Hepatocellular carcinoma: Review of disease and tumor biomarkers.

© The Author(s) 2016.Hepatocellular carcinoma (HCC) is a common malignancy and now the second commonest global cause of cancer death. HCC tumorigenesis is relatively silent and patients experience late symptomatic presentation. As the option for curative treatments is limited to early stage cancers, diagnosis in non-symptomatic individuals is crucial. International guidelines advise regular surveillance of high-risk populations but the current tools lack sufficient sensitivity for early stage tumors on the background of a cirrhotic nodular liver. A number of novel biomarkers have now been suggested in the literature, which may reinforce the current surveillance methods. In addition, recent metabonomic and proteomic discoveries have established specific metabolite expressions in HCC, according to Warburgs phenomenon of altered energy metabolism. With clinical validation, a simple and non-invasive test from the serum or urine may be performed to diagnose HCC, particularly benefiting low resource regions where the burden of HCC is highest

Faraday rotation in the MOJAVE blazars: 3C 273 a case study

Radio polarimetric observations of Active Galactic Nuclei can reveal the magnetic field structure in the parsec-scale jets of these sources. We have observed the gamma-ray blazar 3C 273 as part of our multi-frequency survey with the Very Long Baseline Array to study Faraday rotation in a large sample of jets. Our observations re-confirm the transverse rotation measure gradient in 3C 273. For the first time the gradient is seen to cross zero which is further indication for a helical magnetic field and spine-sheath structure in the jet. We believe the difference to previous epochs is due to a different part of the jet being illuminated in our observations.Comment: 6 pages, 3 figures. To appear in the proceedings of "Beamed and Unbeamed Gamma-rays from Galaxies", held in Muonio, Finland, April 11-15, 2011. Journal of Physics: Conference Serie

Centrality in primate–parasite networks reveals the potential for the transmission of emerging infectious diseases to humans

We thank Randi Griffin, Amy Pedersen, Rosa Menendez, Mark Lineham, and two anonymous reviewers for discussion and comments on a previous draft. This work was funded by the Spanish Ministry of Science (J.M.G. and M.V.), by the Junta de Andalucia (J.M.G.), and by National Science Foundation Grants DEB-0211908 and EF-0723939/0904359 (C.L.N.).Most emerging infectious diseases (EIDs) in humans have arisen from animals. Identifying high-risk hosts is therefore vital for the control and surveillance of these diseases. Viewing hosts as connected through the parasites they share, we use network tools to investigate predictors of parasitism and sources of future EIDs. We generated host-parasite networks that link hosts when they share a parasite, using nonhuman primates as a model system because-owing to their phylogenetic proximity and ecological overlap with humans-they are an important source of EIDs to humans. We then tested whether centrality in the network of host species-a measurement of the importance of a given node (i.e., host species) in the network-is associated with that host serving as a potential EID source. We found that centrality covaries with key predictors of parasitism, such as population density and geographic range size. Importantly, we also found that primate species having higher values of centrality in the primate-parasite network harbored more parasites identified as EIDs in humans and had parasite communities more similar to those found in humans. These relationships were robust to the use of different centrality metrics and to multiple ways of controlling for variation in how well each species has been studied (i.e., sampling effort). Centrality may therefore estimate the role of a host as a source of EIDs to humans in other multispecific host-parasite networks.Spanish GovernmentJunta de AndaluciaNational Science Foundation (NSF) DEB-0211908 EF-0723939/090435

AFLOW-SYM: platform for the complete, automatic and self-consistent symmetry analysis of crystals

Determination of the symmetry profile of structures is a persistent challenge in materials science. Results often vary amongst standard packages, hindering autonomous materials development by requiring continuous user attention and educated guesses. This article presents a robust procedure for evaluating the complete suite of symmetry properties, featuring various representations for the point, factor and space groups, site symmetries and Wyckoff positions. The protocol determines a system-specific mapping tolerance that yields symmetry operations entirely commensurate with fundamental crystallographic principles. The self-consistent tolerance characterizes the effective spatial resolution of the reported atomic positions. The approach is compared with the most used programs and is successfully validated against the space-group information provided for over 54 000 entries in the Inorganic Crystal Structure Database (ICSD). Subsequently, a complete symmetry analysis is applied to all 1.7+ million entries of the AFLOW data repository. The AFLOW-SYM package has been implemented in, and made available for, public use through the automated ab initio framework AFLOW

