bluuebunny/crossref_metadata_2025 huggingface dataset:
The green tea polyphenol, epigallocatechin-3-gallate, inhibits hepatitis C virus entry
Authors: Ciesek Sandra , von Hahn Thomas , Colpitts Che C. , Schang Luis M. , Friesland Martina , Steinmann Jörg , Manns Michael P. , Ott Michael , Wedemeyer Heiner , Meuleman Philip , Pietschmann Thomas , Steinmann Eike
Published: August 2011

Hepatitis C virus (HCV) is a major cause of liver cirrhosis and hepatocellular carcinoma. Current antiviral therapy fails to clear infection in a substantial proportion of cases. Drug development is focused on nonstructural proteins required for RNA replication. Individuals undergoing orthotopic liver transplantation face rapid, universal reinfection of the graft. Therefore, antiviral strategies targeting the early stages of infection are urgently needed for the prevention of HCV infection. In this study, we identified the polyphenol, epigallocatechin-3-gallate (EGCG), as an inhibitor of HCV entry. Green tea catechins, such as EGCG and its derivatives, epigallocatechin (EGC), epicatechin gallate (ECG), and epicatechin (EC), have been previously found to exert antiviral and antioncogenic properties. EGCG had no effect on HCV RNA replication, assembly, or release of progeny virions. However, it potently inhibited Cell-culture–derived HCV (HCVcc) entry into hepatoma cell lines as well as primary human hepatocytes. The effect was independent of the HCV genotype, and both infection of cells by extracellular virions and cell-to-cell spread were blocked. Pretreatment of cells with EGCG before HCV inoculation did not reduce HCV infection, whereas the application of EGCG during inoculation strongly inhibited HCV infectivity. Moreover, treatment with EGCG directly during inoculation strongly inhibited HCV infectivity. Expression levels of all known HCV (co-)receptors were unaltered by EGCG. Finally, we showed that EGCG inhibits viral attachment to the cell, thus disrupting the initial step of HCV cell entry.

Conclusion:

The green tea molecule, EGCG, potently inhibits HCV entry and could be part of an antiviral strategy aimed at the prevention of HCV reinfection after liver transplantation. (Hepatology 2011)
Developing country health systems and the governance of international HIV/AIDS funding
Authors: Poku Nana , Whitman Jim
Published: August 2011

Donor country initiatives for the prevention and mitigation of HIV/AIDS are not a matter of simple burden sharing. Instead, they have brought in their wake many of the complexities and unforeseen effects that have long been associated with more general overseas development assistance. In the case of funding directed toward HIV/AIDS, these effects are by no means either secondary or easily calculable. It is widely acknowledged that there is no consensus framework on how these impacts may be defined, no framework/toolkit for the evaluation of impacts and no longitudinally significant data that could provide the substance for those evaluations.

The subject of this study focuses not on the health outcomes of funding but on how donor–recipient relations could be better deliberated, negotiated and coordinated. We argue that effective leadership and governance of developing country health systems for HIV/AIDS work requires a reconfiguration of how donor–recipient relations are conceived and contracted, and for this purpose, we propose an adaptation of the Organisation for Economic Co‐operation and Development Paris Declaration principles of aid effectiveness. Copyright © 2011 John Wiley & Sons, Ltd.
Thermo‐solutal convection in an inclined porous cavity with various aspect ratios under mixed thermal and species boundary conditions
Authors: Chamkha Ali J. , Al‐Mudhaf Ali , Al‐Meshaiei Eisa
Published: August 2011

The problem of laminar thermo‐solutal convective flow of a binary fluid mixture in an inclined rectangular cavity filled with a uniform porous medium is considered. Mixed heat and mass fluxes and uniform temperature and concentration conditions are applied on two opposing walls of the cavity while the other two walls are kept adiabatic and impermeable to mass transfer. The problem is put in terms of the stream function‐vorticity formulation. A numerical solution based on the finite‐difference methodology is obtained. Representative results illustrating the effects of the inclination angle of the cavity, buoyancy ratio, Darcy number, and the cavity aspect ratio on the contour maps of the streamline, temperature, and concentration as well as the profiles of velocity, temperature, and concentration at mid‐section of the cavity are reported. In addition, numerical results for the average Nusselt and Sherwood numbers as well as some useful correlations are presented for various parametric conditions and discussed. © 2011 Wiley Periodicals, Inc. Heat Trans Asian Res; Published online in Wiley Online Library (wileyonlinelibrary.com/journal/htj). DOI 10.1002/htj.20369
Combined use of spot samples and continuous integrated sampling in a study of storm runoff from a lowland catchment in the south of England
Authors: Gkritzalis‐Papadopoulos A. , Palmer M. R. , Mowlem M. C.
Published: August 2011

We have used two different sampling techniques to study the geochemical response of a small lowland rural catchment to episodic storm runoff. The first method involves traditional daily spot sampling and has been used to develop a standard end‐member mixing analysis (EMMA) of the relative contributions of ground water flow and surface runoff to the total stream flow. The second method utilizes a continuous sampling device, powered by an osmotic pump, to produce an integrated 24‐h sample of the stream flow. When combined with the EMMA results from the spot samples, analyses of the integrated samples reveal the presence of a third component that makes a significant contribution to the dissolved NO3, Ca and K export from the catchment during the rising limb of the hydrographic profile of a storm event following a prolonged dry period. The storm occurred in the middle of the night, so that the response of the stream chemistry was not captured by the daily samples. We hypothesize that this third component is derived from the flushing of stored soil water that contains the geochemical signature of decaying vegetation. Copyright © 2011 John Wiley & Sons, Ltd.
Comparative analysis of relationships between NLDAS‐2 forcings and model outputs
Authors: Xia Youlong , Ek Mike , Wei Helin , Meng Jesse
Published: August 2011

