Structural and Functional Analysis of a β₂-Adrenergic Receptor Complex with GRK5

Komolov, Konstantin E.,Du, Yang,Duc, Nguyen Minh,Betz, Robin M.,Rodrigues, Joã,o P.G.L.M.,Leib, Ryan D.,Patra, Dhabaleswar,Skiniotis, Georgios,Adams, Christopher M.,Dror, Ron O.,Chung, Ka Young Cell Press 2017 Cell Vol. No.

<P><B>Summary</B></P> <P>The phosphorylation of agonist-occupied G-protein-coupled receptors (GPCRs) by GPCR kinases (GRKs) functions to turn off G-protein signaling and turn on arrestin-mediated signaling. While a structural understanding of GPCR/G-protein and GPCR/arrestin complexes has emerged in recent years, the molecular architecture of a GPCR/GRK complex remains poorly defined. We used a comprehensive integrated approach of cross-linking, hydrogen-deuterium exchange mass spectrometry (MS), electron microscopy, mutagenesis, molecular dynamics simulations, and computational docking to analyze GRK5 interaction with the β<SUB>2</SUB>-adrenergic receptor (β<SUB>2</SUB>AR). These studies revealed a dynamic mechanism of complex formation that involves large conformational changes in the GRK5 RH/catalytic domain interface upon receptor binding. These changes facilitate contacts between intracellular loops 2 and 3 and the C terminus of the β<SUB>2</SUB>AR with the GRK5 RH bundle subdomain, membrane-binding surface, and kinase catalytic cleft, respectively. These studies significantly contribute to our understanding of the mechanism by which GRKs regulate the function of activated GPCRs.</P> <P><B>PaperClip</B></P> <P>Display Omitted</P> <P><B>Highlights</B></P> <P> <UL> <LI> GRK5-β<SUB>2</SUB>AR binding is enhanced by receptor and kinase ligands and acidic lipids </LI> <LI> GRK5 binding to the β<SUB>2</SUB>AR involves a multi-site interaction </LI> <LI> Receptor binding triggers substantial conformational changes in GRK5 </LI> <LI> RH/catalytic domain separation in GRK5 is essential for receptor phosphorylation </LI> </UL> </P> <P><B>Graphical Abstract</B></P> <P>[DISPLAY OMISSION]</P>

Dietary Calcium and Non-phytin Phosphorus Interaction on Growth, Bone Mineralization and Mineral Retention in Broiler Starter Chicks

Rao, S.V. Rama,Raju, M.V.L.N.,Reddy, M.R.,Pavani, P.,Sunder, G. Shyam,Sharma, R.P. Asian Australasian Association of Animal Productio 2003 Animal Bioscience Vol.16 No.5

An experiment was conducted to study the requirement of calcium (Ca) and non-phytin phosphorus (NPP) in commercial broilers during starter phase. Seven hundred and twenty day-old Vencob male broiler chicks were randomly distributed into 144 stainless steel battery brooders, 5 birds in each. Four levels each of Ca (6, 7, 8, and 9 g/kg) and NPP (3, 3.5, 4, and 4.5 g/kg diet) were fed in a factorial design in a corn-soya basal diet. Levels of dicalcium phosphate and oyster shell grit were adjusted to obtain the desired levels of Ca and NPP. Each diet was fed ad libidum to chicks in 9 battery brooders from one d to 21 d of age. Body weight gain and feed intake were depressed (p<0.01) by increasing the dietary Ca level (8 and 9 g/kg) at lower levels of NPP (3 and 3.5 g/kg diet). The growth depression observed at lower NPP level was alleviated by reducing the Ca content to 6 g/kg diet. The tibia ash content and tibia breaking strength increased with increase in both Ca (>6 g/kg) and NPP (>3 g/kg) levels. The leg abnormality score decreased (p<0.01) with increase in NPP content in the diet at all levels of Ca tested. The serum Ca and inorganic P levels were increased with increase in the level of the respective mineral in the diet, but the serum concentration of Ca and P were inversely related to the level of NPP and Ca, respectively /kg diet. In general, the excretion of macro minerals (Ca, and P), and micro minerals {zinc (Zn), manganese (Mn), iron (Fe), and copper (Cu)} was significantly lower at lower levels of Ca and NPP tested (6 and 3 g/kg diet, respectively). The mineral excretion increased with increase in dietary Ca and NPP levels, more conspicuously at the disproportionate ratio of these minerals (>2:1, Ca and NPP). Similarly, the retention of Zn, Mn, and Fe in liver was significantly higher (p<0.01) at lower levels of Ca and NPP tested. Results from this study indicate that the commercial broilers do not require more than 3 g NPP and 6g Ca/kg diet during starter phase (up to 21 d of age) for optimum weight gain, feed efficiency and utilization of Ca, P, Zn, Mn, Fe and Cu. However, the requirements of these minerals for optimum bone mineralization were higher than the levels suggested above.

