The role of interleukin-6 trans-signalling on cardiovascular dysfunction in inflammatory arthritis.

OBJECTIVES: Cardiovascular (CV) mortality in RA patients is 50% higher than in the general population. There is increasing recognition that systemic inflammation is a major driver of this. IL-6 is implicated in cardiovascular disease (CVD) in the general population but its role in CVD in RA is undefined. Of the two modes of IL-6 signalling, trans-signalling is pro-inflammatory whereas classical signalling is linked with inflammation resolution. This study examines the role of IL-6 trans-signalling in CVD in a mouse model and patients with RA. METHODS: Myography determined the effect of IL-6 trans-signalling blockade, using sgp130Fc, on aortic constriction in murine collagen-induced arthritis. Serum CCL2 and sVCAM-1 as soluble biomarkers of sIL-6R trans-signalling were investigated in a human cross-sectional study. An observational longitudinal study investigated the association between these biomarkers and progression of subclinical atherosclerosis in early RA by measuring carotid intima-media thickness (CIMT). RESULTS: sgp130Fc reduced arthritis severity, serum CCL2 and sVCAM-1 and restored vascular function in collagen-induced arthritis (CIA). In established RA, sVCAM-1 correlated with the 28-joint DAS (DAS28) and CV risk. In early RA, baseline DAS28 was associated with CIMT change at 6 months. CIMT 'rapid progressors' at 12 months had higher baseline sVCAM-1, haemoglobin A1c, cholesterol:high-density lipoprotein cholesterol ratio and LDL cholesterol. CONCLUSIONS: IL-6 trans-signalling plays a pivotal role in vascular dysfunction in CIA. In early RA, sVCAM-1 was associated with progression of subclinical atherosclerosis. Inflammation from RA onset in CVD-susceptible individuals may accelerate atherosclerosis. IL-6 trans-signalling blockade may be beneficial to RA patients and perhaps for atherosclerosis in the general population.

Is the COVID-19 pandemic even darker for some? Examining dark personality and affective, cognitive, and behavioral responses to the COVID-19 pandemic.

As the COVID-19 pandemic and interventions intended to minimize its spread continue to impact daily life, personality research may help to address the different ways in which people respond to a major global health crisis. The present study assessed the role of dark personality traits in predicting different responses to the pandemic. A nationally representative sample of 412 Americans completed measures of the Dark Tetrad as well as perceptions of COVID-19 threat, emergency beliefs, and positive and negative affect in response to COVID-19. Narcissism and Machiavellianism predicted greater negative affect and perceptions of threat during the pandemic, while psychopathy predicted positive affect. Conversely, sadism predicted greater positive affect. Dark personality also showed some predictive ability in explaining pandemic-related behaviors (e.g., more frequent cleaning) but not others (e.g., social distancing). Our findings provide evidence for differences in how dark personality traits predict individual responses to global crises.

The role of patient-physician relationship on health-related quality of life and pain in cancer patients.

PURPOSE: Health-related quality of life (HRQOL) and pain are important supportive cancer care outcomes. The patient-provider relationship, a modifiable care experience, has been linked to healthcare outcomes; however, less is known about associations between patient-provider relationship and supportive care outcomes in cancer patients. We examined the role of multiple aspects of the patient-provider relationship in explaining patterns of HRQOL and pain among breast and lung cancer patients. METHODS: Our analysis included 283 breast and lung cancer patients from two cancer centers. Clinical data and survey data on patient sociodemographic factors, physical and mental HRQOL, pain, and patient-physician relationship (i.e., doctor's respectfulness, time spent with doctors, patient involvement in decision-making, satisfaction with care, and following doctor's advice/treatment plan) were collected at baseline and during treatment. We estimated adjusted modified Poisson regression models to assess associations between patient-physician relationship factors and physical and mental HRQOL and pain. RESULTS: Compared with patients reporting suboptimal respect from doctors, patients reporting optimal respect were less likely to report below average physical HRQOL (adjusted risk ratio (ARR), 0.73; 95%CI, 0.62-0.86), below average mental HRQOL (ARR, 0.71; 95%CI, 0.54-0.93), and moderate-to-severe pain (ARR, 0.53; 95%CI, 0.35-0.79). Patients reporting optimal involvement in care decision-making and patients who reported following their doctor's advice/treatment plan were less likely to report below average mental HRQOL than their respective counterparts (ARR, 0.64; 95%CI, 0.50-0.83; ARR, 0.65; 95%CI, 0.48-0.86). CONCLUSION: Multiple patient-physician relationship factors account for variations in HRQOL and pain in cancer patients. These findings provide insight into potential targets for improving the patient-provider relationship and supportive cancer care outcomes.