This study reports results from an analysis of the relationship between atmospheric forcing and model‐simulated water and energy fluxes for the North American Land Data Assimilation System Project Phase 2 (NLDAS‐2). The relationships between mean monthly precipitation and total runoff are stronger in the Sacramento (SAC) and variable infiltration capacity (VIC) models, which grew out of the hydrological community, than in the Noah and Mosaic models, which grew out of the soil‐vegetation‐atmosphere transfer (SVAT) community. The reverse is true for the relationship between mean monthly precipitation and evapotranspiration. In addition, surface energy fluxes in VIC are less sensitive to model forcing (except for air temperature) than those in the Noah and Mosaic model. Notwithstanding these general conclusions, the relationships between forcings and model‐simulated water and energy fluxes for all models vary for different seasons, variables, and regions. These findings will ultimately inspire a combination of SVAT‐type model energy components with hydrological model water components to develop a SVAT‐hydrology model to improve both evapotranspiration and total runoff simulations. Copyright © 2011 John Wiley & Sons, Ltd.
Impacts of riparian zone plant water use on temporal scaling of groundwater systems
Authors: Zhu Jianting , Young Michael H. , Osterberg John
Published: August 2011

In this work, we study groundwater system temporal scaling in relation to plant water use and near‐river‐stage fluctuations in riparian zones where phreatophytes exist. Using detrended fluctuation analysis (DFA), we investigate the influence of regular diurnal fluctuations due to phreatophyte water use on temporal scaling properties of groundwater level variations. We found that groundwater use by phreatophytes, at the field site on the Colorado River, USA, results in distinctive crossovers (slope changes when the plots are fitted with straight lines) in the logarithm plots of root‐mean‐square fluctuations of the detrended water level time series versus time scales of groundwater level dynamics. For groundwater levels monitored at wells close to the river, we identified one crossover at ∼1 day in the scaling characteristics of groundwater level variations. When time scale exceeds 1 day, the scaling properties decrease from persistent to close to 1/f noise, where f is the frequency. For groundwater levels recorded at wells further away from the river, the slope of the straight line fit (i.e. scaling exponent) is smallest when the time scale is between 1 and 3 days. When the time scale is < 1 day, groundwater variations become persistent. When the time scale is between 1 and 3 days, the variations are close to white noise, but return to persistent when the time scale is > 3 days. Copyright © 2011 John Wiley & Sons, Ltd.
Zinc–Homocysteine binding in cobalamin‐dependent methionine synthase and its role in the substrate activation: DFT, ONIOM, and QM/MM molecular dynamics studies
Authors: Abdel‐Azeim Safwat , Li Xin , Chung Lung Wa , Morokuma Keiji
Published: August 2011

Cobalamin‐dependent methionine synthase (MetH) is an important metalloenzyme responsible for the biosynthesis of methionine. It catalyzes methyl transfer from N5‐methyl‐tetrahydrofolate to homocysteine (Hcy) by using a zinc ion to activate the Hcy substrate. Density functional theory (B3LYP) calculations on the active‐site model in gas phase and in a polarized continuum model were performed to study the Zn coordination changes from the substrate‐unbound state to the substrate‐bound state. The protein effect on the Zn2+ coordination exchange was further investigated by ONIOM (B3LYP:AMBER)‐ME and EE calculations. The Zn2+‐coordination exchange is found to be highly unfavorable in the gas phase with a high barrier and endothermicity. In the water solution, the reaction becomes exothermic and the reaction barrier is drastically decreased to about 10.0 kcal/mol. A considerable protein effect on the coordination exchange was also found; the reaction is even more exothermic and occurs without barrier. The enzyme was suggested to constrain the zinc coordination sphere in the reactant state (Hcy‐unbound state) more than that in the product state (Hcy‐bound state), which promotes ligation of the Hcy substrate. Molecular dynamics simulations using molecular mechanics (MM) and PM3/MM potentials suggest a correlation between the flexibility of the Zn2+‐binding site and regulation of the enzyme function. Directed in silico mutations of selected residues in the active site were also performed. Our studies support a dissociative mechanism starting with the ZnO(Asn234) bond breaking followed by the ZnS(Hcy) bond formation; the proposed associative mechanism for the Zn2+‐coordination exchange is not supported. © 2011 Wiley Periodicals, Inc. J Comput Chem, 2011
Density functional theory study on electron and hole transport properties of organic pentacene derivatives with electron‐withdrawing substituent
Authors: Chai Shuo , Wen Shu‐Hao , Huang Jin‐Dou , Han Ke‐Li
Published: August 2011

Attaching electron‐withdrawing substituent to organic conjugated molecules is considered as an effective method to produce n‐type and ambipolar transport materials. In this work, we use density functional theory calculations to investigate the electron and hole transport properties of pentacene (PENT) derivatives after substituent and simulate the angular resolution anisotropic mobility for both electron and hole transport. Our results show that adding electron‐withdrawing substituents can lower the energy level of lowest unoccupied molecular orbital (LUMO) and increase electron affinity, which are beneficial to the electron injection and ambient stability of the material. Also the LUMO electronic couplings for electron transport in these pentacene derivatives can achieve up to a hundred meV which promises good electron transport mobility, although adding electron‐withdrawing groups will introduce the increase of electron transfer reorganization energy. The final results of our angular resolution anisotropic mobility simulations show that the electron mobility of these pentacene derivatives can get to several cm2 V−1s−1, but it is important to control the orientation of the organic material relative to the device channel to obtain the highest electron mobility. Our investigation provide detailed information to assist in the design of n‐type and ambipolar organic electronic materials with high mobility performance. © 2011 Wiley Periodicals, Inc. J Comput Chem, 2011
The evolution of heart gene delivery vectors
Authors: Wasala Nalinda B. , Shin Jin‐Hong , Duan Dongsheng
Published: August 2011

