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IgG4-related disease (IgG4-RD) can cause fibroinflammatory lesions in nearly any organ. Correlation among clinical, serological, radiological and pathological data is required for diagnosis. This work was undertaken to develop and validate an international set of classification criteria for IgG4-RD. An international multispecialty group of 86 physicians was assembled by the American College of Rheumatology (ACR) and the European League Against Rheumatism (EULAR). Investigators used consensus exercises; existing literature; derivation and validation cohorts of 1879 subjects (1086 cases, 793 mimickers); and multicriterion decision analysis to identify, weight and test potential classification criteria. Two independent validation cohorts were included. A three-step classification process was developed. First, it must be demonstrated that a potential IgG4-RD case has involvement of at least one of 11 possible organs in a manner consistent with IgG4-RD. Second, exclusion criteria consisting of a total of 32 clinical, serological, radiological and pathological items must be applied; the presence of any of these criteria eliminates the patient from IgG4-RD classification. Third, eight weighted inclusion criteria domains, addressing clinical findings, serological results, radiological assessments and pathological interpretations, are applied. In the first validation cohort, a threshold of 20 points had a specificity of 99.2% (95% CI 97.2% to 99.8%) and a sensitivity of 85.5% (95% CI 81.9% to 88.5%). In the second, the specificity was 97.8% (95% CI 93.7% to 99.2%) and the sensitivity was 82.0% (95% CI 77.0% to 86.1%). The criteria were shown to have robust test characteristics over a wide range of thresholds. ACR/EULAR classification criteria for IgG4-RD have been developed and validated in a large cohort of patients. These criteria demonstrate excellent test performance and should contribute substantially to future clinical, epidemiological and basic science investigations.

Objective: Antibodies to citrullinated and homocitrullinated (also known as carbamylated) proteins, specific for rheumatoid arthritis (RA), are associated with cardiovascular disease (CVD). Immune complexes containing these proteins have been identified in the atherosclerotic plaque of CVD patients. In mice, homocitrullinated low-density lipoprotein (HomoCitLDL) promotes foam cell formation, which is critical in the pathogenesis of atherosclerosis. We aimed to investigate the atherogenic potential of HomoCitLDL and citrullinated low-density lipoprotein (CitLDL) in RA. Method: Human LDL was homocitrullinated in potassium cyanate and citrullinated by rabbit skeletal muscle peptidyl arginine deiminase-2. The modifications were confirmed by mass spectrometry. Primary human monoctyes from healthy subjects (N = 8) were differentiated to macrophages using macrophage colony-stimulating factor and incubated with modified LDL. Foam cells were visualized using Oil Red O staining. Serum from RA patients (N = 101) and controls (N = 32) was tested for immunoglobulin G antibodies to modified LDL using enzyme-linked immunosorbent assay. Results: HomoCitLDL and CitLDL strongly induced foam cell production (> 90%) versus unmodified LDL (11%) (p Conclusions: HomoCitLDL and CitLDL have atherogenic properties in vitro. Antibody responses to HomoCitLDL, but not CitLDL, were detected in RA patients.

Objective IgG4-related disease (IgG4-RD) can cause fibroinflammatory lesions in nearly any organ. Correlation among clinical, serologic, radiologic, and pathologic data is required for diagnosis. This work was undertaken to develop and validate an international set of classification criteria for IgG4-RD. Methods An international multispecialty group of 86 physicians was assembled by the American College of Rheumatology (ACR) and the European League Against Rheumatism (EULAR). Investigators used consensus exercises, existing literature, derivation and validation cohorts of 1,879 subjects (1,086 cases, 793 mimickers), and multicriterion decision analysis to identify, weight, and test potential classification criteria. Two independent validation cohorts were included. Results A 3-step classification process was developed. First, it must be demonstrated that a potential IgG4-RD case has involvement of at least 1 of 11 possible organs in a manner consistent with IgG4-RD. Second, exclusion criteria consisting of a total of 32 clinical, serologic, radiologic, and pathologic items must be applied; the presence of any of these criteria eliminates the patient from IgG4-RD classification. Third, 8 weighted inclusion criteria domains, addressing clinical findings, serologic results, radiology assessments, and pathology interpretations, are applied. In the first validation cohort, a threshold of 20 points had a specificity of 99.2% (95% confidence interval [95% CI] 97.2-99.8%) and a sensitivity of 85.5% (95% CI 81.9-88.5%). In the second, the specificity was 97.8% (95% CI 93.7-99.2%) and the sensitivity was 82.0% (95% CI 77.0-86.1%). The criteria were shown to have robust test characteristics over a wide range of thresholds. Conclusion ACR/EULAR classification criteria for IgG4-RD have been developed and validated in a large cohort of patients. These criteria demonstrate excellent test performance and should contribute substantially to future clinical, epidemiologic, and basic science investigations.

