider-documented and patient-reported urinary tract infection symptoms among veterans with neurogenic bladder.

ABSTRACT: Inappropriate urinary tract infection (UTI) diagnosis in patients with neurogenic bladder (NB) may result from ambiguous symptoms experienced by these patients and contributes to antibiotic overuse. Characterization of patient-reported signs and symptoms may help providers more appropriately diagnose UTIs. A previous study collected signs and symptoms recorded in electronic medical records (EMR) of patients with NB due to spinal cord injury/disorder (SCI/D), multiple sclerosis (MS), and Parkinson's Disease (PD) with at least one UTI diagnosis between 2017-2018 at four medical centers. In this study, twenty-three Veterans from this cohort with UTI diagnoses in the prior year participated in focus groups conducted May 2021 - May 2022. Transcripts were coded using mixed deductive and inductive coding. Qualitative data were compared to EMR data to give a comprehensive picture of signs and symptoms. Both providers and patients attributed non-specific symptoms like urine changes to UTI, but there was discordance between patients and providers in the identification of other signs and symptoms. Several patients described providers disregarding symptoms other than fever or chills. Optimizing UTI care for patients with NB could involve improving patient provider communication about UTI signs and symptoms and emphasizing thorough elicitation and evaluation of all signs and symptoms.

Protocol for rearing and using mosquitoes for flight path tracking and behavioral characterization in wind tunnel bioassays.

Mosquito behavioral assays are an important component in vector research and control tool development. Here, we present a protocol for rearing Anopheles mosquitoes, performing host-seeking behavioral bioassays, and collecting 3D flight tracks in a large wind tunnel. We describe steps for setting up host-seeking landing assays, both as a non-choice and as a dual-choice assay, and analyzing flight tracks. This protocol can be applied in the research of several behavioral traits, including nectar seeking, resting, mating, and oviposition behavior. For complete details on the use and execution of this protocol, please refer to Carnaghi et al.1.

Cultural stressors, youth coping, and mother-adolescent conflict.

OBJECTIVE: This study examined the associations between cultural stressors (i.e., foreigner-based discrimination and acculturation gap conflict) and mother-adolescent relational conflict and the moderating effects of youth coping on these relations. METHOD: Within a sample of 175 Latinx mothers (Mage = 41.84 years; 88% born in Mexico) and adolescents (Mage = 12.89 years; 52% female; 87% U.S. born), we used actor-partner interdependence models to test the dyadic associations of one's cultural stress experiences with their own (i.e., self-effect) and the other family member's (i.e., mother or adolescent effect) perception of relational conflict, and we examined youth coping as a moderator. RESULTS: Adolescents' experiences of cultural stress were positively related to their own perception of relational conflict but not their mother's. Amid higher maternal discrimination experiences, higher youth shift-and-persist coping was related to lower youth-reported relational conflict. Higher youth discrimination experiences were correlated with higher reports of youth support-seeking, but youth support-seeking did not moderate the relation between cultural stress and relational conflict. CONCLUSIONS: Shift-and-persist coping may play a critical role in exacerbating or mitigating the harmful relations between cultural stress and relational conflict, depending upon whether the cultural stressor is external (i.e., foreigner-based discrimination) or family-based (acculturation gap conflict). (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Identifying actionable synthetically lethal cancer gene pairs using mutual exclusivity.

Mutually exclusive loss-of-function alterations in gene pairs are those that occur together less frequently than may be expected and may denote a synthetically lethal relationship (SSL) between the genes. SSLs can be exploited therapeutically to selectively kill cancer cells. Here, we analysed mutation, copy number variation, and methylation levels in samples from The Cancer Genome Atlas, using the hypergeometric and the Poisson binomial tests to identify mutually exclusive inactivated genes. We focused on gene pairs where one is an inactivated tumour suppressor and the other a gene whose protein product can be inhibited by known drugs. This provided an abundance of potential targeted therapeutics and repositioning opportunities for several cancers. These data are available on the MexDrugs website, https://bioinformaticslab.sussex.ac.uk/mexdrugs.

Glycoprotein Acetyls Is a Novel Biomarker Predicting Cardiovascular Complications in Rheumatoid Arthritis.

