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Objectives To compare mammography (MG), contrast-enhanced spectral mammography (CESM), and magnetic resonance imaging (MRI) in the detection and size estimation of histologically proven breast cancers using postoperative histology as the gold standard. Methods After ethical approval, 80 women with newly diagnosed breast cancer underwent MG, CESM, and MRI examinations. CESM was reviewed by an independent experienced radiologist, and the maximum dimension of suspicious lesions was measured. For MG and MRI, routine clinical reports of breast specialists, with judgment based on the BI-RADS lexicon, were used. Results of each imaging technique were correlated to define the index cancer. Fifty-nine cases could be compared to postoperative histology for size estimation. Results Breast cancer was visible in 66/80 MG, 80/80 CESM, and 77/79 MRI examinations. Average lesion largest dimension was 27.31 mm (SD 22.18) in MG, 31.62 mm (SD 24.41) in CESM, and 27.72 mm (SD 21.51) in MRI versus 32.51 mm (SD 29.03) in postoperative histology. No significant difference was found between lesion size measurement on MRI and CESM compared with histopathology. Conclusion Our initial results show a better sensitivity of CESM and MRI in breast cancer detection than MG and a good correlation with postoperative histology in size assessment. Key points • Contrast-enhanced spectral mammography (CESM) is slowly being introduced into clinical practice. • Access to breast MRI is limited by availability and lack of reimbursement. • Initial results show a better sensitivity of CESM and MRI than conventional mammography. • CESM showed a good correlation with postoperative histology in size assessment. • Contrast-enhanced spectral mammography offers promise, seemingly providing information comparable to MRI.

Background: B7-H3, an immunoregulatory protein, is overexpressed in several cancers and is often associated with metastasis and poor prognosis. Here, our aim was to identify microRNAs (miRNAs) regulating B7-H3 and assess their potential prognostic implications in breast cancer. Methods: MicroRNAs targeting B7-H3 were identified by transfecting two breast cancer cell lines with a library of 810 miRNA mimics and quantifying changes of B7-H3 protein levels using protein lysate microarrays. For validations we used western immunoblotting and 3′-UTR luciferase assays. Clinical significance of the miRNAs was assayed by analysing whether their expression levels correlated with outcome in two cohorts of breast cancer patients (142 and 81 patients). Results: We identified nearly 50 miRNAs that downregulated B7-H3 protein levels. Western immunoblotting validated the impact of the 20 most effective miRNAs. Thirteen miRNAs (miR-214, miR-363*, miR-326, miR-940, miR-29c, miR-665, miR-34b*, miR-708, miR-601, miR-124a, miR-380-5p, miR-885-3p, and miR-593) targeted B7-H3 directly by binding to its 3′-UTR region. Finally, high expression of miR-29c was associated with a significant reduced risk of dying from breast cancer in both cohorts. Conclusions: We identified miRNAs efficiently downregulating B7-H3 expression. The expression of miR-29c correlated with survival in breast cancer patients, suggesting a tumour suppressive role for this miRNA.

The phagosomal lumen in macrophages is the site of numerous interacting chemistries that mediate microbial killing, macromolecular degradation, and antigen processing. Using a non-hypothesis-based screen to explore the interconnectivity of phagosomal functions, we found that NADPH oxidase (NOX2) negatively regulates levels of proteolysis within the maturing phagosome of macrophages. Unlike the NOX2 mechanism of proteolytic control reported in dendritic cells, this phenomenon in macrophages is independent of changes to lumenal pH and is also independent of hydrolase delivery to the phagosome. We found that NOX2 mediates the inhibition of phagosomal proteolysis in macrophages through reversible oxidative inactivation of local cysteine cathepsins. We also show that NOX2 activity significantly compromises the phagosome's ability to reduce disulfides. These findings indicate that NOX2 oxidatively inactivates cysteine cathepsins through sustained ablation of the reductive capacity of the phagosomal lumen. This constitutes a unique mechanism of spatiotemporal control of phagosomal chemistries through the modulation of the local redox environment. In addition, this work further implicates the microbicidal effector NOX2 as a global modulator of phagosomal physiologies, particularly of those pertinent to antigen processing.