© The Author 2017. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. Objective. RA is associated with an increased risk of cardiovascular events (CVEs). The objective was to estimate independent effects of RA autoantibodies on the incident CVEs in patients with early RA. Methods. Patients were enrolled in the Canadian Early Inflammatory Arthritis Cohort, a prospective multicentre inception cohort. Incident CVEs, including acute coronary syndromes and cerebrovascular events, were self-reported by the patient and partially validated by medical chart review. Seropositive status was defined as either RF or ACPA positive. Multivariable Cox proportional hazards survival analysis was used to estimate the effects of seropositive status on incident CVEs, controlling for RA clinical variables and traditional cardiovascular risk factors. Results. A total of 2626 patients were included: the mean symptom duration at diagnosis was 6.3 months (S.D. 4.6), the mean age was 53 years (S.D. 15), 72% were female and 86% met classification criteria for RA. Forty-six incident CVEs occurred over 6483 person-years [incidence rate 7.1/1000 person-years (95% confidence interval 5.3, 9.4)]. The CVE rate did not differ in seropositive vs seronegative subjects and seropositivity was not associated with incident CVEs in multivariable Cox regression models. Baseline covariates independently associated with incident CVEs were older age, a history of hypertension and a longer duration of RA symptoms prior to diagnosis. Conclusion. The rate of CVEs early in the course of inflammatory arthritis was low; however, delays in the diagnosis of arthritis increased the rate of CVEs. Hypertension was the strongest independent risk factor for CVEs. Results support early aggressive management of RA disease activity and co-morbidities to prevent severe complications.

Aim: Laparoscopic surgery has become recognized as an established technique for colon diseases and many different surgical techniques have been described. The aim of our study is to show the results of a single institution where a standardized operative and perioperative procedure for laparoscopic left hemicolectomy (LLH) has been used. Methods: Between January 2005 and April 2011, 484 patients underwent LLH for colon diseases. Data collected included age, indication for surgery, ASA class, body mass index, operating time, intra and post-operative complications, conversion rate, length of hospital stay, tumor stage, number of lymph nodes harvested, mortality, and a 30-day readmission rate. Results: We found 299 cancer, 29 large dysplastic polyps and 156 complicated diverticular diseases. Average operation time was 120 minutes. The average hospital stay was 5.7 days. In the cancer group, the average number of lymph nodes harvested was 12.7. The intraoperative and early postoperative complications were 3.3% and 10.7 % respectively. The conversion rate was 3.7%. The 30-day readmission rate was 3%. The 30-day mortality rate was 0.4%. Conclusion: The standardization of the LLH technique might reduce the technical difficulties and complications. Its potential benefits include the standardization of surgical instrument sets, the definition of benchmarks for conversion before making any inappropriate investment in time and equipment, low rates of complications and readmission rate.