The relationship between rheumatoid arthritis (RA) and early onset atherosclerosis is well depicted, each with an important inflammatory component. Glycoprotein acetyls (GlycA), a novel biomarker of inflammation, may play a role in the manifestation of these two inflammatory conditions. The present study examined a potential mediating role of GlycA within the RA-atherosclerosis relationship to determine whether it accounts for the excess risk of cardiovascular disease over that posed by lipid risk factors. The UK Biobank dataset was acquired to establish associations among RA, atherosclerosis, GlycA, and major lipid factors: total cholesterol (TC), high- and low-density lipoprotein (HDL, LDL) cholesterol, and triglycerides (TGs). Genome-wide association study summary statistics were collected from various resources to perform genetic analyses. Causality among variables was tested using Mendelian Randomization (MR) analysis. Genes of interest were identified using colocalization analysis and gene enrichment analysis. MR results appeared to indicate that the genetic relationship between GlycA and RA and also between RA and atherosclerosis was explained by horizontal pleiotropy (p-value = 0.001 and <0.001, respectively), while GlycA may causally predict atherosclerosis (p-value = 0.017). Colocalization analysis revealed several functionally relevant genes shared between GlycA and all the variables assessed. Two loci were apparent in all relationships tested and included the HLA region as well as SLC22A1. GlycA appears to mediate the RA-atherosclerosis relationship through several possible pathways. GlycA, although pleiotropically related to RA, appears to causally predict atherosclerosis. Thus, GlycA is suggested as a significant factor in the etiology of atherosclerosis development in RA.

Critical consciousness and anti-racist action as rooted in family processes.

Racially ethnically marginalized communities in the United States are exposed to structural and interpersonal forms of racism that have harmful effects on their health, wealth, education, and employment (Centers for Disease Control and Prevention, Racism and Health. https://www.cdc.gov/minorityhealth/racism-disparities/index.html, 2021). Although a plethora of research exists outlining these harmful effects, research examining how youth from diverse backgrounds effectively combat racism is lacking. Emerging research demonstrates that families may play a key role in the development of critical consciousness and participation in anti-racist actions (Bañales et al., Journal of Social Issues, 2021, 77, 964; Blanco Martinez et al., American Journal of Community Psychology, 2022, 70, 278; Lozada et al., Journal of Black Psychology, 2017, 43, 493). Yet, many key family processes have not been examined in relation to youth development of anti-racist practices. The current study included a sample of 327 racially ethnically diverse emerging adults (Mage = 18.80, SD = 1.28, range = 18-25), and explored the association between ethnic-racial socialization (cultural socialization, preparation for bias) and youth critical consciousness (reflection, motivation, action) and anti-racist (interpersonal, communal, political change) actions, and how familism values impact these associations. Results found that ethnic-racial socialization was positively associated with all aspects of critical consciousness and anti-racist actions. Results also found that familism significantly interacted with ethnic-racial socialization to predict some aspects of critical consciousness and anti-racist actions, but not others. Implications of the findings and future research directions are discussed.

Compartmentalization proteomics revealed endolysosomal protein network changes in a goat model of atrial fibrillation.

Endolysosomes (EL) are known for their role in regulating both intracellular trafficking and proteostasis. EL facilitate the elimination of damaged membranes, protein aggregates, membranous organelles and play an important role in calcium signaling. The specific role of EL in cardiac atrial fibrillation (AF) is not well understood. We isolated atrial EL organelles from AF goat biopsies and conducted a comprehensive integrated omics analysis to study the EL-specific proteins and pathways. We also performed electron tomography, protein and enzyme assays on these biopsies. Our results revealed the upregulation of the AMPK pathway and the expression of EL-specific proteins that were not found in whole tissue lysates, including GAA, DYNLRB1, CLTB, SIRT3, CCT2, and muscle-specific HSPB2. We also observed structural anomalies, such as autophagic-vacuole formation, irregularly shaped mitochondria, and glycogen deposition. Our results provide molecular information suggesting EL play a role in AF disease process over extended time frames.

A Comparative Study of Organizational Grief Support and Burnout Among Nursing Home Staff.

BACKGROUND AND OBJECTIVES: The purpose of this study was to examine the relationship between dimensions of grief support (recognition of the relationship, acknowledgement of the loss, and inclusion of the griever) and aspects of burnout (emotional exhaustion, depersonalization, and personal accomplishment) among nursing home staff. RESEARCH DESIGN AND METHODS: Data were collected from 553 nursing home workers from 37 nursing home facilities in 5 states during fall of 2022. Responses to the Maslach Burnout Inventory and Grief Support Health Care Scale were analyzed for this study. RESULTS: The study found that recognizing the relationship with deceased patients led to a decrease in exhaustion and depersonalization among workers while simultaneously enhancing their sense of personal accomplishment. Including the griever in the support process lowered all burnout subscales for nursing home staff. Acknowledging the loss was associated with higher levels of personal accomplishment. Registered nurses, nurse practitioners, and physicians experienced higher levels of exhaustion and depersonalization compared to other nursing home staff. Behavioral health workers had the highest personal accomplishment, whereas direct support workers reported the lowest. DISCUSSION AND IMPLICATIONS: These findings have important implications for improving the well-being of nursing home staff, emphasizing the importance of organizational grief support, and tailored interventions to address burnout among different healthcare provider roles in nursing homes.

