Survival rate in patients with hepatocellular carcinoma: a retrospective analysis of 389 patients

Hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide. However, treatment options are limited and often inefficient. The aim of this study was to determine current survival rates for patients diagnosed with HCC and to identify prognostic factors, which will help in choosing optimal therapies for individual patients. A retrospective analysis of medical records was performed on 389 patients who were identified through the central tumour registry at our institution from 1998 to 2003. Clinical parameters, treatments received and survival curves from time of diagnosis were analysed. Overall median survival was 11 months. Liver cirrhosis was diagnosed in 80.5% of all patients. A total of 170 patients received transarterial chemoembolisation (TACE) and/or percutaneous ethanol injections (PEI) with a median survival rate of 16 months for patients receiving TACE, 11 months for patients receiving PEI and 24 months for patients receiving TACE followed by PEI. Independent negative prognostic parameters for survival were the presence of portal vein thrombosis, advanced liver cirrhosis (Child–Pugh score B or C) and a score of >2. This study will help to estimate survival rates for patients with HCC according to their clinical status at diagnosis and the treatments received

Assessment of insulin resistance by a 13C glucose breath test: a new tool for early diagnosis and follow-up of high-risk patients

<p>Abstract</p> <p>Background/Aims</p> <p>Insulin resistance (IR) plays an important role in the pathogenesis of diabetes and non-alcoholic fatty liver disease (NAFLD). Current methods for insulin resistance detection are cumbersome, or not sensitive enough for early detection and follow-up. The BreathID^®system can continuously analyse breath samples in real-time at the point-of-care. Here we determined the efficacy of the BreathID^®using the ¹³C-Glucose breath test (GBT) for evaluation of insulin resistance.</p> <p>Methods</p> <p>Twenty healthy volunteers were orally administered 75 mg of ¹³C-glucose 1-¹³C. An oral glucose tolerance test (OGTT) was performed immediately; followed by serum glucose and insulin level determinations using GBT. GBT and OGTT were repeated following exercise, which alters insulin resistance levels.</p> <p>Results</p> <p>Within-subject correlations of GBT parameters with serum glucose and serum insulin levels were high. Before and after exercise, between-subjects correlations were high between the relative insulin levels and the % dose recoveries at 90 min (PDR 90), and the cumulative PDRs at 60 min (CPDR 60). Pairwise correlations were identified between pre-exercise Homeostasis Model Assessment (HOMA) IR at 90 min and PDR 90; HOMA B (for beta cell function) 120 and CPDR 30; HOMA IR 60 and peak time post-exercise; and HOMA B 150 with PDR 150.</p> <p>Conclusions</p> <p>The non-invasive real-time BreathID^®GBT reliably assesses changes in liver glucose metabolism, and the degree of insulin resistance. It may serve as a non-invasive tool for early diagnosis and follow up of patients in high-risk groups.</p

Initial Characterization of the FlgE Hook High Molecular Weight Complex of

The spirochete periplasmic flagellum has many unique attributes. One unusual characteristic is the flagellar hook. This structure serves as a universal joint coupling rotation of the membrane-bound motor to the flagellar filament. The hook is comprised of about 120 FlgE monomers, and in most bacteria these structures readily dissociate to monomers (∼ 50 kDa) when treated with heat and detergent. However, in spirochetes the FlgE monomers form a large mass of over 250 kDa [referred to as a high molecular weight complex (HMWC)] that is stable to these and other denaturing conditions. In this communication, we examined specific aspects with respect to the formation and structure of this complex. We found that the Lyme disease spirochete Borrelia burgdorferi synthesized the HMWC throughout the in vitro growth cycle, and also in vivo when implanted in dialysis membrane chambers in rats. The HMWC was stable to formic acid, which supports the concept that the stability of the HMWC is dependent on covalent cross-linking of individual FlgE subunits. Mass spectrometry analysis of the HMWC from both wild type periplasmic flagella and polyhooks from a newly constructed ΔfliK mutant indicated that other proteins besides FlgE were not covalently joined to the complex, and that FlgE was the sole component of the complex. In addition, mass spectrometry analysis also indicated that the HMWC was composed of a polymer of the FlgE protein with both the N- and C-terminal regions remaining intact. These initial studies set the stage for a detailed characterization of the HMWC. Covalent cross-linking of FlgE with the accompanying formation of the HMWC we propose strengthens the hook structure for optimal spirochete motility