Strings between branes

D-brane configurations containing fundamental strings are constructed as classical solutions of Yang-Mills theory. The fundamental strings in these systems stretch between D-branes. In the case of D1-branes, this construction gives smooth (classical) resolutions of string junctions and string networks. Using a non-abelian Yang-Mills analysis of the string current, the string charge density is computed and is shown to have support in the region between the D-brane world-volumes. The 't Hooft-Polyakov monopole is analyzed using similar methods, and is shown to contain D-strings whose flux has support off the D-brane world-volume defined by the Higgs scalar field, when this field is interpreted in terms of a transverse dimension. The constructions presented here are used to give a qualitative picture of tachyon condensation in the Yang-Mills limit, where fundamental strings and lower-dimensional D-branes arise in a volume of space-time where brane-antibrane annihilation has occurred.Comment: 35 pages, 16 eps figures, JHEP style; v2: a comment adde

Inhibition of αvβ5 Integrin Attenuates Vascular Permeability and Protects against Renal Ischemia-Reperfusion Injury

Ischemia-reperfusion injury (IRI) is a leading cause of AKI. This common clinical complication lacks effective therapies and can lead to the development of CKD. The αvβ5 integrin may have an important role in acute injury, including septic shock and acute lung injury. To examine its function in AKI, we utilized a specific function-blocking antibody to inhibit αvβ5 in a rat model of renal IRI. Pretreatment with this anti-αvβ5 antibody significantly reduced serum creatinine levels, diminished renal damage detected by histopathologic evaluation, and decreased levels of injury biomarkers. Notably, therapeutic treatment with the αvβ5 antibody 8 hours after IRI also provided protection from injury. Global gene expression profiling of post-ischemic kidneys showed that αvβ5 inhibition affected established injury markers and induced pathway alterations previously shown to be protective. Intravital imaging of post-ischemic kidneys revealed reduced vascular leak with αvβ5 antibody treatment. Immunostaining for αvβ5 in the kidney detected evident expression in perivascular cells, with negligible expression in the endothelium. Studies in a three-dimensional microfluidics system identified a pericyte-dependent role for αvβ5 in modulating vascular leak. Additional studies showed αvβ5 functions in the adhesion and migration of kidney pericytes in vitro Initial studies monitoring renal blood flow after IRI did not find significant effects with αvβ5 inhibition; however, future studies should explore the contribution of vasomotor effects. These studies identify a role for αvβ5 in modulating injury-induced renal vascular leak, possibly through effects on pericyte adhesion and migration, and reveal αvβ5 inhibition as a promising therapeutic strategy for AKI

The Cutaneous Microbiome and Wounds: New Molecular Targets to Promote Wound Healing

The ecological community of microorganisms in/on humans, termed the microbiome, is vital for sustaining homeostasis. While culture-independent techniques have revealed the role of the gut microbiome in human health and disease, the role of the cutaneous microbiome in wound healing is less defined. Skin commensals are essential in the maintenance of the epithelial barrier function, regulation of the host immune system, and protection from invading pathogenic microorganisms. In this review, we summarize the literature derived from pre-clinical and clinical studies on how changes in the microbiome of various acute and chronic skin wounds impact wound healing tissue regeneration. Furthermore, we review the mechanistic insights garnered from model wound healing systems. Finally, in the face of growing concern about antibiotic-resistance, we will discuss alternative strategies for the treatment of infected wounds to improve wound healing and outcomes. Taken together, it has become apparent that commensals, symbionts, and pathogens on human skin have an intimate role in the inflammatory response that highlights several potential strategies to treat infected, non-healing wounds. Despite these promising results, there are some contradictory and controversial findings from existing studies and more research is needed to define the role of the human skin microbiome in acute and chronic wound healing

Hepatic encephalopathy

Hepatic encephalopathy (HE) is a prognostically relevant neuropsychiatric syndrome that occurs in the course of acute or chronic liver disease. Besides ascites and variceal bleeding, it is the most serious complication of decompensated liver cirrhosis. Ammonia and inflammation are major triggers for the appearance of HE, which in patients with liver cirrhosis involves pathophysiologically low-grade cerebral oedema with oxidative/nitrosative stress, inflammation and disturbances of oscillatory networks in the brain. Severity classification and diagnostic approaches regarding mild forms of HE are still a matter of debate. Current medical treatment predominantly involves lactulose and rifaximin following rigorous treatment of so-called known HE precipitating factors. New treatments based on an improved pathophysiological understanding are emerging

PANasta Trial; Cattell Warren versus Blumgart techniques of panreatico-jejunostomy following pancreato-duodenectomy: Study protocol for a randomized controlled trial

PANasta operative manual. (PDF 520 kb