bluuebunny/crossref_metadata_2025 huggingface dataset:
Retroviral promoters in the human genome
Authors: Conley Andrew B. , Piriyapongsa Jittima , Jordan I. King
Published: June 2008

Motivation: Endogenous retrovirus (ERV) elements have been shown to contribute promoter sequences that can initiate transcription of adjacent human genes. However, the extent to which retroviral sequences initiate transcription within the human genome is currently unknown. We analyzed genome sequence and high-throughput expression data to systematically evaluate the presence of retroviral promoters in the human genome.

Results: We report the existence of 51 197 ERV-derived promoter sequences that initiate transcription within the human genome, including 1743 cases where transcription is initiated from ERV sequences that are located in gene proximal promoter or 5′ untranslated regions (UTRs). A total of 114 of the ERV-derived transcription start sites can be demonstrated to drive transcription of 97 human genes, producing chimeric transcripts that are initiated within ERV long terminal repeat (LTR) sequences and read-through into known gene sequences. ERV promoters drive tissue-specific and lineage-specific patterns of gene expression and contribute to expression divergence between paralogs. These data illustrate the potential of retroviral sequences to regulate human transcription on a large scale consistent with a substantial effect of ERVs on the function and evolution of the human genome.

Contact:  king.jordan@biology.gatech.edu

Supplementary information:  Supplementary data are available at Bioinformatics online.
LOT: a tool for linkage analysis of ordinal traits for pedigree data
Authors: Zhang Meizhuo , Feng Rui , Chen Xiang , Hu Buqu , Zhang Heping
Published: June 2008

Summary: Existing linkage-analysis methods address binary or quantitative traits. However, many complex diseases and human conditions, particularly behavioral disorders, are rated on ordinal scales. Herein, we introduce, LOT, a tool that performs linkage analysis of ordinal traits for pedigree data. It implements a latent-variable proportional-odds logistic model that relates inheritance patterns to the distribution of the ordinal trait. The likelihood-ratio test is used for testing evidence of linkage.

Availability: The LOT program is available for download at http://c2s2.yale.edu/software/LOT/

Contact:  heping.zhang@yale.edu
Non-direct estimations of adhesive and elastic properties of materials by depth-sensing indentation
Authors: Borodich Feodor M , Galanov Boris A
Published: June 2008

Using the connection between depth-sensing indentation by spherical indenters and mechanics of adhesive contact, a new method for non-direct determination of adhesive and elastic properties of contacting materials is proposed. At low loads, the force–displacement curves reflect not only elastic properties but also adhesive properties of the contact, and therefore one can try to extract from experiments both the elastic characteristics of contacting materials (such as the reduced elastic modulus) and characteristics of molecular adhesion (such as the work of adhesion and the pull-off force) using a non-direct approach. The direct methods of estimations of the adhesive characteristics of materials currently used in experiments are rather complicated due to the instability of the experimental force–displacement diagrams for ultra-low tensile forces. The proposed method is based on the use of the stable experimental data for the elastic stage of the force–displacement curve and the mechanics of adhesive contact for spherical indenters. Since the experimental data always have some measurement errors, mathematical techniques for solving ill-posed problems are employed.
Brane inflation and defect formation
Authors: Davis Anne-Christine , Brax Philippe , van de Bruck Carsten
Published: June 2008

Brane inflation and the production of topological defects at the end of the inflationary phase are discussed. After a description of the inflationary set-up, we discuss the properties of the cosmic strings produced at the end of inflation. Specific examples of brane inflation are described, such as
D
−

,
D
3/
D
7 and modular inflations.
Foldon‐guided self‐assembly of ultra‐stable protein fibers
Authors: Bhardwaj Anshul , Walker‐Kopp Nancy , Wilkens Stephan , Cingolani Gino
Published: June 2008

A common objective in protein engineering is the enhancement of the thermodynamic properties of recombinant proteins for possible applications in nanobiotechnology. The performance of proteins can be improved by the rational design of chimeras that contain structural elements with the desired properties, thus resulting in a more effective exploitation of protein folds designed by nature. In this paper, we report the design and characterization of an ultra‐stable self‐refolding protein fiber, which rapidly reassembles in solution after denaturation induced by harsh chemical treatment or high temperature. This engineered protein fiber was constructed on the molecular framework of bacteriophage P22 tail needle gp26, by fusing its helical core to the foldon domain of phage T4 fibritin. Using protein engineering, we rationally permuted the foldon upstream and downstream from the gp26 helical core and characterized gp26‐foldon chimeras by biophysical analysis. Our data demonstrate that one specific protein chimera containing the foldon immediately downstream from the gp26 helical core, gp26(1‐140)‐F, displays the highest thermodynamic and structural stability and refolds spontaneously in solution following denaturation. The gp26‐foldon chimeric fiber remains stable in 6.0 M guanidine hydrochloride, or at 80°C, rapidly refolds after denaturation, and has both N and C termini accessible for chemical/biological modification, thereby representing an ideal platform for the design of self‐assembling nanoblocks.
A needle guidance device compared to free hand technique in an ultrasound‐guided interventional task using a phantom
Authors: Van Geffen G.‐J. , Mulder J. , Gielen M. , Van Egmond J. , Scheffer G.‐J. , Bruhn J.
Published: June 2008

