Climate Justice Implications of Natech Disasters: Excess Contaminant Releases during Hurricanes on the Texas Gulf Coast.

Extreme weather events are becoming more severe due to climate change, increasing the risk of contaminant releases from hazardous sites disproportionately located in low-income communities of color. We evaluated contaminant releases during Hurricanes Rita, Ike, and Harvey in Texas and used regression models to estimate associations between neighborhood racial/ethnic composition and residential proximity to hurricane-related contaminant releases. Two-to-three times as many excess releases were reported during hurricanes compared to business-as-usual periods. Petrochemical manufacturing and refineries were responsible for most air emissions events. Multivariable models revealed sociodemographic disparities in likelihood of releases; compared to neighborhoods near regulated facilities without a release, a one-percent increase in Hispanic residents was associated with a 5 and 10% increase in the likelihood of an air emissions event downwind and within 2 km during Hurricanes Rita and Ike (odds ratio and 95% credible interval= 1.05 [1.00, 1.13], combined model) and Harvey (1.10 [1.00, 1.23]), respectively. Higher percentages of renters (1.07 [1.03, 1.11], combined Rita and Ike model) and rates of poverty (1.06 [1.01, 1.12], Harvey model) were associated with a higher likelihood of a release to land or water, while the percentage of Black residents (0.94 [0.89, 1.00], Harvey model) was associated with a slightly lower likelihood. Population density was consistently associated with a decreased likelihood of a contaminant release to air, land, or water. Our findings highlight social inequalities in the risks posed by natural-technological disasters that disproportionately impact Hispanic, renter, low-income, and rural populations.

Prevalence of Mycobacterium leprae and Mycobacterium lepromatosis in roadkill armadillos in Brazil.

To evaluate the prevalence of Mycobacterium leprae and Mycobacterium lepromatosis in road killed armadillos identified along Brazilian regions, samples of liver, spleen, muscle, ear, nose and tail were collected on highways from 78 animals. The armadillos were of four different species, Cabassous tatouay, Dasypus novemcinctus, Dasypus septemcinctus and Euphractus sexcinctus. After DNA extraction from two tissues, specific primers were used for the detection of each pathogen using SYBR green qualitative Real-Time PCR, and amplicons were sequenced. The species with the highest prevalence was Dasypus novemcinctus, mainly in the Central-West, South, and Southeast regions of Brazil. We detected M. leprae DNA in 32 (41%) of the 78 individuals and M. lepromatosis DNA was not identified in any of the examined samples. The zoonotic component of leprosy may play a role in the transmission of the disease in endemic areas in which environmental conditions and contact with reservoirs must be investigated.

Synoviocytes assist in modulating the effect of Ross River virus infection in micromass-cultured primary human chondrocytes.

Introduction. Ross River virus (RRV) is a mosquito-borne virus prevalent in Australia and the islands of the South Pacific, where it causes an arthritogenic illness with a hallmark feature of severe joint pain. The joint space is a unique microenvironment that contains cartilage and synovial fluid. Chondrocytes and synoviocytes are crucial components of the joint space and are known targets of RRV infection.Hypothesis/Gap statement. Understanding the relationship between synoviocytes and chondrocytes during RRV infection will provide further insights into RRV-induced joint pathology.Methodology. To better understand the unique dynamics of these cells during RRV infection, we used primary chondrocytes cultured in physiologically relevant micromasses. We then directly infected micromass chondrocytes or infected primary fibroblast-like synoviocytes (FLS), co-cultured with micromass chondrocytes. Micromass cultures and supernatants were collected and analysed for viral load with a PCR array of target genes known to play a role in arthritis.Results. We show that RRV through direct or secondary infection in micromass chondrocytes modulates the expression of cellular factors that likely contribute to joint inflammation and disease pathology, as well as symptoms such as pain. More importantly, while we show that RRV can infect micromass-cultured chondrocytes via FLS infection, FLS themselves affect the regulation of cellular genes known to contribute to arthritis.Conclusion. Single-cell culture systems lack the complexity of in vivo systems, and understanding the interaction between cell populations is crucial for deciphering disease pathology, including for the development of effective therapeutic strategies.

Nasturtium leaf compounds, diphenyl disulfide and lyral, against Atta sexdens (Hymenoptera: Formicidae) and their symbiotic fungi.