Expression phenotype changes of EBV-transformed lymphoblastoid cell lines during long-term subculture and its clinical significance

Lee, J.-E.,Nam, H.-Y.,Shim, S.-M.,Bae, G.-R.,Han, B.-G.,Jeon, J.-P. Blackwell Publishing Ltd 2010 Cell proliferation Vol.43 No.4

<P>Abstract</P><P>Objectives: </P><P>The EBV-transformed lymphoblastoid cell line (LCL) is a useful resource for population-based human genetic and pharmacogenetic studies. The principal objective here was to assess expression phenotype changes during long-term subculture of LCLs, and its clinical significance.</P><P>Materials and methods: </P><P>We searched for genes that were differentially expressed in 17 LCLs at late (p161) passage compared to early passage (p4) using microarray assay, then validated them by real-time RT-PCR analysis. In addition, we estimated correlations between expression phenotypes of 20 LCL strains at early passage and 23 quantitative clinical traits from blood donors of particular LCL strains.</P><P>Results: </P><P>Transcript sequences of 16 genes including nuclear factor-&kgr;B (NF-&kgr;B) pathway-related genes (such as <I>PTPN13</I>, <I>HERC5</I> and miR-146a) and carcinogenesis-related genes (such as <I>XAF1</I>, <I>TCL1A</I>, <I>PTPN13</I>, <I>CD38</I> and miR-146a) were differentially expressed (>2-fold change) in at least 15 of the 17 LCL strains. In particular, <I>TC2N</I>, <I>FCRL5</I>, <I>CD180</I>, <I>CD38</I> and miR-146a were downregulated in all 17 of the evaluated LCL strains. In addition, we identified clinical trait-associated expression phenotypes in LCLs.</P><P>Conclusion: </P><P>Our results showed that LCLs acquired expression phenotype changes involving expression of NF-&kgr;B pathway- and carcinogenesis-related genes during long-term subculture. These differentially expressed genes can be considered to be a gene signature of LCL immortalization or EBV-induced carcinogenesis. Clinical trait-associated expression phenotypes should prove useful in the discovery of new candidate genes for particular traits.</P>

Chemodosimeter functionalized diatomaceous earth particles for visual detection and removal of trace mercury ions from water

Patil, Pravin,Madhuprasad, Pravin,Bhat, Mahesh P.,Gatti, Manasa G.,Kabiri, Shervin,Altalhi, Tariq,Jung, Ho-Young,Losic, Dusan,Kurkuri, Mahaveer Elsevier 2017 Chemical engineering journal Vol.327 No.-

<P><B>Abstract</B></P> <P>The rhodamine based receptor, P2 has been developed for the detection of environmentally hazardous Hg<SUP>2+</SUP> ions with a limit of detection, 1.5×10<SUP>−6</SUP> M. The P2 showed a significant colour change from colourless to pink upon binding with Hg<SUP>2+</SUP> ions. As a result, a new peak at 533nm was observed in UV–vis spectroscopy which was attributed to spirolactum ring opening followed by through bond energy transfer (TBET). In addition, the presence of other competing cations did not interfere the detection of Hg<SUP>2+</SUP> ions. Further, P2 has been successfully immobilized onto the naturally available and highly porous diatomaceous earth particles (P2D) for removal of Hg<SUP>2+</SUP> ions from water. The covalently attached organic molecule in P2D forms complex with Hg<SUP>2+</SUP> ion present in the water and thus traps the Hg<SUP>2+</SUP> ions. Based on this, a proof-of-concept cartridge has been developed for water purification. The cartridge having 450mg of P2D was able to purify 30mL of water containing 1ppm Hg<SUP>2+</SUP> ions. The efficiency of cartridge could be visualized with a colour change from colourless to pink.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Detection and removal of Hg<SUP>2+</SUP> from water using chemodosimeter P2 were realized. </LI> <LI> P2 has been successfully immobilized onto naturally available diatoms (P2D). </LI> <LI> Organic receptor and hazardous Hg<SUP>2+</SUP> ions were physically contained in diatoms. </LI> <LI> Eco-friendly cartridge containing P2D was developed for the removal of Hg<SUP>2+</SUP> ions. </LI> <LI> Device efficiency (time to replace) could be realized through visual colour change. </LI> </UL> </P>

