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Frogs evolved terrestrial development multiple times, necessitating mechanisms to avoid ammonia toxicity at early stages. Urea synthesis from ammonia is a key adaptation that reduces water dependence after metamorphosis. We tested for early expression and plasticity of enzymatic mechanisms of ammonia detoxification in three terrestrial-breeding frogs: foam-nest-dwelling larvae of Leptodactylus fragilis (Lf) and arboreal embryos of Hyalinobatrachium fleischmanni (Hf) and Agalychnis callidryas (Ac). Activity of two ornithine-urea cycle (OUC) enzymes, arginase and CPSase, and levels of their products urea and CP in tissues were high in Lf regardless of nest hydration, but reduced in experimental low- vs. high-ammonia environments. High OUC activity in wet and dry nests, comparable to that under experimental high ammonia, suggests terrestrial Lf larvae maintain high capacity for urea excretion regardless of their immediate risk of ammonia toxicity. This may aid survival through unpredictably long waiting periods before rain enables their transition to water. Moderate levels of urea and CP were present in Hf and Ac tissues and enzymatic activities were lower than in Lf. In both species, embryos in drying clutches can hatch and enter the water early, behaviorally avoiding ammonia toxicity. Moreover, glutamine synthetase was active in early stages of all three species, condensing ammonia and glutamate to glutamine as another mechanism of detoxification. Enzyme activity appeared highest in Lf, although substrate and product levels were higher in Ac and Lf. Our results reveal that multiple biochemical mechanisms of ammonia detoxification occur in early life stages of anuran lineages that evolved terrestrial development. [ABSTRACT FROM AUTHOR]

Objective: Axial osteoarthritis (OA) is a common cause of back and neck pain, however, few studies have examined its prevalence. The aim was to estimate the prevalence and the characteristics of symptomatic axial OA in Spain. Methods: EPISER2016 is a cross-sectional multicenter population-based study of people aged 40 years or older. Subjects were randomly selected using multistage stratified cluster sampling. Participants were contacted by telephone to complete rheumatic disease screening questionnaires. Two phenotypes were analyzed, patients with Non-exclusive axial OA (NEA-OA) and Exclusive axial OA (EA-OA). To calculate the prevalence and its 95% confidence interval (CI), the sample design was considered and weighting was calculated according to age, sex and geographic origin. Results: Prevalence of NEA-OA by clinical or clinical-radiographic criteria was 19.17% (95% CI: 17.82–20.59). The frequency of NEA-OA increased with age (being 3.6 times more likely in patients aged 80 s or more than in those between 40 and 49 years) and body mass index. It was significantly more frequent in women, as well as in the center of Spain. It was less frequent in those with a higher level of education. Lumbar OA was more frequent than cervical OA. This difference grew with increasing age and was not associated with gender. It was also greater in overweight and obese subjects. Conclusions: This is the first study on the prevalence of axial OA phenotypes in Europe describing the associated socio-demographic, anthropometric, and lifestyle variables. [ABSTRACT FROM AUTHOR]

Cytokines signalling pathway genes are crucial factors of the genetic network underlying the pathogenesis of Immunoglobulin-A vasculitis (IgAV), an inflammatory vascular condition. An influence of the interleukin (IL)33- IL1 receptor like (IL1RL)1 signalling pathway on the increased risk of several immune-mediated diseases has been described. Accordingly, we assessed whether the IL33-IL1RL1 pathway represents a novel genetic risk factor for IgAV. Three tag polymorphisms within IL33 (rs3939286, rs7025417 and rs7044343) and three within IL1RL1 (rs2310173, rs13015714 and rs2058660), that also were previously associated with several inflammatory diseases, were genotyped in 380 Caucasian IgAV patients and 845 matched healthy controls. No genotypes or alleles differences were observed between IgAV patients and controls when IL33 and IL1RL1 variants were analysed independently. Likewise, no statistically significant differences were found in IL33 or IL1RL1 genotype and allele frequencies when IgAV patients were stratified according to the age at disease onset or to the presence/absence of gastrointestinal (GI) or renal manifestations. Similar results were disclosed when IL33 and IL1RL1 haplotypes were compared between IgAV patients and controls and between IgAV patients stratified according to the clinical characteristics mentioned above. Our results suggest that the IL33-IL1RL1 signalling pathway does not contribute to the genetic network underlying IgAV. [ABSTRACT FROM AUTHOR]

