Early detection of interstitial lung disease in rheumatic diseases: A joint statement from the Portuguese Pulmonology Society, the Portuguese Rheumatology Society, and the Portuguese Radiology and Nuclear Medicine Society.

INTRODUCTION: Interstitial lung disease (ILD) contributes significantly to morbidity and mortality in connective tissue disease (CTD). Early detection and accurate diagnosis are essential for informing treatment decisions and prognosis in this setting. Clear guidance on CTD-ILD screening, however, is lacking. OBJECTIVE: To establish recommendations for CTD-ILD screening based on the current evidence. METHOD: Following an extensive literature research and evaluation of articles selected for their recency and relevance to the characterization, screening, and management of CTD-ILD, an expert panel formed by six pulmonologists from the Portuguese Society of Pulmonology, six rheumatologists from the Portuguese Society of Rheumatology, and six radiologists from the Portuguese Society of Radiology and Nuclear Medicine participated in a multidisciplinary discussion to produce a joint statement on screening recommendations for ILD in CTD. RESULTS: The expert panel achieved consensus on when and how to screen for ILD in patients with systemic sclerosis, rheumatoid arthritis, mixed connective tissue disease, Sjögren syndrome, idiopathic inflammatory myopathies and systemic lupus erythematous. CONCLUSIONS: Despite the lack of data on screening for CTD-ILD, an expert panel of pulmonologists, rheumatologists and radiologists agreed on a series of screening recommendations to support decision-making and enable early diagnosis of ILD to ultimately improve outcomes and prognosis in patients with CTD.

Efficiency of ultraviolet light for disinfection of fertile broiler eggs / Eficiência da luz ultravioleta para desinfecção de ovos férteis de matrizes de frangos de corte

This study aimed to evaluate the effectiveness of ultraviolet light in reducing bacterial load of eggshells and the impact of experimental disinfection on hatching, embryo mortality, and time-borne distribution using broiler breeder hens of different ages (38, 42, and 48 weeks old). Fertile eggs were subjected to different exposure periods (5, 7, and 9 minutes) of UV light (UV-C) with a 254 nm wavelength. For controls, eggs disinfected with paraformaldehyde (5.3 g/m3) and eggs not disinfected (NC). After subjection to disinfection protocols, the eggs were placed into sterile plastic bags containing 20 mL of peptone saline solution (0.1% m:v) and massaged for 1 minute to release the bacterial load. Aliquots of this solution were incubated in specific medium for bacterial growth for 48 hours at 37ºC for subsequent CFU counts. To evaluate the effects of disinfection on production, eggs previously disinfected by UV-C (9 min) and paraformaldehyde and NC eggs were candled between incubation days 10 and 13 and at the end of the incubation period to assess embryonic mortality. Hatchability distribution was performed every 8 hours. The 9 minutes 254nm UV-C light exposure was able to disinfect viable eggs and matched the effectiveness of the paraformaldehyde technique.(AU)

Objetivou-se avaliar a eficácia da luz ultravioleta na redução da carga bacteriana de cascas de ovos e o impacto na eclosão e na mortalidade embrionária observando-se a idade das matrizes (38, 42 e 48 semanas). Os ovos foram submetidos a diferentes períodos de exposição (cinco, sete e nove minutos) à luz UV (UV-C) com comprimento de onda de 254nm. Os controles foram ovos desinfetados com paraformaldeído (5,3g/m³) e ovos não desinfetados (NC). Após a desinfecção, os ovos foram colocados em sacos plásticos estéreis contendo 20mL de solução salina peptonada (0,1% m:v) e massageados por um (1) minuto para descolamento das bactérias. Alíquotas dessa solução foram incubadas em meio para crescimento bacteriano por 48 horas a 37ºC e contagem de UFC. Para avaliar os efeitos da desinfecção, ovos previamente desinfetados por UV-C (nove minutos) e ovos com paraformaldeído e NC foram submetidos à ovoscopia entre os dias 10 e 13 de incubação e ao final do período de incubação, para avaliação da mortalidade embrionária. A distribuição da eclodibilidade foi realizada a cada oito horas. A exposição à luz UV-C de 25nm de nove minutos desinfetou os ovos férteis e coincidiu com a eficácia do paraformaldeído.(AU)