High polarity analytes in food - enrofloxacin and sulfadiazine in bovine tissue (CCQM-K141)

Windust, Anthony,McRae, Garnet,Meija, Juris,Mester, Zoltá,n,Melanson, Jeremy E,Croft, Meg,Johnston, Lesley,Murby, John,Rego, Eliane C P do,Violante, Fernando G M,Fernandes, Jane L N,Wollinger, W BUREAU INTERNATIONAL DES POIDS ET MESURES 2019 METROLOGIA -BERLIN- Vol.56 No.-

<P></P> <P>Within the Organic Analysis Working Group (OAWG) of the Comité Consultatif pour la Quantitè de Matiére (CCQM), key comparison CCQM-K141 and associated pilot study CCQM-P178 were coordinated by the National Research Council Canada (NRC). This comparison was a Track A key comparison that formed part of the OAWG 10-year strategic plan. The comparison demonstrated capabilities for measuring high-polarity analytes in a high-fat and high-protein matrix. The measurand chosen as the model system was enrofloxacin and sulfadiazine in bovine tissue. Thirteen National Metrology Institutes or Designated Institutes participated in the CCQM-K141, while two National Metrology Institutes participated in CCQM-P178.</P> <P>The bovine muscle tissue study material was derived from a single live animal that was administered with chemical based pharmaceutical agents prior to processing. Therefore, the study material was naturally incurred, providing a true test of extraction procedures relative to more commonly encountered spiked materials. NRC confirmed excellent homogeneity and stability of the material prior to shipping. Three 10 g bottles of freeze dried powdered muscle tissue were supplied. NRC also provided isotopically labelled solutions of the two measurands, <SUP>13</SUP>C<SUB>6</SUB>-sulfadiazine and enrofloxacin-d<SUB>5</SUB> (HI Salt), to those interested in using isotope dilution mass spectrometry (IDMS) methodologies. Procurement and purity assignment with appropriate metrological traceability of native calibrants were the responsibility of individual participants. The study required extraction, clean-up, analytical separation, and selective detection of the analytes.</P> <P>The level of agreement was reasonable given the measurands and matrix were new for most laboratories. The KCRV values and their uncertainties at the 95% confidence level of 57.81 ± 2.57 μg/kg for enrofloxacin and 2285 ± 68 μg/kg for sulfadiazine were calculated using the DSL means. While one participant's value was voluntarily excluded from the KCRV calculations for enrofloxacin, all other participants demonstrated equivalence for both measurands.</P> <P>Significant effort was undertaken post-study to identify the major sources of variability between results. In particular, the various extraction conditions used by participants were investigated thoroughly. While there appeared to be a correlation between highly acidic conditions and higher recovery, this was not definitive and could not be confirmed. The form of standards employed (i.e. free base vs salts) and potential differential solubility between forms was also a suspected source of variability. Biases could also have been introduced with the choice of solvents used for standard preparation, with some solvents better able to minimize adsorption of the analytes to glass surfaces.</P> <P>KEY WORDS FOR SEARCH</P> <P>enrofloxacin, sulfadiazine, bovine tissue, incurred, key comparison</P> <P></P> <H2>Main text</H2> <P> To reach the main text of this paper, click on <A HREF='https://www.bipm.org/utils/common/pdf/final_reports/QM/K141/CCQM-K141.pdf'>Final Report</A>. Note that this text is that which appears in Appendix B of the BIPM key comparison database <A HREF='http://kcdb.bipm.org/'>kcdb.bipm.org/</A>.</P> <P>The final report has been peer-reviewed and approved for publication by the CCQM, according to the provisions of the CIPM Mutual Recognition Arrangement (CIPM MRA).</P>

Report of the CCQM-K97: measurement of arsenobetaine standard solution and arsenobetaine content in fish tissue (tunafish)

