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Objectives RA and primary SS carry increased atherosclerotic risk, while B-cell activating factor holds a vital role in disease pathogenesis and atherosclerosis. We aimed to compare subclinical atherosclerosis profiles between the two clinical entities and define whether BAFF genetic variants alter atherosclerotic risk. Methods DNA from 166 RA, 148 primary SS patients and 200 healthy controls of similar age and sex distribution was subjected to PCR-based assay for the detection of five single nucleotide polymorphisms of the BAFF gene (rs1224141, rs12583006, rs9514828, rs1041569 and rs9514827). Genotype and haplotype frequencies were determined by SNPStats software and statistical analysis was performed by SPSS and Graphpad Software. Subclinical atherosclerosis was defined by the presence of carotid/femoral plaque formation and arterial wall thickening. Results Atherosclerotic plaque formation was more frequently detected in the RA vs primary SS group (80.7% vs 62.2%, P-value Conclusions Increased inflammatory burden, higher steroid doses and distinct BAFF gene variations imply chronic inflammation and B-cell hyperactivity as key contributors for the augmented atherosclerotic risk among autoimmune patients.

Background Gastropod snails remain strongly understudied, despite their important role in transmitting parasitic diseases. Knowledge of their distribution and population dynamics increases our understanding of the processes driving disease transmission. We report the first study to use high-throughput sequencing (HTS) to elucidate the population genetic structure of the hermaphroditic snail Bulinus truncatus (Gastropoda, Heterobranchia) on a regional (17–150 km) and inter-regional (1000–5400 km) scale. This snail species acts as an intermediate host of Schistosoma haematobium and Schistosoma bovis, which cause human and animal schistosomiasis respectively. Methods Bulinus truncatus snails were collected in Senegal, Cameroon, Egypt and France and identified through DNA barcoding. A single-end genotyping-by-sequencing (GBS) library, comprising 87 snail specimens from the respective countries, was built and sequenced on an Illumina HiSeq 2000 platform. Reads were mapped against S. bovis and S. haematobium reference genomes to identify schistosome infections, and single nucleotide polymorphisms (SNPs) were scored using the Stacks pipeline. These SNPs were used to estimate genetic diversity, assess population structure and construct phylogenetic trees of B. truncatus. Results A total of 10,750 SNPs were scored and used in downstream analyses. The phylogenetic analysis identified five clades, each consisting of snails from a single country but with two distinct clades within Senegal. Genetic diversity was low in all populations, reflecting high selfing rates, but varied between locations due to habitat variability. Significant genetic differentiation and isolation by distance patterns were observed at both spatial scales, indicating that gene flow is not strong enough to counteract the effects of population bottlenecks, high selfing rates and genetic drift. Remarkably, the population genetic differentiation on a regional scale (i.e. within Senegal) was as large as that between populations on an inter-regional scale. The blind GBS technique was able to pick up parasite DNA in snail tissue, demonstrating the potential of HTS techniques to further elucidate the role of snail species in parasite transmission. Conclusions HTS techniques offer a valuable toolbox to further investigate the population genetic patterns of intermediate schistosome host snails and the role of snail species in parasite transmission. Graphical Abstract

Objective: To explore whether the osteoprotegerin (OPG) rs2073618 gene variant and the methylenetetrahydrofolate reductase (MTHFR) rs1801131 and rs1801133 polymorphisms contribute to rheumatoid arthritis (RA) susceptibility and RA related subclinical atherosclerosis.Methods: 283 RA patients and 595 healthy controls (HC) were genotyped for OPG and MTHFR gene variants using PCR based assays. Clinical, laboratory parameters and markers of subclinical atherosclerosis (Carotid/Femoral intima media thickness/plaque formation) along with traditional risk factors for atherosclerosis were assessed in RA patients and 280HC.Results: Increased prevalence of the rs2073618CC genotype was detected in RA patients vs HC (p=0.04), especially in RA patients with high serum titers of rheumatoid factor (RF) or anti-cyclic citrullinated peptide (anti-CCP) antibodies compared to HC (p-values:0.0029 and 0.0077, respectively). This genotype was also associated with higher carotid-IMT scores (p=0.01) and marginally with higher rates of carotid plaque formation (p=0.06). MTHFR 1298CC genotype was more prevalent in the anti-CCP positive group compared to HC, with no associations detected with markers of subclinical atherosclerosis. Reduced rates of carotid/femoral plaque formation were detected among RA patients harboring the MTHFR 677TT genotype (p=0.009).Conclusion: OPG and MTHFR gene variations seem to increase susceptibility for seropositive RA and potentially contribute to subclinical atherosclerosis linked to RA.