Gene therapy holds promise for treating numerous heart diseases. A key premise for the success of cardiac gene therapy is the development of powerful gene transfer vehicles that can achieve highly efficient and persistent gene transfer specifically in the heart. Other features of an ideal vector include negligible toxicity, minimal immunogenicity and easy manufacturing. Rapid progress in the fields of molecular biology and virology has offered great opportunities to engineer various genetic materials for heart gene delivery. Several nonviral vectors (e.g. naked plasmids, plasmid lipid/polymer complexes and oligonucleotides) have been tested. Commonly used viral vectors include lentivirus, adenovirus and adeno‐associated virus. Among these, adeno‐associated virus has shown many attractive features for pre‐clinical experimentation in animal models of heart diseases. We review the history and evolution of these vectors for heart gene transfer. Copyright © 2011 John Wiley & Sons, Ltd.
Radiosynthesis of [5‐[11C]methanesulfonyl‐2‐((S)‐2,2,2‐trifluoro‐1‐methyl‐ethoxy)‐phenyl]‐[5‐(tetrahydro‐pyran‐4‐yl)‐1,3‐dihydro‐isoindol‐2‐yl]‐methanone ([11C]RO5013853), a novel PET tracer for the glycine transporter type I (GlyT1)
Authors: Pinard Emmanuel , Burner Serge , Cueni Philipp , Hartung Thomas , Norcross Roger D. , Schmid Philipp , Waldmeier Pius , Zielinski Guy , Ravert Hayden T. , Holt Daniel P. , Dannals Robert F.
Published: August 2011

The glycine transporter type 1 (GlyT1) has emerged as a key novel target for the treatment of schizophrenia. We have recently discovered and developed [11C]RO5013853 as a novel positron emission tomography tracer for GlyT1 for which a reliable five‐step synthetic route was established. The incorporation of the radioisotope was achieved in the final step through methylation of a sodium sulfinate precursor, itself easily accessible upon reduction of the corresponding sulfonyl‐chloride analog. [11C]RO5013853 was prepared with high specific activity (>49 GBq/µmol) and high radiochemical purity (100%). A validation study of [11C]RO5013853 in animal imaging studies is in progress. Copyright © 2011 John Wiley & Sons, Ltd.
Ventilation‐based segmentation of the lungs using hyperpolarized 3He MRI
Authors: Tustison Nicholas J. , Avants Brian B. , Flors Lucia , Altes Talissa A. , de Lange Eduard E. , Mugler John P. , Gee James C.
Published: August 2011

Purpose:

To develop an automated segmentation method to differentiate the ventilated lung volume on 3He magnetic resonance imaging (MRI).

Materials and Methods:

Computational processing (CP) for each subject consisted of the following three essential steps: 1) inhomogeneity bias correction, 2) whole lung segmentation, and 3) subdivision of the lung segmentation into regions of similar ventilation. Evaluation consisted of two comparative analyses: i) comparison of the number of defects scored by two human readers in 43 subjects, and ii) simultaneous truth and performance level estimation (STAPLE) in 18 subjects in which the ventilation defects were manually segmented by four human readers.

Results:

There was excellent correlation between the number of ventilation defects tabulated by CP and reader #1 (intraclass correlation coefficient [ICC] = 0.86), CP and reader #2 (ICC = 0.85), and between the two readers (ICC = 0.97). The STAPLE results from the second analysis yielded the following sensitivity/specificity numbers: CP (0.898/0.905), radiologist #1 (0.743/0.897), radiologist #2 (0.501/0.985), radiologist #3 (0.898/0.848), and the first author (0.600/0.984).

Conclusion:

We developed and evaluated an automated method for quantifying the ventilated lung volume on 3He MRI. The findings strongly indicate that our proposed algorithmic processing may be a reliable, automatic method for quantitating ventilation defects. J. Magn. Reson. Imaging 2011;. © 2011 Wiley‐Liss, Inc.
Mutations in two PKR‐binding domains in chronic hepatitis C of genotype 3a and correlation with viral loads and interferon responsiveness
Authors: Yokozaki Shouichi , Katano Yoshiaki , Hayashi Kazuhiko , Ishigami Masatoshi , Itoh Akihiro , Hirooka Yoshiki , Nakano Isao , Goto Hidemi
Published: August 2011

Interferon (IFN) induces the double‐stranded RNA‐dependent protein kinase (PKR) to inhibit viral replication. Two motifs of the PKR‐binding domain exist in the E2 and the NS5A regions of the hepatitis C virus (HCV). These regions are called the PKR‐eukaryotic transcription factor (elF2‐alpha) phosphorylation homology domain (PePHD), and the IFN sensitivity‐determining region (ISDR). Both regions are inhibited by PKR. Thus, several studies have reported the relationship between these regions and IFN responsiveness and the HCV viral load. However, the data obtained from these studies remain controversial. The aim of this study was to investigate the genomic heterogeneity of the PePHD and the ISDR in patients with genotype 3a and how this impacts HCV replication and the response to IFN therapy. Twenty‐one male patients infected with HCV genotype 3a were studied. The PePHD was well conserved, and mutations were found in only one amino acid position in two patients. Patients with three or more mutations in the ISDR had lower viral loads than those with fewer than two mutations (192.2 ± 176.7 vs. 1279.4 ± 997.6 KIU/ml, P = 0.0277). Ten (71.4%) of 14 patients achieved a sustained virological response to IFN therapy. No specific amino acid substitutions in the PePHD and the ISDR were associated with IFN responsiveness; however, the number of mutations in the ISDR was significantly associated with the HCV viral load. The findings from this study suggest that the ISDR plays an important role in regulating viral replication in patients infected with HCV genotype 3a. J. Med. Virol. 83:1727–1732, 2011. © 2011 Wiley‐Liss, Inc.
Elevated Epstein–Barr virus seroreactivity among unaffected members of families with nasopharyngeal carcinoma
Authors: Qin Hai‐De , Jia Wei‐Hua , Zhang Lin‐Lin , Liu Na , Zhou Xin‐Xi , Wang Ming‐Hsi , Feng Qi‐Sheng , Chen Li‐Zhen , Zhang Ying , Jorgensen Timothy J. , Zeng Yi‐Xin , Shugart Yin Yao
Published: August 2011