BAFF, APRIL and BAFF-R are key proteins involved in the development of B-lymphocytes and autoimmunity. Additionally, BAFF, APRIL and BAFFR polymorphisms were associated with immune-mediated conditions, being BAFF GCTGT>A a shared insertion-deletion genetic variant for several autoimmune diseases. Accordingly, we assessed whether BAFF, APRIL and BAFFR represent novel genetic risk factors for Immunoglobulin-A vasculitis (IgAV), a predominantly B-lymphocyte inflammatory condition. BAFF rs374039502, which colocalizes with BAFF GCTGT>A, and two tag variants within APRIL (rs11552708 and rs6608) and BAFFR (rs7290134 and rs77874543) were genotyped in 386 Caucasian IgAV patients and 806 matched healthy controls. No genotypes or alleles differences were observed between IgAV patients and controls when BAFF, APRIL and BAFFR variants were analysed independently. Likewise, no statistically significant differences were found in the genotype and allele frequencies of BAFF, APRIL or BAFFR when IgAV patients were stratified according to the age at disease onset or to the presence/absence of gastrointestinal (GI) or renal manifestations. Similar results were disclosed when APRIL and BAFFR haplotypes were compared between IgAV patients and controls and between IgAV patients stratified according to the clinical characteristics mentioned above. Our results suggest that BAFF, APRIL and BAFFR do not contribute to the genetic network underlying IgAV. [ABSTRACT FROM AUTHOR]

Rheumatoid arthritis (RA) is a systemic autoimmune disease whose main extra-articular organ affected is the lung, sometimes in the form of diffuse interstitial lung disease (ILD) and conditions the prognosis. A multicenter, observational, descriptive and cross-sectional study of consecutive patients diagnosed with RA-ILD. Demographic, analytical, respiratory functional and evolution characteristics were analyzed to evaluate the predictors of progression and mortality. 106 patients were included. The multivariate analysis showed that the diagnostic delay was an independent predictor of mortality (HR 1.11, CI 1.01–1.23, p = 0.035). Also, age (HR 1.33, 95% CI 1.09–1.62, p = 0.0045), DLCO (%) (HR 0.85, 95% CI 0.73–0.98, p = 0.0246), and final SatO2 (%) in the 6MWT (HR 0.62, 95% CI 0.39–0.99, p = 0.0465) were independent predictor variables of mortality, as well as GAP index (HR 4.65, 95% CI 1.59–13.54, p = 0.0051) and CPI index (HR 1.12, 95% CI 1.03–1.22, p = 0.0092). The withdrawal of MTX or LFN after ILD diagnosis was associated with disease progression in the COX analysis (HR 2.18, 95% CI 1.14–4.18, p = 0.019). This is the first study that highlights the diagnostic delay in RA-ILD is associated with an increased mortality just like happens in IPF. [ABSTRACT FROM AUTHOR]

To estimate the prevalence of Sjögren's syndrome (SS) in the adult Spanish population we performed a population-based multicenter cross-sectional study. Cases were defined by the American-European Consensus Group criteria proposed in 2002. A total of 4,916 subjects aged 20 years or over were included. The estimated prevalence of SS (including primary and secondary forms) in the adult population in Spain was 0.33% (95% CI 0.21–0.53). Extrapolating to the total population of the country aged ≥ 20 years (around 37.7 million persons), there would be around 125,000 cases of SS in Spain. Considering only primary SS, the estimated prevalence was 0.25% (95% CI 0.15–0.43) or 1 person in 400. The prevalence of primary SS in Spain is comparable to that reported in other European studies with a similar design and diagnostic criteria. Based on these results, primary SS could not be considered a rare (orphan) disease. Only 50% of cases had already been diagnosed with SS prior EPISER 2016 study, confirming the existence of a non-negligible proportion of undiagnosed cases in the general population. [ABSTRACT FROM AUTHOR]