Behavioral aspects of waterbirds / Aspectos comportamentais de aves aquáticas

Abstract Estuaries are used by waterbirds as foraging, resting and nesting sites, serving also as shelter for migratory birds. The dynamics of this avifauna in an aquatic environment may be associated with the differences of time of day, tide height, temperature, wind speed and use of the site by different species. This study had the objective of evaluating behavioral aspects of aquatic birds, relating the influence of environmental variables with their activities. Bird counts were performed at the mouth of two important rivers of the state of Santa Catarina, Brazil, during two-hour intervals throughout the day in monthly samplings between June (2015) and May (2016). A total of 44 species were recorded, ten of which were migratory. The most recorded behaviors were foraging and resting. The Kruskal-Wallis analysis indicated no significant difference in behavior between the sampling intervals. The Bray-Curtis similarity test resulted in three groups: 1) - species that foraged most of the time; 2) - species that rested most of the time; and 3) - same time in both activities. The Indicator Species Analysis showed that 17 species were associated with only one microhabitat and 15 species with more than one. The Canonical Correlation Analysis indicated that only tide height, temperature and rainfall variables were correlated with the behaviors performed and only the resting activity was positively correlated with all variables. This may be associated with thermoregulation and the ability of some species to stay in midlitoral at high tide. The results demonstrate that different waterbird species used the studied areas in different ways. Thus, the heterogeneity of microhabitats in an aquatic environment of extreme importance for the coexistence and maintenance of the diversity of waterbirds.

Resumo Estuários são utilizados por aves aquáticas como locais de forrageio, descanso e nidificação, servindo, também, como pontos de parada para aves migratórias. A dinâmica dessa avifauna em um ambiente pode estar associada a diferenças entre horários do dia, altura da maré, temperatura, velocidade do vento e uso do local. Esse trabalho teve o objetivo de avaliar aspectos comportamentais de aves aquáticas, relacionando a influência de variáveis ambientais com suas atividades. Amostragens mensais foram realizadas na foz de dois importantes rios do Estado de Santa Catarina, Brasil, entre junho de 2015 e maio de 2016, em intervalos de duas horas no decorrer do dia. Um total de 44 espécies foram registradas, dez das quais foram migratórias. Os comportamentos mais observados foram forrageio e descanso. A análise de Kruskall-Wallis não indicou diferenças significativas no comportamento entre os horários de amostragem. O teste de similaridade Bray-Curtis resultou em três agrupamentos: 1) - espécies que forragearam na maior parte do tempo; 2) - espécies que descansaram na maior parte do tempo; e 3) - mesma quantidade de tempo em ambas atividades. A Análise de Espécies Indicadoras mostrou que 17 espécies estiveram associadas com apenas um microhabitat e 15 espécies com mais de um. A Análise de Correlação Canônica indicou que apenas as variáveis maré, temperatura e precipitação foram significativamente correlacionadas com os comportamentos demonstrados e apenas a atividade de descanso foi positivamente correlacionada com as todas as variáveis. Isso pode estar associado com a termorregulação e com a habilidade de algumas espécies de permanecer no mediolitoral durante a maré cheia. Os resultados demonstram que diferentes espécies de aves aquáticas utilizaram as áreas estudadas de diferentes maneiras. Assim, a heterogeneidade de microhabitats em um ambiente aquático é de extrema importância para a coexistência e a manutenção da diversidade de aves.

Behavioral aspects of waterbirds.

