Prognostic implications of immunohistochemically detected YKL-40 expression in breast cancer

BACKGROUND: YKL-40 has been implicated as a mediator of collagen synthesis and extracellular matrix re-modeling as well as mitogenesis. Elevated serum levels of YKL-40 have been associated with worse survival in a variety of malignancies including breast cancer. We wished to determine if immunohistochemically detected expression had prognostic implications in breast cancer. METHODS: A prospectively collected database of breast cancer patients treated at the University Hospital of Newark was used for analysis. Immunohistochemistry was performed on archived tumor tissue from 109 patients for whom full clinical information and follow up was available. RESULTS: YKL-40 expression was noted in 37 patients (34%). YKL-40 immunoreactivity significantly correlated with larger tumor size, poorer tumor differentiation, and a greater likelihood of being estrogen and/or progesterone receptor negative. No significant correlation was demonstrated between YKL-40 status and nodal stage. At a mean follow up of 3.2 years, disease-free survival was significantly worse in the subset of patients whose tumors demonstrated YKL-40 expression compared to the non-expressors. In multivariate analysis, YKL-40 status was independent of T-stage and N-stage in predicting disease recurrence. CONCLUSION: Immunoreactivity for YKL-40 was a significant predictor of breast cancer relapse in this subset of patients. This was independent of T or N-stage and suggests that tumor immunohistochemistry for this protein may be a valuable prognostic marker in breast cancer

Optimized microwave illusion device

This work was funded by the Engineering and Physical Sciences Research Council (EPSRC), UK under a Programme Grant (EP/I034548/1) ‘The Quest for Ultimate Electromagnetics using Spatial Transformations (QUEST

"Death is a better option than being treated like this" : a prevalence survey and qualitative study of depression among multi-drug resistant tuberculosis in-patients

BACKGROUND: Understanding of the relationship between multi-drug resistant tuberculosis and mental health is limited. With growing prevalence of multi-drug resistant tuberculosis, addressing mental ill-health has potential to improve treatment outcomes and well-being. In several low and middle-income contexts hospitalisation during treatment is common. Understanding of the impact on mental ill-health are required to inform interventions for patients with multi-drug resistant tuberculosis. Our aim was to identify the prevalence of comorbid depression among in-patients being treated for multi-drug resistant tuberculosis and to explore their experiences of comorbid disease and the care they received in a large specialist chest hospital in Dhaka, Bangladesh. METHODS: We conducted a quantitative cross-sectional survey among 150 multi-drug resistant tuberculosis in-patients (new cases = 34%, previously treated = 66%) in 2018. A psychiatrist assessed depression was assessed with the Structured Clinical Interview for Depression (SCID DSM-IV). We used multi-level modelling to identify associations with depression. Experience Bangladeshi researchers conducted qualitative interviews with 8 patients, 4 carers, 4 health professionals and reflective notes recorded. Qualitative data was analysed thematically. RESULTS: We found 33.8% (95% CI 26.7%; 41.7%) of patients were depressed. While more women were depressed 39.3% (95% CI 27.6%; 52.4%) than men 30.4% (95% CI 22%; 40.5%) this was not significant. After controlling for key variables only having one or more co-morbidity (adjusted odds ratio [AOR] = 2.88 [95% CI 1.13; 7.33]) and being a new rather than previously treated case (AOR = 2.33 [95% CI 1.06; 5.14]) were associated (positively) with depression. Qualitative data highlighted the isolation and despair felt by patients who described a service predominantly focused on providing medicines. Individual, familial, societal and health-care factors influenced resilience, nuanced by gender, socio-economic status and home location. CONCLUSIONS: Patients with multi-drug resistant tuberculosis are at high risk of depression, particularly those with co- and multi-morbidities. Screening for depression and psycho-social support should be integrated within routine TB services and provided throughout treatment