There are different surgical possibilities for the treatment of oesophageal achalasia ranging from a short extramucosal oesophagomyotomy to an extended esophago-gastric myotomy combined with a partial fundoplication to restore the main antireflux barrier. A total 360 degrees fundoplication is generally regarded as an obstacle to oesophageal emptying. The aim of this study was to evaluate the role and efficacy of total 360 degrees laparoscopic Nissen-Rossetti fundoplication after oesophago gastric myotomy in the treatment of oesophageal achalasia. From 1992 to January 2008, a total of 245 patients (112 males, 133 females), mean age 45.1 years (range: 12-79), were submitted to laparoscopic Nissen-Rossetti fundoplication after a Heller myotomy with endoscopic and manometric intraoperative monitoring. In 3 patients (1.2%), conversion to laparotomy was necessary. Mean operative time was 60 +/- 15 minutes. No mortality was observed. The overall morbidity rate was 1.6%. The mean postoperative hospital stay was 3.5 +/- 1.0 days (range: 1-12 days). A mean clinical follow-up of 100.2 +/- 7 months (range: 3-177) was possible for 228 patients (93.1%), and an excellent or good outcome was observed in 209 patients (91.7%) (DeMeester dysphagia score 0-1). No improvement in dysphagia was observed in 5 (2.2%) patients. Pathological gastro-oesophageal reflux was absent in all patients. Laparoscopic Nissen-Rossetti fundoplication after a Heller myotomy is a safe, effective treatment for oesophageal achalasia with excellent results in terms of dysphagia resolution, affording total protection from the onset of gastrooesophageal reflux.

Imbalance in the network of soluble mediators may play a pivotal role in the pathogenesis of Kaposi's sarcoma (KS). In this study, we demonstrated that KS cells grown in vitro produced and in part released platelet activating factor (PAF), a powerful lipid mediator of inflammation and cell-to-cell communication. IL-1, TNF, and thrombin enhanced the synthesis of PAF. PAF receptor mRNA and specific, high affinity binding site for PAF were present in KS cells. Nanomolar concentration of PAF stimulated the chemotaxis and chemokinesis of KS cells, endothelial cells, and vascular smooth muscle cells. The migration response to PAF was inhibited by WEB 2170, a hetrazepinoic PAF receptor antagonist. Because neoangiogenesis is essential for the growth and progression of KS and since PAF can activate vascular endothelial cells, we examined the potential role of PAF as an instrumental mediator of angiogenesis associated with KS. Conditioned medium (CM) from KS cells (KS-CM) or KS cells themselves induced angiogenesis and macrophage recruitment in a murine model in which Matrigel was injected subcutaneously. These effects were inhibited by treating mice with WEB 2170. Synthetic PAF or natural PAF extracted from plasma of patients with classical KS also induced angiogenesis, which in turn was inhibited by WEB 2170. The action of PAF was amplified by expression of other angiogenic factors and chemokines: these included basic and acidic fibroblast growth factor, placental growth factor, vascular endothelial growth factor and its specific receptor flk-1, hepatocyte growth factor, KC, and macrophage inflammatory protein-2. Treatment with WEB 2170 abolished the expression of the transcripts of these molecules within Matrigel containing KS-CM. These results indicate that PAF may cooperate with other angiogenic molecules and chemokines in inducing vascular development in KS.

The pigment composition of 18 species (51 strains) of the pennate diatom Pseudo-nitzschia was examined using HPLC. The carotenoid composition was typical for diatoms, with fucoxanthin (the major xanthophyll), diadinoxanthin, diatoxanthin, and β,β-carotene. However, a diverse array of chl c pigments was observed in the studied strains. All Pseudo-nitzschia strains contained chl a and chl c2, traces of Mg-2,4-divinyl phaeoporphyrin a5 monomethyl ester (MgDVP), and traces of a chl c2–like pigment originally found in the haptophyte Pavlova gyrans. The distribution of chl c1 and chl c3 was variable among species (present in seven and 14 species, respectively). Based on chl c distribution, three major pigment types were defined: type 1 (chl c1 + c2, four species: P. australis, P. brasiliana, P. multiseries, and P. seriata), type 2 (chl c1 + c2 + c3, three species: P. fraudulenta, P. multistriata, and P. pungens), and type 3 (chl c2 + c3, 11 species: P. arenysensis, P. calliantha, P. cuspidata, P. decipiens, P. delicatissima, P. galaxiae, P. mannii, P. pseudodelicatissima, P. subcurvata, P. cf. subpacifica, and a novel Pseudo-nitzschia species). Type 1 and 2 species also shared the absence of a particular morphological character, the central nodule in the raphe, with the only exception of P. fraudulenta. The implications of such pigment diversity in chemotaxonomy, HAB monitoring, ecology, and phylogeny of Pseudo-nitzschia species are discussed., Sí

