The activity of early-life gene regulatory elements is hijacked in aging through pervasive AP-1-linked chromatin opening.

A mechanistic connection between aging and development is largely unexplored. Through profiling age-related chromatin and transcriptional changes across 22 murine cell types, analyzed alongside previous mouse and human organismal maturation datasets, we uncovered a transcription factor binding site (TFBS) signature common to both processes. Early-life candidate cis-regulatory elements (cCREs), progressively losing accessibility during maturation and aging, are enriched for cell-type identity TFBSs. Conversely, cCREs gaining accessibility throughout life have a lower abundance of cell identity TFBSs but elevated activator protein 1 (AP-1) levels. We implicate TF redistribution toward these AP-1 TFBS-rich cCREs, in synergy with mild downregulation of cell identity TFs, as driving early-life cCRE accessibility loss and altering developmental and metabolic gene expression. Such remodeling can be triggered by elevating AP-1 or depleting repressive H3K27me3. We propose that AP-1-linked chromatin opening drives organismal maturation by disrupting cell identity TFBS-rich cCREs, thereby reprogramming transcriptome and cell function, a mechanism hijacked in aging through ongoing chromatin opening.

Association of Maternal Fish Consumption and Omega-3 Supplement Use During Pregnancy With Child Autism-Related Outcomes: Results from a Cohort Consortium Analysis.

BACKGROUND: Prenatal fish intake is a key source of omega-3 polyunsaturated fatty acids needed for brain development, yet intake is generally low, and studies addressing associations with autism spectrum disorder (ASD) and related traits are lacking. OBJECTIVE: To examine associations of prenatal fish intake and omega-3 supplement use with both autism diagnosis and broader autism-related traits. METHODS: Participants were drawn from 32 cohorts in the Environmental influences on Child Health Outcomes (ECHO) Cohort Consortium. Children were born between 1999 and 2019 and part of ongoing follow-up with data available for analysis by August 2022. Exposures included self-reported maternal fish intake and omega-3/fish oil supplement use during pregnancy. Outcome measures included parent report of clinician-diagnosed ASD and parent-reported autism-related traits measured by the Social Responsiveness Scale (SRS)-Second Edition (n=3939 and n=3609 for fish intake analyses, respectively; n=4537 and n=3925 for supplement intake analyses, respectively). RESULTS: In adjusted regression models, relative to no fish intake, fish intake during pregnancy was associated with reduced odds of autism diagnosis (OR=0.84, 95% CI 0.77 to 0.92), and a modest reduction in raw total SRS scores (b=-1.69, 95% CI -3.3 to -0.08). Estimates were similar across categories of fish consumption from "any" or "less than once per week" to "more than twice per week." For omega-3 supplement use, relative to no use, no significant associations with autism diagnosis were identified, whereas a modest relation with SRS score was suggested (ß=1.98, 95% CI 0.33-3.64). CONCLUSIONS: These results extend prior work by suggesting that prenatal fish intake, but not omega-3 supplement use, may be associated with lower likelihood of both autism diagnosis and related traits. Given the low fish intake in the U.S. general population and the rising autism prevalence, these findings suggest the need for better public health messaging regarding guidelines on fish intake for pregnant individuals.

Prevalence and risk of burnout among HIV service providers in South Africa and Zambia: findings from the HPTN 071 (PopART) trial.