YKL-40 tissue expression and plasma levels in patients with ovarian cancer

<p>Abstract</p> <p>Background</p> <p>YKL-40 (chitinase-3-like-1) is a member of "mammalian chitinase-like proteins". The protein is expressed in many types of cancer cells and the highest plasma YKL-40 levels have been found in patients with metastatic disease, short recurrence/progression-free intervals, and short overall survival. The aim of the study was to determine the expression of YKL-40 in tumor tissue and plasma in patients with borderline ovarian tumor or epithelial ovarian cancer (OC), and investigate prognostic value of this marker.</p> <p>Methods</p> <p>YKL-40 protein expression was determined by immunohistochemistry in tissue arrays from 181 borderline tumors and 473 OC. Plasma YKL-40 was determined by ELISA in preoperative samples from 19 patients with borderline tumor and 76 OC patients.</p> <p>Results</p> <p>YKL-40 protein expression was found in cancer cells, tumor associated macrophages, neutrophils and mast cells. The tumor cell expression was higher in OC than in borderline tumors (p = 0.001), and associated with FIGO stage (p < 0.0001) and histological subtype (p = 0.0009). Positive YKL-40 expression (≥ 5% staining) was not associated with reduced survival. Plasma YKL-40 was also higher in patients with OC than in patients with borderline tumors (p < 0.0001), and it was positively correlated to serum CA-125 (p < 0.0001) and FIGO stage (p = 0.0001). Univariate Cox analysis of plasma YKL-40 showed association with overall survival (p < 0.0001). Multivariate Cox analysis, including plasma YKL-40, serum CA125, FIGO stage, age and radicality after primary surgery as variables, showed that elevated plasma YKL-40 was associated with a shorter survival (HR = 2.13, 95% CI: 1.40–3.25, p = 0.0004).</p> <p>Conclusion</p> <p>YKL-40 in OC tissue and plasma are related to stage and histology, but only plasma YKL-40 is a prognostic biomarker in patients with OC.</p

Simple molecular networks that respond optimally to time-periodic stimulation

<p>Abstract</p> <p>Background</p> <p>Bacteria or cells receive many signals from their environment and from other organisms. In order to process this large amount of information, Systems Biology shows that a central role is played by regulatory networks composed of genes and proteins. The objective of this paper is to present and to discuss simple regulatory network motifs having the property to maximize their responses under time-periodic stimulations. In elucidating the mechanisms underlying these responses through simple networks the goal is to pinpoint general principles which optimize the oscillatory responses of molecular networks.</p> <p>Results</p> <p>We took a look at basic network motifs studied in the literature such as the Incoherent Feedforward Loop (IFFL) or the interlerlocked negative feedback loop. The former is also generalized to a diamond pattern, with network components being either purely genetic or combining genetic and signaling pathways. Using standard mathematics and numerical simulations, we explain the types of responses exhibited by the IFFL with respect to a train of periodic pulses. We show that this system has a non-vanishing response only if the inter-pulse interval is above a threshold. A slight generalisation of the IFFL (the diamond) is shown to work as an ideal pass-band filter. We next show a mechanism by which average of oscillatory response can be maximized by bursting temporal patterns. Finally we study the interlerlocked negative feedback loop, i.e. a 2-gene motif forming a loop where the nodes respectively activate and repress each other, and show situations where this system possesses a resonance under periodic stimulation.</p> <p>Conclusion</p> <p>We present several simple motif designs of molecular networks producing optimal output in response to periodic stimulations of the system. The identified mechanisms are simple and based on known network motifs in the literature, so that that they could be embodied in existing organisms, or easily implementable by means of synthetic biology. Moreover we show that these designs can be studied in different contexts of molecular biology, as for example in genetic networks or in signaling pathways.</p

The Political Economy of Non-Traditional Security: Explaining the Governance of Avian Influenza in Indonesia

Given the common association of non-traditional security (NTS) problems with globalisation, surprisingly little attention has been paid to how the political economy context of given NTS issues shape how they are securitised and managed in practice. We argue that security and its governance are always highly contested because different modes of security governance invariably privilege particular interests and normative agendas in state and society, which relate directly to the political economy. Drawing on critical political geography, we argue that, because NTS issues are perceived as at least potentially transnational, their securitisation often involves strategic attempts by actors and coalitions to ‘rescale’ their governance beyond the national political and institutional arenas, into new, expert-dominated modes of governance. Such efforts are often resisted by other coalitions, for which this rescaling is deleterious. As evidenced by a case study of avian influenza in Indonesia, particular governance outcomes depend upon the nature of the coalitions assembled for and against rescaling in specific situations, while these coalitions’ make-up and relative strength is shaped by the political economy of the industries that rescaling would affect, viewed against the broader backdrop of state-society relations

The Use of High Performance Liquid Chromatography for the Characterization of the Unfolding and Aggregation of Dairy Proteins

peer-reviewedHigh-performance liquid chromatography (HPLC) is routinely used to identify and characterize proteins. HPLC can help to understand protein aggregation processes in dairy products, which are induced by common industrial processing steps such as heat treatment. In this chapter, three complementary chromatographic methods are described, which are based on the principles of size exclusion and reversed-phase chromatography. These methods are used to determine the degree of denaturation and aggregation of proteins, and estimate the molecular weight of these aggregates