Molecular imaging: novel tools in visualizing rheumatoid arthritis

Molecular imaging is a rapidly emerging field in biomedical research, aiming at the visualization, characterization and quantification of molecular and cellular processes non-invasively within intact living organisms. To sense biological processes such as gene expression, angiogenesis, apoptosis or cell trafficking in vivo, imaging reporter agents that interact specifically with molecular targets and appropriate imaging systems are currently under development. In rheumatoid arthritis, these novel tools will be used to evaluate physiological and pathophysiological processes, to facilitate diagnosis and monitor therapeutic regimens, to enable reliable prognosis and to support the development of new therapies. In this review, we summarize the basic principles of molecular imaging, such as the development of molecular imaging agents, the actual capabilities of different imaging modalities and the most recent advances in molecular imaging, demonstrating the potential of this technology. With regard to their applicability in rheumatic diseases, we discuss potential molecular targets, current experimental approaches and the future prospects for molecular imaging in rheumatoid arthriti

A IMUNOLOGIA E A IMUNOPATOLOGIA DAS INFECÇÕES CAUSADAS POR

Chlamydae are obligate intracellular bacterial pathogens of eukariotic cells responsible for a wide variety of important human and animal infections. In humans, Chlamydia trachomatis infections are generally localised on superficial epithelial or mucosal surfaces, are frequently asymptomatic and may persist for long periods of time if untreated, inducing little protective immunity. Nevertheless, neutralizing antibodies of limited efficacy are produced against the main chlamydial outer envelope protein, while gamma interferon (IFNã) is chlamydiastatic and paradoxically may play a role both in chlamydial persistence and in protective immunity. Delayed hypersensitivity responses to chalmydiae caused by repeated or persistent infection are thought to be important in the developement of the severe scarring sequelae characteristic of cicatricial trachoma and of chronic salpingitis. Chlamydial heat shock proteins bearing close homology with their human equivalents may be major targets for immunopathological responses and their expression is upregulated in IFN-ã induced persistent infection. This paper reviews the immunology and immunopathology of Chlamydia trachomatis infections in the context of the clinical evolution of the infection. Key Words: Chlamydia trachomatis, imune response, immunopathology, clinical evolution of the infection.As clamídeas são bactérias intracelulares obrigatórias de células eucarióticas, responsáveis por uma ampla variedade de infecções em humanos e em algumas espécies de animais. Em humanos, as infecções por Chlamydia trachomatis geralmente estão localizadas na superfície de epitélios ou de mucosas, e são freqüentemente assintomáticas, podendo persistir por longos períodos de tempo se não tratadas. Em termos de resposta imune em humanos, observa-se a produção de anticorpos neutralizantes de eficácia moderada, específicos para as principais proteínas do envelope externo, enquanto que o interferon ã (IFN) é clamidiostático e, paradoxalmente, pode exercer tanto uma função facilitadora da ã persistência da infecção quanto de proteção imune. Respostas de hipersensibilidade tardia para clamídea, causadas pela infecção persistente ou re-infecção, são importantes no desenvolvimento de seqüelas graves características do tipo tracoma cicatricial ou salpingite crônica. Proteínas clamidiais de choque térmico dotadas de intensa homologia com proteínas humanas equivalentes, podem ser os alvos principais nas respostas imunopatologicas e sua expressão é estimulada por IFN em infecções persistentes. Este ã trabalho revisa os principais aspectos relacionados à imunologia e imunopatologia das infecções causadas por Chlamydia trachomatis, relacionando os mesmos com a evolução clínica da infecção. Palavras Chave: Chlamydia trachomatis, resposta imune, imunopatologia, evolução clínica da infecção

The inter-rater reliability of the diagnosis of surgical site infection in the context of a clinical trial.

ObjectivesThe diagnosis of surgical site infection following endoprosthetic reconstruction for bone tumours is frequently a subjective diagnosis. Large clinical trials use blinded Central Adjudication Committees (CACs) to minimise the variability and bias associated with assessing a clinical outcome. The aim of this study was to determine the level of inter-rater and intra-rater agreement in the diagnosis of surgical site infection in the context of a clinical trial.Materials and methodsThe Prophylactic Antibiotic Regimens in Tumour Surgery (PARITY) trial CAC adjudicated 29 non-PARITY cases of lower extremity endoprosthetic reconstruction. The CAC members classified each case according to the Centers for Disease Control (CDC) criteria for surgical site infection (superficial, deep, or organ space). Combinatorial analysis was used to calculate the smallest CAC panel size required to maximise agreement. A final meeting was held to establish a consensus.ResultsFull or near consensus was reached in 20 of the 29 cases. The Fleiss kappa value was calculated as 0.44 (95% confidence interval (CI) 0.35 to 0.53), or moderate agreement. The greatest statistical agreement was observed in the outcome of no infection, 0.61 (95% CI 0.49 to 0.72, substantial agreement). Panelists reached a full consensus in 12 of 29 cases and near consensus in five of 29 cases when CDC criteria were used (superficial, deep or organ space). A stable maximum Fleiss kappa of 0.46 (95% CI 0.50 to 0.35) at CAC sizes greater than three members was obtained.ConclusionsThere is substantial agreement among the members of the PARITY CAC regarding the presence or absence of surgical site infection. Agreement on the level of infection, however, is more challenging. Additional clinical information routinely collected by the prospective PARITY trial may improve the discriminatory capacity of the CAC in the parent study for the diagnosis of infection.Cite this article: J. Nuttall, N. Evaniew, P. Thornley, A. Griffin, B. Deheshi, T. O'Shea, J. Wunder, P. Ferguson, R. L. Randall, R. Turcotte, P. Schneider, P. McKay, M. Bhandari, M. Ghert. The inter-rater reliability of the diagnosis of surgical site infection in the context of a clinical trial. Bone Joint Res 2016;5:347-352. DOI: 10.1302/2046-3758.58.BJR-2016-0036.R1