BACKGROUND: In the high disease burden and resource-constrained contexts of sub-Saharan Africa (SSA), health workers experience a range of psychosocial stressors that leave them vulnerable to developing burnout, which can reduce service quality and negatively impact their own health and wellbeing. As universal testing and treatment (UTT) for HIV scales up across SSA, we sought to understand the implications of this human resource-intensive approach to HIV prevention to inform decision-making about health workforce staffing and support needs. METHODS: Using the Maslach Burnout Inventory-Human Services Survey (MBI-HSS), we assessed the prevalence of three domains of burnout-emotional exhaustion, depersonalization, and personal accomplishment-among three cadres of health workers delivering health services in areas receiving a UTT intervention in Zambia and South Africa. These cadres included health facility workers (n = 478), community health workers (n = 159), and a study-specific cadre of community HIV care providers (n = 529). We used linear regression to assess risk factors associated with emotional exhaustion, the only domain with sufficient variation in our sample. RESULTS: The MBI-HSS was completed by 1499/2153 eligible participants (69.6% response rate). Less than 1% of health workers met Maslach's definition for burnout. All groups of health workers reported lower levels of emotional exhaustion than found in previous studies of this type (mean score scores ranged from 10.7 to 15.4 out of 54 across health cadres). Higher emotional exhaustion was associated with higher educational attainment (ßadj = 2.24, 95% CI 0.76 to 3.72), greater years providing HIV services (ßadj = 0.20, 95% CI 0.03 to 0.36), and testing negative for HIV at last HIV test (ßadj = - 3.88 - 95% CI 5.69 to - 2.07). Working as a CHW was significantly associated with lower emotional exhaustion (ßadj = - 2.52, 95% CI - 4.69 to - 0.35). Among all health workers, irrespective of HIV status, witnessing stigmatizing behaviors towards people living with HIV among their co-workers was associated with significantly increased emotional exhaustion (ßadj = 3.38, 95% CI 1.99 to 4.76). CONCLUSIONS: The low level of burnout detected among health workers is reassuring. However, it remains important to assess how UTT may affect levels of emotional exhaustion among health workers over time, particularly in the context of emerging global pandemics, as burnout may impact the quality of HIV services they provide and their own mental health and wellbeing. Interventions to reduce HIV stigma in health facilities may protect against emotional exhaustion among health workers, as well as interventions to increase mindfulness and resilience among health workers at risk of burnout. Trial registration ClinicalTrials.gov number: NCT01900977.

Comparing the stability and reproducibility of brain-behavior relationships found using canonical correlation analysis and partial least squares within the ABCD sample.

Canonical correlation analysis (CCA) and partial least squares correlation (PLS) detect linear associations between two data matrices by computing latent variables (LVs) having maximal correlation (CCA) or covariance (PLS). This study compared the similarity and generalizability of CCA- and PLS-derived brain-behavior relationships. Data were accessed from the baseline Adolescent Brain Cognitive Development (ABCD) dataset (N > 9,000, 9-11 years). The brain matrix consisted of cortical thickness estimates from the Desikan-Killiany atlas. Two phenotypic scales were examined separately as the behavioral matrix; the Child Behavioral Checklist (CBCL) subscale scores and NIH Toolbox performance scores. Resampling methods were used to assess significance and generalizability of LVs. LV1 for the CBCL brain relationships was found to be significant, yet not consistently stable or reproducible, across CCA and PLS models (singular value: CCA = .13, PLS = .39, p < .001). LV1 for the NIH brain relationships showed similar relationships between CCA and PLS and was found to be stable and reproducible (singular value: CCA = .21, PLS = .43, p < .001). The current study suggests that stability and reproducibility of brain-behavior relationships identified by CCA and PLS are influenced by the statistical characteristics of the phenotypic measure used when applied to a large population-based pediatric sample.

Clinical neuroscience research is going through a translational crisis largely due to the challenges of producing meaningful and generalizable results. Two critical limitations within clinical neuroscience research are the use of univariate statistics and between-study methodological variation. Univariate statistics may not be sensitive enough to detect complex relationships between several variables, and methodological variation poses challenges to the generalizability of the results. We compared two widely used multivariate statistical approaches, canonical correlations analysis (CCA) and partial least squares correlation (PLS), to determine the generalizability and stability of their solutions. We show that the properties of the measures inputted into the analysis likely play a more substantial role in the generalizability and stability of results compared to the specific approach applied (i.e., CCA or PLS).

HIV and gender identity expression among transfeminine people in the Western Cape, South Africa - a thematic analysis of data from the HPTN 071 (PopART) trial.