Serum antibodies to Epstein–Barr virus (EBV) antigens can be used to predict the risk of nasopharyngeal carcinoma (NPC). To investigate whether EBV seropositivity rates were higher among healthy family members from multiplex and sporadic families with NPC (i.e., families with multiple or single cases) compared to the general population, a study was conducted on 2,665 unaffected individuals from 140 multiplex and 413 sporadic families. The titers of the IgA antibody to the EBV capsid antigen (VCA‐IgA) were compared to those of 904 controls from the general population. The VCA‐IgA titer was correlated among sibling pairs to a high significance in both family types (P < 0.0001 and P = 0.0005 for the multiplex and the sporadic families, respectively); parent–offspring pairs also showed significant correlation (P < 0.0001 and P = 0.0002, respectively); and spouse pairs were correlated, but at lower significance levels (P = 0.0790 and P = 0.0040, respectively). When compared to the controls, among first‐degree relatives in the multiplex families, the age‐ and gender‐adjusted odds ratio (OR) was 2.06 (95% confidence interval 1.56–2.71), 3.55 (2.24–5.64), and 2.25 (1.57–3.23) for siblings, parents, and children, respectively. In the sporadic families, the adjusted OR was 1.55 (1.21–2.00) and 2.08 (1.51–2.86) for siblings and parents, respectively. The adjusted P‐value of spouses lost significance in the multiplex families, but remained significant in the sporadic families (P = 0.0146). In conclusion, EBV seropositivity rates were elevated among unaffected family members in both multiplex and sporadic families with NPC. J. Med. Virol. 83:1792–1798, 2011. © 2011 Wiley‐Liss, Inc.
Antibody response and avidity of respiratory syncytial virus‐specific total IgG, IgG1, and IgG3 in young children
Authors: Freitas G.R.O. , Silva D.A.O. , Yokosawa J. , Paula N.T. , Costa L.F. , Carneiro B.M. , Ribeiro L.Z.G. , Oliveira T.F.M. , Mineo J.R. , Queiróz D.A.O.
Published: August 2011

Respiratory syncytial virus (RSV) is a major cause of acute respiratory disease in infants and young children. Considering that several aspects of the humoral immune response to RSV infection remain unclear, this study aimed to investigate the occurrence, levels, and avidity of total IgG, IgG1, and IgG3 antibodies against RSV in serum samples from children ≤5 years old. In addition, a possible association between antibody avidity and severity of illness was examined. The occurrence and levels of RSV‐specific IgG depended on age, with infants <3 months old displaying high levels of antibodies, which were probably acquired from the mother. Children ≥24 months old also showed frequent occurrence and high levels of IgG, which was produced actively during infection. In addition, the avidity assay showed that the avidity of RSV‐specific total IgG and IgG1 was lower in infants <3 months old who had acute respiratory disease than in age‐matched controls. The avidity of RSV‐specific IgG detected in children ≥24 months old with lower respiratory infection was lower than that in children with upper respiratory infection. These results indicate that the presence of high avidity RSV‐specific IgG antibodies may lead to better protection against RSV infection in children <3 months old, who may have a lower probability of developing disease of increased severity. In addition, children ≥24 months old with RSV‐specific IgG antibodies of low avidity tended to develop more severe RSV illness. These findings may be helpful in establishing vaccination schedules when a vaccine becomes available. J. Med. Virol. 83:1826–1833, 2011. © 2011 Wiley‐Liss, Inc.
Human papillomavirus genotype detection and viral load in paired genital and urine samples from both females and males
Authors: Bissett Sara L. , Howell‐Jones Rebecca , Swift Craig , De Silva Natasha , Biscornet Leon , Parry John V. , Saunders Nicholas A. , Nathan Mayura , Soldan Kate , Szarewski Anne , Cuzick Jack , Beddows Simon
Published: August 2011

The ability to detect type‐specific high risk HPV (HR‐HPV) infections in samples from females and males is important for monitoring the epidemiology of HPV and the impact of vaccination. Type‐specific detection concordance between paired urine and genital samples from females (n = 264) undergoing routine colposcopy and males (n = 88) attending a genito‐urinary medicine clinic was evaluated using an in‐house genotyping assay. The overall inter‐rater agreement (κ) was 0.781 for female pairs and 0.346 for male pairs. Female urine had sensitivity for detection of HPV16/18 and HR‐HPV of 75% and 84%, respectively, while male urine had sensitivities of 13% and 28%, respectively. Genital samples had a higher HPV DNA copy number than urine although a small proportion (10%) of urine samples had a higher copy number than the corresponding genital sample. The proportion of females with normal cytology positive for HPV16/18 was 19%, increasing to 57% in moderate or severely dyskaryotic samples. The same trend was seen in the corresponding urine (19–43%) compounded by the reduced sensitivity of this sample type. The HPV16 viral load in female genital samples, but not in urine, was weakly associated with cervical disease stage. Despite reduced sensitivity, urine appears to be an appropriate surrogate sample for type‐specific HPV detection in females for epidemiological objectives. The lower sensitivity and lack of association between viral load and disease stage in urine suggest that urine may not be useful for clinical management of HPV infection. The utility of urine for type‐specific detection in males is less certain. J. Med. Virol. 83:1744–1751, 2011. © 2011 Wiley‐Liss, Inc.
Low prevalence of hepatitis B virus pre‐s deletion mutation in Indonesia
Authors: Utama Andi , Siburian Marlinang Diarta , Fanany Ismail , Intan Mariana Destila Bayu , Dhenni Rama , Kurniasih Tri Shinta , Lelosutan Syafruddin A.R. , Achwan Wenny Astuti , Arnelis  , Lukito Benyamin , Yusuf Irawan , Lesmana Laurentius Adrianus , Sulaiman Ali , Tai Susan
Published: August 2011