In this in vitro study, a needle guidance device and a ‘free hand’ technique for ultrasound guided needle insertion were compared in a simulated ultrasound‐guided interventional task using a porcine phantom. Residents inexperienced in using ultrasonography were asked to insert a needle, using an in‐plane techniques, and to make contact with metal rods at a depth of 2 and 4 cm in the phantom. The transducer made angles of 90°, 60° and 45° with the surface of the phantom. The times to perform the procedures were significantly shorter and the needle visualisation was significantly better when using the needle guidance device. The residents ranked their satisfaction with the needle‐guidance device significantly better than the ‘free‐hand’ technique. This device may be beneficial when performing ultrasound guided peripheral nerve blocks, especially by inexperienced operators.
The Papworth BiVent tube: a new device for lung isolation
Authors: Ghosh S. , Falter F. , Goldsmith K. , Arrowsmith J. E.
Published: June 2008

Provision of one lung ventilation can be technically challenging, particularly for anaesthetists who are only occasionally required to isolate one lung from the other. A new double lumen endotracheal tube, the Papworth BiVent Tube, has been designed to enable rapid and reliable lung isolation using any bronchus blocker without the need for fibreoptic endoscopic guidance. In this study, an airway‐training manikin was used to assess ease of tracheal intubation and lung isolation using the Papworth BiVent tube. Ease of intubation was compared to a single lumen endotracheal tube and a conventional double lumen endobronchial tube. Ease of lung isolation when using a bronchus blocker was compared to a single lumen tube combined with a bronchial blocker. Tracheal intubation using the Papworth BiVent tube was found to be easier than when using a conventional double lumen endobronchial tube. Lung isolation using the Papworth BiVent tube used in combination with a bronchus blocker was achieved more reliably and rapidly than when using a single lumen tube and bronchus blocker.
A case series of the use of the ProSeal laryngeal mask airway in emergency lower abdominal surgery
Authors: Fabregat‐López J. , Garcia‐Rojo B. , Cook T. M.
Published: June 2008

The ProSeal laryngeal mask airway (PLMA) has been used routinely for anaesthesia and for difficult airway management including airway rescue in non‐fasted patients. Compared with the classic laryngeal mask airway the PLMA increases protection against gastric inflation and pulmonary aspiration, by separating the respiratory and gastro‐intestinal tracts. The PLMA has potential advantages over use of the tracheal tube including smoother recovery, reduced pharyngolaryngeal morbidity and even reduced postoperative pain. We report a series of patients scheduled for emergency appendicectomy, without other risk factors for regurgitation, managed with the PLMA. Anaesthesia was induced and maintained with remifentanil, target controlled propofol and rocuronium. A series of 102 cases were managed without complications and high rates of first time placement of the PLMA (inserted over a suction tube placed in the oesophagus). With careful patient selection the PLMA may offer an alternative airway for use by experienced anaesthetists in patients undergoing minor lower abdominal surgery.
B‐cell‐activating factor inhibits CD20‐mediated and B‐cell receptor‐mediated apoptosis in human B cells
Authors: Saito Yohei , Miyagawa Yoshitaka , Onda Keiko , Nakajima Hideki , Sato Ban , Horiuchi Yasuomi , Okita Hajime , Katagiri Yohko U. , Saito Masahiro , Shimizu Toshiaki , Fujimoto Junichiro , Kiyokawa Nobutaka
Published: June 2008

B‐cell‐activating factor (BAFF) is a survival and maturation factor for B cells belonging to the tumour necrosis factor superfamily. Among three identified functional receptors, the BAFF receptor (BAFF‐R) is thought to be responsible for the effect of BAFF on B cells though details of how remain unclear. We determined that a hairy‐cell leukaemia line, MLMA, expressed a relatively high level of BAFF‐R and was susceptible to apoptosis mediated by either CD20 or B‐cell antigen receptor (BCR). Using MLMA cells as an in vitro model of mature B cells, we found that treatment with BAFF could inhibit apoptosis mediated by both CD20 and BCR. We also observed, using immunoblot analysis and microarray analysis, that BAFF treatment induced activation of nuclear factor‐κB2 following elevation of the expression level of Bcl‐2, which may be involved in the molecular mechanism of BAFF‐mediated inhibition of apoptosis. Interestingly, BAFF treatment was also found to induce the expression of a series of genes, such as that for CD40, related to cell survival, suggesting the involvement of a multiple mechanism in the BAFF‐mediated anti‐apoptotic effect. MLMA cells should provide a model for investigating the molecular basis of the effect of BAFF on B cells in vitro and will help to elucidate how B cells survive in the immune system in which BAFF‐mediated signalling is involved.
Effect of variety on the heat transfer coefficient during drying of fermented ground cassava
Authors: Ademiluyi Taiwo , Audu Thomas O.K. , Njobuenwu Derrick O. , Akpan Friday E.
Published: June 2008