INTRODUCTION: Transfeminine people in South Africa have a high HIV risk due to structural, behavioural, and psychosocial factors. Transfeminine people and feminine identifying men who have sex with men (MSM) are often conflated or grouped with transgender or MSM categories in HIV service programming, although they don't necessarily identify as either. We aimed to investigate gender expression among feminine identifying people who were assigned male at birth. We examined how local conceptualizations of sexuality and gender intersect with the key population label of 'transgender' imported into local HIV programming. METHODS: A qualitative cohort nested within the HPTN 071 (PopART) trial included longitudinal, in-depth interviews with eight transfeminine people (four who disclosed as living with HIV). Data were collected approximately every six weeks between January 2016 and October 2017. We used a combination of thematic analysis and case study descriptions to explore gender identification among participants. RESULTS: Of the eight participants, only one accepted 'transgender' as a label, and even she used varying terms at different times to describe her identity. For participants, a feminine identity included dressing in normatively feminine clothes; using feminine terms, pronouns and names; and adopting stereotypically feminine mannerisms. Participants would switch between typically feminine and masculine norms in response to contextual cues and audience. For example, some participants accepted identification as masculine gay men amongst their family members. Among peers, they expressed their identity through typically more effeminate gender characteristics, for example self-identifying as "femgay". With partners they often also took on a feminine identity role, for example identifying as women in sexual and romantic relationships (meaning they viewed and expressed themselves as the feminine partner in the relationship). CONCLUSIONS: Our findings are amongst the first exploratory and descriptive data of transfeminine people in South Africa. We show how transfeminine people navigate fluid gender identities that could pose a challenge for accessing and utilizing HIV services that are currently set up for transgender individuals or MSM. More work needs to be done to understand and respond to the diverse and shifting ways people experience their gender identities in this high HIV burden context.

Skeletal effects of sleeve gastrectomy, by sex and menopausal status and in comparison to Roux-en-Y gastric bypass surgery.

Context: Roux-en-Y gastric bypass (RYGB) has deleterious effects on bone mass, microarchitecture, and strength. Data are lacking on the skeletal effects of sleeve gastrectomy (SG), now the most commonly performed bariatric surgical procedure. Objective: We examined changes in bone turnover, areal and volumetric bone mineral density (aBMD, vBMD), and appendicular bone microarchitecture and estimated strength after SG. We compared the results to those previously reported after RYGB, hypothesizing lesser effects after SG than RYGB. Design Setting Participants: Prospective observational cohort study of 54 adults with obesity undergoing SG at an academic center. Main Outcome Measures: Skeletal characterization with biochemical markers of bone turnover, dual-energy X-ray absorptiometry (DXA), quantitative computed tomography (QCT), and high-resolution peripheral QCT (HR-pQCT) was performed preoperatively and 6- and 12-months postoperatively. Results: Over 12 months, mean percentage weight loss was 28.8%. Bone turnover marker levels increased, and total hip aBMD decreased -8.0% (95% CI -9.1%, -6.7%, p<0.01). Spinal aBMD and vBMD declines were larger in postmenopausal women than men. Tibial and radial trabecular and cortical microstructure worsened, as did tibial estimated strength, particularly in postmenopausal women. When compared to data from a RYGB cohort with identical design and measurements, some SG biochemical, vBMD, and radial microstructural parameters were smaller, while other changes were not. Conclusions: Bone mass, microstructure, and strength decrease after SG. Some skeletal parameters change less after SG than after RYGB, while for others, we find no evidence for smaller effects after SG. Postmenopausal women may be at highest risk of skeletal consequences after SG.

Dosimetry of [64Cu]FBP8: a fibrin-binding PET probe.

