Growth factor restriction impedes progression of wound healing following cataract surgery: identification of VEGF as a putative therapeutic target

Secondary visual loss occurs in millions of patients due to a wound-healing response, known as posterior capsule opacification (PCO), following cataract surgery. An intraocular lens (IOL) is implanted into residual lens tissue, known as the capsular bag, following cataract removal. Standard IOLs allow the anterior and posterior capsules to become physically connected. This places pressure on the IOL and improves contact with the underlying posterior capsule. New open bag IOL designs separate the anterior capsule and posterior capsules and further reduce PCO incidence. It is hypothesised that this results from reduced cytokine availability due to greater irrigation of the bag. We therefore explored the role of growth factor restriction on PCO using human lens cell and tissue culture models. We demonstrate that cytokine dilution, by increasing medium volume, significantly reduced cell coverage in both closed and open capsular bag models. This coincided with reduced cell density and myofibroblast formation. A screen of 27 cytokines identified nine candidates whose expression profile correlated with growth. In particular, VEGF was found to regulate cell survival, growth and myofibroblast formation. VEGF provides a therapeutic target to further manage PCO development and will yield best results when used in conjunction with open bag IOL designs

The dependence of dijet production on photon virtuality in ep collisions at HERA

The dependence of dijet production on the virtuality of the exchanged photon, Q^2, has been studied by measuring dijet cross sections in the range 0 < Q^2 < 2000 GeV^2 with the ZEUS detector at HERA using an integrated luminosity of 38.6 pb^-1. Dijet cross sections were measured for jets with transverse energy E_T^jet > 7.5 and 6.5 GeV and pseudorapidities in the photon-proton centre-of-mass frame in the range -3 < eta^jet <0. The variable xg^obs, a measure of the photon momentum entering the hard process, was used to enhance the sensitivity of the measurement to the photon structure. The Q^2 dependence of the ratio of low- to high-xg^obs events was measured. Next-to-leading-order QCD predictions were found to generally underestimate the low-xg^obs contribution relative to that at high xg^obs. Monte Carlo models based on leading-logarithmic parton-showers, using a partonic structure for the photon which falls smoothly with increasing Q^2, provide a qualitative description of the data.Comment: 35 pages, 6 eps figures, submitted to Eur.Phys.J.

Beauty photoproduction measured using decays into muons in dijet events in ep collisions at s\sqrt{s}=318 GeV

The photoproduction of beauty quarks in events with two jets and a muon has been measured with the ZEUS detector at HERA using an integrated luminosity of 110 pb$^{- 1}$. The fraction of jets containing b quarks was extracted from the transverse momentum distribution of the muon relative to the closest jet. Differential cross sections for beauty production as a function of the transverse momentum and pseudorapidity of the muon, of the associated jet and of $x_{\gamma}^{jets}$, the fraction of the photon's momentum participating in the hard process, are compared with MC models and QCD predictions made at next-to-leading order. The latter give a good description of the data.Comment: 32 pages, 6 tables, 7 figures Table 6 and Figure 7 revised September 200

Search for a narrow charmed baryonic state decaying to D^*+/- p^-/+ in ep collisions at HERA

A resonance search has been made in the D^*+/- p^-/+ invariant-mass spectrum with the ZEUS detector at HERA using an integrated luminosity of 126 pb^-1. The decay channels D^*+ -> D^0 pi^+_s -> (K^- pi^+) pi^+_s and D^*+ -> D^0 pi^+_s -> (K^- pi^+ pi^+ pi^-) pi^+_s (and the corresponding antiparticle decays) were used to identify D^*+/- mesons. No resonance structure was observed in the D^*+/- p^-/+ mass spectrum from more than 60000 reconstructed D^*+/- mesons. The results are not compatible with a report of the H1 Collaboration of a charmed pentaquark, Theta^0_c.Comment: 22 pages, 7 figures, 1 table; minor text revisions; 2 references adde