Ma, L D,Wang, J,WEI, C,Kuroiwa, T,Narukawa, T,Ito, N,HIOKI, A,CHIBA, K,Yim, Y H,Lee, K S,Lim, Y R,Turk, G C,Davis, C W,Mester, Z,Yang, L,McCooeye, M,Maxwell, P,Cankur, O,Tokman, N,Coskun, F G BUREAU INTERNATIONAL DES POIDS ET MESURES 2017 METROLOGIA -BERLIN- Vol.54 No.-

<P></P> <P>The CCQM-K97 key comparison was organized by the inorganic analysis working group (IAWG) of CCQM as a follow-up to completed pilot study CCQM-P96 and P96.1 to test the abilities of the national metrology institutes to accurately quantitate the mass fraction of arsenobetaine (AsB) in standard solution and in fish tissue. A pilot study CCQM-P133 was parallelized with this key comparison. National Institute of Metrology (NIM), China and National Metrology Institute of Japan (NMIJ) acted as the coordinating laboratories.</P> <P>Six NMIs participated in CCQM-K97 and two institutes participated in CCQM-P133, and all of them submitted the results. Some NMIs submitted more than one results by different methods. The results were in excellent agreement with each other, and obviously better than those of previous P96 and P96.1. Therefore the calibrant which each NMI used was comparable. It shows that the capabilities of some of the participants have been improved after the previous pilot studies.</P> <H2>Main text</H2> <P> To reach the main text of this paper, click on <A HREF='http://www.bipm.org/utils/common/pdf/final_reports/QM/K97/CCQM-K97.pdf'>Final Report</A>. Note that this text is that which appears in Appendix B of the BIPM key comparison database <A HREF='http://kcdb.bipm.org/'>kcdb.bipm.org/</A>.</P> <P>The final report has been peer-reviewed and approved for publication by the CCQM, according to the provisions of the CIPM Mutual Recognition Arrangement (CIPM MRA).</P>

Photoswitching and photocatalytic functions of Sn_xCu_1−xS nanostructures

Ilanchezhiyan, P.,Kumar, G. Mohan,Siva, C.,Venkatasubbu, G. Devanand,Kang, T.W.,Kim, D.Y. Elsevier 2019 APPLIED SURFACE SCIENCE - Vol.489 No.-

<P><B>Abstract</B></P> <P>Ultra-thin semiconducting nanostructures are garnering strategic importance in energy and environment remediation applications. In this regard, Sn<SUB>x</SUB>Cu<SUB>1−x</SUB>S nanostructures were processed through an eco-friendly chemical route and investigated in detail for photoswitching and photocatalytic functions. X-ray diffraction, FT-IR, Raman, UV–vis absorbance and high-resolution microscopic tools were initially used to examine the physico-chemical traits of Sn<SUB>x</SUB>Cu<SUB>1−x</SUB>S nanostructures. Ambiguous evidence for the substitution of Sn ions in place of Cu ions was attained through X-ray photoelectron spectroscopy. The photocatalytic performance of Sn<SUB>x</SUB>Cu<SUB>1−x</SUB>S systems was investigated through effective remediation of organic dye molecules under visible light. Scavenger based photocatalytic experiments were additionally carried out to infer the degradation mechanism. Type II <I>p-n</I> Sn<SUB>x</SUB>Cu<SUB>1−x</SUB>S/In<SUB>2</SUB>S<SUB>3</SUB> heterojunction diodes were also demonstrated for the first time with improved electrical conductivity and photoelectrical performances. The rectification ratio, forward current values and photo switching capabilities of these diodes were noted to improve in the Current vs. Voltage (I-V) and Current vs. Time (I-T) curves as a function of Sn composition and applied bias potential. The excellent photo switching stability augments the photo generated carriers to be effectively separated along the p-n junctions. The enhanced photoelectronic and photocatalytic functionalities in Sn<SUB>x</SUB>Cu<SUB>1−x</SUB>S has finally been reasoned to the improved charge transfer kinetics in the respective architectures, resulting from the effective Sn interaction in hexagonal host lattice.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Sn<SUB>x</SUB>Cu<SUB>1−x</SUB>S nanostructures were fabricated by hydrothermal route. </LI> <LI> The nanostructures exhibited excellent photocatalytic activity under visible light. </LI> <LI> Sn interaction in hexagonal host lattice promoted their photocatalytic performance. </LI> <LI> p-Sn<SUB>x</SUB>Cu<SUB>1−x</SUB>S/n-In<SUB>2</SUB>S<SUB>3</SUB> diodes demonstrated improved photoswitching performance. </LI> </UL> </P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>