On the influence of tree size on the climate–growth relationship of New Zealand kauri (Agathis australis): insights from annual, monthly and daily growth patterns

Many tree-ring-based climate reconstructions are based on the assumption that the climate reaction of trees is independent of their size. Here, we test this assumption for New Zealand kauri (Agathis australis), one of the longest tree ring-based proxies for the El Niño-Southern Oscillation (ENSO). The most recent kauri chronology contains a large amount of archaeological material, e.g. timber for which the original tree size is often unknown. We analyzed the climate–growth relationship of different-sized kauri in a pristine forest using different temporal scales, i.e. annually, monthly and daily data on tree growth and climate conditions. Trees of different life stages exhibited approximately the same seasonal growth peaks during austral spring (October and November). The dormancy period overlaps with the period where weekly air temperature maxima are below ca. 17–18 °C, and where the corresponding daily minima are below ca. 8 °C. However, both correlation functions between annual growth and seasonal climate as well as Kalman filter regressions between daily growth and climate conditions suggest an influence of tree size on the climate–growth relationship for kauri. Smaller trees (DBH < 40 cm) contain weaker climate signals than larger trees. Therefore, the precautionary stripping of near-pith material (first 20 cm) from kauri chronologies may result in more uniform responses to climate forcing and thus enhance the reliability of long-term climate reconstructions

Environmental incomes and rural livelihoods : a global-comparative assessment

Various case studies have suggested that environmental incomes from forests and other vegetation types are important for rural households in developing countries. However, in most large-scale household surveys these income sources are either underreported or ignored, hence there has been a lack of evidence to support the wider applicability of that claim. This paper reports data from the Poverty Environment Network (PEN), which has gathered comparable income data from about 8,000 households in 360 villages and 58 sites, spread over 24 developing countries. The data collection involved a careful, quarterly recording of all forest and environmental uses, as well as other major income sources over one full year. We find that forest income on average constitutes about one fifth of total household income, while adding other environmental income brings the share to more than one fourth – about the same as incomes from growing crops. Environmental resources and agricultural crops are the two main sources of livelihoods in the survey sites. As expected, forest reliance (share of forest income in total household income) is higher for the poorer income quintiles, but the differences are less pronounced than what was found in most previous studies. We also find that safety net and seasonal gap-filling functions may be less important that often assumed. Ignoring environmental incomes in income surveys and in rural development planning would in quantitative terms amount to ignoring that farmers grow crops. Agricultural area expansion into forests and other vegetation types may well come to increase household incomes, but corresponding income losses from losing forest cover and forest degradation could be larger than previously assumed. Depriving poor people of access to forest product extraction, for instance through highly exclusionary conservation policies, could jeopardize the livelihoods of people depending on these resources

An evaluation of isotopic (δ2H) methods to provide estimates of avian breeding and natal dispersal

Natal and breeding dispersal represents an important component of animal demography and metapopulation theory. This phenomenon also has implications for conservation and management because understanding movements of individuals potentially allows the identification of key habitats that may be acting as population sources or sinks. Intrinsic markers such as stable isotope abundance in tissues that can be associated with provenance can provide a coarse but pragmatic solution to understanding such movements. Different methodologies have been proposed to quantify natal and breeding dispersal by using stable isotope analyses of keratinous tissues (hair, feathers), each of them with their own advantages and limitations. Here, we compared results provided by four different methods to estimate dispersal (three already published and one novel) in animals using stable isotope measurements. We used a single large dataset of feather δ2H values from golden‐winged warblers (Vermivora chrysoptera) representing five different populations breeding in North America to compare model results. We propose one method as the most adequately supported by data, and we used this method to demonstrate how biological factors explaining dispersal status can be identified and geographical origins of immigrants inferred. Our results point to a generalized methodological approach to using stable isotope data to study immigration and dispersal in birds and other animals

p53 missense but not truncation mutations are associated with low levels of p21CIP1/WAF1 mRNA expression in primary human sarcomas

Many growth-suppressing signals converge to control the levels of the CDK inhibitor p21CIP1/WAF1. Some human cancers exhibit low levels of expression of p21CIP1/WAF1and mutations in p53 have been implicated in this down-regulation. To evaluate whether the presence of p53 mutations was related to the in vivo expression of p21CIP1/WAF1 mRNA in sarcomas we measured the p21CIP1/WAF1 mRNA levels for a group of 71 primary bone and soft tissue tumours with known p53 status. As expected, most tumours with p53 mutations expressed low levels of p21CIP1/WAF1 mRNA. However, we identified a group of tumours with p53 gene mutations that exhibited normal or higher levels of p21CIP1/WAF1 mRNA. The p53 mutations in the latter group were not the common missense mutations in exons 4–9, but were predominantly nonsense mutations predicted to result in truncation of the p53 protein. The results of this study suggest that different types of p53 mutations can have different effects on the expression of downstream genes such as p21CIP1/WAF1 in human sarcomas. © 2001 Cancer Research Campaign http://www.bjcancer.co