Purpose: This study presents the biodistribution, clearance and dosimetry estimates of [64Cu]Fibrin Binding Probe #8 ([64Cu]FBP8) in healthy subjects. Procedures: This prospective study included 8 healthy subjects to evaluate biodistribution, safety and dosimetry estimates of [64Cu]FBP8, a fibrin-binding positron emission tomography (PET) probe. All subjects underwent up to 3 sessions of PET/Magnetic Resonance Imaging (PET/MRI) 0-2 hours, 4h and 24h post injection. Dosimetry estimates were obtained using OLINDA 2.2 software. Results: Subjects were injected with ~400 MBq of [64Cu]FBP8. Subjects did not experience adverse effects due to the injection of the probe. [64Cu]FBP8 PET images demonstrated fast blood clearance (half-life = 67 min) and renal excretion of the probe, showing low background signal across the body. The organs with the higher doses were: the urinary bladder (0.075 vs. 0.091 mGy/MBq for males and females, respectively); the kidneys (0.050 vs. 0.056 mGy/MBq respectively); and the liver (0.027 vs. 0.035 mGy/MBq respectively). The combined mean effective dose for males and females was 0.016 ± 0.0029 mSv/MBq, lower than the widely used [18F]fluorodeoxyglucose ([18F]FDG, 0.020mSv/MBq). Conclusions: This study demonstrates the following properties of the [64Cu]FBP8 probe: low dosimetry estimates; fast blood clearance and renal excretion; low background signal; and whole-body acquisition within 20 minutes in a single session. These properties provide the basis for [64Cu]FBP8 to be an excellent candidate for whole-body non-invasive imaging of fibrin, an important driver/feature in many cardiovascular, oncological and neurological conditions.

Upper respiratory Streptococcus pneumoniae colonization among working-age adults with prevalent exposure to overcrowding.

Most pneumococcal disease occurs among infants and older adults and is thought to be driven by the transmission of Streptococcus pneumoniae from young children to these vulnerable age groups. However, pneumococcal disease outbreaks also affect non-elderly adults living or working in congregate, close-contact settings. Little is known about pneumococcal carriage in such populations. From July to November 2020, we collected saliva from low-income adult farmworkers in Monterey County, California, and tested for pneumococcal carriage following culture enrichment via quantitative PCR assays targeting the pneumococcal lytA and piaB genes. Participants were considered to carry pneumococci if lytA and piaB cycle threshold values were both below 40. Among 1,283 participants enrolled in our study, 117 (9.1%) carried pneumococci. Carriers tended more often than non-carriers to be exposed to children aged <5 years [odds ratio (OR) = 1.45 (0.95-2.20)] and overcrowding [OR = 1.48 (0.96-2.30) and 2.84 (1.20-6.73), respectively, for participants in households with >2-4 and >4 persons per bedroom vs ≤2 persons per bedroom]. Household overcrowding remained associated with increased risk of carriage among participants not exposed to children aged <5 years [OR = 2.05 (1.18-3.59) for participants living in households with >2 vs ≤2 persons per bedroom]. Exposure to children aged <5 years and overcrowding were each associated with increased pneumococcal density among carriers [piaB cT difference of 2.04 (0.36-3.73) and 2.44 (0.80-4.11), respectively]. While exposure to young children was a predictor of pneumococcal carriage, associations of overcrowding with increased prevalence and density of carriage in households without young children suggest that transmission also occurs among adults in close-contact settings.IMPORTANCEAlthough infants and older adults are the groups most commonly affected by pneumococcal disease, outbreaks are known to occur among healthy, working-age populations exposed to overcrowding, including miners, shipyard workers, military recruits, and prisoners. Carriage of Streptococcus pneumoniae is the precursor to pneumococcal disease, and its relation to overcrowding in adult populations is poorly understood. We used molecular methods to characterize pneumococcal carriage in culture-enriched saliva samples from low-income adult farmworkers in Monterey County, CA. While exposure to children in the household was an important risk factor for pneumococcal carriage, living in an overcrowded household without young children was an independent predictor of carriage as well. Moreover, participants exposed to children or overcrowding carried pneumococci at higher density than those without such exposures, suggesting recent transmission. Our findings suggest that, in addition to transmission from young children, pneumococcal transmission may occur independently among adults in overcrowded settings.

Assessing the Survival of Human Plasma Cells Ex Vivo.

One way memory B cells provide protection is by rapidly differentiating into plasma cells. Plasma cells are vital in providing long-term protection against pathogens; however, they can also be detrimental to health in the case of antibody-mediated autoimmunity. Therefore, compounds which modulate the survival of plasma cells have been of interest for therapeutic intervention. Investigation of ex vivo plasma cell survival has previously been limited by the low frequency of plasma cells in the blood. Here we describe a novel ex vivo culture system that only requires 3000-5000 cells per condition. This method permits the assessment of human plasma cell survival derived from blood and can assess the impact of small molecule inhibitors on plasma cell viability.