The effect of variety on the heat transfer coefficient of four cassava cultivars (TMS 30555, TMS 30572, NR 8082 and one Native type) was investigated. The cultivars were dried at an air temperature of 142 °C, air velocity of 1.397 m/s−1 and relative humidity of 55%. The heat transfer coefficient obtained varied from 0.0622 to 0.0725 kJ kg s °C. The heat transfer coefficient varied for some cultivars, while some cultivars had close heat transfer coefficient. NR 8082 had the lowest heat transfer coefficient while TMS 30555 had the highest heat transfer coefficient. The cultivars with high heat transfer coefficient were found to have low bulk density, smaller particle diameter, high drying rate, low specific heat capacity and high carbohydrate fat and protein contents than other cultivars.
Comparison of hot air‐drying and freeze‐drying on the physicochemical properties and antioxidant activities of pumpkin (Cucurbita moschata Duch.) flours
Authors: Que Fei , Mao Linchun , Fang Xuehua , Wu Tao
Published: June 2008

Freeze‐drying and hot air‐drying were applied in the preparation of pumpkin flours to investigate the effects of drying methods on the antioxidant activities and physicochemical properties. The antioxidant activities of methanol extracts from pumpkin flours were studied in terms of total antioxidant activity, reducing power, free radical scavenging, superoxide anion radical scavenging and metal chelating activities. Hot air‐dried pumpkin flour showed stronger antioxidant activities than freeze‐dried flour. The percentage inhibition of peroxidation in linoleic acid system by 15 mg mL−1 extracts from hot air‐dried and freeze‐dried pumpkin flours was found to be 92.4% and 86.1% after 120 h of incubation, respectively. Hot air‐dried pumpkin flour exhibited higher reducing power, free radical scavenging and metal chelating activities than freeze‐dried flour. This study also indicated that freeze‐drying significantly reduced the browning and preserved the redness of pumpkin flours. Hot air‐drying reduced the oil absorption capacity, water absorption and porosity of pumpkin flours, while it markedly increased the water solubility and bulk density.
Economic evaluation of alternative technologies for tartrate stabilisation of wines
Authors: Low Lin Lin , O’Neill Brian , Ford Chris , Godden Jim , Gishen Mark , Colby Christopher
Published: June 2008

Cold stabilisation is a widely used industrial process to prevent tartrate instability in bottled wines. In this article, current knowledge regarding performance and cost of cold stabilisation and alternative technologies for tartrate stabilisation is reviewed. Whilst there have been occasional cost comparisons between cold stabilisation and alternative technologies published in the literature, existing data is not satisfactory to permit an accurate economic evaluation of the different process options. Therefore, alternative technologies to cold stabilisation, including the Westfalia process, nanofiltration and electrodialysis were compared for both technical and economic performance. The engineering calculations and conceptual cost estimates were based on real world data from an Australian winery. Product loss was a key cost driver in differentiating tartrate stabilisation processes. Cold stabilisation was found to be the most economic treatment process irrespective of scale or winery size. Westfalia process and nanofiltration were the next most cost effective options.
Microwave‐assisted encapsulation of citric acid using hydrocolloids
Authors: Abbasi Soleiman , Rahimi Somayeh
Published: June 2008

This study elucidates the capability of a novel technique for producing microcapsules at an enormously short time and low cost. This technique is based on the difference between dielectric constants of core and coat materials. Edible citric acid was mixed with various biomacromolecules at ratios of 1:5, 1:10, and 1:100. Each mixture was treated up to 600 s at various powers (120–1200 W) in a microwave oven. Subsequently, the microcapsules were separated by distinct sieves, and their apparent structure and quality were evaluated using binoculars, and photographs were taken for visual comparisons. Our observations showed that only five hydrocolloids were able to produce high‐quality and efficient encapsulation [casein > inulin > carboxymethylcellulose (CMC) > low methoxyl (LM) pectin (9/5%) > sorbitol]. Moreover, the highest coating efficiency was seen at highest intensity (1200 W) at a mixing ratio of 1:10. Furthermore, the optimum treating time periods for those five efficient coating materials were about 400, 75, 400, 100, and 100 s.
Adhesion of Listeria monocytogenes to materials commonly found in domestic kitchens
Authors: Teixeira Pilar , Lima Joana , Azeredo Joana , Oliveira Rosário
Published: June 2008

The aim of this work was to investigate the adhesion of Listeria monocytogenes ATCC 15313 to glass, granite, marble, polypropylene from a bowl (PPb), polypropylene from a cutting board (PPcb) and stainless steel (SS), which are materials commonly used in kitchens. Marble and granite were chosen because they are applied as kitchen bench covers and pavements in many countries and there are no literature reports on their behaviour in terms of microbial adhesion. The effect of surface hydrophobicity and roughness on the adhesion process was also analysed. The results showed that the highest extent of adhesion of L. monocytogenes occurred to stainless steel, followed by glass and in less extent to the other materials studied. However, it was not possible to establish a correlation between surface hydrophobicity or roughness and the extent of adhesion of L. monocytogenes. The adherence of L. monocytogenes should be dependent on other factors, like the presence of exopolymers and surface charge.
Inhibition of Alicyclobacillus acidoterrestris spores by natural compounds
Authors: Bevilacqua A. , Corbo M.R. , Sinigaglia M.
Published: June 2008