Case report - Introduction Rheumatoid arthritis is a chronic inflammatory autoimmune systemic disorder of unknown aetiology that predominantly affects the joints. Moreover, it is a systemic illness associated with a variety of extraarticular manifestations, including haematological complications such as lymphoma. We are presenting a case highlighting the importance of surveillance in these patients, particularly elderly patients with longstanding disease. Case report - Case description A 72-year-old female patient of African-Caribbean origin was referred to the rheumatology department from the community clinic for RA deterioration. She was diagnosed with RA RF anti-CCP positive in 2007 and was treated with sc MTX 25 mg weekly, HQ 200 mg bd, pred 5 mg and naproxen 250 mg. Her past medical history included HTN, OA, R TKR and degenerative lower back pain. Patient reported: ‘Doctor, I ‘ve had RA for many years, but never before I had such a pain’. She was complaining of multiple joint pains, morning stiffness of up to 2hrs, widespread pain and fatigue. She reported weight loss of 5 pounds in the last 2 months. For the last 2 weeks, she was suffering from lower back pain, L leg sciatica, with pins and needles, L leg weakness and incontinence. She was otherwise well. On examination she had 8 mildly swollen, 0 tender joints, VAS score was 90/100. DAS-28 was 4.92. Blood tests showed normocytic anaemia Hb 107, raised ESR 58 and CRP 124, previously 22 and 5.8. Anaemia screening, immunoglobulins and free light chains were normal. Biologic screening was normal. Repeating the blood tests following IM steroid injection, ESR was 81 and CRP 187. Alternative diagnosis such as infection and malignancy were suspected. A plan was made to review in the clinic and arrange further investigations with a CT scan. MRI spine was arranged which identified multiple osseous deposits L3-L5, T8-T12, T1, C2, retroperitoneal psoas mass, paravertebral mass and multiple retroperitoneal lymph nodes. CT revealed lung nodules and splenic lesions possible metastatic and right ileac destructive lesion. PET CT showed multiple active uptake in lymph nodes above and below diaphragm, the spleen and lung nodules, axial and appendicular skeleton. Patient had a bone marrow biopsy which revealed diffuse large B-cell lymphoma. Case report - Discussion This is a case of a patient with a 13-year history of rheumatoid arthritis, who was stable until last year and presented with worsening joint pain. Joint examination did not correlate with the severity of her pain. However. fluctuations in disease activity and variation throughout the day are common in rheumatoid arthritis and patient reported morning stiffness. Differential diagnosis initially included RA flare up with the possibility that osteoarthritis, fibromyalgia and degenerative spinal disease could also exacerbate her pain. However, ESR and CRP were significantly raised disproportionally for the joint count. Moreover, she had systemic symptoms with weight loss and fatigue raising the question of an alternative diagnosis such as malignancy or infection. Patient did not have obvious symptoms or signs of infection, and baseline investigations, such as CXR and urine dipstick were normal and TB spot was negative. However, there was concern for an occult infection. Malignancy could be a potential diagnosis as the risk increases with age, and haematological malignancies, particularly lymphoma, have been associated with RA. Myeloma could be an alternative diagnosis, based on anaemia and back pain; however, myeloma screening came back normal. Patient was diagnosed with stage IVB diffuse large B-cell lymphoma with metastatic bone disease, paravertebral mass, retroperitoneal lymph nodes, psoas mass, pulmonary nodules, and splenic lesions. Her joint and back pain were related to metastatic bone disease. She was treated with 2 cycles R-CHOP, 4 cycles R mini-CHOP. She repeated the PET CT which showed improvement. CRP dropped to 1.3. Case report - Key learning points Rheumatoid arthritis is a systemic disease and the raised inflammatory markers do not necessarily indicate RA flare. We should consider other causes in our differential diagnosis, such as infection and malignancy. Studies have shown 2-fold increased risk for lymphoma in RA patients, HL, NHL and particularly the diffuse large B-cell Lymphoma. The risk of having lymphoma correlates with disease activity. DMARD treatment including anti-TNF does not seem to increase the risk which is probably driven by the systemic inflammation causing persistent immunologic stimulation, B cell clonal expansion and transformation along with decreased T suppressor cells and NK activity. Therefore, EULAR recommends systemic screening for infections and malignancy, along with other co-morbidities as part of the routine care in patients with rheumatoid arthritis. At the end, we should always listen to the patient’s story.

