The parasitic worm-derived immunomodulator, ES-62 and its drug-like small molecule analogues exhibit therapeutic potential in a model of chronic asthma

Chronic asthma is associated with persistent lung inflammation and long-term remodelling of the airways that have proved refractory to conventional treatments such as steroids, despite their efficacy in controlling acute airway contraction and bronchial inflammation. As its recent dramatic increase in industrialised countries has not been mirrored in developing regions, it has been suggested that helminth infection may protect humans against developing asthma. Consistent with this, ES-62, an immunomodulator secreted by the parasitic worm Acanthocheilonema viteae, can prevent pathology associated with chronic asthma (cellular infiltration of the lungs, particularly neutrophils and mast cells, mucus hyper-production and airway thickening) in an experimental mouse model. Importantly, ES-62 can act even after airway remodelling has been established, arresting pathogenesis and ameliorating the inflammatory flares resulting from repeated exposure to allergen that are a debilitating feature of severe chronic asthma. Moreover, two chemical analogues of ES-62, 11a and 12b mimic its therapeutic actions in restoring levels of regulatory B cells and suppressing neutrophil and mast cell responses. These studies therefore provide a platform for developing ES-62-based drugs, with compounds 11a and 12b representing the first step in the development of a novel class of drugs to combat the hitherto intractable disorder of chronic asthma

Dynamic Reorganization of Functional Connectivity Reveals Abnormal Temporal Efficiency in Schizophrenia.

Emerging evidence suggests that schizophrenia is associated with brain dysconnectivity. Nonetheless, the implicit assumption of stationary functional connectivity (FC) adopted in most previous resting-state functional magnetic resonance imaging (fMRI) studies raises an open question of schizophrenia-related aberrations in dynamic properties of resting-state FC. This study introduces an empirical method to examine the dynamic functional dysconnectivity in patients with schizophrenia. Temporal brain networks were estimated from resting-state fMRI of 2 independent datasets (patients/controls = 18/19 and 53/57 for self-recorded dataset and a publicly available replication dataset, respectively) by the correlation of sliding time-windowed time courses among regions of a predefined atlas. Through the newly introduced temporal efficiency approach and temporal random network models, we examined, for the first time, the 3D spatiotemporal architecture of the temporal brain network. We found that although prominent temporal small-world properties were revealed in both groups, temporal brain networks of patients with schizophrenia in both datasets showed a significantly higher temporal global efficiency, which cannot be simply attributable to head motion and sampling error. Specifically, we found localized changes of temporal nodal properties in the left frontal, right medial parietal, and subcortical areas that were associated with clinical features of schizophrenia. Our findings demonstrate that altered dynamic FC may underlie abnormal brain function and clinical symptoms observed in schizophrenia. Moreover, we provide new evidence to extend the dysconnectivity hypothesis in schizophrenia from static to dynamic brain network and highlight the potential of aberrant brain dynamic FC in unraveling the pathophysiologic mechanisms of the disease

Diagnosis of lung cancer – improving survival rates

Lung cancer is a major global health burden with high incidence rates but poor long-term survival. Currently, the majority of cases are diagnosed at an advanced stage when surgical resection is not feasible. Screening for lung cancer has been a major focus of research for the last 40 years. Despite this, there is still a lack of evidence to promote its use outside clinical trials. More recently, interest has focused on promoting earlier recognition of symptomatic disease among both the general public and primary care physicians in order to encourage more timely investigation and referral to secondary care. The hope is that this approach may increase the proportion of disease identified in the early tages, allowing more surgical resections and improved five-year survival rates. This article provides an overview of the current evidence base in terms of early diagnosis of lung cancer and provides some examples of innovations to promote this

Assessing the potential of the unexploited Atlantic purple sea urchin, Arbacia punctulata, for the edible market