Estuaries are used by waterbirds as foraging, resting and nesting sites, serving also as shelter for migratory birds. The dynamics of this avifauna in an aquatic environment may be associated with the differences of time of day, tide height, temperature, wind speed and use of the site by different species. This study had the objective of evaluating behavioral aspects of aquatic birds, relating the influence of environmental variables with their activities. Bird counts were performed at the mouth of two important rivers of the state of Santa Catarina, Brazil, during two-hour intervals throughout the day in monthly samplings between June (2015) and May (2016). A total of 44 species were recorded, ten of which were migratory. The most recorded behaviors were foraging and resting. The Kruskal-Wallis analysis indicated no significant difference in behavior between the sampling intervals. The Bray-Curtis similarity test resulted in three groups: 1) - species that foraged most of the time; 2) - species that rested most of the time; and 3) - same time in both activities. The Indicator Species Analysis showed that 17 species were associated with only one microhabitat and 15 species with more than one. The Canonical Correlation Analysis indicated that only tide height, temperature and rainfall variables were correlated with the behaviors performed and only the resting activity was positively correlated with all variables. This may be associated with thermoregulation and the ability of some species to stay in midlitoral at high tide. The results demonstrate that different waterbird species used the studied areas in different ways. Thus, the heterogeneity of microhabitats in an aquatic environment of extreme importance for the coexistence and maintenance of the diversity of waterbirds.

Alternative and complementary therapies in osteoarthritis and cartilage repair.

Osteoarthritis (OA) is the most common joint condition and, with a burgeoning ageing population, is due to increase in prevalence. Beyond conventional medical and surgical interventions, there are an increasing number of 'alternative' therapies. These alternative therapies may have a limited evidence base and, for this reason, are often only afforded brief reference (or completely excluded) from current OA guidelines. Thus, the aim of this review was to synthesize the current evidence regarding autologous chondrocyte implantation (ACI), mesenchymal stem cell (MSC) therapy, platelet-rich plasma (PRP), vitamin D and other alternative therapies. The majority of studies were in knee OA or chondral defects. Matrix-assisted ACI has demonstrated exceedingly limited, symptomatic improvements in the treatment of cartilage defects of the knee and is not supported for the treatment of knee OA. There is some evidence to suggest symptomatic improvement with MSC injection in knee OA, with the suggestion of minimal structural improvement demonstrated on MRI and there are positive signals that PRP may also lead to symptomatic improvement, though variation in preparation makes inter-study comparison difficult. There is variability in findings with vitamin D supplementation in OA, and the only recommendation which can be made, at this time, is for replacement when vitamin D is deplete. Other alternative therapies reviewed have some evidence (though from small, poor-quality studies) to support improvement in symptoms and again there is often a wide variation in dosage and regimens. For all these therapeutic modalities, although controlled studies have been undertaken to evaluate effectiveness in OA, these have often been of small size, limited statistical power, uncertain blindness and using various methodologies. These deficiencies must leave the question as to whether they have been validated as effective therapies in OA (or chondral defects). The conclusions of this review are that all alternative interventions definitely require clinical trials with robust methodology, to assess their efficacy and safety in the treatment of OA beyond contextual and placebo effects.

Asthma app use and interest among patients with asthma: a multicenter study

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Effects of a respiratory functional training program on pain and sleep quality in patients with fibromyalgia: A pilot study.

OBJECTIVE: To evaluate the effect of 8-week respiratory functional training program on pain tolerance, sleep, and urinary antioxidant and cortisol levels in 18 patients with fibromyalgia. METHODS: Participants underwent a 12-week intervention: 4 weeks as control and 8 weeks of breathing exercises. Pain tolerance assay was done by using an algometer, whereas sleep quality was evaluated by actigraphy and by the Pittsburgh Sleep Quality Index. Cortisol and antioxidant levels were determined using commercial assay kits. RESULTS: Increases in the pain tolerance threshold were detected in the occiput point after one month of intervention as well as in the low cervical and second rib points after one and two months. Actigraphy revealed a decrease in sleep latency, whereas sleep questionnaire showed improvements in sleep quality, sleep duration and sleep efficiency. No changes in cortisol and antioxidant levels were detected. CONCLUSION: The 8-week breathing exercise intervention reduced pain and improved sleep quality.

Impact of ERG3 mutations and expression of ergosterol genes controlled by UPC2 and NDT80 in Candida parapsilosis azole resistance.