Juvenile Atlantic salmon (Salmo salar) meristic and morphometric characteristics were examined from 47 European and North American river populations. The relative importance of continental origin, stream gradient, overall temperature regime, and seasonal temperatures in explaining the phenotypic variation of these populations was evaluated using multi-way ANOVA. Ecological factors explained a greater percentage of the variance than continental origin for both meristic and morphometric characters. Stream gradient was the most important factor explaining morphometric variation and April-May mean temperature was the most important factor explaining meristic variation.

Since the mid-19th century, numerous attempts have been made to restore or enhance populations of the Atlantic salmon, Salmo salar, within the endemic range, and to establish the species in other parts of the world. Despite all efforts, salmon have become naturalized locally only in eastern North America, Argentina, the Faeroe Islands, and New Zealand. Principal factors affecting the disappearance, restoration, or naturalization of populations are water temperature and availability of suitable spawning and nursery sites. Commercial exploitation of the species in coastal and offshore waters is viewed internationally as a factor of increased importance in the numerical regulation of river spawning runs. A further expansion of the world distribution of Atlantic salmon by naturalization seems unlikely except in areas where preliminary plantings have been made or brood stocks are presently held. Atlantic salmon produced by commercial sea farming operations in Norway, Scotland, Spain, and France are considered to be of comparable quality to fish harvested from the wild. Also, there is presently interest in the potential of sea ranching of Atlantic salmon. Key words: zoogeography, endemic range, naturalized range, artificial propagation, environmental impact, exploitation, aquaculture

Effects of various loadings of a test gravel incubation substrate (32- to >4-mm pebble) with a single sediment mix (−1). Mean survival (75%) from ova burial to juvenile emergence was not influenced significantly by different sediment loadings. However, time to first and median emergence, duration of emergence, stage of development at emergence, and within-substrate behaviour were each correlated positively with mean particle size (r ≥ 0.72) and negatively with sediment loading rates (r ≥ −0.68).

Lake trout, Salvelinus namaycush, released into Tadenac Lake as juveniles, show a pronounced acceleration in growth rate, following a change in diet from benthic invertebrates to rainbow smelt, Osmerus mordax, beginning at age 6 (> 30 cm). An abrupt increase in the rate of mercury accumulation in white muscle of these fish occurs at the same time. Mercury levels in lake trout ([Formula: see text] = 0.24–3.44 μg/g) and coresident smelt ([Formula: see text] = 0.06–0.48 μg/g) from Tadenac and eight neighboring lakes reveal maximum levels reaching 10.0 and 0.84 μg/g, respectively. Mercury levels in lake trout from Tadenac Lake, an undisturbed PreCambrian Shield ecosystem without detected indigenous sources, exceed the "safe" level (0.5 μg/g) at sexual maturity and at a size less than generally acceptable for human utilization. Mercury accumulation by the trout is correlated with length (r = 0.92) in each lake population examined, but substantial among-lake differences occur in fish of comparable ages. As the growth rates are similar in various waters, differences in extent of mercury accumulation is attributed to differences in mercury availability among lakes. In view of a strong correlation (r = 0.96) between mercury levels in smelt and trout calculated at standardized length, it is proposed that the smelt is an appropriate indicator species for the ranking of cold-water lakes relative to the availability of mercury for uptake by lake trout and other living aquatic organisms.Key words: mercury uptake, lake trout, rainbow smelt, growth rate, diet

Random samples of rainbow smelt, Osmerus mordax, from commercial summer trawl harvests in the Central and Eastern basins of Lake Erie are examined. Analysis of the meristic, morphometric, and electrophoretic data indicates no statistical evidence of genetic differences between basin populations. However, significant differences in size and growth data between basin populations occur and are attributed to differences in limnological conditions between basins which affect the time of spawning, length of growing season, and growth rate. Thus, these differences indicate an ecophenotypic distinction between the Central and Eastern Basin populations because of between-basin limnological dissimilarities.

