Biological therapy for the prevention and treatment of postoperative endoscopic recurrence in Crohn's disease: time for acceptance?

In most patients, postoperative endoscopic recurrence (PER) occurs 1 year after abdominal resection for Crohn’s disease (CD). Preventing PER is essential for disease control, as most patients develop further clinical and surgical recurrences. Conventional therapy with nitroimidazoles, aminosalicylates, and immunomodulators have limited efficacy for preventing PER. Initial trials with biological therapy (infliximab and adalimumab) showed promising results in preventing PER, and the efficacy of these drugs seems higher than that with conventional therapy. The aim of this review is to outline the results of studies that used infliximab or adalimumab for preventing and treating PER in CD patients. Data with both agents are available, and a few, small prospective trials have shown the efficacy of these drugs in patients with a high risk for recurrence. We believe that, in 2013, biological agents will be better accepted for the prevention PER in CD patients, in addition to the already existing data. Larger trials are still underway, and their results will certainly determine the role of these agents in PER, which develops after bowel resection for CD.

Comparative efficacy and safety of biosimilar infliximab and other biological treatments in ankylosing spondylitis: systematic literature review and meta-analysis.

OBJECTIVES: To compare the efficacy and safety of infliximab-biosimilar with other biological drugs for the treatment of active ankylosing spondylitis (AS). METHODS: Systematic literature review for randomized controlled trials (RCTs) with adalimumab, etanercept, golimumab, infliximab and infliximab-biosimilar in AS was performed and indirect meta-analysis (Bayesian mixed treatment comparison) was carried out. The proportion of patients reaching 20 % improvement by the assessment of Spondyloarthritis International Society response criteria (ASAS20) at weeks 12 and 24 was used as efficacy endpoints, and the occurrence of serious adverse events at week 24 was applied to compare the safety of the biologicals. RESULTS: Altogether, 13 RCTs, identified by the systematic literature search, were included in the analysis. Results on the ASAS20 efficacy endpoint were reported for week 12 in 12 RCTs involving 2,395 patients, and for week 24 in 5 RCTs comprising 1,337 patients. All the five biological agents proved to be significantly superior to placebo. Infliximab showed the highest odds ratio (OR) of 7.2 (95 % CI 3.68-13.19) compared to placebo, followed by infliximab-biosimilar with OR 6.25 (95 % CI 2.55-13.14), both assessed at week 24. No significant difference was found between infliximab-biosimilar and other biological treatments regarding their efficacy and safety. CONCLUSIONS: This is the first study which includes a biosimilar drug in the meta-analysis of biological treatments in AS. The results have proven the similar efficacy and safety profile of infliximab-biosimilar treatment compared to other biologicals.

Efficacy and safety of infliximab-biosimilar compared to other biological drugs in rheumatoid arthritis: a mixed treatment comparison.

OBJECTIVE: The aim of this meta-analysis was to compare the efficacy and safety of infliximab-biosimilar and other available biologicals for the treatment of rheumatoid arthritis (RA), namely abatacept, adalimumab, certolizumab pegol, etanercept, golimumab, infliximab, rituximab and tocilizumab. METHODS: A systematic literature review of MEDLINE database until August 2013 was carried out to identify relevant randomized controlled trials (RCTs). Bayesian mixed treatment comparison method was applied for the pairwise comparison of treatments. Improvement rates by the American College of Rheumatology criteria (ACR20 and ACR50) at week 24 were used as efficacy endpoints, and the occurrence of serious adverse events was considered to assess the safety of the biologicals. RESULTS: Thirty-six RCTs were included in the meta-analysis. All the biological agents proved to be superior to placebo. For ACR20 response, certolizumab pegol showed the highest odds ratio (OR) compared to placebo, OR 7.69 [95 % CI 3.69-14.26], followed by abatacept OR 3.7 [95 % CI 2.17-6.06], tocilizumab OR 3.69 [95 % CI 1.87-6.62] and infliximab-biosimilar OR 3.47 [95 % CI 0.85-9.7]. For ACR50 response, certolizumab pegol showed the highest OR compared to placebo OR 8.46 [3.74-16.82], followed by tocilizumab OR 5.57 [95 % CI 2.77-10.09], and infliximab-biosimilar OR 4.06 [95 % CI 1.01-11.54]. Regarding the occurrence of serious adverse events, the results show no statistically significant difference between infliximab-biosimilar and placebo, OR 1.87 [95 % CI 0.74-3.84]. No significant difference regarding efficacy and safety was found between infliximab-biosimilar and the other biological treatments. CONCLUSION: This is the first indirect meta-analysis in RA that compares the efficacy and safety of biosimilar-infliximab to the other biologicals indicated in RA. We found no significant difference between infliximab-biosimilar and other biological agents in terms of clinical efficacy and safety.