Examining the association between prenatal cannabis exposure and child autism traits: A multi-cohort investigation in the environmental influences on child health outcome program.

This study examined the association between prenatal cannabis exposure and autism spectrum disorder (ASD) diagnoses and traits. A total sample of 11,570 children (ages 1-18; 53% male; 25% Hispanic; 60% White) from 34 cohorts of the National Institutes of Health-funded environmental influences on child health outcomes consortium were included in analyses. Results from generalized linear mixed models replicated previous studies showing that associations between prenatal cannabis exposure and ASD traits in children are not significant when controlling for relevant covariates, particularly tobacco exposure. Child biological sex did not moderate the association between prenatal cannabis exposure and ASD. In a large sample and measuring ASD traits continuously, there was no evidence that prenatal cannabis exposure increases the risk for ASD. This work helps to clarify previous mixed findings by addressing concerns about statistical power and ASD measurement.

Improved HbA1c and body weight in GADA-positive individuals treated with tirzepatide: A post hoc analysis of SURPASS.

CONTEXT: People with clinically diagnosed type 2 diabetes (T2D) but positive anti-glutamic acid decarboxylase autoantibodies (GADA), referred to here as latent autoimmune diabetes in adults (LADA), may experience more rapid glycemic deterioration than those with T2D and may benefit from effective diabetes treatment with additional metabolic benefits. OBJECTIVE: Assess glycated hemoglobin (HbA1c) and body weight (BW) changes associated with tirzepatide in GADA-positive versus GADA-negative participants with clinical T2D diagnosis. DESIGN: Post hoc analyses based on pooled data from SURPASS 2-5, using mixed-model repeated measures from the efficacy analysis set, adjusting for study and baseline covariates including age, sex, baseline values, body mass index (BMI), and GADA status. SETTING: N/A. PATIENTS: N = 3791. INTERVENTION: Tirzepatide (5, 10, 15 mg). MAIN OUTCOME MEASURE(S): Change from baseline in HbA1c at Weeks 40 (SURPASS-2, -3, -5) and 42 (SURPASS-4)by GADA status. RESULTS: In participants with confirmed GADA status, 3671 (96.8%) were GADA-negative and 120 (3.2%) were GADA-positive (76 [63.3%] with low and 44 [36.7%] with high GADA levels). Baseline characteristics were similar between groups, except for slightly lower BMI in GADA-positive versus GADA-negative participants (mean [SD] BMI 32.2 [6.1] versus 33.6 [6.3] kg/m2). At Week 40/42, both groups achieved robust reductions in HbA1c (-2.11% versus -2.32%) and BW (9.2 kg versus -9.6 kg) (p < 0.001, both groups). HbA1c reductions were greater in GADA-negative participants (estimated difference [95% CI]: 0.21% [0.03, 0.39]; p = 0.024) and BW reductions did not differ between groups (0.38 kg [-0.99, 1.75]; p = 0.588). CONCLUSIONS: In this post hoc analysis, tirzepatide was associated with substantial reductions in HbA1c and BW irrespective of GADA status in adults diagnosed with T2D, suggesting that tirzepatide may improve glycemic control in individuals with LADA.

Keratin-Positive Giant Cell Tumor of Bone and Soft Tissue With HMGA2::NCOR2 Fusion in Children Under 10 With Response to Imatinib Therapy: A Case Series.

HMGA2::NCOR2 keratin-positive giant cell tumors in children with response to imatinib in an infant.

Revision of Initial Referral Diagnosis following Genotypic Confirmation of Familial Exudative Vitreoretinopathy.