Inhibition of CCL3 abrogated precursor cell fusion and bone erosions in human osteoclast cultures and murine collagen-induced arthritis.

Objective: Macrophage inflammatory protein 1-alpha (CCL3) is a chemokine that regulates macrophage trafficking to the inflamed joint. The agonistic effect of CCL3 on osteolytic lesions in patients with multiple myeloma is recognized; however, its role in skeletal damage during inflammatory arthritis has not been established. The aim of the study was to explore the role of osteoclast-associated CCL3 upon bone resorption, and to test its pharmacological blockade for protecting against bone pathology during inflammatory arthritis. Methods: CCL3 production was studied during osteoclast differentiation from osteoclast precursor cells: human CD14-positive mononuclear cells. Mice with CIA were treated with an anti-CCL3 antibody. The effect of CCL3 blockade through mAb was studied through osteoclast number, cytokine production and bone resorption on ivory disks, and in vivo through CIA progression (clinical score, paw diameter, synovial inflammation and bone damage). Results: Over time, CCL3 increased in parallel with the number of osteoclasts in culture. Anti-CCL3 treatment achieved a concentration-dependent inhibition of osteoclast fusion and reduced pit formation on ivory disks (P ⩽ 0.05). In CIA, anti-CCL3 treatment reduced joint damage and significantly decreased multinucleated tartrate-resistant acid phosphatase-positive osteoclasts and erosions in the wrists (P < 0.05) and elbows (P < 0.05), while also reducing joint erosions in the hind (P < 0.01) and fore paws (P < 0.01) as confirmed by X-ray. Conclusion: Inhibition of osteoclast-associated CCL3 reduced osteoclast formation and function whilst attenuating arthritis-associated bone loss and controlling development of erosion in murine joints, thus uncoupling bone damage from inflammation. Our findings may help future innovations for the diagnosis and treatment of inflammatory arthritis.

Effectiveness of an Educational Intervention to Increase Human Papillomavirus Knowledge in High-Risk Minority Women.

OBJECTIVES: The aims of the study were to evaluate human papillomavirus (HPV) and cervical cancer knowledge in a population at high risk for cervical cancer and to determine whether knowledge and attitudes toward HPV vaccination improve after educational intervention. MATERIALS AND METHODS: This pre-post survey design study was conducted at the John H. Stroger Hospital of Cook County colposcopy clinic. An HPV knowledge and awareness survey was given to participants before their clinical encounter. Afterward, participants watched an educational video and repeated the survey, which was administered again at the follow-up visit. Knowledge scores and acceptability of HPV vaccination were compared across all surveys. RESULTS: Among the 104 participants who completed baseline and immediate postintervention surveys, the average baseline score was 9.6 of 20. Knowledge scores improved after the educational intervention (mean = 14.1, p < .0001) and remained elevated in the 44 participants that completed long-term follow-up (mean = 13.5, p < .0001). Acceptability of HPV vaccination for participants themselves increased from 47.1% to 76% (p < .0001) and for children/grandchildren increased from 30.8% to 71.2% (p < .0001) after the intervention. Overall, women were worried about HPV and cervical cancer for themselves and their children/grandchildren at baseline. However, the intervention improved perceptions about HPV vaccination cost, safety, adverse effects, and efficacy. CONCLUSIONS: Knowledge of HPV, cervical cancer, and HPV vaccination is low in this high-risk population and may improve with a simple educational intervention. Increased knowledge was associated with an increase in vaccine acceptability and improved perceptions about HPV vaccination. Educational interventions targeted toward high-risk women are necessary to decrease cervical cancer incidence and mortality.

Benefits and challenges of linking green infrastructure and highway planning in the United States.