Microassembly fabrication of tissue engineering scaffolds with customized design

Browse > Journals> Automation Science and Enginee ...> Volume: 5 Issue: 3 Microassembly Fabrication of Tissue Engineering Scaffolds With Customized Design 4468741 abstract Han Zhang; Burdet, E.; Poo, A.N.; Hutmacher, D.W.; GE Global Res. Center Ltd., Shanghai This paper appears in: Automation Science and Engineering, IEEE Transactions on Issue Date: July 2008 Volume: 5 Issue:3 On page(s): 446 - 456 ISSN: 1545-5955 Digital Object Identifier: 10.1109/TASE.2008.917011 Date of Current Version: 02 July 2008 Sponsored by: IEEE Robotics and Automation Society Abstract This paper presents a novel technique to fabricate scaffold/cell constructs for tissue engineering by robotic assembly of microscopic building blocks (of volume 0.5$,times,$0.5$,times,$0.2 ${hbox{mm}}^{3}$ and 60 $mu {hbox{m}}$ thickness). In this way, it becomes possible to build scaffolds with freedom in the design of architecture, surface morphology, and chemistry. Biocompatible microparts with complex 3-D shapes were first designed and mass produced using MEMS techniques. Semi-automatic assembly was then realized using a robotic workstation with four degrees of freedom integrating a dedicated microgripper and two optical microscopes. Coarse movement of the gripper is determined by pattern matching in the microscopes images, while the operator controls fine positioning and accurate insertion of the microparts. Successful microassembly was demonstrated using SU-8 and acrylic resin microparts. Taking advantage of parts distortion and adhesion forces, which dominate at micro-level, the parts cleave together after assembly. In contrast to many current scaffold fabrication techniques, no heat, pressure, electrical effect, or toxic chemical reaction is involved, a critical condition for creating scaffolds with biological agents.

Does the p38 MAP kinase inhibitor pamapimod have potential for the treatment of rheumatoid arthritis?

Background: Methotrexate alone or in combination with other agents is the standard treatment for moderate-to-severe rheumatoid arthritis. As the biological agents are expensive, they are not usually used until methotrexate has failed to give a good response. Thus, there is scope for the development of cheaper drugs that can be used instead of methotrexate or in addition to methotrexate. Objectives/methods: Pamapimod is a p38α inhibitor being developed for use in the treatment of rheumatoid arthritis. The objective was to evaluate the recent clinical trials of pamapimod in subjects with rheumatoid arthritis. Results: There is no clear cut evidence that pamapimod alone or in the presence of methotrexate is efficacious in subjects with rheumatoid arthritis, but it does cause adverse effects. Conclusion: It is unlikely that pamapimod will be useful in the treatment of rheumatoid arthritis.