OBJECTIVES: Candida parapsilosis is a healthcare-related fungal pathogen particularly common among immunocompromised patients. Our understanding of antifungal resistance mechanisms in C. parapsilosis remains very limited. We previously described an azole-resistant strain of C. parapsilosis (BC014RPSC), obtained following exposure in vitro to posaconazole. Resistance was associated with overexpression of ergosterol biosynthetic genes (ERG genes), together with the transcription factors UPC2 (CPAR2-207280) and NDT80 (CPAR2-213640). The aim of this study was to identify the mechanisms underlying posaconazole resistance of the BC014RPSC strain. METHODS: To identify the causative mutation, we sequenced the genomes of the susceptible (BC014S) and resistant (BC014RPSC) isolates, using Illumina technology. Ergosterol content was assessed in both strains by mass spectrometry. UPC2 and NDT80 genes were deleted in BC014RPSC strain. Mutants were characterized regarding their azole susceptibility profile and ERG gene expression. RESULTS: One homozygous missense mutation (R135I) was found in ERG3 (CPAR2-105550) in the azole-resistant isolate. We show that Erg3 activity is completely impaired, resulting in a build up of sterol intermediates and a failure to generate ergosterol. Deleting UPC2 and NDT80 in BC014RPSC reduces the expression of ERG genes and restores susceptibility to azole drugs. CONCLUSIONS: A missense mutation in the ERG3 gene results in azole resistance and up-regulation of ERG genes expression. We propose that this mutation prevents the formation of toxic intermediates when cells are treated with azoles. Resistance can be reversed by deleting Upc2 and Ndt80 transcription factors. UPC2 plays a stronger role in C. parapsilosis azole resistance than does NDT80.

EULAR revised recommendations for the management of fibromyalgia.

OBJECTIVE: The original European League Against Rheumatism recommendations for managing fibromyalgia assessed evidence up to 2005. The paucity of studies meant that most recommendations were 'expert opinion'. METHODS: A multidisciplinary group from 12 countries assessed evidence with a focus on systematic reviews and meta-analyses concerned with pharmacological/non-pharmacological management for fibromyalgia. A review, in May 2015, identified eligible publications and key outcomes assessed were pain, fatigue, sleep and daily functioning. The Grading of Recommendations Assessment, Development and Evaluation system was used for making recommendations. RESULTS: 2979 titles were identified: from these 275 full papers were selected for review and 107 reviews (and/or meta-analyses) evaluated as eligible. Based on meta-analyses, the only 'strong for' therapy-based recommendation in the guidelines was exercise. Based on expert opinion, a graduated approach, the following four main stages are suggested underpinned by shared decision-making with patients. Initial management should involve patient education and focus on non-pharmacological therapies. In case of non-response, further therapies (all of which were evaluated as 'weak for' based on meta-analyses) should be tailored to the specific needs of the individual and may involve psychological therapies (for mood disorders and unhelpful coping strategies), pharmacotherapy (for severe pain or sleep disturbance) and/or a multimodal rehabilitation programme (for severe disability). CONCLUSIONS: These recommendations are underpinned by high-quality reviews and meta-analyses. The size of effect for most treatments is relatively modest. We propose research priorities clarifying who will benefit from specific interventions, their effect in combination and organisation of healthcare systems to optimise outcome.

The role of calcium supplementation in healthy musculoskeletal ageing : An expert consensus meeting of the European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO) and the International Foundation for Osteoporosis (IOF).

The place of calcium supplementation, with or without concomitant vitamin D supplementation, has been much debated in terms of both efficacy and safety. There have been numerous trials and meta-analyses of supplementation for fracture reduction, and associations with risk of myocardial infarction have been suggested in recent years. In this report, the product of an expert consensus meeting of the European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO) and the International Foundation for Osteoporosis (IOF), we review the evidence for the value of calcium supplementation, with or without vitamin D supplementation, for healthy musculoskeletal ageing. We conclude that (1) calcium and vitamin D supplementation leads to a modest reduction in fracture risk, although population-level intervention has not been shown to be an effective public health strategy; (2) supplementation with calcium alone for fracture reduction is not supported by the literature; (3) side effects of calcium supplementation include renal stones and gastrointestinal symptoms; (4) vitamin D supplementation, rather than calcium supplementation, may reduce falls risk; and (5) assertions of increased cardiovascular risk consequent to calcium supplementation are not convincingly supported by current evidence. In conclusion, we recommend, on the basis of the current evidence, that calcium supplementation, with concomitant vitamin D supplementation, is supported for patients at high risk of calcium and vitamin D insufficiency, and in those who are receiving treatment for osteoporosis.