The use of perennial metal hyperaccumulators in phytoextraction provides an excellent gateway toward the removal of heavy metals from polluted sites, and the opportunity for the phytomining of valuable metals. In order to further advance our understanding of the effect of cropping systems on metal phytoextraction, it is important to investigate the effect of harvesting time. This study focuses on the variation in biomass production, Ni concentration and Ni mass across the different phenological stages, populations and organs of Alyssum lesbiacum, in order to evaluate when Ni phytoextraction is at a maximum. We sampled 60 single-phenological stage plots in three A. lesbiacum populations and we determined biomass production and Ni concentration at the plant organ level. Based on spontaneous A. lesbiacum vegetation, we were able to record remarkably high values of Ni phytoextraction. Biomass production and Ni concentration were found to be maximal on the third and fourth year of the A. lesbiacum life cycle respectively, while maximum phytoextraction capacity was reached in the third year. Our results: (1) demonstrate the significant variation in Ni phytoextraction across different phenological stages, populations and organs of A. lesbiacum, (2) imply that its phytoextraction potential is mostly influenced by biomass production and (3) suggest that perennial harvests could be an interesting alternative to consider in the future.

Purpose Support service provisions for domestic abuse victims have typically focussed on the immediate risk and etiological factors associated with abuse. Consequently, there is limited research exploring more persistent and pervasive factors involved in this cycle of abuse, such as subjective experiences and beliefs held by victims of domestic abuse. The purpose of this paper is to preliminary explore individual experience of domestic abuse including the belief systems of participants. Increasing our understanding of key factors and beliefs in the experience of domestic abuse could enable support services to create more long-term sustainable support for victims. Design/methodology/approach In total, 12 women with a history of domestic abuse participated in an exploratory interview about their general beliefs and thoughts surrounding their domestic abuse experience. Interviews were analysed using thematic analysis. Findings The thematic analysis identified four belief themes: personal responsibility, antisocial attitudes, environmental factors and negative attitudes towards police. Practical implications The paper highlights the value of understanding subjective, personalized experiences and beliefs of domestic abuse victims; identifies the importance of belief systems as potential treatment targets for domestic abuse victims; and acknowledges an avenue for more effective support provision for victims of domestic abuse. Originality/value This preliminary study offers new insights into the role of belief systems amongst a sample of domestically abused women. Understanding the significance of personalized, subjective experiences of domestic abuse victims is a step towards designing and implementing effective interventions. The findings further emphasize the need for more empirical research and theory development within the area of beliefs and domestic abuse victims.

Purpose – While there is a large body of research exploring the various avenues of support for domestic abuse victims and the risk factors which put women at risk of victimization, there is little research exploring the perceptions of these women. The purpose of this paper is therefore to explore the personal views of victimized women; in particular, the risk factors that they believe put them at risk for abuse and what they feel support services should offer. Design/methodology/approach – In total, 12 women were interviewed about their experiences of domestic violence. Interviews were analyzed using thematic analysis which resulted in three themes: first intimate relationship; quality of life; and supporting services. Findings – The results from the analysis highlighted some prominent risk factors and, most importantly, emphasized the need for alternative forms of support. Overall, the findings provide an innovative way of viewing domestic violence by understanding it through victim ' s narratives, which can further aid to inform current support services within the UK and elsewhere. Research limitations/implications – The quality of life around the time of abuse is a factor that should be explored further in relation to the victimization of women. Practical implications – Ambivalent first sexual encounters may be an important risk factor for future relationship violence. Social implications – Support services for domestically abused women need to offer more internal support for vocational and educational services. Originality/value – There is little research exploring the personal views and perceptions of victimized women, in particular, the risk factors that they believe put them at risk for domestic abuse and what they feel support services should offer. The value of this research is therefore founded in the exploring this gap in literature and provide victims with a voice to aid researchers in understanding domestic abuse from another perspective. Investigating a victim ' s personal account is one pathway into beginning to understand the underlying thought processes and beliefs they attach to an event. If themes within a personal narrative account could be identified within victims of domestic abuse, it may allow a new aetiological perspective to develop in regard to the understanding and needs of abused women.