Development of SYK NanoBRET Cellular Target Engagement Assays for Gain-of-Function Variants.

Spleen tyrosine kinase (SYK) is a non-receptor tyrosine kinase that is activated by phosphorylation events downstream of FcR, B-cell and T-cell receptors, integrins, and C-type lectin receptors. When the tandem Src homology 2 (SH2) domains of SYK bind to phosphorylated immunoreceptor tyrosine-based activation motifs (pITAMs) contained within these immunoreceptors, or when SYK is phosphorylated in interdomain regions A and B, SYK is activated. SYK gain-of-function (GoF) variants were previously identified in six patients that had higher levels of phosphorylated SYK and phosphorylated downstream proteins JNK and ERK. Furthermore, the increased SYK activation resulted in the clinical manifestation of immune dysregulation, organ inflammation, and a predisposition for lymphoma. The knowledge that the SYK GoF variants have enhanced activity was leveraged to develop a SYK NanoBRET cellular target engagement assay in intact live cells with constructs for the SYK GoF variants. Herein, we developed a potent SYK-targeted NanoBRET tracer using a SYK donated chemical probe, MRL-SYKi, that enabled a NanoBRET cellular target engagement assay for SYK GoF variants, SYK(S550Y), SYK(S550F), and SYK(P342T). We determined that ATP-competitive SYK inhibitors bind potently to these SYK variants in intact live cells. Additionally, we demonstrated that MRL-SYKi can effectively reduce the catalytic activity of SYK variants, and the phosphorylation levels of SYK(S550Y) in an epithelial cell line (SW480) stably expressing SYK(S550Y).

The association of lumbar intervertebral disc degeneration with low back pain is modified by underlying genetic propensity to pain.

BACKGROUND CONTEXT: Associations between magnetic resonance imaging (MRI)-detected lumbar intervertebral disc degeneration (LDD) and LBP are often of modest magnitude. This association may be larger in specific patient subgroups. PURPOSE: To examine whether the association between LDD and LBP is modified by underlying genetic predispositions to pain. STUDY DESIGN: Cross-sectional study in UK Biobank (UKB) and Twins UK. PATIENT SAMPLES: A genome-wide association study (GWAS) of the number of anatomical chronic pain locations was conducted in 347,538 UKB participants. The GWAS was used to develop a genome-wide polygenic risk score (PRS) in a holdout sample of 30,000 UKB participants. The PRS model was then used in analyses of 645 TwinsUK participants with standardized LDD MRI assessments. OUTCOME MEASURES: Ever having had LBP associated with disability lasting ≥1 month (LBP1). METHODS: Using the PRS as a proxy for "genetically-predicted propensity to pain", we stratified TwinsUK participants into PRS quartiles. A "basic" model examined the association between an LDD summary score (LSUM) and LBP1, adjusting for covariates. A "fully-adjusted" model also adjusted for PRS quartile and LSUM x PRS quartile interaction terms. RESULTS: In the basic model, the odds ratio (OR) of LBP1 was 1.8 per standard deviation of LSUM (95% confidence interval [CI] 1.4-2.3). In the fully-adjusted model, there was a statistically significant LSUM-LBP1 association in quartile 4, the highest PRS quartile (OR=2.5 [95% CI 1.7-3.7], p=2.6×10-6), and in quartile 3 (OR=2.0, [95% CI 1.3-3.0]; p=.002), with small-magnitude and/or nonsignificant associations in the lowest 2 PRS quartiles. PRS quartile was a significant effect modifier of the LSUM-LBP1 association (interaction p≤.05). CONCLUSIONS: Genetically-predicted propensity to pain modifies the LDD-LBP association, with the strongest association present in people with the highest genetic propensity to pain. Lumbar MRI findings may have stronger connections to LBP in specific subgroups of people.

Racism in obstetric care: a psychometric study of the Gendered Racial Microaggressions Scale among Global Majority birthing people in obstetric contexts.