Behavioral aspects of waterbirds

Abstract Estuaries are used by waterbirds as foraging, resting and nesting sites, serving also as shelter for migratory birds. The dynamics of this avifauna in an aquatic environment may be associated with the differences of time of day, tide height, temperature, wind speed and use of the site by different species. This study had the objective of evaluating behavioral aspects of aquatic birds, relating the influence of environmental variables with their activities. Bird counts were performed at the mouth of two important rivers of the state of Santa Catarina, Brazil, during two-hour intervals throughout the day in monthly samplings between June (2015) and May (2016). A total of 44 species were recorded, ten of which were migratory. The most recorded behaviors were foraging and resting. The Kruskal-Wallis analysis indicated no significant difference in behavior between the sampling intervals. The Bray-Curtis similarity test resulted in three groups: 1) - species that foraged most of the time; 2) - species that rested most of the time; and 3) - same time in both activities. The Indicator Species Analysis showed that 17 species were associated with only one microhabitat and 15 species with more than one. The Canonical Correlation Analysis indicated that only tide height, temperature and rainfall variables were correlated with the behaviors performed and only the resting activity was positively correlated with all variables. This may be associated with thermoregulation and the ability of some species to stay in midlitoral at high tide. The results demonstrate that different waterbird species used the studied areas in different ways. Thus, the heterogeneity of microhabitats in an aquatic environment of extreme importance for the coexistence and maintenance of the diversity of waterbirds.

Resumo Estuários são utilizados por aves aquáticas como locais de forrageio, descanso e nidificação, servindo, também, como pontos de parada para aves migratórias. A dinâmica dessa avifauna em um ambiente pode estar associada a diferenças entre horários do dia, altura da maré, temperatura, velocidade do vento e uso do local. Esse trabalho teve o objetivo de avaliar aspectos comportamentais de aves aquáticas, relacionando a influência de variáveis ambientais com suas atividades. Amostragens mensais foram realizadas na foz de dois importantes rios do Estado de Santa Catarina, Brasil, entre junho de 2015 e maio de 2016, em intervalos de duas horas no decorrer do dia. Um total de 44 espécies foram registradas, dez das quais foram migratórias. Os comportamentos mais observados foram forrageio e descanso. A análise de Kruskall-Wallis não indicou diferenças significativas no comportamento entre os horários de amostragem. O teste de similaridade Bray-Curtis resultou em três agrupamentos: 1) - espécies que forragearam na maior parte do tempo; 2) - espécies que descansaram na maior parte do tempo; e 3) - mesma quantidade de tempo em ambas atividades. A Análise de Espécies Indicadoras mostrou que 17 espécies estiveram associadas com apenas um microhabitat e 15 espécies com mais de um. A Análise de Correlação Canônica indicou que apenas as variáveis maré, temperatura e precipitação foram significativamente correlacionadas com os comportamentos demonstrados e apenas a atividade de descanso foi positivamente correlacionada com as todas as variáveis. Isso pode estar associado com a termorregulação e com a habilidade de algumas espécies de permanecer no mediolitoral durante a maré cheia. Os resultados demonstram que diferentes espécies de aves aquáticas utilizaram as áreas estudadas de diferentes maneiras. Assim, a heterogeneidade de microhabitats em um ambiente aquático é de extrema importância para a coexistência e a manutenção da diversidade de aves.

The economic impact of early retirement attributed to rheumatic diseases: results from a nationwide population-based epidemiologic study.