The aim of this study was to evaluate the antimicrobial effectiveness of some natural compounds (cinnamaldehyde, eugenol, limonene) and sodium benzoate against two strains of Alicyclobacillus acidoterrestris (c8 and γ4). The antimicrobial compounds (10–500 ppm) were solved in malt extract broth, inoculated separately with 103 spores mL−1 of each strain; the samples were incubated at 44 °C and the outgrowth of spores was evaluated every day by measuring the absorbance of the medium at 420 nm; inoculated samples without active compounds were used as controls. The results pointed out that limonene was not effective in inhibiting the outgrowth of A. acidoterrestris spores; 100 ppm of cinnamaldehyde or sodium benzoate slowed the spore germination, whereas 500 ppm of eugenol inhibited the growth of microbial targets for 13 days. Strain c8 was more resistant than isolate γ4 and cinnamaldehyde was the most effective compound in inhibiting the germination of A. acidoterrestris spores.
Optimisation of osmotic dehydration of ‘Tommy Atkins’ mango fruit
Authors: Azoubel Patrícia Moreira , Da Silva Francinaide Oliveira
Published: June 2008

Osmotic dehydration of mango in sucrose solution as influenced by temperature (30–50 °C), immersion time (60–150 min) and solution concentration (40–60% w/w) was studied through response surface methodology. Responses of water loss and solid gain were fitted to polynomials, with multiple correlation coefficients ranging from 0.72 to 0.95, respectively. The fitted functions were optimised for maximum water loss and minimised incorporation of solids in order to obtain a product resembling non‐processed fruit. Optimum conditions to obtain water removal >25% with solid uptake lower than 6% could be obtained using a 44% (w/w) sucrose solution concentration, temperatures up to 38 °C and immersion times up to 80 min.
Characterisation of the main enzymatic activities present in six commercial macerating enzymes and their effects on extracting colour during winemaking of Monastrell grapes
Authors: Romero‐Cascales Inmaculada , Fernández‐Fernández José Ignacio , Ros‐García José María , López‐Roca José María , Gómez‐Plaza Encarna
Published: June 2008

Numerous studies have reported on the use of enzymes in wineries to facilitate the extraction of grape phenolics and to aid colour stability, although no clear conclusions were reached. Information concerning the enzymatic activities of industrial preparations is very difficult to obtain despite its importance. The aim of this work was to characterise and quantify the activities of six macerating enzyme preparations to optimise their use, and to study their effect on the chromatic characteristics of a Monastrell wine. The results indicate that differences exist in the type of enzymatic activities present in the preparations and in their concentration. The chromatic characteristics of the resulting wines, both at the end of alcoholic fermentation and after 12 months of storage in stainless steel tanks, showed differences with the use of the different maceration enzymes when comparing with control wine, although very little differences were observed between the different enzyme treatments. The enzyme‐treated wines showed, at the end of alcoholic fermentation, a higher OD280 and tannin content, and after 12 months, a higher colour intensity too. The main effect of all the preparations was an increase in the total phenol content, probably by facilitating the release of skin tannins.
Hypothalamic Corticotrophin‐Releasing Factor and Norepinephrine Mediate Sympathetic and Cardiovascular Responses to Acute Intracarotid Injection of Tumour Necrosis Factor‐α in the Rat
Authors: Zhang Z.‐H. , Felder R. B.
Published: June 2008

Systemic administration of tumour necrosis factor (TNF)‐α induces the release of norepinephrine in the paraventricular nucleus (PVN) of hypothalamus and an increase in expression of corticotrophin‐releasing factor (CRF) and CRF type 1 receptors. We explored the hypothesis that CRF and norepinephrine in PVN mediate the cardiovascular and sympathetic responses to acute systemic administration of TNF‐α. In anaesthetised rats, the increases in arterial pressure and heart rate induced by intracarotid artery injection of TNF‐α were attenuated by intracerebroventricular (ICV) injection of either the α1‐adrenergic antagonist prazosin or the CRF antagonist α‐helical CRF. Prazosin blocked the TNF‐α‐induced increase in renal sympathetic nerve activity (RSNA), whereas α‐helical CRF substantially reduced the RSNA response. Conversely, CRF and the α1‐adrenergic agonist phenylephrine, administered ICV, both elicited increases in PVN neuronal activity, RSNA, arterial pressure and heart rate. Microinjection of CRF and phenylephrine directly into PVN evoked smaller responses. These results are consistent with the hypothesis that norepinephrine and CRF in the PVN mediate the cardiovascular and sympathetic responses to acute systemic administration of TNF‐α.
Blood–brain barrier impairment with enhanced SP, NK‐1R, GFAP and Claudin‐5 expressions in experimental cerebral toxocariasis
Authors: LIAO C.‐W. , CHO W.‐L. , KAO T.‐C. , SU K.‐E. , LIN Y.‐H. , FAN C.‐K.
Published: June 2008

Infection byToxocara canisin humans may cause cerebral toxocariasis (CT). Appreciable numbers ofT. canislarvae cross the blood–brain barrier (BBB) to invade the brain thus causing CT. In the present studies, we evaluated the BBB permeability and BBB injury as assessed by the cerebral Evans blue (EB) concentration as well as by pathological changes and glial fibrillary acidic protein (GFAP) expression inT. canis‐infected mice monitored from 3 days (dpi) to 8 weeks post‐infection (wpi). The vasodilation neuropeptides, the expressions of substance P (SP) and its preferred binding neurokinin‐1 receptor (NK‐1R) as well as claudin‐5 of tight‐junction proteins associated with BBB impairment were also assessed by Western blotting and reverse‐transcriptase polymerase chain reaction. Results revealed that BBB permeability increased as evidenced by a significantly elevated EB concentration in brains of infected mice. BBB injury appeared due to enhanced GFAP protein and mRNA expressions from 4 to 8 wpi. Leukocytes might have been unrelated to BBB impairment because there was no inflammatory cell infiltration despiteT. canislarvae having invaded the brain; whereas markedly elevated SP protein and NK‐1R mRNA expressions concomitant with enhanced claudin‐5 expression seemed to be associated with persistent BBB impairment in this experimental CT model.
Controls on Holocene deep‐water sedimentation in the northern Gioia Basin, Tyrrhenian Sea
Authors: GAMBERI FABIANO , MARANI MICHAEL
Published: June 2008