Moments of the spin structure functions g1p and g1d for 0.05<^Q2<3.0^GeV2

Prok, Y.,Bosted, P.,Burkert, V.D.,Deur, A.,Dharmawardane, K.V.,Dodge, G.E.,Griffioen, K.A.,Kuhn, S.E.,Minehart, R.,Adams, G.,Amaryan, M.J.,Anghinolfi, M.,Asryan, G.,Audit, G.,Avakian, H.,Bagdasaryan, Elsevier 2009 Physics letters: B Vol.672 No.1

<P><B>Abstract</B></P><P>The spin structure functions <SUB>g1</SUB> for the proton and the deuteron have been measured over a wide kinematic range in <I>x</I> and <SUP>Q2</SUP> using 1.6 and 5.7 GeV longitudinally polarized electrons incident upon polarized NH<SUB>3</SUB> and ND<SUB>3</SUB> targets at Jefferson Lab. Scattered electrons were detected in the CEBAF Large Acceptance Spectrometer, for 0.05<<SUP>Q2</SUP><5<SUP> GeV2</SUP> and W<3 GeV. The first moments of <SUB>g1</SUB> for the proton and deuteron are presented – both have a negative slope at low <SUP>Q2</SUP>, as predicted by the extended Gerasimov–Drell–Hearn sum rule. The first extraction of the generalized forward spin polarizability of the proton γ0p is also reported. This quantity shows strong <SUP>Q2</SUP> dependence at low <SUP>Q2</SUP>. Our analysis of the <SUP>Q2</SUP> evolution of the first moment of <SUB>g1</SUB> shows agreement in leading order with Heavy Baryon Chiral Perturbation Theory. However, a significant discrepancy is observed between the γ0p data and Chiral Perturbation calculations for γ0p, even at the lowest <SUP>Q2</SUP>.</P>

HCV, Alcoholic : PE-134 ; Hemoglobin decline during peginterferon Alfa-2B (PEG-2B)/ribavirin (RBV) treatment in real-Life is associated with favorable SVR rates in difficult-to-treat patients with HCV genotype 1 (G1) infection

( G Teuber ),( S Mauss ),( D Huppe ),( E Zehnter ),( M P Manns ),( T Dahhan6 ),( U Meyer ),( T Witthoft ),( B Moller9,),( N Dikopoulos ),( J Brack ),( B Stade ),( M Bilzer ),( The Bng Hepatitis Study 대한간학회 2012 춘·추계 학술대회 (KASL) Vol.2012 No.-

Background and Aims: Recently, it has been shown for the overall G1 population that anemia as well as the maximal hemoglobin (Hb) decline during peginterferon/RBV treatment is associated with higher SVR rates. We here investigated whether the maximal Hb decline influences SVR rates in difficult-to-treat patients undergoing Peg2b/RBV therapy for HCV G1 infection in real-life. Methods: Data of patients treated for G1 infection within the German Peg2b/RBV observational study were retrospectively analyzed. In this real-life cohort study G1 infection was treated with Peg2b 1.5 μg/kg/wk + weight-based RBV (800-1200 mg/day) for up to 48 wks at 285 sites. Subjects who discontinued for non-response or for any other reasons were included in the analysis. SVR was defined as undetectable serum HCV-RNA 24 wks after EOT response. Only one patient received erythropoietin treatment for anemia. Results: 1851 patients had baseline and at least one Hb measurement during therapy. Overall SVR rate was 42.6% (789/1851). SVR rates were only slightly higher for subjects with an absolute Hb decline >3 g/dL (44.3%, 493/1114) compared to those with maximum Hb declines <3 g/dL (40.2%, 296/737) (p=0.08). In contrast, a significant (p=0.0004) difference in SVR rates was obtained by comparing subjects with Hb declines >2 g/dL (44.6%, 673/1510) with those who experienced Hb declines <2 g/dL (34.0%, 116/341). Similar SVR rates of 46.1% (164/356) and 44.1% (509/1154) in patients with Hb declines >2 g/dL even if they did/did not become anemic (Hb<10 g/dL) strongly support Hb decline, and not anemia, as primary beneficial mechanism improving SVR. As summarized in the table, Hb declines >2 g/dl were significantly associated with higher SVR rates in difficult-to-treat patients, such as subjects elder than 50 years or subjects with high baseline viral load >600.000 IU/ml. Interestingly no beneficial effect was observed in patients with low platelet count (<150/nL), an indicator of advanced fibrosis/cirrhosis. Patients who first developed a Hb decline >2 g/dL during weeks 0-4 were likely to achieve similar SVR (41.3%, 365/883) than those who developed a Hb decline <2 g/dL (44.9%, 386/859). In contrast, a Hb decline >2 g/dL compared to <2 g/dL during weeks 0-4 was associated with a 2-3 fold higher risk of anemia in female (16.6% vs 40.5%) and male patients (7.3% vs 19.0%) when compared with a Hb decline <2 g/dL. Conclusions: Patients with HCV genotype 1 infection and in particular the subgroup of difficult-to-treat patients elder than 50 years or with HVL, achieve up to 15% higher SVR rates when they develop a Hb decline >2 g/dL during Peg2b/RBV therapy. However, patients with low platelet count <150/nL do not achieve this beneficial virologic effect.