Landscape-level green infrastructure creates a network of natural and semi-natural areas that protects and enhances ecosystem services, regenerative capacities, and ecological dynamism over long timeframes. It can also enhance quality of life and certain economic activity. Highways create a network for moving goods and services efficiently, enabling commerce, and improving mobility. A fundamentally profound conflict exists between transportation planning and green infrastructure planning because they both seek to create connected, functioning networks across the same landscapes and regions, but transportation networks, especially in the form of highways, fragment and disconnect green infrastructure networks. A key opportunity has emerged in the United States during the last ten years with the promotion of measures to link transportation and environmental concerns. In this article we examined the potential benefits and challenges of linking landscape-level green infrastructure planning and implementation with integrated transportation planning and highway project development in the United States policy context. This was done by establishing a conceptual model that identified logical flow lines from planning to implementation as well as the potential interconnectors between green infrastructure and highway infrastructure. We analyzed the relationship of these activities through literature review, policy analysis, and a case study of a suburban Maryland, USA landscape. We found that regionally developed and adopted green infrastructure plans can be instrumental in creating more responsive regional transportation plans and streamlining the project environmental review process while enabling better outcomes by enabling more targeted mitigation. In order for benefits to occur, however, landscape-scale green infrastructure assessments and plans must be in place before integrated transportation planning and highway project development occurs. It is in the transportation community's interests to actively facilitate green infrastructure planning because it creates a more predictable environmental review context. On the other hand, for landscape-level green infrastructure, transportation planning and development is much more established and better funded and can provide a means of supporting green infrastructure planning and implementation, thereby enhancing conservation of ecological function.

Examining American Adult's Mental Well and Ill-Being During the 2020 COVID-19 Pandemic Using a Self-Determination Theory Perspective.

Objectives: The COVID-19 pandemic is an international health crisis that has caused unprecedented shifts in people's environments and has threatened people's wellbeing. The current study uses self-determination theory (SDT: 10) to understand how people were handling the pandemic, which proposes three basic psychological needs (autonomy, competence, and relatedness) are vital for human growth and thriving. Furthermore, we examined how people's wellbeing and ill-being changed over the course of the pandemic. Methods: A sample of 193 American adults from around the country reported on their need satisfaction and frustration as well as well and ill-being at three time periods during the pandemic (April 2020, late July/early August 2020, and late January/early February 2021). Results: There was much variability in how people were handling the pandemic, but on average, wellbeing increased, and ill-being decreased over time. Consistent with SDT, the basic needs significantly predicted well and ill-being even during such unprecedented times of disruption. Conclusion: Our results suggest that public health officials should help individuals to focus on autonomy, competence, and relatedness behaviors during times of upheaval.

Evaluating Potential Racial Inequities in Low-dose Computed Tomography Screening for Lung Cancer.

BACKGROUND: Lung cancer is the leading cause of cancer death in the US, and significant racial disparities exist in lung cancer outcomes. For example, Black men experience higher lung cancer incidence and mortality rates than their White counterparts. New screening recommendations for low-dose computed tomography (LDCT) promote earlier detection of lung cancer in at-risk populations and can potentially help mitigate racial disparities in lung cancer mortality if administered equitably. Yet, little is known about the extent of racial differences in uptake of LDCT. OBJECTIVE: To evaluate potential racial disparities in LDCT screening in a large community-based cancer center in central North Carolina. METHODS: We conducted a retrospective study of the initial patients undergoing LDCT in a community-based cancer center (n = 262). We used the Pearson chi-squared test to assess potential racial disparities in LDCT screening. RESULTS: Study results suggest that Black patients may be less likely than White patients to receive LDCT screening when eligible (χ2 = 51.41, p < 0.0001). CONCLUSION: Collaboration among healthcare providers, researchers, and decision makers is needed to promote LDCT equity.

The Association Between Multiple Abortions Within 1 Year and Previous Postabortal Desired Contraception at an Urban, Public Hospital.