The northern Gioia Basin of the south‐east Tyrrhenian Sea is a slope basin, ∼ 20 km wide and ∼ 50 km long, with a bathymetry of ≤ 1300 m, bounded by the Calabro‐Sicilian landmass and the Aeolian Island Arc. Coarse sediment is supplied from the Calabrian margin, where the shelf is very narrow to non‐existent, whereas the wider shelf on the Sicilian margin prevents supply by storing river‐fed sediments. The basin is dominated by the Gioia–Mesima canyon/channel system paralleled by a tongue‐shaped depositional lobe. Multibeam bathymetric surveys, sea floor reflectivity data and airgun seismic profiles reveal the recent evolution of the submarine system. Slope canyons and basin‐floor levéed channels formed where major rivers built deltas at the shelfless Calabrian margin and strong hyperpycnal flows predominated. The channels are a few hundred metres wide and a few tens of metres deep, with a downslope change from a straight to meandering pattern where the slope gradient decreases from 3·2% to 1·7%. The Mesima Channel has its lower segment abandoned because of avulsion and crevasse‐splay formation at an upslope bend. The adjacent Gioia Channel has had its upper segment straightened and lower segment entrenched because of erosional deepening of the Stromboli Valley into which it debouches and which acts as the local base level. Overbank features include levées, coalescent splays and ‘yazoo’ channels; their nature and surface characteristics depend upon the magnitude and sediment grain‐size of spill‐over flows. On an adjoining narrow shelf sliver of the Calabrian margin, in contrast, the coalescing plumes of sediment suspension supplied by an array of smaller coastal streams were apparently spilling over the shelf edge, scouring a funnel‐shaped bypass depression with chutes and forming an elongate, non‐channellized depositional lobe at the slope base. The study demonstrates the impact of sediment source type, shelf width, basin‐floor gradient and base‐level change on the style of deep‐water sedimentation.
Influence of cancer‐related gene polymorphisms on clinicopathological features in colorectal cancer
Authors: Yoshiya Gen , Takahata Takenori , Hanada Naoyuki , Suzuki Kazuhiro , Ishiguro Atsushi , Saito Masato , Sasaki Mutsuo , Fukuda Shinsaku
Published: June 2008

Background and Aim:  Single nucleotide polymorphisms (SNP) are shown to be related with cancer incidence. It has been reported that CCND1, p21cip1DCC, MTHFR, and EXO1 are related with the risk of malignant neoplasm, but few studies have mentioned the prognosis of the patients. We investigated the SNP of patients and related this to clinicopathological features, including survival rate.

Method:  DNA from the tissues of primary colorectal cancer was obtained from surgical resections of 114 patients (68 males and 46 females, 29–83 years). The CCND1 polymorphism was analyzed by polymerase chain reaction‐restriction fragment length polymorphism (PCR‐RFLP) and those of other genes were investigated by the TaqMan method. The polymorphisms obtained were statistically analyzed for the relationship with clinicopathological features.

Results:  The CG + GG allele was more invasive than the CC allele in histological tumor depth in the DCC codon 201 (P = 0.0086). The 677TT allele in MTHFR had a larger tumor size than the 677CC allele (P = 0.028). In EXO1 P757L polymorphism, patients with the TT allele had a statistically reduced survival rate compared with the other alleles. In CCND1 polymorphisms, we found no statistical significance in clinicopathological features.

Conclusions:  From these preliminary data, these polymorphisms would be candidates predicting the clinicopathological features of colorectal cancer, but further more systematic gene analyses are warranted.
Ribavirin in the treatment of chronic hepatitis C
Authors: Martin Paul , Jensen Donald M
Published: June 2008

Background and Aim:  Current practice guidelines recommend that individuals chronically infected with the hepatitis C virus (HCV) be treated with pegylated interferon plus ribavirin. Ribavirin, however, is associated with serious adverse events (AE), especially anemia. We review its mechanism of action, its importance in treating chronic hepatitis C (CHC) patients, the AE associated with its use, and techniques used to lessen these AE.

Methods:  Medline searches were performed using the keywords ribavirin and hepatitis, together with the keywords mechanism, anemia, liver transplant, renal function, pharmacokinetics, and dose reduction. Searches of abstracts of recent Digestive Diseases Week, American Association for the Study of Liver Diseases, and European Association for the Study of Liver Diseases meetings were also performed.

Results:  Ribavirin may be effective in treating CHC by affecting the virus or the host; for example by inducing viral mutations, blocking cellular enzymes, or affecting the host immune response. Although the pegylated interferons are the primary drugs used to treat CHC, a combination with ribavirin is more effective than pegylated interferon alone. Ribavirin‐associated AE may be lessened by ribavirin dose reductions and by maintenance of the hematocrit.