Progressive connective tissue disease (CTD)-related lung disease is a challenging condition that requires lung transplantation in some patients. Treatment with rituximab may improve lung function. To evaluate the effect of rituximab in patients with progressive CTD-related lung disease who met criteria for inclusion in waiting list for a lung transplant. Retrospective study of patients with progressive CTD-related lung disease with criteria for lung transplant (FVC < 60% and/or DLCO < 40%) that started treatment with rituximab because of disease progression. Clinical variables, pulmonary function tests and chest computed tomography were used to monitor the effect of rituximab. The cohort included 18 patients; systemic sclerosis (7), rheumatoid arthritis (5), systemic lupus erythematosus (4), Sjögren syndrome (1) and antisynthetase syndrome (1). The radiologic patterns observed were: usual interstitial pneumonia (1), non-specific interstitial pneumonia (9), lymphoid interstitial pneumonia (1), emphysema-usual interstitial pneumonia (1), shrinking lung syndrome (3) and undetermined pattern (3). Over the previous year to rituximab initiation a decline in FVC (− 3.8%, p = 0.095) and DLCO (− 8.4%, p = 0.004) was observed. After 2 years of treatment, DLCO significantly improved (+ 12.4%, p < 0.001 at 1 year and + 15.3%, p = 0.001 at 2 years). Six patients (33.3%) presented adverse events related to rituximab. No patient required lung transplant or died during the study period. Rituximab is an effective treatment for patients with severe and progressive CTD-related lung disease, which allows to delay lung transplantation in some cases. [ABSTRACT FROM AUTHOR]

With the aim to develop and validate a clinical + ultrasound (US) inflammation score in rheumatoid arthritis (RA) for use in clinical practice, a mixed-method study was conducted. The theoretical development of the index was achieved with qualitative methodology (discussion group and Delphi survey). Subsequently, a cross-sectional study was carried out to analyse issues related to scoring and validation of the new index. RA patients underwent clinical [28 swollen and tender joints count, patient and physician global assessment (PhGA), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP)], and US assessments [synovitis or tenosynovitis by grey-scale (GS) and power Doppler (PD) of 42 structures]. An index was created based on statistical models and expert interaction. Construct validity was tested by correlation with DAS28, SDAI, CDAI, and PhGA. Reliability was evaluated in a subgroup of patients with the intraclass correlation coefficient (ICC). US assessment, CRP, and swollen joints were the items that passed the prioritization phase (Delphi study). For the cross-sectional study, 281 patients were randomly divided into design (n = 141) and validation samples (n = 140). The combination of US sites chosen (7 bilaterally) detected the maximum proportion of synovitis and PD present. Three scoring methods were tested: semiquantitative (0–3 GS + 0–3 PD), dichotomous (0/1 GS + 0/1 PD), and qualitative (0/1 based on algorithm). All showed strong correlation with activity measures (ρ ≥ 0.60), and reliability (ICC 0.89–0.93). The index with best parameters of validity, feasibility, and reliability was the qualitative. The final index chosen was the sum of swollen joint count, US qualitative score, and CRP. The UltraSound Activity score is a valid and reliable measure of inflammation in RA equal to the sum of 28 SJC, a simplified (0/1) US assessment of 11 structures and CRP. It is necessary further investigation to demonstrate additional value over existing indices. [ABSTRACT FROM AUTHOR]

The aim of the study is to benchmark the use and attributed importance of well-established prognostic factors in rheumatoid arthritis (RA) in daily clinical practice, and to contrast the use of factors with their ability to predict outcome. Medline was searched (inception-Sep. 2016) for systematic reviews on factors predicting death, disability, structural damage or remission in RA. All factors identified were compiled in a matrix of factors × outcomes, and scoping reviews for each cell were then performed. A survey to 42 rheumatologists randomly selected explored the use of the list of prognostic factors and inquired about the perceived strength of association with poor prognosis. In a second round, participants were exposed to evidence from the matrix and to responses from other participants. Change on perceived strength of association was evaluated. Rheumatologists report using prognostic factors in clinical practice on a daily basis. Very young onset, joint counts at diagnosis, rheumatoid factor, ACPA, and radiographic erosions are used frequently and correctly recognized as strong predictors. Comorbidities and other associated problems, such as obesity, low bone mineral density, cardiovascular disease, or extra-articular manifestations, are perceived as moderately associated to prognosis but, nevertheless, rheumatologists also use them profusely. Genetic and other biomarkers and osteitis by magnetic resonance are less accessible in daily practice and they obtained better results on second round (probably after knowing the strength of association with prognosis). Rheumatologists use widely most prognostic factors with a strong predictive value. However, factors with low evidence of prognostic value are also used and some factors are not used despite good evidence. [ABSTRACT FROM AUTHOR]