A rapid and sensitive UPLC-ESI MS method for analysis of isofraxidin, a natural antistress compound, and its metabolites in rat plasma

Isofraxidin is one of the main bioactive constituents in the root of Acanthopanax senticosus, which has antifatigue, antistress, and immuno-accommondating effects. In this study, an ultraperformance LC (UPLC)-ESI MS method was developed for analyzing isofraxidin and its metabolites in rat plasma. The analysis was performed on a UPLC coupled with ESI MS (quadropole MS tandem TOF MS). The lower LOD (LLOD) for isofraxidin was 0.25 ng/mL, the intraday precision was less than 10%, the interday precision was less than 10%, and the extraction recovery was more than 80%. Isofraxidin and two metabolites (M1 and M2) were detected in rat plasma after oral administration of isofraxidin, and the molecular polarities of M1 and M2 were both increased compared to isofraxidin. The metabolites were identified as 5,6-dihydroxyl-7-methoxycoumarin and 5-hydroxyl-6,7-dimethoxycoumarin when subjected to parent ion spectra, product ion spectra, and extract mass and element composition analyses.

Environmental contributions to childhood cancers

Recent increases in incidence of childhood cancers cannot be explained by genetic factors. Identifying the environmental risk factors that may explain increases in cancer incidence is an important step to reduce the overall burden of disease. The risk factors for which the most evidence exists include ionising radiation, ultraviolet radiation and chemicals such as benzene and pesticides, biological agents as well as parental smoking and parental substance use. Regarding the link between exposure to non-ionising radiation and development of cancer, the evidence was limited. Maternal vitamin supplementation may reduce the risk of cancer in offspring. Environmental exposures encountered during development and early childhood may be even more important contributors to the risk of cancer than exposures in adulthood and the early developmental period presents an important opportunity for cancer prevention.

Robotic detection and tracking of Crown-Of-Thorns starfish

This paper presents a novel vision-based underwater robotic system for the identification and control of Crown-Of-Thorns starfish (COTS) in coral reef environments. COTS have been identified as one of the most significant threats to Australia's Great Barrier Reef. These starfish literally eat coral, impacting large areas of reef and the marine ecosystem that depends on it. Evidence has suggested that land-based nutrient runoff has accelerated recent outbreaks of COTS requiring extensive use of divers to manually inject biological agents into the starfish in an attempt to control population numbers. Facilitating this control program using robotics is the goal of our research. In this paper we introduce a vision-based COTS detection and tracking system based on a Random Forest Classifier (RFC) trained on images from underwater footage. To track COTS with a moving camera, we embed the RFC in a particle filter detector and tracker where the predicted class probability of the RFC is used as an observation probability to weight the particles, and we use a sparse optical flow estimation for the prediction step of the filter. The system is experimentally evaluated in a realistic laboratory setup using a robotic arm that moves a camera at different speeds and heights over a range of real-size images of COTS in a reef environment.

Nuisance fly management on cattle feedlots

The Project will assess the impact of chemical applications and more targeted cleaning on nuisance fly control in feedlots. It will develop and evaluate new, biological agents for the control of nuisance flies and explore options for integration of these.

The emerging role of microRNAs in resistance to lung cancer treatments

One of the major challenges in the treatment of lung cancer is the development of drug resistance. This represents a major obstacle in the treatment of patients, limiting the efficacy of both conventional chemotherapy and biological therapies. Deciphering the mechanisms of resistance is critical to further understanding the multifactorial pathways involved, and in developing more specific targeted treatments. To date, numerous studies have reported the potential role of microRNAs (miRNAs) in resistance to various cancer treatments. MicroRNAs are a family of small non-coding RNAs that regulate gene expression by sequence-specific targeting of mRNAs causing translational repression or mRNA degradation. More than 1200 validated human miRNAs have been identified to date. While as little as one miRNA can regulate hundreds of targets, a single target can also be affected by multiple miRNAs. Evidence suggests that dysregulation of specific miRNAs may be involved in the acquisition of resistance to a number of cancer treatments, thereby modulating the sensitivity of cancer cells to such therapies. Therefore, targeting miRNAs may be an attractive strategy for developing novel and more effective individualized therapies, improving drug efficiency, and for predicting patient response to different treatments. In this review, we provide an overview on the role of miRNAs in resistance to current lung cancer therapies and novel biological agents.