Evolution of Anolis Lizard Dewlap Diversity

BACKGROUND: The dewlaps of Anolis lizards provide a classic example of a complex signaling system whose function and evolution is poorly understood. Dewlaps are flaps of skin beneath the chin that are extended and combined with head and body movements for visual signals and displays. They exhibit extensive morphological variation and are one of two cladistic features uniting anoles, yet little is known regarding their function and evolution. We quantified the diversity of anole dewlaps, investigated whether dewlap morphology was informative regarding phylogenetic relationships, and tested two separate hypotheses: (A) similar Anolis habitat specialists possess similar dewlap configurations (Ecomorph Convergence hypothesis), and (B) sympatric species differ in their dewlap morphologies to a greater extent than expected by chance (Species Recognition hypothesis). METHODOLOGY/PRINCIPAL FINDINGS: We found that dewlap configurations (sizes, patterns and colors) exhibit substantial diversity, but that most are easily categorized into six patterns that incorporate one to three of 13 recognizable colors. Dewlap morphology is not phylogenetically informative and, like other features of anoles, exhibits convergence in configurations. We found no support for the Ecomorph Convergence hypothesis; species using the same structural habitat were no more similar in dewlap configuration than expected by chance. With one exception, all sympatric species in four communities differ in dewlap configuration. However, this provides only weak support for the Species Recognition hypothesis because, due to the great diversity in dewlap configurations observed across each island, few cases of sympatric species with identical dewlaps would be expected to co-occur by chance alone. CONCLUSIONS/SIGNIFICANCE: Despite previous thought, most dewlaps exhibit easily characterizable patterns and colorations. Nevertheless, dewlap variation is extensive and explanations for the origin and evolution of this diversity are lacking. Our data do not support two hypothesized explanations for this diversity, but others such as sexual selection remain to be tested

Quantitative detection of myocardial ischaemia by stress echocardiography; a comparison with SPECT

<p>Abstract</p> <p>Aims</p> <p>Real-time perfusion (RTP) adenosine stress echocardiography (ASE) can be used to visually evaluate myocardial ischaemia. The RTP power modulation technique angio-mode (AM), provides images for off-line perfusion quantification using Qontrast^®software, generating values of peak signal intensity (A), myocardial blood flow velocity (β) and myocardial blood flow (Axβ). By comparing rest and stress values, their respective reserve values (A-r, β-r, Axβ-r) are generated. We evaluated myocardial ischaemia by RTP-ASE Qontrast^®quantification, compared to visual perfusion evaluation with ^99mTc-tetrofosmin single-photon emission computed tomography (SPECT).</p> <p>Methods and Results</p> <p>Patients admitted to SPECT underwent RTP-ASE (SONOS 5500) using AM during Sonovue^®infusion, before and throughout adenosine stress, also used for SPECT. Visual myocardial perfusion and wall motion analysis, and Qontrast^®quantification, were blindly compared to one another and to SPECT, at different time points off-line.</p> <p>We analyzed 201 coronary territories (left anterior descendent [LAD], left circumflex [LCx] and right coronary [RCA] artery territories) in 67 patients. SPECT showed ischaemia in 18 patients and 19 territories. Receiver operator characteristics and kappa values showed significant agreement with SPECT only for β-r and Axβ-r in all segments: area under the curve 0.678 and 0.665; P < 0.001 and < 0.01, respectively. The closest agreements were seen in the LAD territory: kappa 0.442 for both β-r and Axβ-r; P < 0.01. Visual evaluation of ischaemia showed good agreement with SPECT: accuracy 93%; kappa 0.67; P < 0.001; without non-interpretable territories.</p> <p>Conclusion</p> <p>In this agreement study with SPECT, RTP-ASE Qontrast^®quantification of myocardial ischaemia was less accurate and less feasible than visual evaluation and needs further development to be clinically useful.</p