The molecular epidemiological study of hepatitis B virus (HBV) in Indonesia is still limited. This study was aimed to identify the prevalence of HBV pre‐S deletion/insertion mutations, and to assess the association of pre‐S deletion mutation with liver disease progression in Indonesia. Pre‐S mutations were identified by direct sequencing. Of the 265 subjects, 32 samples (12.1%) harbored pre‐S deletion/insertion mutations. The prevalence of those pre‐S mutations was 2.7% (2/75), 12.9% (8/62), 16.7% (11/66), and 17.7% (11/62) in asymptomatic carrier, chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma groups, respectively. Statistical analysis showed significant difference among them (P = 0.024). In HBV genotype B (HBV/B), pre‐S1, pre‐S1/S2, and pre‐S2 deletion mutations were detected respectively in 3 (17.6%), 4 (23.5%), and 9 (52.9%) of 17 samples. On the other hand, in HBV/C, 12 of 15 samples (80.0%) showed a pre‐S2 deletion mutation, and only 2 samples (13.3%) demonstrated a pre‐S1/S2 deletion mutation. These results suggest that in HBV/B deletion mutation tends to occur in pre‐S1 or pre‐S1/S2 region, while in HBV/C the deletion mutation usually occurs in the pre‐S2 region. Analysis of complete genome of four viruses confirmed that 3 isolates were classified into HBV/B3, and 1 isolate was HBV/C1. However, SimPlot and BootScan analyses showed that isolate 08.10.002 was an intragenotypic recombinant between HBV/B3 and HBV/B4. As conclusion, the prevalence of HBV pre‐S mutations was relatively low in Indonesian patients compared to those from Taiwan, Japan, and other Asian countries. There was a weak association between pre‐S deletion mutation and progressive liver disease. J. Med. Virol. 83:1717–1726, 2011. © 2011 Wiley‐Liss, Inc.
Acute hepatitis C in Brazil: Results of a national survey
Authors: Ferreira Adalgisa de Souza Paiva , Perez Renata de Mello , Ferraz Maria Lucia Gomes , Lewis‐Ximenez Lia Laura , Pereira João Luis , de Almeida Paulo Roberto Lerias , de Mattos Angelo Alves ,   on behalf of The Acute Hepatitis C Study Group of The Brazilian Society of Hepatology
Published: August 2011

The incidence of acute hepatitis C has decreased in the world. However, new cases are still reported. The objective of this study was to obtain data of acute hepatitis C in Brazil and to identify risk factors of transmission, diagnostic criteria, clinical presentation, evolution, and treatment. A questionnaire was sent to all members of the Brazilian Society of Hepatology. Sixteen centers participated with a total of 170 cases between 2000 and 2008. Among them, 37 had chronic renal failure on hemodialysis and were evaluated separately. The main diagnostic criterion in non‐uremic patients was ALT (alanine aminotransferase) elevation associated with risk factors. In patients with chronic renal failure, anti‐hepatitis C virus (HCV) seroconversion was the most frequent criterion. Among the 133 non‐uremic patients the main risk factors were hospital procedures, whereas in hemodialysis patients, dialysis was the single risk factor in 95% of the cases. Jaundice was more frequent in non‐uremic patients (82% vs. 13%; P < 0.001) and ALT levels were higher in these individuals (P < 0.001). Spontaneous clearance was more frequent in non‐uremic patients (51% vs. 3%; P < 0.001). Sixty‐five patients were treated: 39 non‐uremic patients and 26 on dialysis. Sustained virological response rates were 60% for non‐uremic and 58% for uremic patients (P = 0.98). There was no association of these rates with the study variables. These findings show that cases of acute hepatitis C are still occurring and have been related predominantly to hospital procedures. Measures to prevent nosocomial transmission should be adopted rigorously and followed to minimize this important source of infection observed in this survey. J. Med. Virol. 83:1738–1743, 2011. © 2011 Wiley‐Liss, Inc.
Detection and genetic diversity of human metapneumovirus in hospitalized children with acute respiratory infections in India
Authors: Banerjee Sagarika , Sullender Wayne M. , Choudekar Avinash , John Cherian , Tyagi Vikas , Fowler Karen , Lefkowitz Elliot J. , Broor Shobha
Published: August 2011