Although MR imaging has been increasingly recognized as a useful tool in the diagnosis of early rheumatoid arthritis (RA) and in the assessment of disease activity, these applications have not yet been usually included in the routine management of this condition. Our goal is to review the current role of MRI in the everyday clinical management of patients with RA. The usefulness of MRI in the evaluation of articular and para-articular changes in specific locations, mainly the craniocervical region and the temporomandibular joint, are reviewed. Clinical problems derived from local extra-articular involvement, such as tenosynovitis, "rice-bodies" bursitis, and Baker's cyst rupture, are also described. Finally, we also review the value of MRI in evaluation of some complications of RA such as tendinous rupture, osteonecrosis, stress fracture, and septic arthritis/osteomyelitis. [ABSTRACT FROM AUTHOR]

To assess the impact of the application of the European League against Rheumatism (EULAR) task force recommendations in the cardiovascular (CV) risk of a series of Spanish patients diagnosed with rheumatoid arthritis (RA) . Two hundred consecutive RA patients seen at the rheumatology outpatient clinics of Bellvitge Hospital, Barcelona, were studied. Information on clinical features of the disease, classic CV risk factors, and history of CV events was assessed. Both the systematic coronary risk evaluation (SCORE) CV risk index and the modified SCORE (mSCORE) according to the last EULAR recommendations were calculated. Based on the classic CV risk factors, the mean ± standard deviation SCORE was 2.1 ± 2.3% (median, 2; interquartile range [IQR], 1-3). Twenty-three (11%) patients were above the threshold of high CV risk for the Spanish population (≥5%). Following the EULAR recommendations, a change in the score was required in 119 (59%) patients. Therefore, the mean mSCORE was 2.7 ± 2.9% (median, 2; IQR, 1-3) and, due to this, 28 (14%) patients were above the threshold of high CV risk. Nine (5%) had at least one ischemic CV event. Patients with CV events were older and had more CV risk factors and higher SCORE and mSCORE than those without CV events. Although a large proportion of patients from this series fulfilled the criteria for the application of the EULAR recommendations, the final impact on the calculated CV risk was low and clinically significant in only a few patients. However, an association between the mSCORE and the presence of ischemic CV events was observed. [ABSTRACT FROM AUTHOR]

Objectives: This study explores several factors potentially associated with reduced fecundability among women working in cut flowers production. Methods: A cross-sectional study of first pregnancies was undertaken in 47 Colombian floriculture companies. Two thousand and eighty-five women were interviewed regarding potential reproductive, lifestyle and work history predictors of time-to-pregnancy (TTP), measured in months. Fecundability odds ratios (fOR) were estimated using a discrete time analogue of Cox’s proportional hazard model. Results: Associated with longer TTP were: irregular relationships with her partner (fOR 0.82, 95% CI 0.73–0.91), illness in the year prior to pregnancy (fOR 0.78, 95% CI 0.62–0.98), smoking tobacco (fOR 0.71, 95% CI 0.59–0.85), and work in flower production, less than 24 months (fOR 0.86 95% CI 0.75–0.98) or 2 years or more (fOR 0.73, 95% CI 0.63–0.84). Conclusions: Work in flower production, irregular relationship, illness and tobacco exposure would be associated with impaired fecundability. [ABSTRACT FROM AUTHOR]

The clinical diagnosis of synovial tumors and tumorlike lesions is difficult, and radiographic findings may establish a confident diagnosis only in some cases. MR imaging has become the modality of choice in evaluating these lesions, because with it a presumptive diagnosis can be made in most cases. Our goal is to review the MR features of pigmented villonodular synovitis, giant-cell tumor of the tendon sheath, synovial chondromatosis, synovial hemangioma, lipoma arborescens, synovial cysts and synovial sarcoma, emphasizing those findings that suggest a specific diagnosis. [ABSTRACT FROM AUTHOR]

We report a case of MFH of the mandible in a 16-year-old girl. The mandible is a rare location of MFH of bone, with only 21 cases described in the literature. Clinical, pathologic, and radiologic features are discussed, with special emphasis on the unusual pathologic and radiographic features. [ABSTRACT FROM AUTHOR]