OBJECTIVES: To measure early retirement due to self-reported rheumatic diseases (RDs) and to estimate the respective indirect costs and years of working life lost (YWLL). METHODS: We used individual level data from the national, cross-sectional, population-based EpiReumaPt study (September 2011-December 2013) where 10,661 inhabitants were randomly surveyed in order to capture and characterize all cases of RD within a representative sample of the Portuguese population. In this analysis, we used all participants aged between 50 and 64 years, near the official retirement age. A national database was used to calculate productivity values by gender, age and region, using the human capital approach. YWLL were estimated as the difference between each participant's current age and the respective retirement age, while the potential years of working life lost (PYWLL) were given by the difference between official and actual retirement ages. We also calculated the percentage of time in inactivity (inactivity ratio = YWLL/Active age-range [15-64 years old]). RESULTS: 29.9% of the Portuguese population with ages between 50 and 64 years were retired with 13.1% self-reporting retirement due to RD. The estimated annual indirect cost following premature retirement attributed to RD was €910 million (€555 per capita; €1625 per self-reported RD patient and €13,592 per early retiree due to RD). Females contributed with 84% for these costs (€766 million; €882 per capita vs €187 from males). We observed a total number of 389,939 accumulated YWLL (228 per 1000 inhabitants) and 684,960 PYWLL (401 per 1000 inhabitants). The mean YWLL and PYWLL inactivity ratios were 12% and 21%, respectively. RD patients with higher values of disability have the highest risk of early retirement. CONCLUSIONS: Early retirement attributed to self-reported RD amounts to approximately 0.5% of the national gross domestic product (GDP) in 2013, due to large YWLL. Both the public health concern and the economic impact highlight the need to prioritize investments in health and social protection policies targeting patients with rheumatic conditions.

Effect of Comedication With Conventional Synthetic Disease-Modifying Antirheumatic Drugs on Retention of Tumor Necrosis Factor Inhibitors in Patients With Spondyloarthritis: A Prospective Cohort Study.

OBJECTIVE: To evaluate whether use of comedication with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) influences the retention of tumor necrosis factor inhibitors (TNFi) in patients with spondyloarthritis (SpA). METHODS: Patients with SpA from the Rheumatic Diseases Portuguese Register who started treatment with their first TNFi between 2001 and 2014 were included in this study. Cox regression analysis was used to estimate the effect of comedication with csDMARDs on TNFi retention in 2 types of models: a model in which baseline (time-fixed) variables were included, and a second model incorporating time-varying variables, including sociodemographic features, measures of disease activity, measures of physical function, and cotreatment with other drugs (nonsteroidal antiinflammatory drugs and oral steroids). To control for possible confounding by indication, the effect of csDMARD comedication on TNFi retention was also tested after adjustment for the treatment propensity score. RESULTS: In total, 954 patients were included in the study, of whom 289 (30.3%) discontinued treatment with their first TNFi after a median follow-up time of 2.5 years (range 0.08-13 years). Inefficacy was the most common reason for TNFi discontinuation (55.7% of patients). In the multivariable analyses, comedication with csDMARDs had no measurable effect on TNFi retention, neither in the baseline model (hazard ratio [HR] 0.83, 95% confidence interval [95% CI] 0.59-1.16) nor during follow-up in the model adjusted for time-varying covariates (HR 1.07, 95% CI 0.68-1.68). The effect of csDMARD comedication remained nonsignificant after propensity score adjustment. CONCLUSION: Comedication with csDMARDs does not prolong TNFi retention in patients with SpA in clinical practice, suggesting that there is no benefit conferred by the concomitant use of these drugs.

Childhood trauma, family history, and their association with mood disorders in early adulthood.

OBJECTIVE: To assess the prevalence of childhood trauma and types of trauma on mood disorders among young adults in a population-based sample. We further gathered data on family history of mood disorders to test the hypothesis that childhood trauma is a mediating factor for the association between family history of mood disorder and mood disorder in adulthood. METHOD: This is a cross-sectional study, including young adults with bipolar disorder, major depressive disorder, and matched controls without any mood disorder. Childhood trauma was assessed using the Childhood Trauma Questionnaire (CTQ). The Hicks and Tingley implementation was employed to assess whether trauma is a mediator of the effect of family history on diagnosis of any mood disorder. RESULTS: All types of trauma were associated with both major depression and bipolar disorder, with the exception of sexual abuse, which was only associated with bipolar disorder. Moreover, family history of psychiatric illness was also associated with mood disorder in adulthood and with childhood trauma. Using the presence of any mood disorder as the outcome, a third of the effect of having any family history of mood disorder was mediated via childhood trauma. CONCLUSION: This investigation provides further support, in a population-based sample of young adults, of the association between childhood trauma and mood disorders, with sexual abuse being specifically linked with bipolar disorder. The hypothesis that childhood trauma would function as a partial mediator of the association between family history of mood disorder and mood disorder in adulthood was also confirmed.