Human metapneumovirus (hMPV) causes acute respiratory infections in children and adults. It is classified into two major genetic lineages and each lineage into two sublineages. The purpose of the study was to identify and characterize hMPV in children who presented to the All India Institute of Medical Sciences, New Delhi, India with acute respiratory infection from April 2005 to March 2007. By reverse‐transcription polymerase chain reaction, hMPV was detected in 21 (3%) of the 662 nasopharyngeal samples from children with acute respiratory infection and in none of the 120 control children. Seven of the 21 (33%) children infected with hMPV required hospital admission for pneumonia or bronchiolitis. Most hMPV detections were during the winter and spring seasons. The majority (67%, 11/21) of children positive for hMPV were within 24 months of age. Phylogenetic analysis of partial F and N gene and the full G gene sequences showed three sub‐lineages of hMPV circulated during the study period, B1, B2, and the novel sub‐lineage A2b. The circulation pattern of hMPV genotypes varied by season. Comparison of the F and G genes of eight strains revealed incongruencies in lineage assignments, raising the possibility that recombination had occurred. Sequence analysis also revealed the F gene was relatively conserved whereas the G gene was more variable between the A and B lineages. This study demonstrates that hMPV is an important contributor to acute respiratory infection in children in India, resulting in both outpatient visits and hospitalizations. J. Med. Virol. 83:1799–1810, 2011. © 2011 Wiley‐Liss, Inc.
Hepatitis E virus infection in patients infected with the human immunodeficiency virus
Authors: Kaba Mamadou , Richet Hervé , Ravaux Isabelle , Moreau Jacques , Poizot‐Martin Isabelle , Motte Anne , Nicolino‐Brunet Corinne , Dignat‐George Françoise , Ménard Amélie , Dhiver Catherine , Brouqui Philippe , Colson Philippe
Published: August 2011

Hepatitis E virus (HEV) is a newly‐identified causative agent of acute and chronic hepatitis in severely immunocompromized patients. The present study sought to assess the prevalences of past, recent, on‐going, and chronic HEV infections in patients infected with human immunodeficiency virus (HIV) in Marseille, South‐eastern France, and to determine if they were correlated with the patients' immunological status or with cirrhosis. Anti‐HEV IgG and IgM and HEV RNA testing were concurrently performed on the plasma from 184 patients infected with HIV, including 81 with a CD4+ T‐lymphocyte count (CD4 count) <50 cells/mm3 and 32 with a cirrhosis. Prevalence of anti‐HEV IgG and IgM was 4.4% (8/184) and 1.6% (3/184), respectively. Past, recent, and on‐going infections were observed in 3.3% (6/184), 1.6% (3/184), and 0.5% (1/184) of the patients, respectively. Anti‐HEV antibodies prevalence did not differ significantly according to CD4 count, cirrhosis, sex, age, mode of HIV transmission, and infection with hepatitis B or C virus. Anti‐HEV IgG seroreversion was observed in two patients. The patient whose plasma tested positive for HEV RNA had a CD4 count <50 cells/mm3; HEV genotype was 3f. In this patient, longitudinal testing showed HEV RNA positivity during a 10‐month period, indicating chronic HEV infection; in contrast, anti‐HEV IgG never tested positive. Further studies are needed to evaluate the performance of commercial HEV serological assays in patients infected with HIV and to assess the actual incidence, prevalence, and outcome of HEV infection in this special group of patients. HEV RNA testing is necessary for such purposes. J. Med. Virol. 83:1704–1716, 2011. © 2011 Wiley‐Liss, Inc.
Congenital cytomegalovirus infection in the Netherlands: Birth prevalence and risk factors
Authors: de Vries Jutte J.C. , Korver Anna M.H. , Verkerk Paul H. , Rusman Lisette , Claas Eric C.J. , Loeber J. Gerard , Kroes Aloys C.M. , Vossen Ann C.T.M.
Published: August 2011

Congenital cytomegalovirus (CMV) infection is the most common congenital viral infection worldwide. The sequela encountered most frequently is hearing impairment, affecting approximately one out of five infants congenitally infected. Data on the birth prevalence and risk factors of congenital CMV infection in the Netherlands are scarce. The aim of this study was to determine the birth prevalence of congenital CMV in the Netherlands. A sample of 6,500 dried blood spots (DBS) from infants born in the Netherlands was tested anonymously for CMV DNA. The sample was stratified by the number of live births in different regions of the Netherlands of the year 2007. Additionally, on a regional level, risk factors for congenital CMV were analyzed. The birth prevalence of congenital CMV in the Netherlands was 0.54% (35/6,433, 95%CI 0.36–0.72). Congenital CMV infection was significantly higher in regions with more than 15% young children (0–5 years) compared with regions with a lower proportion of young children (OR 5.9, 95%CI 1.4–25.2). Congenital CMV infection was significantly higher in regions with more than 30% immigrants compared with regions with a lower proportion of immigrants (OR 2.2, 95%CI 1.1–4.6). This association was strongest for regions with more than 30% non‐Western immigrants (OR 3.3, 95%CI 1.5–7.5). Based on the knowledge of the natural history of congenital CMV infection, approximately 1,000 children are born with congenital CMV infection in the Netherlands annually, of whom eventually approximately 180 children (0.1% of all newborns) will be affected by long term sequelae, with hearing loss being the symptom encountered most frequently. J. Med. Virol. 83:1777–1782, 2011. © 2011 Wiley‐Liss, Inc.
Antiretroviral resistance patterns and factors associated with resistance in adult patients failing NNRTI‐based regimens in the western cape, South Africa
Authors: van Zyl Gert U. , van der Merwe Lize , Claassen Mathilda , Zeier Michele , Preiser Wolfgang
Published: August 2011

