bluuebunny/crossref_metadata_2025_split huggingface dataset:
Antibodies with High Avidity to the gp120 Envelope Protein in Protection from Simian Immunodeficiency Virus SIV
mac251
Acquisition in an Immunization Regimen That Mimics the RV-144 Thai Trial
Authors: Pegu Poonam , Vaccari Monica , Gordon Shari , Keele Brandon F. , Doster Melvin , Guan Yongjun , Ferrari Guido , Pal Ranajit , Ferrari Maria Grazia , Whitney Stephen , Hudacik Lauren , Billings Erik , Rao Mangala , Montefiori David , Tomaras Georgia , Alam S. Munir , Fenizia Claudio , Lifson Jeffrey D. , Stablein Donald , Tartaglia Jim , Michael Nelson , Kim Jerome , Venzon David , Franchini Genoveffa 
Published: November 2012

ABSTRACT

The recombinant canarypox vector, ALVAC-HIV, together with human immunodeficiency virus (HIV) gp120 envelope glycoprotein, has protected 31.2% of Thai individuals from HIV acquisition in the RV144 HIV vaccine trial. This outcome was unexpected, given the limited ability of the vaccine components to induce CD8
+
T-cell responses or broadly neutralizing antibodies. We vaccinated macaques with an immunization regimen intended to mimic the RV144 trial and exposed them intrarectally to a dose of the simian immunodeficiency virus SIV
mac251
that transmits few virus variants, similar to HIV transmission to humans. Vaccination induced anti-envelope antibodies in all vaccinees and CD4
+
and CD8
+
T-cell responses. Three of the 11 macaques vaccinated with ALVAC-SIV/gp120 were protected from SIV
mac251
acquisition, but the result was not significant. The remaining vaccinees were infected and progressed to disease. The magnitudes of vaccine-induced SIV
mac251
-specific T-cell responses and binding antibodies were not significantly different between protected and infected animals. However, sera from protected animals had higher avidity antibodies to gp120, recognized the variable envelope regions V1/V2, and reduced SIV
mac251
infectivity in cells that express high levels of α
4
β
7
integrins, suggesting a functional role of antibodies to V2. The current results emphasize the utility of determining the titer of repeated mucosal challenge in the preclinical evaluation of HIV vaccines.
Disulfide Bonds in Hepatitis C Virus Glycoprotein E1 Control the Assembly and Entry Functions of E2 Glycoprotein
Authors: Wahid Ahmed , Helle François , Descamps Véronique , Duverlie Gilles , Penin François , Dubuisson Jean 
Published: November 2012

ABSTRACT
Class II membrane fusion proteins have been described in viruses in which the envelope proteins are derived from a precursor polyprotein containing two transmembrane glycoproteins arranged in tandem. Although the second protein, which carries the membrane fusion function, is in general well characterized, the companion protein, which is a protein chaperone for the folding of the fusion protein, is less well characterized for some viruses, like hepatitis C virus (HCV). To investigate the role of the class II companion glycoprotein E1 of HCV, we chose to target conserved cysteine residues in the protein, and we systematically mutated them in a full-length infectious HCV clone by reverse genetics. All the mutants were infectious, albeit with lower titers than the wild-type virus. The reduced infectivity was in part due to a decrease in viral assembly, as revealed by measurement of intracellular infectivity and by quantification of core protein released from cells transfected with mutant genomes. Analyses of mutated proteins did not show any major defect in folding. However, the mutations reduced virus stability, and they could also affect the density of infectious viral particles. Mutant viruses also showed a defect in cell-to-cell transmission. Finally, our data indicate that HCV glycoprotein E1 can also affect the fusion protein E2 by modulating its recognition by the cellular coreceptor CD81. Therefore, in the context of HCV, our data identify an additional function of a class II companion protein as a molecule that can control the binding capacity of the fusion protein.
Aerosol Transmission of Chronic Wasting Disease in White-Tailed Deer
Authors: Denkers Nathaniel D. , Hayes-Klug Jeanette , Anderson Kelly R. , Seelig Davis M. , Haley Nicholas J. , Dahmes Sallie J. , Osborn David A. , Miller Karl V. , Warren Robert J. , Mathiason Candace K. , Hoover Edward A. 
Published: November 2012