In the United States, maternal health inequities disproportionately affect Global Majority (e.g., Asian, Black, and Hispanic) populations. Despite a substantial body of research underscoring the influence of racism on these inequities, little research has examined how experiences of gendered racial microaggressions during pregnancy and birth impact racially and ethnically diverse Global Majority pregnant and birthing people in obstetric hospital settings. We evaluated the psychometric properties of an adapted version of Lewis & Neville's Gendered Racial Microaggressions Scale, using data collected from 417 Global Majority birthing people. Findings from our study indicate that our adapted GRMS is a valid tool for assessing the experiences of gendered racial microaggressions in hospital-based obstetric care settings among Global Majority pregnant and birthing people whose preferred languages are English or Spanish. Item Response Theory (IRT) analysis demonstrated high construct validity of the adapted GRMS scale (Root Mean Square Error of Approximation = 0.1089 (95% CI 0.0921, 0.1263), Comparative Fit Index = 0.977, Standardized Root Mean Square Residual = 0.075, log-likelihood c2 = -85.6, df = 8). IRT analyses demonstrated that the unidimensional model was preferred to the bi-dimensional model as it was more interpretable, had lower AIC and BIC, and all items had large discrimination parameters onto a single factor (all discrimination parameters > 3.0). Given that we found similar response profiles among Black and Hispanic respondents, our Differential Item Functioning analyses support validity among Black, Hispanic, and Spanish-speaking birthing people. Inter-item correlations demonstrated adequate scale reliability, α = 0.97, and empirical reliability = 0.67. Pearsons correlations was used to assess the criterion validity of our adapted scale. Our scale's total score was significantly and positively related to postpartum depression and anxiety. Researchers and practitioners should seek to address instances of gendered racial microaggressions in obstetric settings, as they are manifestations of systemic and interpersonal racism, and impact postpartum health.

Nicotine and fluoxetine alter adolescent dopamine-mediated behaviors via 5-HT1A receptor activation.

Introduction: Abuse or misuse of tobacco, e-cigarettes, or antidepressants may have serious clinical consequences during adolescence, a sensitive period during brain development when the distinct neurobiology of adolescent serotonin (5-HT) and dopamine (DA) systems create unique behavioral vulnerabilities to drugs of abuse. Methods: Using a pharmacological approach, we modeled the behavioral and neurochemical effects of subchronic (4-day) nicotine (60µg/kg, i.v.) or fluoxetine (1mg/kg, i.v.) exposure in adolescent and adult male rats. Results: Nicotine and fluoxetine significantly enhance quinpirole-induced locomotor activity and initial cocaine self-administration in adolescents, but not adults. These effects were blocked by serotonin 5-HT1A receptor antagonists, WAY-100,635 (100 µg/kg, i.v.) or S-15535 (300 µg/kg, i.v.). Neurochemical and anatomical autoradiographic analysis of 8-OH-DPAT-stimulated [35S]GTPγS reveal that prior exposure to nicotine and fluoxetine results in both overlapping and distinct effects on regional 5-HT1A receptor activity. Both fluoxetine and nicotine enhance adolescent 5-HT1A receptor activity in the primary motor cortex (M1), whereas fluoxetine alone targets prefrontal cortical neurocircuitry and nicotine alone targets the amygdala. Discussion: Given their different pharmacological profiles, comparison between WAY-100,635 and S-15535 indicates that postsynaptic 5-HT1A receptors mediate the behavioral effects of prior nicotine and fluoxetine exposure. In addition, within the adolescent M1, maladaptive changes in 5-HT signaling and 5-HT1A activity after nicotine or fluoxetine exposure may potentiate hyper-responsiveness to dopaminergic drugs and prime adolescent vulnerability for future substance abuse.

Language proficiency and ethnic-racial orientation among Latine mother-adolescent dyads.

Language proficiencies have implications for how parents and children can communicate effectively and how culture and heritage can be transferred across generations. Previous research has sought to understand the relationship between parent language (mainstream, heritage) proficiencies and the ethnic-racial orientation of their children, though prior studies have not investigated the relationship between child language proficiencies and parent ethnic-racial orientation. This study examined the actor-partner effects of Latine mother-child dyads (N = 175; youth mean age = 12.86 years) regarding their proficiencies in English and Spanish and their Latine and White orientations. Our results revealed that youth Spanish language proficiency was positively linked to youth White orientation, and youth English proficiency was also positively associated with youth White orientation but only in instances when youth-reported acculturation conflict was lower or average. There were two partner effects observed, with youth English proficiency positively relating to mother's White orientation and mothers' Spanish proficiency being negatively related to youth White orientation. Regarding Latine orientation, both English and Spanish were positively related to greater Latine orientation for both mothers and their children. However, at higher levels of mother-reported acculturation conflict, higher mother English proficiency was related to lower youth Latine orientation. Overall, language proficiencies for Latine mothers and their children contribute to the development of bicultural orientations, though varying degrees of acculturation conflict can have differential impacts on these linkages.