Epidemiological studies have shown that arsenic exposure increases atherosclerosis, but the mechanisms underlying this relationship are unknown. Monocytes, macrophages and platelets play an important role in the initiation of atherosclerosis. Circulating monocytes and macrophages bind to the activated vascular endothelium and migrate into the sub-endothelium, where they become lipid-laden foam cells. This process can be facilitated by platelets, which favour monocyte recruitment to the lesion. Thus, we assessed the effects of low-to-moderate arsenic exposure on monocyte adhesion to endothelial cells, platelet activation and platelet-monocyte interactions. We observed that arsenic induces human monocyte adhesion to endothelial cells in vitro. These findings were confirmed ex vivo using a murine organ culture system at concentrations as low as 10 ppb. We found that both cell types need to be exposed to arsenic to maximize monocyte adhesion to the endothelium. This adhesion process is specific to monocyte/endothelium interactions. Hence, no effect of arsenic on platelet activation or platelet/leukocyte interaction was observed. We found that arsenic increases adhesion of mononuclear cells via increased CD29 binding to VCAM-1, an adhesion molecule found on activated endothelial cells. Similar results were observed in vivo, where arsenic-exposed mice exhibit increased VCAM-1 expression on endothelial cells and increased CD29 on circulating monocytes. Interestingly, expression of adhesion molecules and increased binding can be inhibited by antioxidants in vitro and in vivo. Together, these data suggest that arsenic might enhance atherosclerosis by increasing monocyte adhesion to endothelial cells, a process that is inhibited by antioxidants.

Chronic arsenic exposure is associated with a number of systemic diseases, including cardiovascular disease. Selenium has been shown to promote arsenic excretion from the body. We investigated if a high-selenium lentil diet has an effect on blood pressure and plasma lipid levels in an arsenic-exposed population by conducting a 6-month randomized controlled dietary intervention trial with 405 participants.

Introduction and hypothesis To compare depressive symptoms in women with and without prolapse and evaluate impact on quality of life. Methods This is a secondary analysis of a case–control study assessing the effect of prolapse on body image. Cases had prolapse and sought surgery (Pelvic Organ Prolapse Quantification stage ≥2). Controls had stage ≤1. Subjects completed the Pelvic Floor Impact Questionnaire (PFIQ), Pelvic Floor Distress Inventory, and the Patient Health Questionnaire-9 (PHQ-9) at baseline. Cases completed measures 6 months post-operatively. We report: (1) the comparison of cases and controls at baseline and (2) comparison of baseline and post-operative scores in cases. Results Baseline questionnaires were completed by 75 cases and 65 controls; 57 cases completed post-operative measures. Cases were 5-fold more likely than controls to have depressive symptoms. Cases with depressive symptoms had higher PFIQ scores than cases without symptoms. PHQ-9 scores improved post-operatively. Conclusions Depressive symptoms are common in women with prolapse and a decrease following surgical treatment.

A longitudinal cohort study of sexually active women 18–30 years of age was conducted to identify variables associated with the acquisition of herpes simplex virus type 2 (HSV-2) infections. Six hundred seventy HSV-2–seronegative women were followed up at 4-month intervals for 1 year; acquisition of HSV-2 antibodies was detected in 32 of these women. Black race, ⩽12 years of education, having a new sex partner, and bacterial vaginosis (BV) were associated with HSV-2 seroconversion on univariate analysis. Antecedent HSV-1 infection was not protective against HSV-2 acquisition. After controlling for other identified risk factors in multivariable models, the diagnosis of BV remained associated with an increased risk of acquiring HSV-2 infection (hazard ratio, 2.1; 95% confidence interval, 1.0–4.5; P = .05). In this study, the population attributable risk of BV for HSV-2 seroconversion was 21%. Additional studies are needed to determine whether screening and treatment of BV could reduce susceptibility to the acquisition of HSV-2 in women.