ABSTRACT
While the facile transmission of chronic wasting disease (CWD) remains incompletely elucidated, studies in rodents suggest that exposure of the respiratory mucosa may be an efficient pathway. The present study was designed to address this question in the native cervid host. Here, we demonstrate aerosol transmission of CWD to deer with a prion dose >20-fold lower than that used in previous oral inoculations. Inhalation of prions may facilitate transmission of CWD and, perhaps, other prion infections.
Reactive Oxygen Species Are Induced by Kaposi's Sarcoma-Associated Herpesvirus Early during Primary Infection of Endothelial Cells To Promote Virus Entry
Authors: Bottero Virginie , Chakraborty Sayan , Chandran Bala 
Published: November 2012

ABSTRACT

The entry of Kaposi's sarcoma-associated herpesvirus (KSHV) into human dermal microvascular endothelial cells (HMVEC-d), natural
in vivo
target cells, via macropinocytosis is initiated through a multistep process involving the binding of KSHV envelope glycoproteins with cell surface α3β1, αVβ3, and αVβ5 integrin molecules and tyrosine kinase ephrin-A2 receptor, followed by the activation of preexisting integrin-associated signaling molecules such as focal adhesion kinase (FAK), Src, c-Cbl, phosphoinositide 3-kinase (PI-3K), and Rho-GTPases. Many viruses, including KSHV, utilize cellular reactive oxygen species (ROS) for viral genomic replication and survival within host cells; however, the role of ROS in early events of viral entry and the induction of signaling has not been elucidated. Here we show that KSHV induced ROS production very early during the infection of HMVEC-d cells and that ROS production was sustained over the observation period (24 h postinfection). ROS induction was dependent on the binding of KSHV to the target cells, since pretreatment of the virus with heparin abolished ROS induction. Pretreatment of HMVEC-d cells with the antioxidant
N
-acetylcysteine (NAC) significantly inhibited KSHV entry, and consequently gene expression, without affecting virus binding. In contrast, H
2
O
2
treatment increased the levels of KSHV entry and infection. In addition, NAC inhibited KSHV infection-induced translocation of αVβ3 integrin into lipid rafts, actin-dependent membrane perturbations, such as blebs, observed during macropinocytosis, and activation of the signal molecules ephrin-A2 receptor, FAK, Src, and Rac1. In contrast, H
2
O
2
treatment increased the activation of ephrin-A2, FAK, Src, and Rac1. These studies demonstrate that KSHV infection induces ROS very early during infection to amplify the signaling pathways necessary for its efficient entry into HMVEC-d cells via macropinocytosis.
Descriptive analysis of the respiratory health status of persons exposed to Libby amphibole asbestos
Authors: Winters Charlene A , Hill Wade G , Rowse Kimberly , Black Brad , Kuntz Sandra W , Weinert Clarann 
Published: November 2012

ObjectiveDescribe respiratory health and quality of life in persons exposed to Libby amphibole asbestos (LAA) contaminated vermiculite.DesignCross-sectional descriptive.SettingAsbestos-related disease clinic in Libby, Montana USA.Participants329 individuals exposed to LAA; mostly men, married, between 50 and 69 years; two-thirds lived in the surrounding county; one-third lived elsewhere in the state and USA.Primary outcome measuresChest radiograph (CXR), pulmonary function data and the St George Respiratory Questionnaire (SGRQ).ResultsExposure categories included vermiculite workers=7.6%; family/household contact of vermiculite worker=32%; and environmental exposure only=60%. Of the participants, 55% had only pleural abnormalities; 5.4% had only interstitial abnormalities; nearly 21% had both abnormalities and 18% had no lung abnormality on chest x-ray. Mean forced vital capacity (FVC) 95.3% (SD=18.7); forced expiratory volume (FEV1) mean 87% (SD=20.2); ratio of FEV11/FVC 95.5% (SD=12.0); and diffusing capacity (DLCO) of 83% (SD=21.7) of the percent predicted. The mean total SGRQ (38.5; SD=22.1) indicated a lower quality of life than healthy persons and persons with other chronic conditions. SGRQ subscale means were Symptoms 52.1 (SD=24.9), activity 49.4 (SD=26.9) and impacts 27.5 (SD=21.9). Participants with normal CXR differed significantly from those with both interstitial and pleural abnormalities on total, activity and impacts scores. For activity alone, subjects with normal CXR differed significantly from those with pleural disease; no differences were found for those with interstitial disease. Significant findings were found for smoking history across all pulmonary measures, and for exposure status, radiographic findings, age and gender for select pulmonary parameters. Subjects with any smoking history had significantly worse average total and subscale scores on the SGRQ.ConclusionsOf 329 persons exposed to LAA, the majority (182) had pleural abnormalities identified on CXR. SGRQ scores for persons with abnormalities (pleural, interstitial or both) (269) differed significantly from those with a normal CXR.
A randomised clinical trial of comprehensive cardiac rehabilitation versus usual care for patients treated for infective endocarditis—the CopenHeartIEtrial protocol
Authors: Rasmussen Trine Bernholdt , Zwisler Ann-Dorthe , Sibilitz Kirstine Lærum , Risom Signe Stelling , Bundgaard Henning , Gluud Christian , Moons Philip , Winkel Per , Thygesen Lau Caspar , Hansen Jane Lindschou , Norekvål Tone Merete , Berg Selina Kikkenborg ,   the CopenHeartIE Group
Published: November 2012

