The role of dietary polyphenols in the moderation of the inflammatory response in early stage colorectal cancer

Current focus in colorectal cancer management is on reducing overall mortality by increasing the number of early stage cancers diagnosed and treated with curative intent. Despite the success of screening programmes in down-staging colorectal cancer, interval cancer rates are substantial and other strategies are desirable. Sporadic colorectal cancer is largely associated with lifestyle factors including diet. Polyphenols are phytochemicals ingested as part of a normal diet which are abundant in plant foods including fruits/berries and vegetables. These may exert their anti-carcinogenic effects via the modulation of inflammatory pathways. Key signal transduction pathways are fundamental to the association of inflammation and disease progression including those mediated by NF-κB and STAT, PI3K and COX. Our aim was to examine the evidence for the effect of dietary polyphenols intake on tumour and host inflammatory responses to determine if polyphenols may be effective as part of a dietary intervention. There is good epidemiological evidence of a reduction in colorectal cancer risk from case-control and cohort studies assessing polyphenol intake. It would be premature to suggest a major public health intervention to promote their consumption however, dietary change is safe and feasible, emphasising the need for further investigation of polyphenols and colorectal cancer risk

Comparison of the prognostic value of measures of the tumor inflammatory cell infiltrate and tumor-associated stroma in patients with primary operable colorectal cancer

The aim of the present study was to compare the clinical utility of two measures of the inflammatory cell infiltrate - a H&E-based assessment of the generalised inflammatory cell infiltrate (the Klintrup-Mäkinen (KM) grade), and an immunohistochemistry-based assessment of combined CD3+ and CD8+ T-cell density (the “Immunoscore”), in conjunction with assessment of the tumor stroma percentage (TSP) in patients undergoing resection of stage I-III colorectal cancer (CRC). 246 patients were identified from a prospectively maintained database of CRC resections in a single surgical unit. Assessment of KM grade and TSP was performed using full H&E sections. CD3+ and CD8+ T-cell density was assessed on full sections and the Immunoscore calculated. KM grade and Immunoscore were strongly associated (P<0.001). KM grade stratified cancer-specific survival (CSS) from 88% to 66% (P=0.002) and Immunoscore from 93% to 61% (P<0.001). Immunoscore further stratified survival of patients independent of KM grade from 94% (high KM, Im4) to 60% (low KM, Im0/1). Furthermore, TSP stratified survival of patients with a weak inflammatory cell infiltrate (low KM: from 75% to 47%; Im0/1: from 71% to 38%, both P<0.001) but not those with a strong inflammatory infiltrate. On multivariate analysis, only Immunoscore (HR 0.44, P<0.001) and TSP (HR 2.04, P<0.001) were independently associated with CSS. These results suggest that the prognostic value of an immunohistochemistry-based assessment of the inflammatory cell infiltrate is superior to H&E-based assessment in patients undergoing resection of stage I-III CRC. Furthermore, assessment of the tumor-associated stroma, using TSP, further improves prediction of outcome

The thermal Casimir effect in lipid bilayer tubules

We calculate the thermal Casimir effect for a dielectric tube of radius $R$ and thickness delta formed from a membrane in water. The method uses a field-theoretic approach in the grand canonical ensemble. The leading contribution to the Casimir free energy behaves as -k_BTL kappa_C/R giving rise to an attractive force which tends to contract the tube. We find that kappa_C ~ 0.3 for the case of typical lipid membrane t-tubules. We conclude that except in the case of a very soft membrane this force is insufficient to stabilize such tubes against the bending stress which tends to increase the radius.Comment: 4 pages no figures RevTe

The field theory of symmetrical layered electrolytic systems and the thermal Casimir effect

We present a general extension of a field-theoretic approach developed in earlier papers to the calculation of the free energy of symmetrically layered electrolytic systems which is based on the Sine-Gordon field theory for the Coulomb gas. The method is to construct the partition function in terms of the Feynman evolution kernel in the Euclidean time variable associated with the coordinate normal to the surfaces defining the layered structure. The theory is applicable to cylindrical systems and its development is motivated by the possibility that a static van der Waals or thermal Casimir force could provide an attractive force stabilising a dielectric tube formed from a lipid bilayer, an example of which are t-tubules occurring in certain muscle cells. In this context, we apply the theory to the calculation of the thermal Casimir effect for a dielectric tube of radius $R$ and thickness $\delta$ formed from such a membrane in water. In a grand canonical approach we find that the leading contribution to the Casimir energy behaves like $-k_BTL\kappa_C/R$ which gives rise to an attractive force which tends to contract the tube radius. We find that $\kappa_C \sim 0.3$ for the case of typical lipid membrane t-tubules. We conclude that except in the case of a very soft membrane this force is insufficient to stabilise such tubes against the bending stress which tend to increase the radius. We briefly discuss the role of lipid membrane reservoir implicit in the approach and whether its nature in biological systems may possibly lead to a stabilising mechanism for such lipid tubes.Comment: 28 pages, 2 figures, LaTe

Precise charm to strange mass ratio and light quark masses from full lattice QCD

By using a single formalism to handle charm, strange and light valence quarks in full lattice QCD for the first time, we are able to determine ratios of quark masses to 1%. For $m_c/m_s$ we obtain 11.85(16), an order of magnitude more precise than the current PDG average. Combined with 1% determinations of the charm quark mass now possible this gives $\bar{m}_s(2{\rm GeV}) =$ 92.4(1.5) MeV. The MILC result for $m_s/m_l = 27.2(3)$ yields $\bar{m}_l(2{\rm GeV})$ = 3.40(7) MeV for the average of $u$ and $d$ quark masses.Comment: 4 pages, 2 figures. Version accepted by Physical Review Letters. Changes include modifying the title, using the MILC value for m_s/m_l which changes slightly the resulting up and down quark masses and their average, adding some references and making other small adjustments to the text for space reasons

Sediment Sorting and Rounding in a Basaltic Glacio-Fluvio-Aeolian Environment: hrisjkull Glacier, Iceland

Sediments and sedimentary rocks preserve a rich history of environment and climate. Identifying these signals requires an understanding of the physical and chemical processes that have affected sedimentary deposits [1]. Such processes include sorting and rounding during transport and chemical alteration through weathering and diagenesis. Although these processes have long been studied in quartz-dominated sedimentary systems [2], a lack of studies of basaltic sedimentary systems limits our interpretations of the environment and climate where mafic source rocks dominate, such as on Mars [3,4]. As part of the SAND-E: Semi-Autonomous Navigation for Detrital Environments project [5], which uses robotic operations to examine physical and chemical changes to sediments in basaltic glacio-fluvialaeolian environments, this research studies changes in sorting and rounding of fluvial-aeolian sediments along a glacier-proximal-to-glacier-distal transect in the outwash-plain of the risjkull glacier in SW Iceland (Fig. 1

Field theoretic calculation of the surface tension for a model electrolyte system

We carry out the calculation of the surface tension for a model electrolyte to first order in a cumulant expansion about a free field theory equivalent to the Debye-H\"uckel approximation. In contrast with previous calculations, the surface tension is calculated directly without recourse to integrating thermodynamic relations. The system considered is a monovalent electrolyte with a region at the interface, of width h, from which the ionic species are excluded. In the case where the external dielectric constant epsilon_0 is smaller than the electrolyte solution's dielectric constant epsilon we show that the calculation at this order can be fully regularized. In the case where h is taken to be zero the Onsager-Samaras limiting law for the excess surface tension of dilute electrolyte solutions is recovered, with corrections coming from a non-zero value of epsilon_0/epsilon.Comment: LaTeX, 14 pages, 3 figures, 1 tabl