Antiretroviral drug resistance in patients failing non‐nucleoside reverse transcriptase inhibitor (NNRTI)‐based first‐line combination antiretroviral treatment (ART) is influenced by: regimen choice, HIV‐1 subtype, detection of and response to therapy failure. In order to describe resistance patterns by genotypic testing, at the time of first‐line ART failure and to describe associations with having M184I/V, K65R, three or more thymidine analog mutations (TAMs) and etravirine (ETV) resistance, the prevalence of antiretroviral drug resistance associated mutations in a cross‐sectional study, at two South African public health clinic settings, at the time of virologic failure (HIV‐1 RNA load >400 copies/ml) are described. Also reported are associations of therapy choice, prolonged virologic failure, and concurrent HIV viral load and CD4 count with the presence of M184I/V, TAMs, K65R, and resistance to ETV. Of 167 adult patients with virologic failure on first‐line ART, 28 (17%) had no resistance, 137 (82%) had NNRTI resistance, 101 (60%) M184I/V, 20 (12%) TAMs, of which 4 had 3 or more TAMs, and 7 (4%) had K65R, of which 6 were on D4T and one on AZT. A prolonged estimated period of failure was associated with having ≥3 TAMs. Patients treated with nevirapine (NVP) were more likely to have ETV resistance than those treated with efavirenz (EFV). Major protease inhibitor mutations were not detected. A delayed response to ART failure may risk accumulation of TAMs in patients on an NNRTI‐based regimen. The use of NVP rather than EFV was associated with ETV resistance. J. Med. Virol. 83:1764–1769, 2011. © 2011 Wiley‐Liss, Inc.
Persistence of West Nile virus immunoglobulin M antibodies, Greece
Authors: Papa Anna , Danis Kostas , Athanasiadou Afroditi , Delianidou Maria , Panagiotopoulos Takis
Published: August 2011

A major outbreak of West Nile virus (WNV) lineage 2 infections was observed in 2010 in Greece. In order to check the persistence of WNV IgM antibodies, a second serum sample taken 75–180 days after onset of the illness from 29 patients with WNV infection was tested. A third sample was obtained 181–270 days after onset of the illness from 8 of the 12 patients with IgM‐positive second sample. Mixed effects linear regression analysis indicated that the approximate time at which IgM index became negative was 164 (95% confidence interval, 95% CI 99–236) days after the symptoms' onset. Persistence of IgM antibodies was observed in 12% of patients at 181–270 days of follow‐up. A sharp decrease in the IgM levels was observed, mainly in patients who had high IgM index value in the acute phase. All patients were WNV IgG positive at the follow‐up. J. Med. Virol. 83:1857–1860, 2011. © 2011 Wiley‐Liss, Inc.
Partial protection against enterovirus 71 (EV71) infection in a mouse model immunized with recombinant newcastle disease virus capsids displaying the EV71 VP1 fragment
Authors: Ch'ng Wei‐Choong , Stanbridge Eric J. , Ong Kien‐Chai , Wong Kum‐Thong , Yusoff Khatijah , Shafee Norazizah
Published: August 2011

Enterovirus 71 (EV71) infection may cause severe neurological complications, particularly in young children. Despite the risks, there are still no commercially available EV71 vaccines. Hence, a candidate vaccine construct, containing recombinant Newcastle disease virus capsids that display an EV71 VP1 fragment (NPt‐VP11‐100) protein, was evaluated in a mouse model of EV71 infection. Previously, it was shown that this protein construct provoked a strong immune response in vaccinated adult rabbits. That study, however, did not address the issue of its effectiveness against EV71 infection in young animals. In the present study, EV71 viral challenge in vaccinated newborn mice resulted in more than 40% increase in survival rate. Significantly, half of the surviving mice fully recovered from their paralysis. Histological analysis of all of the surviving mice revealed a complete clearance of EV71 viral antigens from their brains and spinal cords. In hind limb muscles, the amounts of the antigens detected correlated with the degrees of tissue damage and paralysis. Findings from this study provide evidence that immunization with the NPt‐VP11‐100 immunogen in a newborn mouse model confers partial protection against EV71 infection, and also highlights the importance of NPt‐VP11‐100 as a possible candidate vaccine for protection against EV71 infections. J. Med. Virol. 83:1783–1791, 2011. © 2011 Wiley‐Liss, Inc.
Intratype variations of HPV 31 and 58 in Italian women with abnormal cervical cytology
Authors: Cento Valeria , Rahmatalla Noor , Ciccozzi Massimo , Perno Carlo Federico , Ciotti Marco
Published: August 2011

Oncogenic human papillomaviruses (HPVs) are the recognized etiological agents of cervical cancer. A number of epidemiological, etiological, and molecular data suggest that variants of the same HPV type are distinct biologically and may confer differential pathogenic risks. Therefore, investigation of genome variants of clinically important HPV types may be important for the identification of pathogenically important variants. In this study, the genomic regions of L1, E6, E7, and long control region (LCR) of HPV 31 and 58, identified in women with abnormal cervical smear, were investigated. Several mutations were identified in the regions examined. Of the mutations found in the L1 region of HPV 31 and 58, the novel mutations described in this study fall within a protein region which may play a critical role in the binding of neutralizing antibodies against different HPV types. No significant association was found between the E6 and E7 mutations of both HPV types and the cytological lesion found. Some mutations found in the LCR of HPV 31 and 58 encompassed known transcription binding sites with possible consequences on the transcription of the oncogenic genes. Intratype genetic characterization of HPV types may help to define the pathogenetic risk of HPV variants. J. Med. Virol. 83:1752–1761, 2011. © 2011 Wiley‐Liss, Inc.
Thriving at work—A diary study
Authors: Niessen Cornelia , Sonnentag Sabine , Sach Friederike
Published: August 2011