Service innovations for people with multiple long-term conditions: reflections of a rapid evaluation team.

Background: People living with multiple long-term conditions represent a significant concern for National Health Service policy and practice, and their care is a major theme in the 2019 National Health Service Long Term Plan. The Birmingham RAND and Cambridge Rapid Evaluation Centre team has undertaken a thematic synthesis of the 10 evaluations it has conducted from 2018 to 2023, exploring the needs, priorities and implications for people with multiple long-term conditions. Objectives: The aims for this overarching study were to: (1) build a body of learning about service innovations in primary and community settings for people of all ages with multiple long-term conditions, focused on questions that matter most to people with multimorbidity; and (2) develop methodological insights about how rapid evaluation can be used to inform the scoping, testing and implementation of service innovations for people with multiple long-term conditions. Design: The focus on multiple long-term conditions came from a Birmingham RAND and Cambridge Rapid Evaluation Centre prioritisation process undertaken in 2018 using James Lind Alliance methods. Cross-analysis of the findings from the 10 individual rapid evaluations was supplemented by (1) building aspects of multimorbidity into the design of later evaluations; (2) interviewing national and regional stakeholders (n=19) working in or alongside integrated care systems; (3) undertaking a rapid review of evidence on remote monitoring for people with multiple long-term conditions (19 papers included); and (4) testing overall insights with organisations representing patients and carers through a patient, public and professional engagement workshop with 10 participants plus members of the research team. Results: While living with multiple long-term conditions is common and is the norm for people over the age of 50 using health and care services, it is not often a focus of health service provision or innovation, nor of research and evaluation activity. We discuss six themes emerging from the totality of the study: (1) our health system is mainly organised around single conditions and not multiple long-term conditions; (2) research calls and studies usually focus on single conditions and associated services; (3) building opportunities for engaged, informed individuals and carers and improved self-management; (4) the importance of measures that matter for patients and carers; (5) barriers to developing and implementing service innovations for people with multiple long-term conditions; and (6) what is needed to make patients with multiple long-term conditions a priority in healthcare planning and delivery. Limitations: Care of people with multiple long-term conditions was not the principal focus of several of the rapid evaluations. While this was a finding in itself, it limited our learning about designing and implementing, as well as methodological approaches to evaluating, service innovations for people with multiple long-term conditions. Conclusions: Through a thematic analysis of the portfolio of evaluations, we have deduced a set of suggested implications for how the needs of people with multiple long-term conditions can be better embedded in policy, research and practice. Future work: Areas of uncertainty related to the care of people with multiple long-term conditions should be further explored, including developing and testing measures of patient experience of (un)co-ordinated care across settings, and interrogating the experience of health and care staff when working with people with multiple long-term conditions, to understand what works. Funding: This award was funded by the National Institute for Health and Care Research (NIHR) Health and Social Care Delivery Research programme (NIHR award ref: NIHR134284) and is published in full in Health and Social Care Delivery Research; Vol. 12, No. 15. See the NIHR Funding and Awards website for further award information.

Many people in England live with two or more physical and/or mental health conditions that are expected to last for years. Estimates vary, but it is likely that a majority of National Health Service services are serving people living with two or more long-term conditions. We wanted to find out how well the needs of this group are taken into account when new types of health care are introduced, or existing services are reorganised. To do this, we went back to all 10 of the health service innovations that had been studied by our Birmingham RAND and Cambridge Evaluation Centre from 2018 to 2023. We did some extra research, including discussions with patient representatives and interviews with National Health Service policy-makers and managers at national and regional levels. We also looked at what new research had been published about one example of a new healthcare technology that is intended to help people who have several long-term health conditions: monitors that can be used by health service staff to measure patients' symptoms when they are in their own home. Our main finding was that most National Health Service attention is given to organising care for single conditions, often treating them in isolation. Patients' many treatments and needs are not routinely considered all at the same time by healthcare staff, nor by researchers. Care for one condition is too often not co-ordinated with care for other health problems that a patient may have. Although the situation of people living with several long-term health conditions is in principle understood by healthcare staff, managers and researchers, relatively little is done in practice to meet their needs. We conclude by suggesting ways that policy-makers, healthcare staff and researchers could improve how they help people living with multiple long-term conditions.