Conclusions:  Treatments of ribavirin toxicities, especially anemia, can allow patients to continue full‐dose combination therapy with peginterferon and ribavirin, enhancing their probability of attaining a sustained virologic response (SVR). Treatment of CHC should be tailored to individual patients, especially those with renal dysfunction, and should include agents that treat the side‐effects of CHC treatment. Monitoring of plasma ribavirin concentrations during treatment may help in the future.
Second‐generation argon plasma coagulation: Two‐center experience with 600 patients
Authors: Manner Hendrik , Enderle Markus D , Pech Oliver , May Andrea , Plum Nicola , Riemann Jürgen F , Ell Christian , Eickhoff Axel
Published: June 2008

Background and Aim:  Second‐generation argon plasma coagulation (APC; APC 2/VIO APC) with its modes ‘forced’, ‘pulsed’, and ‘precise’ is a further development of the ICC/APC 300 system (first‐generation APC). Until now, only limited data has existed on the use of APC 2.

Methods:  Fundamental data on the characteristics of the various APC 2 modes and clinical data from more than 600 patients treated in two high‐volume endoscopy centers were analyzed. On the basis of these data, recommendations for the use of APC in daily gastroenterological practice were made.

Results:  In comparison to the ICC system, second‐generation APC offers a broadened bandwidth of settings including different APC modes and a range of power settings from 1 to 120 W. Using the various modes of APC 2 in a variety of gastrointestinal diseases, minor complications were observed in 9–21% of patients. Major complications occurred in 1–7% of patients.

Conclusions:  In a two‐center experience treating a large group of patients with a wide variety of gastrointestinal conditions, the different APC 2 modes appeared to be safe and effective. Certain preventive measures before and during clinical application are recommended in order to avoid complications.
The NCAM‐derived P2 peptide facilitates recovery of cognitive and motor function and ameliorates neuropathology following traumatic brain injury
Authors: Klementiev B. , Novikova T. , Korshunova I. , Berezin V. , Bock E.
Published: June 2008

The neural cell adhesion molecule (NCAM) plays a crucial role during development and regeneration of the nervous system, mediating neuronal differentiation, survival and plasticity. Moreover, NCAM regulates learning and memory. A peptide termed P2, corresponding to a 12‐amino‐acid sequence in the second immunoglobulin (Ig)‐like module of NCAM, represents the natural cis‐binding site for the first NCAM Ig module. The P2 peptide targets NCAM, thereby inducing a number of intracellular signaling events leading to the stimulation of neurite outgrowth and promotion of neuronal survival in vitro. The present study evaluated the effect of the P2 peptide on functional and histological outcomes following traumatic brain injury inflicted by a cortical cryogenic lesion. Lesioned rats were injected subcutaneously with P2 peptide, 5 mg/kg daily for 15 days beginning 2 h after injury. This treatment significantly improved postlesion recovery of motor and cognitive function, reduced neuronal degeneration, protected cells against oxidative stress, and increased reactive astrogliosis and neuronal plasticity in the sublesional area. P2 appeared rapidly in blood and cerebrospinal fluid after subcutaneous administration and remained detectable in blood for up to 5 h. The results suggest that P2 has therapeutic potential for the treatment of traumatic brain injury.
COX‐2, but not COX‐1, activity is necessary for the induction of perforant path long‐term potentiation and spatial learningin vivo
Authors: Cowley T. R. , Fahey B. , O’Mara S. M.
Published: June 2008

The objectives of this research were to investigate the role played by the enzyme cyclooxygenase (COX) in learning and memory, synaptic plasticity and synaptic transmission in the rat brainin vivo. Male Wistar rats were treated with isoform‐selective inhibitors for COX‐1 and COX‐2, either chronically and tested in the watermaze or acutely before electrophysiological recordings were made. We found a significant impairment in acquisition of the watermaze with inhibition of COX‐2. Furthermore, we found COX‐2 but not COX‐1 inhibition significantly blocked long‐term potentiation (LTP) induction but had no effect on already established LTP. Moreover, exogenous replacement of the main metabolite of COX‐2 activity, PGE2, was sufficient to restore LTP induction and for normal downstream signalling to ensue, namely extracellular signalling‐regulated kinase (ERK)‐phosphorylation and c‐FOS expression. We conclude that endogenous basal levels of PGE2resulting from COX‐2 but not COX‐1 activity are necessary for synaptic plasticity and memory acquisition.
Stimulus‐driven and strategic neural responses to fearful and happy facial expressions in humans
Authors: Williams Mark A. , McGlone Francis , Abbott David F. , Mattingley Jason B.
Published: June 2008

The human amygdala responds selectively to consciously and unconsciously perceived facial expressions, particularly those that convey potential threat such as fear and anger. In many social situations, multiple faces with varying expressions confront observers yet little is known about the neural mechanisms involved in encoding several faces simultaneously. Here we used event‐related fMRI to measure neural activity in pre‐defined regions of interest as participants searched multi‐face arrays for a designated target expression (fearful or happy). We conducted separate analyses to examine activations associated with each of the four multi‐face arrays independent of target expression (stimulus‐driven effects), and activations arising from the search for each of the target expressions, independent of the display type (strategic effects). Comparisons across display types, reflecting stimulus‐driven influences on visual search, revealed activity in the amygdala and superior temporal sulcus (STS). By contrast, strategic demands of the task did not modulate activity in either the amygdala or STS. These results imply an interactive threat‐detection system involving several neural regions. Crucially, activity in the amygdala increased significantly when participants correctly detected the target expression, compared with trials in which the identical target was missed, suggesting that the amygdala has a limited capacity for extracting affective facial expressions.
Specific role of the posterior dorsal hippocampus–prefrontal cortex in short‐term working memory
Authors: Izaki Yoshinori , Takita Masatoshi , Akema Tatsuo
Published: June 2008