Increased prevalence of testicular microlithiasis in men with familial testicular cancer and their relatives

Testicular germ cell tumours (TGCT) cluster in families, but responsible genes remain unidentified. The association between testicular microlithiasis (TM) and testicular carcinoma in situ (CIS) suggests that TM may be a TC risk factor. We report testicular ultrasound findings in men with familial TGCT (FTGCT) and their unaffected relatives. A total of 81 men (48 affected and 33 unaffected) from 31 families with ⩾2 TC cases underwent testicular ultrasound. Testicular microlithiasis was defined as either ‘classic' (⩾5 microliths) or ‘limited' (<5 microliths). Statistical analyses used Fisher's exact test and permutation testing. Testicular microlithiasis was more frequent in the contralateral testicles of men with a history of TGCT (affected men) than in unaffected men (48 vs 24%, P=0.04). The association appeared stronger for classic TM (21 vs 9%) than for limited TM (27 vs 15%). Testicular microlithiases were bilateral in six out of seven (87%) unaffected men. Among affected men, TM was not associated with histology, age at diagnosis or cancer treatment. Of the 31 families, 10 accounted for a majority (61%) of the TM cases identified (P=0.11). Testicular microlithiasis was more prevalent among FTGCT family members than described previously in the general population, and was more common among FTGCT cases vs unaffected blood relatives. Testicular microlithiasis appeared to cluster in certain families. These findings suggest both a familial predisposition to TM and an association between TM and FTGCT. If proven, this could be clinically important to men in FTGCT families, and may be useful in identifying specific genes involved in FTGCT

Can large scintillators be used for solar-axion searches to test the cosmological axion-photon oscillation proposal?

Solar-axion interaction rates in NaI, CsI and Xe scintillators via the axio-electric effect were calculated. A table is presented with photoelectric and axioelectric cross sections, solar-axion fluxes, and the interaction rates from 2.0 to 10.0 keV. The results imply that annual-modulation data of large NaI and CsI arrays, and large Xe scintillation chambers, might be made sensitive enough to probe coupling to photons at levels required to explain axion-photon oscillation phenomena proposed to explain the survival of high-energy photons traveling cosmological distances. The DAMAA/LIBRA data are used to demonstrate the power of the model-independent annual modulation due to the seasonal variation in the earth sun distance.Comment: 7 pages and no figure

5-aminosalicylic acid inhibits stem cell function in human adenoma derived cells: Implications for chemoprophylaxis in colorectal tumorigenesis

Background: Most colorectal cancers (CRC) arise sporadically from precursor lesions: colonic polyps. Polyp resection prevents progression to CRC. Risk of future polyps is proportional to the number and size of polyps detected at screening, allowing identification of high-risk individuals who may benefit from effective chemoprophylaxis. We aimed to investigate the potential of 5-aminosalicylic acid (5-ASA), a medication used in the treatment of ulcerative colitis, as a possible preventative agent for sporadic CRC. Methods: Human colorectal adenoma (PC/AA/C1, S/AN/C1 and S/RG/C2), transformed adenoma PC/AA/C1/SB10 and carcinoma cell lines (LS174T and SW620) were treated with 5-ASA. The effect on growth in two- and three-dimensional (3D) culture, β-catenin transcriptional activity and on cancer stemness properties of the cells were investigated. Results: 5-ASA was shown, in vitro, to inhibit the growth of adenoma cells and suppress β-catenin transcriptional activity. Downregulation of β-catenin was found to repress expression of stem cell marker LGR5 (leucine-rich G protein-coupled receptor-5) and functionally suppress stemness in human adenoma and carcinoma cells using 3D models of tumorigenesis. Conclusions: 5-ASA can suppress the cancer stem phenotype in adenoma-derived cells. Affordable and well-tolerated, 5-ASA is an outstanding candidate as a chemoprophylactic medication to reduce the risk of colorectal polyps and CRC in those at high risk