Social insect pests, particularly leaf-cutting ants, present a considerable challenge in terms of control. Leaf-cutting ants are significant agricultural, forestry, and pasture pests, and understanding their behavior and defense mechanisms is essential for managing their colonies effectively. While toxic ant baits are a primary control method, the limited availability of effective insecticides and concerns over their hazardous nature has spurred the search for alternative solutions, particularly natural compounds, which aligns with the goals of forest certification groups. In the light of previous evidence demonstrating the efficacy of nasturtium leaves (Tropaeolum majus L. (Brassicales: Tropaeolaceae)) in suppressing leaf-cutting ant colonies, this study investigates 2 active components of nasturtium leaf extracts: diphenyl disulfide and lyral. We tested their impact on Atta sexdens (L.) (Hymenoptera: Formicidae), the most prevalent leaf-cutter ant species in Brazil, and their symbiotic fungus, Leucoagaricus gongylophorus (Möller) Singer (Agaricales: Agaricaceae). We conducted experiments with increasing concentrations of diphenyl disulfide and lyral, assessing their effects on the symbiotic fungus and on forager workers and gardeners of A. sexdens colonies. Our findings revealed no fungicidal activity, and ant mortality was minimal in both topical and ingestion bioassays with the exception of gardeners topically exposed to diphenyl sulfide. Furthermore, the compounds did not affect leaf ingestion, but diphenyl disulfide did increase interactions among foragers. These results suggest that neither diphenyl disulfide nor lyral are the primary contributors to the suppression of leaf-cutting ant colonies by nasturtium leaves. However, they may enhance the formicidal activity of other compounds present in nasturtium leaves.

Contributions of neighborhood physical and social environments to racial and ethnic disparities in birth outcomes in California: A mediation analysis.

BACKGROUND: Racially minoritized populations experience higher rates of adverse birth outcomes than White populations in the U.S. We estimated the mediating effect of neighborhood social and physical environments on disparities in adverse birth outcomes in California. METHOD: We used birthing parent's residential address for California live birth records from 2019 to estimate census block group Area Deprivation Index and census tract level measures of ambient fine particulate matter (PM2.5), drinking water contamination, tree canopy coverage, as a measure of greenspace, potential heat vulnerability, and noise. We performed mediation analysis to assess whether neighborhood factors explain racial/ethnic disparities in preterm birth (PTB) and term-birth low birth weight (TLBW) comparing Black, Latinx, and Asian with White births after controlling for individual-level factors. RESULTS: Black, Latinx, and Asian parents had PTB rates that were 67%, 36%, and 11% higher, and TLBW rates that were 150%, 38%, and 81% higher than Whites. Neighborhood deprivation contributed 7% (95% CI: 3%, 11%) to the Black-White and 9% (95% CI: 6%, 12%) to the Latinx-White disparity in PTB, and 8% (95% CI: 3%, 12%) of the Black-White and 9% (95% CI: 5%, 15%) of the Latinx-White disparity in TLBW. Drinking water contamination contributed 2% (95% CI: 1%, 4%) to the Latinx-White disparity in PTB. Lack of greenspace accounted for 7% (95% CI: 2%, 10%) of the Latinx-White PTB disparity and 7% (95% CI: 3%, 12%) of the Asian-White PTB disparity. PM2.5 contributed 11% (95% CI: 5%, 18%), drinking water contamination contributed 3% (95% CI: 1%, 7%), and potential heat vulnerability contributed 2% (95% CI: 1%, 3%) to the Latinx-White TLBW disparity. Lack of green space contributed 3% (95% CI: 1%, 6%) to the Asian-White TLBW disparity. CONCLUSIONS: Our study suggests social environments explain portions of Black/Latinx-White disparities while physical environments explain Latinx/Asian-White disparities in PTB and TLBW.

PFAS-Contaminated Pesticides Applied near Public Supply Wells Disproportionately Impact Communities of Color in California.