IntroductionInfective endocarditis (IE) is among the most serious infectious diseases in the western world. Treatment requires lengthy hospitalisation, high-dosage antibiotic therapy and possible valve replacement surgery. Despite advances in treatment, the 1-year mortality remains at 20–40%. Studies indicate that patients experience persisting physical symptoms, diminished quality of life and difficulties returning to work up to a year postdischarge. No studies investigating the effects of rehabilitation have been published. We present the rationale and design of the CopenHeartIEtrial, which investigates the effect of comprehensive cardiac rehabilitation versus usual care for patients treated for IE.Methods and analysisWe will conduct a randomised clinical trial to investigate the effects of comprehensive cardiac rehabilitation versus usual care on the physical and psychosocial functioning of patients treated for IE. The trial is a multicentre, parallel design trial with 1 : 1 individual randomisation to either the intervention or control group. The intervention consists of five psychoeducational consultations provided by specialised nurses and a 12-week exercise training programme. The primary outcome is mental health (MH) measured by the standardised Short Form 36 (SF-36). The secondary outcome is peak oxygen uptake measured by the bicycle ergospirometry test. Furthermore, a number of exploratory analyses will be performed. Based on sample size calculation, 150 patients treated for left-sided (native or prosthetic valve) or cardiac device endocarditis will be included in the trial. A qualitative and a survey-based complementary study will be undertaken, to investigate postdischarge experiences of the patients. A qualitative postintervention study will explore rehabilitation participation experiences.Ethics and disseminationThe study complies with the Declaration of Helsinki and was approved by the regional research ethics committee (no H-1-2011-129) and the Danish Data Protection Agency (no 2007-58-0015). Study findings will be disseminated widely through peer-reviewed publications and conference presentations.RegistrationClinicaltrials.gov identifier:NCT01512615.
Coordinate My Care: a clinical service that coordinates care, giving patients choice and improving quality of life
Authors: Smith Clare , Hough Libby , Cheung Chi-Chi , Millington-Sanders Catherine , Sutton Eileen , Ross Joy R , Thick Michael , Riley Julia 
Published: November 2012

IntroductionIf palliative care is to lead the way towards a new model for integrated care, the ability to share information across the whole of health and social care is essential. Coordinate My Care (CMC) is a service dedicated to preserving dignity and autonomy at the end of life. Its care pathways enable health professionals from primary and secondary care to put the patient at the centre of health care delivery. This service is underpinned by an electronic solution. The CMC record can be accessed 24/7 by all health and social care professionals who have a legitimate relationship with the patient.Patients and methodsThe record displays diagnosis, prognosis, advanced care plan, resuscitation status and patients wishes for end of life care patients across London. This article is a review of CMC use and outcomes from August 2010- March 2012.Results1087 CMC patient records were analysed. The primary diagnosis was non-cancer in 52.3%, cancer in 46.3% and unknown in 1.4%, 42% of all patients were cared for by generalist only and had no specialist palliative care involvement. At the time of analysis 207 had died. Actual place of death was home 38.6%, care/nursing home 16.4%, hospice 12.1% and 30% in hospital. This equates to 55% of patients dying in their usual place of residence and reflects that 70% died outside of hospital.ConclusionThe CMC service has a well defined pathway underpinned by an electronic solution. It has been shown to change culture and deliver fully integrated, personalised end of life care. A pan-London CMC roll out will take place over the next 12 months.
The impact of adding clinical assistants on patient waiting time in a crowded emergency department
Authors: Huang Edward Pei-Chuan , Liu Sot Shih-Hung , Fang Cheng-Chung , Chou Hao-Chang , Wang Chih-Hung , Yen Zui-Shen , Chen Shyr-Chyr 
Published: November 2012