Avaliação das condições ambientais e de trabalho em salas cirúrgicas e de necropsia - estudos de casos em hospitais públicos e IMLs da região metropolitana do Rio de Janeiro

A qualidade do ar é um importante indicador de saúde ambiental, sendo o seu monitoramento contínuo necessário. Apesar da relevância do tema, há muitos países em que os limites de exposição para agentes biológicos ainda não foram estabelecidos ou foram definidos de forma inadequada, podendo comprometer a qualidade ambiental. Os ambientes hospitalares, assim como as salas de necropsia podem apresentar problemas de contaminação do ar por agentes microbiológicos, necessitando de monitoramento contínuo a fim de evitar a ocorrência de doenças nos trabalhadores e na população em geral. Este estudo realizou a avaliação microbiológica do ar em hospitais públicos e IMLs da região metropolitana do Rio de Janeiro em salas cirúrgicas e de necropsia. A pesquisa exploratória e descritiva baseou-se em levantamento bibliográfico e investigação de campo, através de estudos de casos. Os dados foram obtidos por meio de entrevistas e observação direta nos locais de trabalho, onde foram realizadas as avaliações microbiológicas do ar. As variações em salas cirúrgicas para bactérias e fungos foram respectivamente de 14,99 ufc/m3 88,29 ufc/m3 e de 45,93 ufc/m3 - 742,09 ufc/m3. Já nas salas de necropsia os valores para bactérias e fungos variaram respectivamente de 18,96 ufc/m3 54,9 ufc/m3 e de 144,87 ufc/m3 - 1152,01 ufc/m3. Foram identificados tanto no ambiente cirúrgico como nas salas de necropsia a presença dos seguintes fungos: Aspergillus sp., Neurospora sp., Penicillium sp., Fusarium sp., Cladosporium sp., Curvularia sp., e Trichoderma sp. Já em relação às bactérias foram identificadas as presenças de Staphilococcus sp., Streptococcus sp. e Micrococcus sp. Foram traçadas recomendações para melhoria da qualidade ambiental e do ar. Os resultados indicaram que os valores são elevados quando comparados com as recomendações das normas internacionais. Foram encontrados valores inferiores aos sugeridos pela CP n. 109 da ANVISA. A presença de microrganismos patogênicos sugere adoção de medidas de controle ambiental. O estudo apontou a necessidade urgente do estabelecimento de valores de referência para ambientes hospitalares no Brasil a fim de garantir condições seguras que não venham a comprometer a saúde dos pacientes e profissionais de saúde envolvidos.

Direct detection of Yersinia pestis from the infected animal specimens by a fiber optic biosensor

The FOB-3, anew type fiber optic biosensor, is designed to rapidly detect a variety of biological agents or analytes with better stability, sensitivity and specificity. In order to detect Y. Pestis, a sandwich immunoassay was developed by using the purified antibody against antigen FI immobilized on polystyrene probes as the capture antibody and the monoclonal antibody-Cy5 conjugate as the detector. After a series of optimization for the stability, sensitivity and specificity of the FOB-3, 50-1000 ng/ml of antigen FI and 6 x 10(1)-6 x 10(7) CFU/ml Y. pestis could be detected constantly in about 20 min, and Y pestis could be detected specifically from Y. pseudotuberculosis, Y. enterocolitica, B. anthracis and E. coli. Then, 39 blind samples, including 27 tissues of mice infected with Y pestis and 12 tissues of healthy mice as negative control, were detected with the FOB-3. 92.6% infected tissues were identified from the tissues of healthy mice and the tissues containing more than 100 CFU/ml bacteria could be detected by the biosensor. The results demonstrated the feasibility of the FOB-3 as an effective method to detect Y. pestis rapidly and directly from the infected animal specimens with the advantage of portability, simple-operation as well as high sensitivity and specificity. (c) 2006 Elsevier B.V. All rights reserved.