Working memory in rats involves neural projections from the hippocampus (HP) to the prefrontal cortex (PFC), based on delayed task experiments in a radial‐arm maze, in which the time span of working memory is longer than seconds. To determine whether the HP–PFC pathway is involved in short‐term (on the order of seconds) working memory function, we lesioned the PFC and/or HP, and measured performance in an operant delayed alternation task. The posterior dorsal (pdHP) and ventral HP (vHP) were assessed separately. The bilateral PFC and bilateral pdHP ibotenate lesions produced significant working memory deficits, but the vHP lesion did not. Unilateral pdHP lesions combined with a PFC lesion in the opposite hemisphere reproduced the effects of bilaterally symmetrical lesions. By contrast, unilateral lesions of the pdHP combined with a PFC lesion in the same hemisphere had no effect on delayed alternation. These results indicate that the pdHP–PFC pathway is essential for working memory on the order of seconds in rats, and suggest that the pdHP and vHP pathways to the PFC play different behavioral roles.
The effect on pain experienced by male patients of watching their office‐based flexible cystoscopy
Authors: Cornel Erik B. , Oosterwijk Egbert , Kiemeney Lambertus A.
Published: June 2008

OBJECTIVE

To confirm the recently published positive effect on visual analogue pain (VAS) scale levels for men watching their flexible cystoscopy.

PATIENTS AND METHODS

From June 2007 to September 2007, 154 men had a flexible cystoscopy for various indications, all carried out by one urologist. Patients were randomized into two groups; those in group 1 were allowed to watch the video screen together with the urologist during the procedure; those in group 2 were not allowed to watch the procedure on the video screen. All patients received the same real‐time explanation during the cystoscopy. After the cystoscopy procedure the patients were asked to record their experience of pain on the 100 mm VAS as soon as they left the room. The two groups were further stratified by the number of previous cystoscopies experienced to evaluate the possible modifying effect of their previous experience.

RESULTS

Although the results suggested a small decrease in perceived pain there were no statistically significant differences between the groups, regardless of cystoscopy experience.

CONCLUSIONS

Our results show that, in contrast to an earlier report, the pain experienced by men undergoing a first or repeated flexible cystoscopy is not strongly influenced by watching the procedure.
Associations of lower urinary tract symptoms with prostate‐specific antigen levels, and screen‐detected localized and advanced prostate cancer: a case‐control study nested within the UK population‐based ProtecT (Prostate testing for cancer and Treatment) study
Authors: Collin Simon M. , Metcalfe Chris , Donovan Jenny , Lane J. Athene , Davis Michael , Neal David , Hamdy Freddie , Martin Richard M.
Published: June 2008

OBJECTIVE

To determine associations of lower urinary tract symptoms (LUTS) with prostate‐specific antigen (PSA) levels and screen‐detected localized and advanced prostate cancer.

SUBJECTS AND METHODS

A case‐control study nested within the UK population‐based ProtecT (Prostate testing for cancer and Treatment) study. Men aged 50–69 years were invited for PSA testing and those with a PSA level of ≥3.0 ng/mL were invited for biopsy. We determined whether LUTS were associated with a PSA level of ≥3.0 ng/mL and prostate cancer using logistic regression models adjusted for age, family history of prostate cancer and PSA level as appropriate. Areas under receiver operating characteristic curves (AUC) were compared between models with and without symptoms.

RESULTS

In all, 65 871 men had a PSA test: 7251 had a PSA level of ≥3.0 ng/mL including 2467 subsequently diagnosed with prostate cancer (2119 localized, 348 advanced). LUTS were positively associated with a PSA level of ≥3.0 ng/mL: odds ratios (ORs) were 1.18 (95% confidence interval, CI 1.01–1.38), 1.69 (95% CI 1.32–2.16), and 1.60 (95% CI 1.33–1.93) for daytime urination frequency (hourly vs less frequent), urgency and hesitancy (most/all the time vs never), respectively. LUTS among men with a PSA level of ≥3 ng/mL were negatively associated with prostate cancer: ORs were 0.44 (95% CI 0.22–0.83), 0.74 (95% CI 0.63–0.87), and 0.83 (95% CI 0.73–0.94) for nocturia (4+ vs 0), leakage and hesitancy (occasionally/sometimes vs never), respectively. LUTS improved the prediction of a PSA level of ≥3.0 ng/mL (AUC 0.635 vs 0.606, P < 0.001) and prostate cancer (AUC 0.661 vs 0.638; P < 0.001).