BackgroundEmergency department (ED) crowding causes prolonged waiting times.ObjectiveTo evaluate the potential benefit of introducing clinical assistants to a busy and crowded ED.MethodsThis was a retrospective cohort study at an urban, academic tertiary medical centre. We introduced one clinical assistant to each ED shift. The main task of clinical assistants was managing the flow of incoming ED patients. The case group consisted of all adult non-trauma emergency patients during the case period from 1 September to 30 November 2008. The first control group consisted of all adult non-trauma emergency patients between 1 June and 31 August 2008 and the second control group consisted of all patients treated between 1 September and 30 November 2007. The primary outcome was the ‘waiting time’, defined as the time from triage to the time of the first medical order entered into the computer system. The secondary outcome was the number of adult non-trauma emergency patients who left the ED without being seen.ResultsThere were 12 257 cases and 25 950 controls. The mean and median waiting times were significantly shorter in the case group. The mean waiting time of the case group was 20.86 min, which was 4.51 min (17.8%) shorter than that of the first control group and 7.41 min (26.2%) shorter than that of the second control group. The median waiting time of the case group was also significantly shorter than those of the control groups. The number of the patients who left without being seen was significantly smaller in the case period.ConclusionsIn a busy and crowded ED, the introduction of clinical assistants to an existing emergency health service effectively reduces patient waiting times and decreases the number of patients leaving without being seen.
Human alpha-actinin-3 genotype association with exercise-induced muscle damage and the repeated-bout effect
Authors: Venckunas Tomas , Skurvydas Albertas , Brazaitis Marius , Kamandulis Sigitas , Snieckus Audrius , Moran Colin N. 
Published: November 2012

Alpha-actinin-3 (ACTN3) is an integral part of the Z line of the sarcomere. The ACTN3 R577X (rs1815739) polymorphism determines the presence or absence of functional ACTN3, which may influence the extent of exercise-induced muscle damage. This study aimed to compare the impact of, and recovery from, muscle-damaging eccentric exercise on subjects with or without functional ACTN3. Seventeen young men (20–33 years old), homozygous for the R (n = 9) or X (n = 8) alleles, performed two bouts of stretch–shortening exercise (50 drop jumps) two weeks apart. Muscle soreness, plasma creatine kinase (CK) activity, jump height, maximal voluntary isometric torque (MVC), peak concentric isokinetic torque (IT), and electrically stimulated knee extension torques at 20 and 100 Hz were measured at baseline and at a number of time points up to 14 days after each bout. There were no significant baseline differences between the groups. However, significant time point × genotype interactions were observed for MVC (p = 0.021) and IT (p = 0.011) for the immediate effect of eccentric exercise in bout 1. The RR group showed greater voluntary force decrements (RR vs. XX: MVC, –33.3% vs. –24.5%; IT, –35.9% vs. –23.2%) and slower recovery. A repeated-bout effect was clearly observed, but there were no differences by genotype group. The ACTN3 genotype modulates the response of muscle function to plyometric jumping exercise, although the differences are modest. The ACTN3 genotype does not influence the clearly observed repeated-bout effect; however, XX homozygotes recover baseline voluntary torque values faster and thus may be able to undertake more frequent training sesssions.
Dietary sodium citrate supplementation enhances rehydration and recovery from rapid body mass loss in trained wrestlers
Authors: Timpmann Saima , Burk Andres , Medijainen Luule , Tamm Maria , Kreegipuu Kairi , Vähi Mare , Unt Eve , Ööpik Vahur 
Published: November 2012