This note supplements the original paper by MacCrimmon and Marshall (J. Fish. Res. Bd. Canada 25: 2527–2548, 1968) in presenting modified and more complete information on the native range, attempted introductions, and present world distribution of the brown trout.

This note supplements the original paper by MacCrimmon and Campbell (J. Fish. Res. Bd. Canada 26: 1699–1725, 1969) by presenting additional information on the native range, attempted introductions, and present world distribution of the brook trout.

In recent years, the Italian television scenario has become fully convergent, and social TV is an activity – and a hip buzzword – indicating both a rich set of possibilities for the audience to engage with TV shows, and an important asset developed by the television industry to provide such engagement, with promotional and economic goals. Mainly adopting the perspective of the production cultures of Italian broadcasters, the essay will explore the “Italian way to social television”, highlighting the strategies adopted by networks and production companies to encourage online television discourse and to exploit it as a content, a marketing device or a source of supplementary income.

Human immunodeficiency virus-1 (HIV-1)-Tat, the transactivating gene product of HIV-1, has been shown to interact with different cell types, inducing gene expression, altering their growth and migratory behavior. In this study we examined whether Tat might affect functions of acquired immunodeficiency syndrome (AIDS)-related non-Hodgkin’s lymphoma (NHL), relevant to the in vivo dissemination. Our results show that Tat significantly augmented the motility of the two AIDS-related Burkitt’s lymphoma cell lines (AS283 and PA682PB) and AIDS-primary effusion lymphoma cell line (HBL-6-AIDS-PEL). Mutations in RGD or basic domain of Tat (KGE-MBP and LxI-MBP, respectively) sharply reduced migration compared with wild type, suggesting that both domains are required for migration. In contrast, a Tat protein mutation outside the active domains (NH2-TAT-GST) did not reduce lymphoma cell migration. The treatment of lymphoma cells with Tat did not influence their adhesion to matrix proteins or to human vascular endothelial cells, but endothelial cells treated with Tat became more adhesive to lymphoma cells. Flow cytometric analysis showed that treatment of endothelial cells with Tat induced the cell surface expression of the adhesion molecules vascular cell adhesion molecule-1 (VCAM-1) and E-selectin and increased the expression of intercellular adhesion molecule-1 (ICAM-1). Only antibodies against VCAM-1 on endothelial cells or against the VLA-4 integrin expressed on AS283 cells inhibited the increment of adhesion, indicating the relevance of this pathway in the adhesion of lymphoma cells to vascular endothelium. In our work, we show for the first time that Tat can enhance the migration of lymphoma cells and their adhesion to endothelial cells, two processes that may contribute to the malignant behavior of NHL in patients with AIDS.

Human immunodeficiency virus type 1 (HIV-1) Tat transactivates viral genes and is released by infected cells, acting as a soluble mediator. In endothelial cells (EC), it activates a proangiogenic program by activating vascular endothelial growth factor receptor type 2 (VEGFR-2) and integrins. A structure-activity relationship study was performed by functional analysis of Tat substitution and deletion variants to define the Tat determinants necessary for EC activation. Variants were made (i) in the basic and (ii) in the cysteine-rich domains and (iii) in the C-terminal region containing the RGD sequence required for integrin recognition. Our results led to the following conclusions. (i) Besides a high-affinity binding site corresponding to VEGFR-2, EC express low-affinity binding sites. (ii) The basic and the cysteine-rich variants bind only to the low-affinity binding sites and do not promote tyrosine phosphorylation of VEGFR-2. Furthermore, they have a reduced ability to activate EC in vitro, and they lack angiogenic activity. (iii) Mutants with mutations in the C-terminal region are partially defective for in vitro biological activities and in vivo angiogenesis, but they activate VEGFR-2 as Tat wild type. In conclusion, regions encoded by the first exon oftatare necessary and sufficient for activation of VEGFR-2. However, the C-terminal region, most probably through RGD-mediated integrin engagement, is indispensable for full activation of an in vitro and in vivo angiogenic program.