HCV : PE-134 ; Hemoglobin decline during peginterferon Alfa-2B (PEG-2B)/ribavirin (RBV) treatment in real-life is associated with favorable SVR rates in difficult-to-treat patients with HCV genotype 1 (G1) infection

( G Teuber ),( S Mauss ),( D Huppe ),( E Zehnter ),( M P Manns ),( T Dahhan ),( U Meyer ),( T Witthoft ),( B Moller ),( N Dikopoulos ),( J Brack ),( B Stade ),( M Bilzer ),( Bng Hepatitis Study Group 대한간학회 2012 춘·추계 학술대회 (KASL) Vol.2012 No.1

Background and Aims: Recently, it has been shown for the overall G1 population that anemia as well as the maximal hemoglobin (Hb) decline during peginterferon/RBV treatment is associated with higher SVR rates. We here investigated whether the maximal Hb decline influences SVR rates in difficult-to-treat patients undergoing Peg2b/RBV therapy for HCV G1 infection in real-life. Methods: Data of patients treated for G1 infection within the German Peg2b/RBV observational study were retrospectively analyzed. In this real-life cohort study G1 infection was treated with Peg2b 1.5 μg/kg/wk + weight-based RBV (800-1200 mg/day) for up to 48 wks at 285 sites. Subjects who discontinued for non-response or for any other reasons were included in the analysis. SVR was defined as undetectable serum HCV-RNA 24 wks after EOT response. Only one patient received erythropoietin treatment for anemia. Results: 1851 patients had baseline and at least one Hb measurement during therapy. Overall SVR rate was 42.6% (789/1851). SVR rates were only slightly higher for subjects with an absolute Hb decline >3 g/dL (44.3%, 493/1114) compared to those with maximum Hb declines <3 g/dL (40.2%, 296/737) (p=0.08). In contrast, a significant (p=0.0004) difference in SVR rates was obtained by comparing subjects with Hb declines >2 g/dL (44.6%, 673/1510) with those who experienced Hb declines <2 g/dL (34.0%, 116/341). Similar SVR rates of 46.1% (164/356) and 44.1% (509/1154) in patients with Hb declines >2 g/dL even if they did/did not become anemic (Hb<10 g/dL) strongly support Hb decline, and not anemia, as primary beneficial mechanism improving SVR. As summarized in the table, Hb declines >2 g/dl were significantly associated with higher SVR rates in difficult-to-treat patients, such as subjects elder than 50 years or subjects with high baseline viral load >600.000 IU/ml. Interestingly no beneficial effect was observed in patients with low platelet count (<150/nL), an indicator of advanced fibrosis/cirrhosis. Patients who first developed a Hb decline >2 g/dL during weeks 0-4 were likely to achieve similar SVR (41.3%, 365/883) than those who developed a Hb decline <2 g/dL (44.9%, 386/859). In contrast, a Hb decline >2 g/dL compared to <2 g/dL during weeks 0-4 was associated with a 2-3 fold higher risk of anemia in female (16.6% vs 40.5%) and male patients (7.3% vs 19.0%) when compared with a Hb decline <2 g/dL. Conclusions: Patients with HCV genotype 1 infection and in particular the subgroup of difficult-to-treat patients elder than 50 years or with HVL, achieve up to 15% higher SVR rates when they develop a Hb decline >2 g/dL during Peg2b/RBV therapy. However, patients with low platelet count <150/nL do not achieve this beneficial virologic effect.