Contaminated drinking water from widespread environmental pollutants such as perfluoroalkyl and polyfluoroalkyl substances (PFAS) poses a rising threat to public health. PFAS monitoring in groundwater is limited and fails to consider pesticides found to contain PFAS as a potential contamination source. Given previous findings on the disproportionate exposure of communities of Color to both pesticides and PFAS, we investigated disparities in PFAS-contaminated pesticide applications in California based on community-level sociodemographic characteristics. We utilized statewide pesticide application data from the California Department of Pesticide Regulation and recently reported concentrations of PFAS chemicals detected in eight pesticide products to calculate the areal density of PFAS applied within 1 km of individual community water systems' (CWSs) supply wells. Spatial regression analyses suggest that statewide, CWSs that serve a greater proportion of Latinx and non-Latinx People of Color residents experience a greater areal density of PFAS applied and greater likelihood of PFAS application near their public supply wells. These results highlight agroecosystems as potentially important sources of PFAS in drinking water and identify areas that may be at risk of PFAS contamination and warrant additional PFAS monitoring and remediation.

Hurricane Harvey and the risk of spontaneous preterm and early-term birth.

Background: Hurricane Harvey made landfall in August 2017 and resulted in catastrophic flooding in Houston, Texas. Prior studies of hurricanes and preterm birth have found conflicting results. We tested the hypotheses that exposure to Hurricane Harvey was associated with a higher risk of spontaneous pre- and early-term birth and assessed vulnerable subpopulations. Methods: We conducted a retrospective study of singleton births using administrative birth records in the nine-county greater Houston area from 2015 to 2019. We estimated the likelihood of pre- and early-term births using logistic regression, comparing births occurring during or within 1, 2, or 4 weeks of Hurricane Harvey to unexposed reference periods encompassing the same dates 2 years prior and after. Stratified models assessed effect modification by degree of flooding, birth parent age, high- vs. low-risk pregnancy, race/ethnicity, and prenatal care. Results: Among 15,564 births, we found no association between exposure to Hurricane Harvey and spontaneous preterm birth within 1 week adjusted (odds ratio [OR], 1.06; 95% confidence interval [CI] = 0.91, 1.25) but a 14% higher odds of spontaneous early-term birth (OR, 1.14; 95% CI = 1.04, 1.25). The odds of early-term birth were even higher in neighborhoods with severe flooding (OR, 1.21; 95% CI = 1.05, 1.38), segregated neighborhoods (OR, 1.23; 95% CI = 1.03, 1.47), and among foreign-born Hispanics (OR, 1.21; 95% CI = 1.04, 1.53) and pregnant people receiving no prenatal care (OR, 1.37; 95% CI = 1.03, 1.82). Effect estimates were attenuated or null when considering 2-week or 4-week lags to define exposure. Conclusions: Hurricane Harvey was associated with higher odds of spontaneous early-term birth up to 1 week later, especially among socially marginalized populations.

Investigating cognitive-motor effects during slacklining using mobile EEG.

Balancing is a very important skill, supporting many daily life activities. Cognitive-motor interference (CMI) dual-tasking paradigms have been established to identify the cognitive load of complex natural motor tasks, such as running and cycling. Here we used wireless, smartphone-recorded electroencephalography (EEG) and motion sensors while participants were either standing on firm ground or on a slackline, either performing an auditory oddball task (dual-task condition) or no task simultaneously (single-task condition). We expected a reduced amplitude and increased latency of the P3 event-related potential (ERP) component to target sounds for the complex balancing compared to the standing on ground condition, and a further decrease in the dual-task compared to the single-task balancing condition. Further, we expected greater postural sway during slacklining while performing the concurrent auditory attention task. Twenty young, experienced slackliners performed an auditory oddball task, silently counting rare target tones presented in a series of frequently occurring standard tones. Results revealed similar P3 topographies and morphologies during both movement conditions. Contrary to our predictions we observed neither significantly reduced P3 amplitudes, nor significantly increased latencies during slacklining. Unexpectedly, we found greater postural sway during slacklining with no additional task compared to dual-tasking. Further, we found a significant correlation between the participant's skill level and P3 latency, but not between skill level and P3 amplitude or postural sway. This pattern of results indicates an interference effect for less skilled individuals, whereas individuals with a high skill level may have shown a facilitation effect. Our study adds to the growing field of research demonstrating that ERPs obtained in uncontrolled, daily-life situations can provide meaningful results. We argue that the individual CMI effects on the P3 ERP reflects how demanding the balancing task is for untrained individuals, which draws on limited resources that are otherwise available for auditory attention processing. In future work, the analysis of concurrently recorded motion-sensor signals will help to identify the cognitive demands of motor tasks executed in natural, uncontrolled environments.