The present diary study examines how employees thrive at work in response to resources (i.e., positive meaning, relational resources, and knowledge). Thriving is conceptualized as the joint experience of vitality and learning. A total of 121 employees working in the social services sector responded to three daily surveys (in the morning, at lunchtime, and at the end of the work day) for a period of five work days. Intra‐individual analyses (hierarchical linear modeling) revealed that on days when employees experience positive meaning at work in the morning, they feel more vital at the end of the work day and have a higher sense of learning. Work behaviors such as task focus and exploration mediated the relation between positive meaning and both components of thriving. Copyright © 2011 John Wiley & Sons, Ltd.
Mouse model of chronic post‐arthroplasty infection: Noninvasive in vivo bioluminescence imaging to monitor bacterial burden for long‐term study
Authors: Pribaz Jonathan R. , Bernthal Nicholas M. , Billi Fabrizio , Cho John S. , Ramos Romela Irene , Guo Yi , Cheung Ambrose L. , Francis Kevin P. , Miller Lloyd S.
Published: August 2011

Post‐arthroplasty infections are a devastating problem in orthopaedic surgery. While acute infections can be treated with a single stage washout and liner exchange, chronic infections lead to multiple reoperations, prolonged antibiotic courses, extended disability, and worse clinical outcomes. Unlike previous mouse models that studied an acute infection, this work aimed to develop a model of a chronic post‐arthroplasty infection. To achieve this, a stainless steel implant in the knee joints of mice was inoculated with a bioluminescent Staphylococcus aureus strain (1 × 102–1 × 104 colony forming units, CFUs) and in vivo imaging was used to monitor the bacterial burden for 42 days. Four different S. aureus strains were compared in which the bioluminescent construct was integrated in an antibiotic selection plasmid (ALC2906), the bacterial chromosome (Xen29 and Xen40), or a stable plasmid (Xen36). ALC2906 had increased bioluminescent signals through day 10, after which the signals became undetectable. In contrast, Xen29, Xen40, and Xen36 had increased bioluminescent signals through 42 days with the highest signals observed with Xen36. ALC2906, Xen29, and Xen40 induced significantly more inflammation than Xen36 as measured by in vivo enhanced green fluorescence protein (EGFP)‐neutrophil flourescence of LysEGFP mice. All four strains induced comparable biofilm formation as determined by variable‐pressure scanning electron microscopy. Using a titanium implant, Xen36 had higher in vivo bioluminescence signals than Xen40 but had similar biofilm formation and adherent bacteria. In conclusion, Xen29, Xen40, and especially Xen36, which had stable bioluminescent constructs, are feasible for long‐term in vivo monitoring of bacterial burden and biofilm formation to study chronic post‐arthroplasty infections and potential antimicrobial interventions. © 2011 Orthopaedic Research Society Published by Wiley Periodicals, Inc. J Orthop Res 30:335–340, 2012
Caribbean hydrological variability during the Holocene as reconstructed from crater lakes on the island of Grenada
Authors: Fritz Sherilyn C. , Björck Svante , Rigsby Catherine A. , Baker Paul A. , Calder‐Church Amy , Conley Daniel J.
Published: August 2011

Contemporary precipitation patterns in the Caribbean region are spatially variable, and the small number of Holocene paleoclimatic records may not adequately capture patterns of variation in the past. The hydrological history of Grenada was inferred from paleolimnological analyses of sediment cores from two crater lakes on the island. The basins were formed by volcanic activity some time during the Last Termination, but were dry between ca. 13 000 and ca. 7200 cal. a BP. After filling, the lakes were initially very shallow, and sedimentation was interrupted by a hiatus ca. 6300–5500 cal. a BP, followed by deposition of a thick tephra in both sites. After 5500 cal. a BP, lake level shows considerable multi‐centennial variability, superimposed upon a long‐term trend of generally higher lake level after 3200 cal. a BP. The pattern of lake‐level variation in Grenada shows some similarity with other Caribbean paleoclimatic records in terms of the timing of transitions, but differs from several classic studies in the sign of inferred precipitation change. The differences among records may reflect spatially variable precipitation patterns in the past in response to the position of the Intertropical Convergence Zone and to sea surface temperature influences on the trade winds and Caribbean low‐level jet. Copyright © 2011 John Wiley & Sons, Ltd.
The role of radical amputations for extremity tumors: A single institution experience and review of the literature
Authors: Parsons Colin M. , Pimiento Jose M. , Cheong David , Marzban Suroosh S. , Gonzalez Ricardo J. , Johnson David , Letson G. Douglas , Zager Jonathan S.
Published: August 2011

Background

Major amputations are indicated for advanced tumors when limb‐preservation techniques have been exhausted. Radical surgery can result in significant palliation and possible cure.

Methods

We identified 40 patients who underwent forequarter (FQ) or hindquarter (HQ) amputations between May 2000 and January 2011. Patient demographics, tumor‐related factors, and outcomes were reviewed.

Results

There were 30 FQ and 10 HQ amputations. The most common diagnoses were sarcoma (55%) and squamous cell carcinoma (25%). Patients presented with primary tumors (35%), regional recurrence (57.5%), or unresectable limb metastatic disease (7.5%). Presenting symptoms included fungating wounds (35%), intractable pain (78%), and limb dysfunction (65%). Operations were performed with curative intent (10%), curative/palliative intent (70%), or palliation alone (20%). Wound complications occurred in 35%. Pain was improved in 78% of patients following surgery. Despite a 91% negative margin rate, 79% of patients recurred either locally or distantly. Median overall survival was 10.9, 13.2, and 3.4 months in the curative, curative/palliative, and palliative groups, respectively.

Conclusions

In the absence of conservative options, major amputations are indicated for the management of advanced tumors. These operations can be performed safely, resulting in effective palliation of debilitating symptoms. While recurrence rates remain high, some patients can achieve prolonged survival. J. Surg. Oncol. 2012; 105:149–155. © 2011 Wiley Periodicals, Inc.