CONCLUSIONS

A history of LUTS before PSA testing marginally improves the prediction of an individual’s risk for prostate cancer; men with a PSA level of ≥3 ng/mL and LUTS were more likely to be diagnosed with benign disease than prostate cancer.
617. ORYCHOPHRAGMUS VIOLACEUS
Authors: Taylor Nigel , Zappi Daniela
Published: June 2008

Summary The now little known but garden‐worthy oriental crucifer, Orychophragmus violaceus, is illustrated and its botanical history, relationship, horticultural requirements and morphology are discussed.
620. TRICHOSTEMA LANATUM
Authors: Lewis Harlan
Published: June 2008

Summary Trichostema lanatum Bentham is illustrated and described. Its distribution, taxonomic history and relationship to other species are discussed as is the position of the genus in Lamiaceae.
HOW TO ANALYZE IMMEDIATE EXPERIENCE:
Authors: OVERGAARD SØREN
Published: June 2008

Abstract: This article discusses Jaakko Hintikka's interpretation of the aims and method of Husserl's phenomenology. I argue that Hintikka misrepresents Husserl's phenomenology on certain crucial points. More specifically, Hintikka misconstrues Husserl's notion of “immediate experience” and consequently fails to grasp the functions of the central methodological tools known as the “epoché” and the “phenomenological reduction.” The result is that the conception of phenomenology he attributes to Husserl is very far from realizing the philosophical potential of Husserl's position. Hence if we want a fruitful rapprochement between analytical philosophy and Continental phenomenology of the kind that is Hintikka's ultimate aim, then Hintikka's account of Husserl needs correcting on a number of crucial points.
LANGUAGE, MIND, AND WORLD: CAN'T WE ALL JUST GET ALONG?
Authors: WOLF MICHAEL P.
Published: June 2008

Abstract:This article addresses recent claims made by Richard Rorty about antirepresentationalist theories of meaning. Rorty asserts that a faithful rendering of the core antirepresentationalist assumptions precludes even revised pieces of representationalist semantics like “refers” or “true” and epistemological correlates like “answering to the facts.” Rorty even asserts that such notions invite reactionary authoritarian elements that would impede the development of a democratic humanism. I reject this claim and assert that such notions (suitably constructed) pose no greater threat to democratic humanism than the alternatives and in fact are crucial to its maintenance and continuing success. These notions (suitably constructed) reflect a metatheoretical stance that I call “openness,” which I believe lies at the heart of both democratic humanism and the pragmatism from which Rorty claims to take his inspiration.
NATURAL DOUBTS
Authors: RUDD ANTHONY
Published: June 2008

Abstract: Many philosophers now argue that the doubts of the philosophical sceptic are unnatural ones, in that they are not forced on us by considerations that any reasonable person would have to accept as compelling but only arise if one has already accepted certain controversial theoretical commitments. In this article I defend the naturalness of philosophical scepticism against such criticisms. After defining “global ontological scepticism,” I examine the work of a number of anti‐sceptical philosophers—Michael Huemer, Michael Williams, and John McDowell. Although McDowell does move the debate to a deeper level by interpreting scepticism as a challenge to the very possibility of the mind's apprehending reality by being in a rational rather than a merely causal relation to it, none of them succeeds in showing that global ontological scepticism is, in the relevant sense, unnatural. This is not to say that the sceptic is correct; simply that it has not been shown that we can reasonably dismiss the sceptical questions and thereby evade the need to engage seriously with the sceptical arguments.
HIV testing strategies across European countries
Authors: Mounier‐Jack S , Nielsen S , Coker RJ
Published: June 2008

With universal access to effective combination antiretroviral therapy (ART), people in need can gain effective treatment but are only able to benefit from these advances if they are aware of their serostatus and have effectively accessed testing services. Despite the expectation that ART would lead individuals to seek earlier testing, this trend has not been observed in practice, with stable or even increasing rates of late diagnosis in Europe being witnessed. Ahead of a gathering of key European stakeholders in Brussels in November 2007, we reviewed testing strategies across European countries. We show differences in policy and practices. Moreover, HIV testing strategies are changing, in line with new global guidelines issued by World Health Organization headquarters, and a number of countries are promoting an expansion of routine and opt‐out testing. However, gaps in our understanding of effective testing strategies remain and, as a consequence, national policies across Europe remain incoherent and often lack an evidence base. This is likely to have serious public health implications.
Indicator disease‐guided testing for HIV – the next step for Europe?
Authors: Gazzard B , Clumeck N , D'Arminio Monforte A , Lundgren JD
Published: June 2008

HIV should preferably be diagnosed in its earlier stages. To optimize the chances of doing so, HIV testing in patients presenting with one of several indicator diseases and conditions is recommended. Patients presenting with tuberculosis and other AIDS‐defining conditions should be tested. Patients with sexually transmitted diseases should be offered an HIV test, as should patients with certain types of cancers and laboratory abnormalities. Governments should consider adopting opt‐out testing for pregnant women. These recommendations should be considered for implementation by all types of health professionals across Europe, and audits to study the extent of their being followed, conducted and reported to the European AIDS Clinical Society webpage (http://www.eacs.eu).
Maximum Effect of Triptans in Migraine? A Comment
Authors: Tfelt-Hansen P
Published: June 2008

The efficacy of triptans in the treatment of migraine was recently contested. How high is then the maximum effect of a triptan?

After subcutaneous naratriptan 10 mg a 88% pain-free response was observed. This result was obtained despite the fact that more half of the patients had a migraine duration of > 4 h. These results indicate that subcutaneous naratriptan in a high dose can overcome central sensitization that occurs in migraine attacks.