Exploring latent clusters in pediatric OCD based on symptoms, severity, age, gender, and comorbidity.

Given diverse symptom expression and high rates of comorbid conditions, the present study explored underlying commonalities among OCD-affected children and adolescents to better conceptualize disorder presentation and associated features. Data from 830 OCD-affected participants presenting to OCD specialty centers was aggregated. Dependent mixture modeling was used to examine latent clusters based on their age- and gender adjusted symptom severity (as measured by the Children's Yale-Brown Obsessive-Compulsive Scale; CY-BOCS), symptom type (as measured by factor scores calculated from the CY-BOCS symptom checklist), and comorbid diagnoses (as assessed via diagnostic interviews). Fit statistics favored a four-cluster model with groups distinguished primarily by symptom expression and comorbidity type. Fit indices for 3-7 cluster models were only marginally different and characteristics of the clusters remained largely stable between solutions with small clusters of distinct presentations added in more complex models. Rather than identifying a single classification system, the findings support the utility of integrating dimensional, developmental, and transdiagnostic information in the conceptualization of OCD-affected children and adolescents. Identified clusters point to the centrality of contamination concerns to OCD, relationships between broader symptom expression and higher levels of comorbidity, and the potential for complex/neurodevelopmental presentations.

Applying self-determination theory to internalized weight stigma and mental health correlates among young and middle adult women: A structural equation model.

Limited research has explored the relationship between self-determination theory constructs (basic psychological needs, autonomous/controlled regulation) and internalized weight stigma (IWS). This cross-sectional, online study surveyed 480 U.S. women aged 18-40 between 2021 and 2022. We hypothesized that need frustration and controlled weight regulation would relate to higher IWS, which would be associated with dysfunctional eating, distress, and lower life satisfaction. Conversely, we predicted that need satisfaction, autonomous regulation, and body satisfaction would be associated with reduced IWS, dysfunctional eating and distress, and higher life satisfaction. Structural equation modeling demonstrated an acceptable model fit (CMIN/DF = 2.95, CFI = 0.90, RMSEA = 0.06, SRMR = 0.07), accounting for 74% of IWS variance. Findings indicate the relevance of self-determination theory in understanding IWS, supporting a dual-process model whereby adverse and adaptive outcomes follow distinct pathways. Longitudinal studies are warranted to validate psychological needs and regulatory styles as mechanisms for IWS development and to assess generalizability across diverse populations.

Genetic linkage mapping and quantitative trait locus (QTL) analysis of sweet basil (Ocimum basilicum L.) to identify genomic regions associated with cold tolerance and major volatiles.

Chilling sensitivity is one of the greatest challenges affecting the marketability and profitability of sweet basil (Ocimum basilicum L.) in the US and worldwide. Currently, there are no sweet basils commercially available with significant chilling tolerance and traditional aroma profiles. This study was conducted to identify quantitative trait loci (QTLs) responsible for chilling tolerance and aroma compounds in a biparental mapping population, including the Rutgers advanced breeding line that served as a chilling tolerant parent, 'CB15', the chilling sensitive parent, 'Rutgers Obsession DMR' and 200 F2 individuals. Chilling tolerance was assessed by percent necrosis using machine learning and aroma profiling was evaluated using gas chromatography (GC) mass spectrometry (MS). Single nucleotide polymorphism (SNP) markers were generated from genomic sequences derived from double digestion restriction-site associated DNA sequencing (ddRADseq) and converted to genotype data using a reference genome alignment. A genetic linkage map was constructed and five statistically significant QTLs were identified in response to chilling temperatures with possible interactions between QTLs. The QTL on LG24 (qCH24) demonstrated the largest effect for chilling response and was significant in all three replicates. No QTLs were identified for linalool, as the population did not segregate sufficiently to detect this trait. Two significant QTLs were identified for estragole (also known as methyl chavicol) with only qEST1 on LG1 being significant in the multiple-QTL model (MQM). QEUC26 was identified as a significant QTL for eucalyptol (also known as 1,8-cineole) on LG26. These QTLs may represent key mechanisms for chilling tolerance and aroma in basil, providing critical knowledge for future investigation of these phenotypic traits and molecular breeding.