Introduction To determine the prevalence and clinical/laboratory associations of subclinical atherosclerosis and impaired bone health in primary Sjogren’s syndrome (SS). Methods 64 consecutive patients with primary SS, 77 with rheumatoid arthritis (RA) and 60 healthy controls (HC) οf similar age and sex distribution were enrolled. Demographics, clinical/laboratory features, classical risk factors for atherosclerosis and osteoporosis (OP) were recorded. Intima-medial thickness scores (IMT) and carotid/femoral (C/F) plaque formation, as well as bone mineral density (BMD) and fractures were evaluated. Determinants of IMT/BMD levels and the presence of plaque were assessed by univariate and multivariate models. Serum levels of the Wnt signaling mediators Dickkopf-related protein 1(DKK1) and sclerostin were determined in primary SS patients and HC. Results Increased arterial wall thickening (IMT > 0.90 mm) and impaired bone health (defined as OP or osteopenia), were detected in approximately two-thirds of primary SS and RA patients, with a mean IMT value being significantly increased compared to HC. The presence of primary SS emerged as an independent risk factor for arterial wall thickening when traditional risk factors for cardiovascular disease (CVD) including age, sex, hypertension, smoking (pack/years), LDL and HDL levels were taken into account in a multivariate model [adjusted OR 95% (CI): 2.8 (1.04-7.54)]. In primary SS, age was revealed as independent predictor of increased IMT scores; age and lymphopenia as well as increased urine pH as independent determinants of C/F plaque formation and OP/osteopenia, respectively. An independent association of OP/osteopenia with plaque formation was observed when independent predictors for both variables were considered, with low DKK1 levels being associated with both plaque formation and lower BMD levels. Conclusions Comorbidities such as subclinical atherosclerosis and impaired bone health occur frequently in primary SS, in association with disease related features and traditional risk factors. Wnt signaling mediators are potentially involved in the pathogenesis of both entities. Electronic supplementary material The online version of this article (doi:10.1186/s13075-015-0613-6) contains supplementary material, which is available to authorized users.

We present the synthesis and characterization of a novel metal-organic molecular solid using the ligand 4,8-disulfonaphthalene-2,6-dicarboxylic acid. The solid features a sulfonated, isolated supertetrahedra, [Fe(16)Omicron(4)(SO(4))(12)(L2)(6)], built from mixed-valence [Fe(3)(3+)Fe(2+)(mu(3)-Omicron)(mu(3)-SO(4))(3)(-CO(2))(3)] clusters.

Beta-catenin has a crucial role in cell-cell adhesion as well as a signaling role as a member of the Wnt pathway. The aim of this study was to examine the clinicopathological and prognostic value of phosphorylated beta-catenin, as well as its relation to the tumors' phenotype, in breast cancer. Immunohistochemistry was applied on 141 paraffin-embedded breast tissue specimens for the detection of phospho-beta-catenin, ER, PR, c-erbB-2, p53, Ki-67, bcl-2, uPAR and TIMP-1. For each case, a phospho-beta-catenin index was determined by image analysis. Phospho-beta-catenin staining was detected in the cytoplasm and the nucleus of the malignant cells. Cytoplasmic phospho-beta-catenin was statistically higher in carcinomas of smaller tumor size (P = 0.030), lower stage (P = 0.026), decreased Ki-67 and high c-erbB-2 immunoreactivity (P = 0.052 and P = 0.037, respectively). Nuclear phospho-beta-catenin showed a parallel correlation with ER and ERbeta (P = 0.022 and P = 0.043, respectively), bcl-2 (P = 0.042), uPAR in cancer cells (P = 0.041) and TIMP-1, although the correlation was borderline (P = 0.066). Cytoplasmic phospho-beta-catenin was found to be independently correlated with prolonged disease-free and overall survival (P = 0.046 and P = 0.002, respectively), whereas nuclear localization was correlated with a shortened overall survival (P = 0.046). In conclusion, phospho-beta-catenin may have a different involvement in invasive breast carcinomas, according to its subcellular distribution. Nuclear localization seems to be related to an aggressive tumor phenotype, negatively affecting patients' overall survival, whereas cytoplasmic localization is associated with a favorable tumor phenotype and a longer disease-free and overall survival.