The global demand for sea urchin as seafood is currently unmet. Despite exploitation of \u3e 40 species across the world, there is a need to identify other candidate species, especially in regions where diversification in production is sought where species are considered native. The Eastern US presents an opportunity to determine the marketability of the currently unexploited Arbacia punctulata which is naturally distributed from Massachusetts and southwards into the Gulf of Mexico. To determine whether A. punctulata had market potential, it was fed one of the following diets to determine whether the gonad tissue (uni) could be manipulated to increase gonad mass and improve gonad color for the market: dried Ulva lactuca, Salmon pellets (Skretting), Tilapia pellets (Ziegler) or an Urchinomics diet designed for sea urchins either fed for 8 weeks or 12 weeks. All of the pelleted feeds (Salmon, Tilapia and Urchinomics) increased gonad mass and altered the color. The colors of the uni were generally darker than the colors that the market would typically prefer but some individuals did exhibit colors which have been classed as acceptable to the European market. This work highlights that further research is worthwhile to assess the market potential of A. punctulata

Long-term effects of altered PH and temperature on the feeding energetics of the Antarctic sea urchin, Sterechinus neumayeri

This study investigated the effects of long-term incubation to near-future combined warming (+2 °C) and ocean acidification (−0.3 and −0.5 pH units) stressors, relative to current conditions (−0.3 °C and pH 8.0), on the energetics of food processing in the Antarctic sea urchin, Sterechinus neumayeri. After an extended incubation of 40 months, energy absorbed, energy lost through respiration and lost as waste were monitored through two feeding cycles. Growth parameters (mass of somatic and gonad tissues and the CHN content of gonad) were also measured. There were no significant effects of combined ocean acidification (OA) and temperature stressors on the growth of somatic or reproductive tissue. Despite more food being consumed in the low temperature control, once food processing and maintenance costs were subtracted, there were no significant effects of treatment on the scope for growth. The biggest significant differences were between amounts of food consumed during the two feeding cycles. More food was consumed by the low temperature (0 °C) control animals, indicating a potential effect of the changed conditions on digestive efficiency. Also, in November, more food was consumed, with a higher absorption efficiency, which resulted in a higher scope for growth in November than September and may reflect increased energetic needs associated with a switch to summer physiology. The effect of endogenous seasonal cycles and environmental variability on organism capacity is discussed

Behavioural interventions for primary and secondary dysmenorrhoea

Background: Dysmenorrhoea refers to the occurrence of painful menstrual cramps of uterine origin and is a common gynaecological condition with considerable morbidity. The behavioural approach assumes that psychological and environmental factors interact with, and influence, physiological processes. Behavioural interventions for dysmenorrhoea may include both physical and cognitive procedures and focus on both physical and psychological coping strategies for dysmenorrhoeic symptoms rather than modification of any underlying organic pathology. Objectives: To determine the effectiveness of any behavioural interventions for the treatment of primary or secondary dysmenorrhoea when compared to each other, placebo, no treatment, or conventional medical treatments for example non-steroidal anti-inflammatory drugs (NSAIDs). Search strategy: We searched the Cochrane Menstrual Disorders and Subfertility Group Trials Register (searched April 2005), Cochrane Central Register of Controlled Trials (CENTRAL on The Cochrane Library, Issue 2, 2005), MEDLINE (1966 to April 2005), EMBASE (1980 to April 2005), Social Sciences Index (1980 to April 2005), PsycINFO (1972 to April 2005) and CINAHL (1982 to April 2005) and reference lists of articles. Selection criteria: Randomised controlled trials comparing behavioural interventions with placebo or other interventions in women with dysmenorrhoea. Data collection and analysis: Two authors independently assessed trial quality and extracted data. Main results: Five trials involving 213 women were included. Behavioural intervention vs control: One trial of pain management training reported reduction in pain and symptoms compared to a control. Three trials of relaxation compared to control reported varied results, two trials showed no difference in symptom severity scores however one trial reported relaxation was effective for reducing symptoms in menstrual sufferers with spasmodic symptoms. Two trials reported less restriction in daily activities following treatment with either relaxation of pain management training compared to a control. One trial also reported less time absent from school following treatment wit pain management training compared to a control. Behavioural intervention vs other behavioural interventions: Three trials showed no difference between behavioural interventions for the outcome of improvement in symptoms. One trial showed that relaxation resulted in a decrease in the need for resting time compared to the relaxation and imagery. Authors' conclusions: There is some evidence from five RCTs that behavioural interventions may be effective for dysmenorrhoea however results should be viewed with caution as they varied greatly between trials due to inconsistency in the reporting of data, small trial size, poormethodological quality and age of the trials