Defining domains: developing consensus-based definitions for foundational domains in OMERACT core outcome sets.

OBJECTIVE: To develop a set of detailed definitions for foundational domains commonly used in OMERACT (Outcome Measures in Rheumatology) core domain sets. METHODS: We identified candidate domain definitions from prior OMERACT publications and websites and publications of major organizations involved in outcomes research for six domains commonly used in OMERACT Core Domain Sets: pain intensity, pain interference, physical function, fatigue, patient global assessment, and health-related quality of life. We conducted a two-round survey of OMERACT working groups, patient research partners, and then the OMERACT Technical Advisory Group to establish their preferred domain definitions. Results were presented at the OMERACT 2023 Methodology Workshop, where participants discussed their relevant lived experience and identified potential sources of variability giving the needed detail in our domain definitions. RESULTS: One-hundred four people responded to both rounds of the survey, and a preferred definition was established for each of the domains except for patient global assessment for which no agreement was reached. Seventy-five participants at the OMERACT 2023 Methodology Workshop provided lived experience examples, which were used to contextualise domain definition reports for each of the five domains. CONCLUSION: Using a consensus-based approach, we have created a detailed definition for five of the foundational domains in OMERACT core domain sets; patient global assessment requires further research. These definitions, although not mandatory for working groups to use, may facilitate the initial domain-match assessment step of instrument selection, and reduce the time and resources required by future OMERACT groups when developing core outcome sets.

Embracing unity at OMERACT: Valuing equity, promoting diversity, fostering inclusivity.

OBJECTIVE: To increase awareness and understanding of the principles of Equity, Diversity, and Inclusivity (EDI) within Outcome Measures in Rheumatology's (OMERACT) members. For this, we aimed to obtain ideas on how to promote and foster these principles within the organization and determine the diversity of the current membership in order to focus future efforts. METHODS: We held a plenary workshop session at OMERACT 2023 with roundtable discussions on barriers and solutions to increased diversity within OMERACT. We conducted an anonymous, web-based survey of members to record characteristics including population group, gender identity, education level, age, and ability. RESULTS: The workshop generated ideas to increase diversity of participants across the themes of building relationships [12 topics], materials and methods [5 topics], and conference-specific [6 topics]. Four hundred and seven people responded to the survey (25 % response rate). The majority of respondents were White (75 %), female (61 %), university-educated (94 %), Christian (42 %), spoke English at home (60 %), aged 35 to 55 years (50 %), and did not report a disability (64 %). CONCLUSION: OMERACT is committed to improving its diversity. Next steps include strategic recruitment of members to the EDI working group, drafting an EDI mission statement centering equity and inclusivity in the organization, and developing guidance for the OMERACT Handbook to help all working groups create actionable plans for promoting EDI principles.

Digital cognitive behavioural therapy for insomnia reduces insomnia in nurses suffering from shift work disorder: A randomised-controlled pilot trial.

Insomnia is a primary symptom of shift work disorder, yet it remains undertreated. This randomised-controlled pilot trial examined the efficacy of a digital, guided cognitive behavioural therapy for insomnia adapted to shift work (SleepCare) in nurses with shift work disorder. The hypothesis was that SleepCare reduces insomnia severity compared with a waitlist control condition. A total of 46 unmedicated nurses suffering from shift work disorder with insomnia (age: 39.7 ± 12.1 years; 80.4% female) were randomised to the SleepCare group or the waitlist control group. The primary outcome measure was the Insomnia Severity Index. Other questionnaires on sleep, mental health and occupational functioning, sleep diary data and actigraphy data were analysed as secondary outcomes. Assessments were conducted before (T0), after the intervention/waitlist period (T1), and 6 months after treatment completion (T2). The SleepCare group showed a significant reduction in insomnia severity from T0 to T1 compared with the control condition (ß = -4.73, SE = 1.12, p < 0.001). Significant improvements were observed in sleepiness, dysfunctional beliefs about sleep, pre-sleep arousal, sleep effort, self-reported sleep efficiency and sleep onset latency. No significant effect was found in actigraphy data. Depressive and anxiety symptoms, cognitive irritation and work ability improved significantly. Overall, satisfaction and engagement with the intervention was high. SleepCare improved insomnia severity, sleep, mental health and occupational functioning. This is the first randomised-controlled trial investigating the efficacy of digital cognitive behavioural therapy for insomnia in a population suffering from shift work disorder with insomnia. Future research should further explore these effects with larger sample sizes and active control conditions.