PURPOSE: To describe common referral diagnoses of FEVR (Familial Exudative Vitreoretinopathy) DESIGN: Retrospective case series. SUBJECTS: Patients with phenotypic FEVR evaluated by the pediatric retina service at Bascom Palmer Eye Institute from March 1, 2019 to May 31, 2023. METHODS: A retrospective detailed review of history, imaging, and genetic testing was performed for all patients included in the study. MAIN OUTCOME MEASURES: The primary outcome measures included genetic evaluation, clinical imaging and characteristics. Secondary outcome measures were age and stage of disease at diagnosis. RESULTS: Fifty-five patients with phenotypic and genetically confirmed FEVR were identified. Of these, the initial diagnosis was incorrect upon referral in 33 cases (60%). The referral diagnoses included Coats disease (n =2, 7%), toxoplasmosis (n=2, 7%), retinal detachment (n=6, 18%), persistent fetal vasculature (PFV) (n =5, 15%), suspected inherited retinal disease (n=2, 7%), myopia (n=3, 9%), retinopathy of prematurity (ROP) with preterm gestational age (n=7, 21%), and ROP at moderate to late preterm gestational age (n=6, 18%). The mean age at diagnosis was 8.78 years and 6.42 years for patients with revised diagnosis versus initial diagnosis of FEVR, respectively (p =0.4). There was no correlation between age of diagnosis and stage of disease (p =0.8). CONCLUSIONS: A high index of suspicion for FEVR must be maintained given the heterogeneity of phenotypes. Atypical cases of PFV, Coats disease, and ROP should prompt fluorescein angiography and genetic evaluation.

Fasting before Intra-Gastric Dosing with Antigen Improves Intestinal Humoral Responses in Syrian Hamsters.

Oral vaccines, unlike injected, induce intestinal secretory immunoglobulin A (sIgA) mimicking our natural defense against gut pathogens. We previously observed sIgA responses after administering the Clostridioides difficile colonisation factor CD0873 orally in enteric capsules to hamsters. Enteric-coated capsules are designed to resist dissolution in the stomach and disintegrate only at the higher pH of the small intestine. However, the variable responses between animals led us to speculate suboptimal transit of antigens to the small intestine. The rate of gastric emptying is a controlling factor in the passage of oral drugs for subsequent availability in the small intestine for absorption. Whilst in humans, food delays gastric emptying, in rats, capsules can empty quicker from fed stomachs than from fasted. To test in hamsters if fasting improves the delivery of antigens to the small intestine, as inferred from the immune responses generated, 24 animals were dosed intragastrically with enteric capsules containing recombinant CD0873. Twelve hamsters were fasted for 12 h prior to each dose and the other 12 fed. Significantly higher sIgA titres, with significantly greater bacterial-adherence-blocking activity, were detected in small intestinal lavages in the fasted group. We conclude that fasting in hamsters improves intestinal delivery leading to more robust responses.

Clinical outcomes after liver transplant in people with cystic fibrosis: A systematic review and meta-analysis.

BACKGROUND: Data on the impact of liver transplantation (LT) in cystic fibrosis (CF) on lung function and exacerbations are limited. The objective of this study was to summarize the literature on lung function, nutritional status, survival, and complications following LT in people with CF. METHODS: Three databases were searched until September 2023, to identify the impact of LT in CF. Lung transplant prior to LT and simultaneous liver-lung transplant were excluded. Pooled hazard ratios were calculated using random-effects models. RESULTS: Thirty studies were included in this review, with 3 and 9 studies included in meta-analyses for nutritional status and lung function, respectively. Eighty-three percent of the studies used data that was more than a decade old. There was a significant increase in percent-predicted forced expiratory volume with mean change of 7.16 % (2.13, 12.19; p = 0.005) one year post-LT. Pulmonary exacerbations decreased in the short-term, however there was no significant change in body mass index (BMI). One-year survival post-LT ranged between 75 and 100 %, while five-year survival was lower at 64-89 %. CONCLUSION: Existing data suggest that LT improves lung function in the short term and does not increase the likelihood of pulmonary exacerbations, despite ongoing immunosuppression in the setting of chronic lung infection.

The Legacy of Redlining: Increasing Childhood Asthma Disparities Through Neighborhood Poverty.