Objectives: To determine the proportion of women undergoing multiple abortions within 1 year at an urban, public hospital and the association with desired contraception after the index abortion. Materials and Methods: We conducted a retrospective analysis of all women undergoing abortion up to 13 weeks and 6 days gestation at Stroger Hospital from June 1, 2012 to May 31, 2014. We examined the proportion of women with additional abortions up to 1 year after the index abortion and contraception desired at the index abortion. We also collected data about Chlamydia trachomatis (CT) and Neisseria gonorrhea (GC) infection in surgical abortion patients, to assess suitability for intrauterine device insertion immediately postabortion. Results: Of the 5,104 women with an abortion in the study period, 720 (14.1%) had at least one additional abortion within 1 year. Among women with multiple abortions, 153 (21.3%) selected Tier 1 contraception, 359 (49.8%) Tier 2, 103 (14.3%) Tier 3, and 105 (14.6%) were undecided or desired no method. The contraception desired at the index abortion did not differ significantly between women with and without subsequent abortions (p = 0.107). CT/GC coinfection and CT infection alone were associated with having multiple abortions over the 1-year period (p = 0.020 and p = 0.006). Conclusions: Among women presenting for abortion at an urban, public hospital, desired contraception did not differ significantly between women with multiple abortions versus one abortion within 1 year, but prevalence of CT/GC did. Women at high risk for multiple abortions may benefit from immediate postabortion IUD insertion to avoid unintended pregnancy, provided risk of infection is carefully evaluated.

HER2+ breast cancer cells undergo apoptosis upon exposure to tannic acid released from remodeled cross-linked collagen type I.

Tannic acid (TA) is a naturally occurring polyphenol that cross-links collagen type I and possesses anticancer potential. In previous studies, we demonstrated the increased sensitivity of estrogen receptor-positive (ER+ ) breast cancer cells to TA as opposed to triple negative breast cancer cells and normal human breast epithelial cells. In the current study, human pre-adipocytes and HER2+ breast cancer cells were grown on TA cross-linked collagen type I beads. Cell attachment, growth, and proliferation of the cells result in remodeling of the collagen matrix and release of the cross-linking TA. TA concentrations in the conditioned media were determined. Induced apoptosis of cells grown on the TA cross-linked collagen type I beads was imaged and quantified. Viability of HER2+ breast cancer cells and normal breast epithelial cells after exposure TA released from bead remodeling was quantified. Caspase gene expression and protein expression were evaluated. HER2+ breast cancer cells underwent caspase-mediated apoptosis in response to TA exposure. TA-induced apoptosis in a concentration- and time-dependent manner, with HER2+ breast cancer cells demonstrating an increased sensitivity to the TA effects. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 26-32, 2018.

CCL3 and MMP-9 are induced by TL1A during death receptor 3 (TNFRSF25)-dependent osteoclast function and systemic bone loss.

Reduced bone density and secondary osteoporosis, resulting in increased risk of fracture, is a significant complicating factor in the inflammatory arthritides. While the exact etiology of systemic bone loss is not fully elucidated, recent insights into the tumor necrosis factor super family (TNFSF) revealed a potential role for death receptor 3 (DR3/TNFRSF25) and one of its ligands, TNF-like protein 1A (TL1A/TNFSF15). The mechanisms by which DR3/TL1A signalling modulates bone loss are unclear. We investigated the effect of DR3/TL1A signalling upon osteoclast-dependent chemokine and MMP production to unravel novel mechanisms whereby this pathway regulates OC formation and OC-dependent bone resorption. Collagen induced arthritis (CIA) was established in DR3wt and DR3ko mice, joints were sectioned and analysed histologically for bone damage while systemic trabecular bone loss distal to the affected joints was compared by micro-CT. Ablation of DR3 protected DBA/1 mice against the development and progression of CIA. In DR3ko, joints of the ankle and mid-foot were almost free of bone erosions and long bones of mice with CIA were protected against systemic trabecular bone loss. In vitro, expression of DR3 was confirmed on primary human CD14+ osteoclast precursors by flow cytometry. These cells were treated with TL1A in osteoclast differentiation medium and TRAP+ osteoclasts, bone resorption, levels of osteoclast-associated chemokines (CCL3, CCL2 and CXCL8) and MMP-9 measured. TL1A intensified human osteoclast differentiation and bone resorption and increased osteoclast-associated production of CCL3 and MMP-9. Our data reveals the DR3 pathway as an attractive therapeutic target to combat adverse bone pathology associated with inflammatory arthritis. We demonstrate that DR3 is critical in the pathogenesis of murine CIA and associated secondary osteoporosis. Furthermore, we identify a novel mechanism by which the DR3/TL1A pathway directly enhances human OC formation and resorptive activity, controlling expression and activation of CCL3 and MMP-9.