Association of Neighborhood Opportunity with Infant Brain Activity and Cognitive Development.

BACKGROUND AND OBJECTIVES: Neighborhood socioeconomic disadvantage is associated with lower neurocognitive scores and differences in brain structure among school-age children. Associations between positive neighborhood characteristics, infant brain activity, and cognitive development are underexplored. We examined direct and indirect associations between neighborhood opportunity, brain activity, and cognitive development. METHODS: This longitudinal cohort study included infants from 2 primary care clinics in Boston and Los Angeles. Using a sample of 65 infants, we estimated path models to examine associations between neighborhood opportunity (measured by the Child Opportunity Index), infant electroencephalography (EEG) at 6 months, and infant cognitive development (measured using the Mullen Scales of Early Learning) at 12 months. A mediation model tested whether EEG power explained associations between neighborhood opportunity and infant cognition. RESULTS: Neighborhood opportunity positively predicted infant absolute EEG power across multiple frequency bands: low ( b = 0.12, 95% CI 0.01-0.24, p = 0.04, = 0.21); high ( b = 0.11, 95% CI 0.01-0.21, p = 0.03, = 0.23); ( b = 0.10, 95% CI 0.00-0.19, p = 0.04, = 0.20); and ( b = 0.12, 95% CI 0.02-0.22, p = 0.02, = 0.24). The results remained statistically significant after applying a Benjamini-Hochberg false discovery rate of 0.10 to adjust for multiple comparisons. No significant associations emerged between neighborhood opportunity, relative EEG power, and infant cognition. Mediation was not significant. CONCLUSION: Neighborhood opportunity is positively associated with some forms of infant brain activity, suggesting that positive neighborhood characteristics may play a salient role in early development.

The gut microbiomes of Channel Island foxes and island spotted skunks exhibit fine-scale differentiation across host species and island populations.

California's Channel Islands are home to two endemic mammalian carnivores: island foxes (Urocyon littoralis) and island spotted skunks (Spilogale gracilis amphiala). Although it is rare for two insular terrestrial carnivores to coexist, these known competitors persist on both Santa Cruz Island and Santa Rosa Island. We hypothesized that examination of their gut microbial communities would provide insight into the factors that enable this coexistence, as microbial symbionts often reflect host evolutionary history and contemporary ecology. Using rectal swabs collected from island foxes and island spotted skunks sampled across both islands, we generated 16S rRNA amplicon sequencing data to characterize their gut microbiomes. While island foxes and island spotted skunks both harbored the core mammalian microbiome, host species explained the largest proportion of variation in the dataset. We further identified intraspecific variation between island populations, with greater differentiation observed between more specialist island spotted skunk populations compared to more generalist island fox populations. This pattern may reflect differences in resource utilization following fine-scale niche differentiation. It may further reflect evolutionary differences regarding the timing of intraspecific separation. Considered together, this study contributes to the growing catalog of wildlife microbiome studies, with important implications for understanding how eco-evolutionary processes enable the coexistence of terrestrial carnivores-and their microbiomes-in island environments.

FOXM1 Participates in Trophoblast Migration and Early Trophoblast Invasion: Potential Role in Blastocyst Implantation.