RATIONALE: Identifying the root causes of racial disparities in childhood asthma is critical for health equity. OBJECTIVES: To determine if the 1930's racist policy of redlining led to present-day disparities in childhood asthma by increasing community-level poverty and decreasing neighborhood socioeconomic position (SEP). METHODS: We categorized census tracts at birth of participants from the Children's Respiratory and Environmental Workgroup birth cohort consortium into A, B, C, or D categories as defined by the Home Owners Loan Corporation (HOLC), with D being the highest perceived risk. Surrogates of present-day neighborhood-level SEP were determined for each tract including the percentage of low-income households, the CDC's social vulnerability index (SVI), and other tract-level variables. We performed causal mediation analysis, which, under the assumption of no unmeasured confounding, estimates the direct and mediated pathways by which redlining may cause asthma disparities through census tract-level mediators adjusting for individual-level covariates. MEASUREMENTS AND MAIN RESULTS: Of 4,849 children, the cumulative incidence of asthma through age 11 was 26.6% and 13.2% resided in census tracts with a HOLC grade of D. In mediation analyses, residing in grade D tracts (aOR = 1.03 [95%CI 1.01,1.05]) was significantly associated with childhood asthma, with 79% of this increased risk mediated by percentage of low-income households; results were similar for SVI and other tract-level variables. CONCLUSIONS: The historical structural racist policy of redlining led to present-day asthma disparities in part through decreased neighborhood SEP. Policies aimed at reversing the effects of structural racism should be considered to create more just, equitable, and healthy communities.

Planning for the forgotten fourth trimester of pregnancy: A parallel group randomized control trial to test a postpartum planning intervention vs. standard prenatal care.

BACKGROUND: Black and brown birthing people experience persistent disparities in adverse maternal health outcomes, partially due to inadequate perinatal care. The goal of this study is to design and evaluate a patient-centered intervention for obstetric patients with one or more cardiometabolic risk factors for severe maternal morbidity [gestational diabetes, diabetes mellitus, hypertensive disorders of pregnancy (chronic hypertension, preeclampsia, eclampsia, or gestational hypertension), or preconception obesity (BMI > 30)] to promote postpartum visit attendance. METHODS: To address identified unmet needs for postpartum support and barriers to postpartum care, we developed 20 thematic postpartum planning modules, each with corresponding patient educational materials, community resources, care coordination protocols, and clinician support tools (decision aids, electronic medical record prompts and fields). During prenatal care encounters, a research coordinator delivers the educational content (in English or Spanish), facilitates the participant's planning and shared decision-making, provides the participant with resources, and documents decisions in the electronic medical record. We will randomize 320 eligible patients with a 1:1 ratio to the intervention or standard prenatal care and evaluate the impact on postpartum visit attendance at 4-12 weeks and secondary outcomes (postpartum mental health, perceived future maternal and cardiometabolic risk, contraceptive use, primary care use, readmission, and patient satisfaction with care). DISCUSSION: Through engagement with patients and community stakeholders, we developed a guideline-based, locally tailored intervention to address drivers of engagement with postpartum care for high-risk obstetric patients. If demonstrated to be effective, the educational materials and electronic medical record based-tool can be adapted to other settings. TRIAL REGISTRATION: This trial was registered on ClinicalTrials.gov (NCT05430815) on June 23, 2022.

Associations between HIV stigma and health-related quality-of-life among people living with HIV: cross-sectional analysis of data from HPTN 071 (PopART).

People living with HIV (PLHIV) report lower health-related quality-of-life (HRQoL) than HIV-negative people. HIV stigma may contribute to this. We explored the association between HIV stigma and HRQoL among PLHIV. We used cross-sectional data from 3991 randomly selected PLHIV who were surveyed in 2017-2018 for HPTN 071 (PopART), a cluster randomised trial in Zambia and South Africa. Participants were 18-44 years, had laboratory-confirmed HIV infection, and knew their status. HRQoL was measured using the EuroQol-5-dimensions-5-levels (EQ-5D-5L) questionnaire. Stigma outcomes included: internalised stigma, stigma experienced in the community, and stigma experienced in healthcare settings. Associations were examined using logistic regression. Participants who had experienced community stigma (n = 693/3991) had higher odds of reporting problems in at least one HRQoL domain, compared to those who had not (adjusted odds ratio, aOR: 1.51, 95% confidence interval, 95% Cl: 1.16-1.98, p = 0.002). Having experienced internalised stigma was also associated with reporting problems in at least one HRQoL domain (n = 552/3991, aOR: 1.98, 95% CI: 1.54-2.54, p < 0.001). However, having experienced stigma in a healthcare setting was less common (n = 158/3991) and not associated with HRQoL (aOR: 1.04, 95% CI: 0.68-1.58, p = 0.850). A stronger focus on interventions for internalised stigma and stigma experienced in the community is required.