Engaging stakeholders in research to address water-energy-food (WEF) nexus challenges

The water–energy–food (WEF) nexus has become a popular, and potentially powerful, frame through which to analyse interactions and interdependencies between these three systems. Though the case for transdisciplinary research in this space has been made, the extent of stakeholder engagement in research remains limited with stakeholders most commonly incorporated in research as end-users. Yet, stakeholders interact with nexus issues in a variety of ways, consequently there is much that collaboration might offer to develop nexus research and enhance its application. This paper outlines four aspects of nexus research and considers the value and potential challenges for transdisciplinary research in each. We focus on assessing and visualising nexus systems; understanding governance and capacity building; the importance of scale; and the implications of future change. The paper then proceeds to describe a novel mixed-method study that deeply integrates stakeholder knowledge with insights from multiple disciplines. We argue that mixed-method research designs—in this case orientated around a number of cases studies—are best suited to understanding and addressing real-world nexus challenges, with their inevitable complex, non-linear system characteristics. Moreover, integrating multiple forms of knowledge in the manner described in this paper enables research to assess the potential for, and processes of, scaling-up innovations in the nexus space, to contribute insights to policy and decision making

Microcalcifications Detection using PFCM and ANN

This work presents a method to detect Microcalcifications in Regions of Interest from digitized mammograms. The method is based mainly on the combination of Image Processing, Pattern Recognition and Artificial Intelligence. The Top-Hat transform is a technique based on mathematical morphology operations that, in this work is used to perform contrast enhancement of microcalcifications in the region of interest. In order to find more or less homogeneous regions in the image, we apply a novel image sub-segmentation technique based on Possibilistic Fuzzy c-Means clustering algorithm. From the original region of interest we extract two window-based features, Mean and Deviation Standard, which will be used in a classifier based on a Artificial Neural Network in order to identify microcalcifications. Our results show that the proposed method is a good alternative in the stage of microcalcifications detection, because this stage is an important part of the early Breast Cancer detectio

Testing small molecule analogues of acanthocheilonema viteae immunomodulator ES-62 against clinically relevant allergens

ES-62 is a glycoprotein secreted by the filarial nematode Acanthocheilonema viteae that protects against ovalbumin (OVA)-induced airway hyper-responsiveness in mice by virtue of covalently attached anti-inflammatory phosphorylcholine (PC) residues. We have recently generated a library of Small Molecule Analogues (SMAs) of ES-62 based around its active PC moiety as a starting point in novel drug development for asthma, and isolated two compounds - termed 11a and 12b – that mirror ES-62’s protective effects. In the present study we have moved away from OVA, a model allergen, to test the two SMAs against two clinically relevant allergens – house dust mite (HDM) and cockroach allergen (CR) extract. We show that whereas both SMAs offer some protection against development of lung allergic responses to CR, in particular reducing eosinophil infiltration, only SMA 12b is effective in protecting against eosinophil-dependent HDM-induced allergy. These data therefore suggest that helminth molecule-induced protection against model antigens may not necessarily translate to clinically relevant antigens. Nevertheless, in the present study we have managed to demonstrate that it is possible to produce synthetic drug-like molecules based on a parasitic worm product that show therapeutic potential with respect to asthma resulting from known triggers in humans