Successful implantation requires coordinated migration and invasion of trophoblast cells into a receptive endometrium. Reduced forkhead box M1 (FOXM1) expression limits trophoblast migration and angiogenesis in choriocarcinoma cell lines, and in a rat model, placental FOXM1 protein expression was significantly upregulated in the early stages of pregnancy compared to term pregnancy. However, the precise role of FOXM1 in implantation events remains unknown. By analyzing mice blastocysts at embryonic day (E3.5), we have demonstrated that FOXM1 is expressed as early as the blastocyst stage, and it is expressed in the trophectoderm of the blastocyst. Since controlled oxygen tension is determinant for achieving normal implantation and placentation and a chronic hypoxic environment leads to shallow trophoblast invasion, we evaluated if FOXM1 expression changes in response to different oxygen tensions in the HTR-8/SVneo first trimester human trophoblast cell line and observed that FOXM1 expression was significantly higher when trophoblast cells were cultured at 3% O2, which coincides with oxygen concentrations in the uteroplacental interface at the time of implantation. Conversely, FOXM1 expression diminished in response to 1% O2 that resembles a hypoxic environment in utero. Migration and angiogenesis were assessed following FOXM1 knockdown and overexpression at 3% O2 and 1% O2, respectively, in HTR-8/SVneo cells. FOXM1 overexpression increased transmigration ability and tubule formation. Using a 3D trophoblast invasion model with trophospheres from HTR-8/SVneo cells cultured on a layer of MATRIGEL and of mesenchymal stem cells isolated from menstrual fluid, we observed that trophospheres obtained from 3D trophoblast invasion displayed higher FOXM1 expression compared with pre-invasion trophospheres. Moreover, we have also observed that FOXM1-overexpressing trophospheres increased trophoblast invasion compared with controls. HTR-8/SVneo-FOXM1-depleted cells led to a downregulation of PLK4, VEGF, and MMP2 mRNA expression. Our current findings suggest that FOXM1 participates in embryo implantation by contributing to trophoblast migration and early trophoblast invasion, by inducing transcription activation of genes involved in these processes. Maternal-fetal communication is crucial for trophoblast invasion, and maternal stromal cells may induce higher levels of FOXM1 in trophoblast cells.

Consensus on the definitions and descriptions of the domains of the OMERACT Core Outcome Set for shared decision making interventions in rheumatology trials.

OBJECTIVE: To gain consensus on the definitions and descriptions of the domains of the Outcome Measures in Rheumatology (OMERACT) core domain set for rheumatology trials evaluating shared decision making (SDM) interventions. METHODS: Following the OMERACT Handbook methods, our Working Group (WG), comprised of 90 members, including 17 patient research partners (PRPs) and 73 clinicians and researchers, had six virtual meetings in addition to email exchanges to develop draft definitions and descriptions. The WG then conducted an international survey of its members to gain consensus on the definitions and descriptions. Finally, the WG members had virtual meetings and e-mail exchanges to review survey results and finalize names, definitions and descriptions of the domains. RESULTS: WG members contributed to developing the definitions. Fifty-two members representing four continents and 13 countries completed the survey, including 15 PRPs, 33 clinicians and 37 researchers. PRPs and clinicians/researchers agreed with all definitions and descriptions with agreements ranging from 87% to 100%. Respondents suggested wording changes to the names, definitions and descriptions to better reflect the domains. Discussions led to further simplification and clarification to address common questions/concerns about the domains. CONCLUSION: Our WG reached consensus on the definitions and descriptions of the domains of the core domain set for rheumatology trials of SDM interventions. This step is crucial to understand each domain and provides the foundation to identify instruments to measure each domain for inclusion in the Core Outcome Measurement Set. CLINICAL SIGNIFICANCE: The current study provides consensus-based definitions and descriptions for the domains of the OMERACT core domain set for shared decision making interventions from patients/caregivers, clinicians and researchers. This is a crucial step to understand each domain and provides the foundation to identify instruments to measure each domain for inclusion in the Core Outcome Measurement Set for trials of SDM interventions.

Oral nanotherapeutic formulation of insulin with reduced episodes of hypoglycaemia.

Injectable insulin is an extensively used medication with potential life-threatening hypoglycaemic events. Here we report on insulin-conjugated silver sulfide quantum dots coated with a chitosan/glucose polymer to produce a responsive oral insulin nanoformulation. This formulation is pH responsive, is insoluble in acidic environments and shows increased absorption in human duodenum explants and Caenorhabditis elegans at neutral pH. The formulation is sensitive to glucosidase enzymes to trigger insulin release. It is found that the formulation distributes to the liver in mice and rats after oral administration and promotes a dose-dependent reduction in blood glucose without promoting hypoglycaemia or weight gain in diabetic rodents. Non-diabetic baboons also show a dose-dependent reduction in blood glucose. No biochemical or haematological toxicity or adverse events were observed in mice, rats and non-human primates. The formulation demonstrates the potential to orally control blood glucose without hypoglycaemic episodes.