Background Millions of people worldwide are exposed to dangerous levels of arsenic (above the WHO water standard of 10 ppb) in drinking water and food. Lack of nutritious foods exacerbates the adverse health effects of arsenic poisoning. The micronutrient selenium is a known antagonist to arsenic, promoting the excretion of arsenic from the body. Studies are in progress examining the potential of using selenium supplement pills to counteract arsenic toxicity. We are planning a clinical trial to test whether high-selenium lentils, as a whole food solution, can improve the health of arsenic-exposed Bangladeshi villagers. Methods/design A total of 400 participants (about 80 families) will be divided into two groups via computer-generated block randomization. Eligibility criteria are age (≥14) years) and arsenic concentration in the household tube well (≥100 ppb). In this double-blind study, one group will eat high-selenium lentils grown in western Canada; the other will consume low-selenium lentils grown in Idaho, USA. Each participant will consume 65 g of lentils each day for 6 months. At the onset, midterm, and end of the trial, blood, urine and stool, plus hair (day 1 and at 6 months only) samples will be collected and a health examination conducted including assessment of acute lung inflammation, body mass and height, and blood pressure. The major outcome will be arsenic excretion in urine and feces, as well as arsenic deposition in hair and morbidity outcomes as assessed by a biweekly questionnaire. Secondary outcomes include antioxidant status, lipid profile, lung inflammation status, and blood pressure. Discussion Selenium pills as a treatment for arsenic exposure are costly and inconvenient, whereas a whole food approach to lower the toxic burden of arsenic may be a practical remedy for Bangladeshi people while efforts to provide safe drinking water are continuing. If high-selenium lentils prove to be effective in counteracting arsenic toxicity, agronomic partnerships between Canada and Bangladesh will work to improve the selenium content of the Bangladeshi-grown lentil crops. Results will be presented to the community to promote informed food choices, which may include increasing selenium in their diet. Trial registration ClinicalTrials.gov NCT02429921

Background The value of magnetic resonance imaging (MRI) in the detection of erosions on the sacroiliac joints (SI-joints) is controversial. Structural changes on the other hand are getting more and more into scientific focus. Objectives The aim of this study is a comparison between x-ray, low dose computed tomography (CT) and MRI. The presented data are preliminary results from the sacroiliac joint magnetic resonance imaging and computed tomography (SIMACT) study. Methods We investigated prospectively 30 patients with lower back pain and the suspicion of axSpA expressed by an experienced rheumatologist. All patients underwent a low dose CT (Somatom Definition Flash, Siemens, Germany) and an MRI (3.0T Magnetom Skyra, Siemens, Germany) of the SI-joints. Imaging data were compared with X-ray of the pelvis. The MRI protocol contained these sequences: T1-weighted spine echo (T1-SE), short tau inversion recovery (STIR), T1-weighted 3D volumetric interpolated breath hold examination (VIBE) high resolution sequence, all in paracoronal orientation. The grade of the disease was scored in X-ray according to the modified New York criteria and the erosions were counted by quadrant by a blinded reader. The final diagnosis made by the rheumatologist was also used for comparison. Results CT and T1-SE showed no significant differences in detecting erosions. 3D-VIBE found significantly more erosions in patients with axSpA compared to CT and T1-SE. (n=22; CT 178 erosions, T1 163, VIBE 421; average CT 5.9, T1 5.4, VIBE 14.0; p<0.001). In other diagnosis (osteoarthritis N=4, triangular hyperostosis N=3, others N=1) there were no significant differences among imaging modalities. The erosion count in 3D-VIBE correlated with the grade of sacroiliitis in X-ray (r=0.123, p=0.007). Conclusions High-resolution 3D MR sequences like 3D-VIBE are more suitable in detecting erosions on the SI-joints than conventional MRI (T1-SE) and even low dose CT. They are therefore a reasonable supplement to any MRI protocol and may improve the ability of MRI for diagnosis both in early and advanced SpA. Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.2145

This study focuses on the interrelationship between premature or precocious transitions to adult statuses and roles and the use of alcohol and drugs. Panel data from early adolescence to young adulthood for a sample of youth who were at high risk for serious delinquent behavior is used. The results indicate that use of alcohol and drugs in early adolescence increases the risk of dropping out of school, becoming pregnant or impregnanting someone, becoming a teenage parent, and living independently from parents or guardians prematurely. In turn, experiencing these precocious transitions increases the risk of the use of alcohol and drugs when respondents are young adults. The importance of these findings to the life course perspective generally and to interactional theory specifically are discussed.