A critical review of the limitations of current diagnostic techniques for schistosomiasis

Schistosomiasis is a parasitic disease that is endemic in tropical and subtropical areas. Its diagnosis is crucial for effective treatment and control, particularly in resource-limited settings where the disease burden is high. Various diagnostic methods are available. However, these methods are associated with low accuracy, efficiency or accessibility. This review summarizes the published literature on the diagnostics of schistosomiasis based on the techniques of microscopy, serology, molecular, antigen-based and aptamer-based assays. The limitations of each technique were summarized to encourage future research. Furthermore, we highlight the need for point-of-care diagnostics that are sensitive, specific, and easy to use in resource-limited settings may address the challenges associated with commonly used diagnostic techniques. The review concludes that further research and development are needed to improve the diagnosis of schistosomiasis and enable effective treatment and control of this debilitating disease

The Role of Fibrocytes in Sickle Cell Lung Disease

<div><h3>Background</h3><p>Interstitial lung disease is a frequent complication in sickle cell disease and is characterized by vascular remodeling and interstitial fibrosis. Bone marrow-derived fibrocytes have been shown to contribute to the pathogenesis of other interstitial lung diseases. The goal of this study was to define the contribution of fibrocytes to the pathogenesis of sickle cell lung disease.</p> <h3>Methodology/Principal Findings</h3><p>Fibrocytes were quantified and characterized in subjects with sickle cell disease or healthy controls, and in a model of sickle cell disease, the NY1DD mouse. The role of the chemokine ligand CXCL12 in trafficking of fibrocytes and phenotype of lung disease was examined in the animal model. We found elevated concentration of activated fibrocytes in the peripheral blood of subjects with sickle cell disease, which increased further during vaso-occlusive crises. There was a similar elevations in the numbers and activation phenotype of fibrocytes in the bone marrow, blood, and lungs of the NY1DD mouse, both at baseline and under conditions of hypoxia/re-oxygenation. In both subjects with sickle cell disease and the mouse model, fibrocytes expressed a hierarchy of chemokine receptors, with CXCR4 expressed on most fibrocytes, and CCR2 and CCR7 expressed on a smaller subset of cells. Depletion of the CXCR4 ligand, CXCL12, in the mouse model resulted in a marked reduction of fibrocyte trafficking into the lungs, reduced lung collagen content and improved lung compliance and histology.</p> <h3>Conclusions</h3><p>These data support the notion that activated fibrocytes play a significant role in the pathogenesis of sickle cell lung disease.</p> </div

Pre-operative chemotherapy in early stage resectable non-small-cell lung cancer: a randomized feasibility study justifying a multicentre phase III trial

Surgical resection offers the best chance for cure for early stage non-small-cell lung cancer (NSCLC, stage I, II, IIIA), but the 5-year survival rates are only moderate, with systemic relapse being the major cause of death. Pre-operative (neo-adjuvant) chemotherapy has shown promise in small trials restricted to stage IIIA patients. We believe similar trials are now appropriate in all stages of operable lung cancer. A feasibility study was performed in 22 patients with early stage (IB, II, IIIA) resectable NSCLC; randomized to either three cycles of chemotherapy [mitomycin-C 8 mg m−2, vinblastine 6 mg m−2 and cisplatin 50 mg m−2 (MVP)] followed by surgery (n = 11), or to surgery alone. Of 40 eligible patients, 22 agreed to participate (feasibility 55%) and all complied with the full treatment schedule. All symptomatic patients achieved either complete (50%) or partial (50%) relief of tumour-related symptoms with pre-operative chemotherapy. Fifty-five per cent achieved objective tumour response, and a further 27% minor tumour shrinkage; none had progressive disease. Partial pathological response was seen in 50%. No severe (WHO grade III–IV) toxicities occurred. No significant deterioration in quality of life was detected during chemotherapy. Pre-operative MVP chemotherapy is feasible in early stage NSCLC, and this study has now been initiated as a UK-wide Medical Research Council phase III trial. © 1999 Cancer Research Campaig

Identification of Estrogen Receptor Dimer Selective Ligands Reveals Growth-Inhibitory Effects on Cells That Co-Express ERα and ERβ

Estrogens play essential roles in the progression of mammary and prostatic diseases. The transcriptional effects of estrogens are transduced by two estrogen receptors, ERα and ERβ, which elicit opposing roles in regulating proliferation: ERα is proliferative while ERβ is anti-proliferative. Exogenous expression of ERβ in ERα-positive cancer cell lines inhibits cell proliferation in response to estrogen and reduces xenografted tumor growth in vivo, suggesting that ERβ might oppose ERα's proliferative effects via formation of ERα/β heterodimers. Despite biochemical and cellular evidence of ERα/β heterodimer formation in cells co-expressing both receptors, the biological roles of the ERα/β heterodimer remain to be elucidated. Here we report the identification of two phytoestrogens that selectively activate ERα/β heterodimers at specific concentrations using a cell-based, two-step high throughput small molecule screen for ER transcriptional activity and ER dimer selectivity. Using ERα/β heterodimer-selective ligands at defined concentrations, we demonstrate that ERα/β heterodimers are growth inhibitory in breast and prostate cells which co-express the two ER isoforms. Furthermore, using Automated Quantitative Analysis (AQUA) to examine nuclear expression of ERα and ERβ in human breast tissue microarrays, we demonstrate that ERα and ERβ are co-expressed in the same cells in breast tumors. The co-expression of ERα and ERβ in the same cells supports the possibility of ERα/β heterodimer formation at physio- and pathological conditions, further suggesting that targeting ERα/β heterodimers might be a novel therapeutic approach to the treatment of cancers which co-express ERα and ERβ

Emerging themes to support ambitious UK marine biodiversity conservation

Healthy marine ecosystems provide a wide range of resources and services that support life on Earth and contribute to human wellbeing. Marine Protected Areas (MPAs) are accepted as an important tool for the restoration and maintenance of marine ecosystem structure, function, health and ecosystem integrity through the conservation of significant species, habitats, or entire ecosystems. In recent years there has been a rapid expansion in the area of ocean designated as an MPA. Despite this progress in spatial protection targets and the progressive knowledge of the essential interdependence between the human and the ocean system, marine biodiversity continues to decline, placing in jeopardy the range of ecosystem services benefits humans rely on. There is a need to address this shortcoming. Ambitious marine conservation:• Requires a shift from managing individual marine features within MPAs to whole-sites to enable repair and renewal of marine systems;• Reflects an ambition for sustainable livelihoods by fully integrating fisheries management with conservation (Ecosystem Based Fisheries Management) as the two are critically interdependent;• Establishes a world class and cost effective ecological and socio-economic monitoring and evaluation framework that includes the use of controls and sentinel sites to improve sustainability in marine management; and• Challenges policy makers and practitioners to be progressive by integrating MPAs into the wider seascape as critical functional components rather than a competing interest and move beyond MPAs as the only tool to underpin the benefits derived from marine ecosystems by identifying other effective area-based conservation measures (OECMs) to establish synergies with wider governance frameworks