Iron overload in a murine model of hereditary hemochromatosis is associated with accelerated progression of osteoarthritis under mechanical stress.

OBJECTIVE: Hereditary hemochromatosis (HH) is a disease caused by mutations in the Hfe gene characterised by systemic iron overload and associated with an increased prevalence of osteoarthritis (OA) but the role of iron overload in the development of OA is still undefined. To further understand the molecular mechanisms involved we have used a murine model of HH and studied the progression of experimental OA under mechanical stress. DESIGN: OA was surgically induced in the knee joints of 10-week-old C57BL6 (wild-type) mice and Hfe-KO mice. OA progression was assessed using histology, micro CT, gene expression and immunohistochemistry at 8 weeks after surgery. RESULTS: Hfe-KO mice showed a systemic iron overload and an increased iron accumulation in the knee synovial membrane following surgery. The histological OA score was significantly higher in the Hfe-KO mice at 8 weeks after surgery. Micro CT study of the proximal tibia revealed increased subchondral bone volume and increased trabecular thickness. Gene expression and immunohistochemical analysis showed a significant increase in the expression of matrix metallopeptidase 3 (MMP-3) in the joints of Hfe-KO mice compared with control mice at 8 weeks after surgery. CONCLUSIONS: HH was associated with an accelerated development of OA in mice. Our findings suggest that synovial iron overload has a definite role in the progression of HH-related OA.

Recommendations for an update of the 2010 European regulatory guideline on clinical investigation of medicinal products used in the treatment of osteoarthritis and reflections about related clinically relevant outcomes: expert consensus statement.

OBJECTIVE: The European Society on Clinical and Economic aspects of Osteoporosis and Osteoarthritis (ESCEO) organised a working group to evaluate the need for updating the current European guideline on clinical investigation of drugs used in the treatment of osteoarthritis (OA). DESIGN: Areas of potential attention were identified and the need for modifications, update or clarification was examined. Proposals were then developed based on literature reviews and through a consensus process. RESULTS: It was agreed that the current guideline overall still reflects the current knowledge in OA, although two possible modifications were identified. The first relates to the number and timing of measurements required as primary endpoints during clinical trials of symptom-relieving drugs, either drugs with rapid onset of action or slow acting drugs. The suggested modifications are intended to take into consideration the time related clinical need and expected time response to these drugs - i.e., a more early effect for the first category in addition to the maintenance of effect, a more continuous benefit over the long-term for the latter - in the timing of assessments. Secondly, values above which a benefit over placebo should be considered clinically relevant were considered. Based on literature reviews, the most consensual values were determined for primary endpoints of both symptom-relieving drugs (i.e., pain intensity on a visual analogue scale (VAS)) and disease-modifying drugs (i.e., radiographic joint-space narrowing). CONCLUSIONS: This working document might be considered by the European regulatory authorities in a future update of the guideline for the registration of drugs in OA.

Feeding habits of the congeneric species Stellifer rastrifer and Stellifer brasiliensis (Acanthopterygii: Sciaenidae) co-occurring in the coast of the state of Santa Catarina, Brazil.

The objective of the present study was to investigate the feeding habits allowing the occurrence of the congeneric species Stellifer rastrifer and Stellifer brasiensis, collected on a seasonal basis, in the operating area of the artisanal seabob-shrimp trawl fishery in Porto Belo, an important fishing area on the southern Brazilian coast. Fish were collected seasonally from November 2009 to August 2010, in isobaths of 10, 20 and 30 m. Of the 450 stomachs analyzed, 194 belonged to Stellifer rastrifer and 242 to Stellifer brasiliensis. From the totality of analyzed stomachs 33.49% were empty and 66.52% had some content. Crustacea were the predominant food category in the diet of S. rastrifer and S. brasiliensis, and the shrimp Acetes americanus was the most frequent crustacean in stomachs of both studied species. The overlapping in the diet of the species was high, however when analyzing the overlap in each season it was found that it occurred only during spring and winter. Although the most important items in the diet of these species are the same, the intake of each alternates in time, suggesting a difference in predation pressure, which leads to less direct competition in a given time.