Profiling Trait Anxiety: Transcriptome Analysis Reveals Cathepsin B (Ctsb) as a Novel Candidate Gene for Emotionality in Mice

Behavioral endophenotypes are determined by a multitude of counteracting but precisely balanced molecular and physiological mechanisms. In this study, we aim to identify potential novel molecular targets that contribute to the multigenic trait “anxiety”. We used microarrays to investigate the gene expression profiles of different brain regions within the limbic system of mice which were selectively bred for either high (HAB) or low (LAB) anxiety-related behavior, and also show signs of comorbid depression-like behavior

The GABA transporter 1 (SLC6A1): a novel candidate gene for anxiety disorders

Recent evidence suggests that the GABA transporter 1 (GAT-1; SLC6A1) plays a role in the pathophysiology and treatment of anxiety disorders. In order to understand the impact of genetic variation within SLC6A1 on pathological anxiety, we performed a case–control association study with anxiety disorder patients with and without syndromal panic attacks. Using the method of sequential addition of cases, we found that polymorphisms in the 5′ flanking region of SLC6A1 are highly associated with anxiety disorders when considering the severity of syndromal panic attacks as phenotype covariate. Analysing the effect size of the association, we observed a constant increase in the odds ratio for disease susceptibility with an increase in panic severity (OR ~ 2.5 in severely affected patients). Nominally significant association effects were observed considering the entire patient sample. These data indicate a high load of genetic variance within SLC6A1 on pathological anxiety and highlight GAT-1 as a promising target for treatment of anxiety disorders with panic symptoms

Emergence and Modular Evolution of a Novel Motility Machinery in Bacteria

Bacteria glide across solid surfaces by mechanisms that have remained largely mysterious despite decades of research. In the deltaproteobacterium Myxococcus xanthus, this locomotion allows the formation stress-resistant fruiting bodies where sporulation takes place. However, despite the large number of genes identified as important for gliding, no specific machinery has been identified so far, hampering in-depth investigations. Based on the premise that components of the gliding machinery must have co-evolved and encode both envelope-spanning proteins and a molecular motor, we re-annotated known gliding motility genes and examined their taxonomic distribution, genomic localization, and phylogeny. We successfully delineated three functionally related genetic clusters, which we proved experimentally carry genes encoding the basal gliding machinery in M. xanthus, using genetic and localization techniques. For the first time, this study identifies structural gliding motility genes in the Myxobacteria and opens new perspectives to study the motility mechanism. Furthermore, phylogenomics provide insight into how this machinery emerged from an ancestral conserved core of genes of unknown function that evolved to gliding by the recruitment of functional modules in Myxococcales. Surprisingly, this motility machinery appears to be highly related to a sporulation system, underscoring unsuspected common mechanisms in these apparently distinct morphogenic phenomena

Increased sporulation underpins adaptation of Clostridium difficile strain 630 to a biologically–relevant faecal environment, with implications for pathogenicity

Abstract Clostridium difficile virulence is driven primarily by the processes of toxinogenesis and sporulation, however many in vitro experimental systems for studying C. difficile physiology have arguably limited relevance to the human colonic environment. We therefore created a more physiologically–relevant model of the colonic milieu to study gut pathogen biology, incorporating human faecal water (FW) into growth media and assessing the physiological effects of this on C. difficile strain 630. We identified a novel set of C. difficile–derived metabolites in culture supernatants, including hexanoyl– and pentanoyl–amino acid derivatives by LC-MSn. Growth of C. difficile strain 630 in FW media resulted in increased cell length without altering growth rate and RNA sequencing identified 889 transcripts as differentially expressed (p < 0.001). Significantly, up to 300–fold increases in the expression of sporulation–associated genes were observed in FW media–grown cells, along with reductions in motility and toxin genes’ expression. Moreover, the expression of classical stress–response genes did not change, showing that C. difficile is well–adapted to this faecal milieu. Using our novel approach we have shown that interaction with FW causes fundamental changes in C. difficile biology that will lead to increased disease transmissibility