Advanced carbon nanotubes and carbon nanotube fibers for biosensing applications

Since the discovery of Carbon Nanotubes (CNTs) by Iijima in 1991[1, 2], there has been an explosion of research into the physical and chemical properties of this novel material. CNT based biosensors can play an important role in amperometric, immunosensor and nucleic-acid sensing devices, e.g. for detection of life threatening biological agents in time of war or in terrorist attacks, saving life and money for the NHS. CNTs offer unique advantages in several areas, like high surfacevolume ratio, high electrical conductivity, chemical stability and strong mechanical strength, and CNT based sensors generally have higher sensitivities and lower detection limit than conventional ones. In this review, recent advances in biosensors utilising carbon nanotubes and carbon nanotube fibres will be discussed. The synthesis methods, nanostructure approaches and current developments in biosensors using CNTs will be introduced in the first part. In the second part, the synthesis methods and up-to-date progress in CNT fibre biosensors will be reviewed. Finally, we briefly outline some exciting applications for CNT and CNT fibres which are being targeted. By harnessing the continual advancements in micro and nano- technology, the functionality and capability of CNT-based biosensors will be enhanced, thus expanding and enriching the possible applications that can be delivered by these devices. © 2012 Bentham Science Publishers. All rights reserved.

Introduction to the BASIN Special Issue: State of art, past present a view to the future

Marine ecosystems are complex networks of organisms interacting either directly or indirectly while under the influence of the physical and chemical properties of the medium they inhabit. The interplay between these biological agents and their abiotic environment results in complex non-linear responses to individual and multiple stressors, influenced by feedbacks between these organisms and their environment. These ecosystems provide key services that benefit humanity such as food provisioning via the transfer of energy to exploited fish populations or climate regulation via the sinking, subsequent mineralization and ultimately storage of carbon in the ocean interior. These key characteristics or emergent features of marine ecosystems are subject to rapid change (e.g. regime shifts; Alheit et al., 2005 and Scheffer et al., 2009), with outcomes that are largely unpredictable in a deterministic sense. The North Atlantic Ocean is host to a number of such systems which are collectively being influenced by the unique physical and chemical features of this ocean basin, such as the Atlantic Meridional Overturning Circulation (AMOC), the basin’s ventilation with the Arctic Ocean, the dynamics of heat transport via the Gulf Stream and the formation of deep water at high latitudes. These features drive the solubility and biological pumps and support the production and environments that results in large exploited fish stocks. Our knowledge of its functioning as a coupled system, and in particular how it will respond to change, is still limited despite the scientific effort exerted over more than 100 years. This is due in part to the difficulty of providing synoptic overviews of a vast area, and to the fact that most fieldwork provides only snapshots of the complex physical, chemical and biological processes and their interactions. These constraints have in the past limited the development of a mechanistic understanding of the basin as a whole, and thus of the services it provides.

Direct, positive feedbacks produce instability in models of interrelationships among soil structure, plants and arbuscular mycorrhizal fungi

Current conceptual models of reciprocal interactions linking soil structure, plants and arbuscular mycorrhizal fungi emphasise positive feedbacks among the components of the system. However, dynamical systems with high dimensionality and several positive feedbacks (i.e. mutualism) are prone to instability. Further, organisms such as arbuscular mycorrhizal fungi (AMF) are obligate biotrophs of plants and are considered major biological agents in soil aggregate stabilization. With these considerations in mind, we developed dynamical models of soil ecosystems that reflect the main features of current conceptual models and empirical data, especially positive feedbacks and linear interactions among plants, AMF and the component of soil structure dependent on aggregates. We found that systems become increasingly unstable the more positive effects with Type I functional response (i.e., the growth rate of a mutualist is modified by the density of its partner through linear proportionality) are added to the model, to the point that increasing the realism of models by adding linear effects produces the most unstable systems. The present theoretical analysis thus offers a framework for modelling and suggests new directions for experimental studies on the interrelationship between soil structure, plants and AMF. Non-linearity in functional responses, spatial and temporal heterogeneity, and indirect effects can be invoked on a theoretical basis and experimentally tested in laboratory and field experiments in order to account for and buffer the local instability of the simplest of current scenarios. This first model presented here may generate interest in more explicitly representing the role of biota in soil physical structure, a phenomenon that is typically viewed in a more process- and management-focused context. (C) 2011 Elsevier Ltd. All rights reserved.