This study assessed the effects of dietary sodium citrate supplementation during a 16 h recovery from 5% rapid body mass loss (RBML) on physiological functions, affective state, and performance in trained wrestlers. Sixteen wrestlers performed an upper body intermittent sprint performance (UBISP) test under three conditions: before RBML, after RBML, and after a 16 h recovery from RBML. During recovery, the subjects ate a prescribed diet supplemented with sodium citrate (600 mg·kg–1; CIT group, N = 8) or placebo (PLC group, N = 8) and drank water ad libitum. RBML reduced (p < 0.05) UBISP mean power and increased urine specific gravity (USG). Reduction in mean power was associated with changes in plasma volume (PV) (r = 0.649, p = 0.006) and USG (r = –0.553, p = 0.026). During the 16 h recovery, increases in body mass (BM) and PV were greater (p < 0.05) in the CIT group than in the PLC group. BM gain was associated with water retention in the CIT group (r = 0.899, p = 0.002) but not in the PLC group (r = 0.335, p = 0.417). Blood pH, HCO3–concentration, and base excess increased (p < 0.05) only in the CIT group. Changes in UBISP, general negative affect, and general positive affect did not differ in the two groups. In conclusion, ingestion of sodium citrate increases blood buffering capacity and PV and stimulates BM regain during a 16 h recovery from RBML in trained wrestlers. However, sodium citrate does not improve UBISP nor does it have an impact on the affective state.
Modulating fibroblast growth factor 21 in hyperphagic OLETF rats with daily exercise and caloric restriction
Authors: Fletcher Justin A. , Meers Grace M. , Laughlin M. Harold , Ibdah Jamal A. , Thyfault John P. , Rector R. Scott 
Published: November 2012

Chronic treatment with fibroblast growth factor 21 (FGF-21) favorably improves obesity and nonalcoholic fatty liver disease (NAFLD) outcomes; however, FGF-21 expression is paradoxically elevated in obese conditions. Here, we sought to determine the effects of obesity prevention by daily exercise (EX) vs. caloric restriction (CR) on hepatic FGF-21 in the hyperphagic, Otsuka Long-Evans Tokushima Fatty (OLETF) rat. Four-week-old male OLETF rats were randomized into groups (n = 7–8 per group) of ad libitum fed, sedentary (OLETF-SED), voluntary wheel running exercise (OLETF-EX), or CR (OLETF-CR; 70% of SED) until 40 weeks of age. Nonhyperphagic, Long-Evans Tokushima Otsuka (LETO-SED) rats served as controls. Both daily EX and CR prevented obesity and NAFLD development observed in the OLETF-SED animals. This was associated with significantly (p < 0.01) lower serum FGF-21 (~80% lower) and hepatic FGF-21 mRNA expression (~65% lower) in the OLETF-EX and OLETF-CR rats compared with the OLETF-SED rats. However, hepatic FGF-21 protein content was reduced to the greatest extent in the OLETF-EX animals (50% of OLETF-SED) and did not differ between the OLETF-SED and OLETF-CR rats. Hepatic FGF-21 signaling mediators — hepatic FGF-21 receptor 2 (FGFR2, mRNA expression), hepatic FGF-21 receptor substrate 2 (FRS2, protein content), and co-receptor β-Klotho (protein content) — were all elevated (60%–100%, ~40%, and +30%–50%, respectively) in the OLETF-EX and OLETF-CR animals compared with the OLETF-SED animals. Daily exercise and caloric restriction modulate hepatic FGF-21 and its primary signaling mediators in the hyperphagic OLETF rat. Enhanced metabolic action of FGF-21 may partially explain the benefits of exercise and caloric restriction on NAFLD outcomes.
Predicting doubly labeled water energy expenditure from ambulatory activity
Authors: Tudor-Locke Catrine , Martin Corby K. , Brashear Meghan M. , Rood Jennifer C. , Katzmarzyk Peter T. , Johnson William D. 
Published: November 2012

The purpose of this study was to evaluate the potential for using accelerometer-determined ambulatory activity indicators (steps per day and cadence) to predict total energy expenditure (TEE) and physical activity energy expenditure (PAEE) derived from doubly labeled water (DLW). Twenty men and 34 women (20–36 years of age) provided complete anthropometric, accelerometer, resting metabolic rate (RMR), and DLW data. TEE and PAEE were determined for the same week that accelerometers were worn during waking hours. Accelerometer data included mean steps per day, peak 30-min cadence (average steps per minute for the highest 30 min of the day), and time spent in each incremental cadence band: 0 (nonmovement), 1–19 (incidental movement), 20–39 (sporadic movement), 40–59 (purposeful steps), 60–79 (slow walking), 80–99 (medium walking), 100–119 (brisk walking), and 120+ steps·min–1 (indicative of all faster ambulatory activities). Regression analyses were employed to develop sex-specific equations for predicting TEE and PAEE. The final model predicting TEE included body weight, steps per day, and time in incremental cadence bands and explained 79% (men) and 65% (women) of the variability. The final model predicting PAEE included peak 30-min cadence, steps per day, and time in cadence bands and explained 76% (men) and 46% (women) of the variability. Time in cadence bands alone explained 39%–73% of the variability in TEE and 30%–63% of the variability in PAEE. Prediction models were stronger for men than for women.