Environmental and structural factors associated with bacterial diversity in household dust across the Arizona-Sonora border.

We previously reported that asthma prevalence was higher in the United States (US) compared to Mexico (MX) (25.8% vs. 8.4%). This investigation assessed differences in microbial dust composition in relation to demographic and housing characteristics on both sides of the US-MX Border. Forty homes were recruited in the US and MX. Home visits collected floor dust and documented occupants' demographics, asthma prevalence, housing structure, and use characteristics. US households were more likely to have inhabitants who reported asthma when compared with MX households (30% vs. 5%) and had significantly different flooring types. The percentage of households on paved roads, with flushing toilets, with piped water and with air conditioning was higher in the US, while dust load was higher in MX. Significant differences exist between countries in the microbial composition of the floor dust. Dust from Mexican homes was enriched with Alishewanella, Paracoccus, Rheinheimera genera and Intrasporangiaceae family. A predictive metagenomics analysis identified 68 significantly differentially abundant functional pathways between US and MX. This study documented multiple structural, environmental, and demographic differences between homes in the US and MX that may contribute to significantly different microbial composition of dust observed in these two countries.

Patient-Reported and Clinical Outcomes of Surgically Treated Patients With Symptomatic Spinal Metastases: Results From Epidemiology, Process, and Outcomes of Spine Oncology (EPOSO), a Prospective, Multi-Institutional and International Study.

BACKGROUND AND OBJECTIVES: The palliative impact of spine surgery for metastatic disease is evolving with improvements in surgical technique and multidisciplinary cancer care. The goal of this study was to prospectively evaluate long-term clinical outcomes including health-related quality-of-life (HRQOL) measures, using spine cancer-specific patient-reported-outcome (PRO) measures, in patients with symptomatic spinal metastases who underwent surgical management. METHODS: The Epidemiology, Process, and Outcomes of Spine Oncology (EPOSO, ClinicalTrials.gov identifier: NCT01825161) trial is a prospective-observational cohort study that included 10 specialist centers in North America and Europe. Patients aged 18 to 75 years who underwent surgery for spinal metastases were included. Prospective assessments included both spine tumor-specific and generic PRO tools which were collected for a minimum of 2 years post-treatment or until death. RESULTS: Two hundred and eighty patients (51.8% female, mean age 57.9 years) were included. At presentation, the mean Charlson Comorbidity Index was 6.0, 35.7% had neurological deficits as defined by the American Spinal Cord Injury Association scores, 47.2% had high-grade epidural spinal cord compression (2-3), and 89.6% had impending or frank instability as measured by a Spinal Instability Neoplastic Score of ≥7. The most common primary tumor sites were breast (20.2%), lung (18.8%), kidney (16.2%), and prostate (6.5%). The median overall survival postsurgery was 501 days, and the 2-year progression-free-survival rate was 38.4%. Compared with baseline, significant and durable improvements in HRQOL were observed at the 6-week, 12-week, 26-week, 1-year, and 2-year follow-up assessments from a battery of PRO questionnaires including the spine cancer-specific, validated, Spine Oncology Study Group Outcomes Questionnaire v2.0, the Short Form 36 version 2, EuroQol-5 Dimension (3L), and pain numerical rating scale score. CONCLUSION: Multi-institutional, prospective-outcomes data confirm that surgical decompression and/or stabilization provides meaningful and durable improvements in multiple HRQOL domains, including spine-specific outcomes based on the Spine Oncology Study Group Outcomes Questionnaire v2.0, for patients with metastatic spine disease.