bluuebunny/crossref_metadata_2025_split huggingface dataset:
Estimating the Stoichiometry of Human Immunodeficiency Virus Entry
Authors: Magnus Carsten , Rusert Peter , Bonhoeffer Sebastian , Trkola Alexandra , Regoes Roland R. 
Published: November 2008

ABSTRACT
To enter target cells, human immunodeficiency virus (HIV) first attaches to the cells and fuses with the cell membrane. Attachment and fusion involve envelope glycoprotein trimers on the surface of the virion and the CD4 receptor and chemokine coreceptors on the surface of the target cell. The stoichiometry of entry, that is, the number of bonds between such trimers and CD4 that are required for infection, is unknown. Pseudotyped virions that express mixed trimers consisting of functional and nonfunctional envelope proteins have been used to study how many trimer-receptor interactions are required for virus entry. However, to extract information on the stoichiometry of entry from data generated in in vitro infectivity assays with such viruses, mathematical models are required. Here, we describe mathematical models that can be used to infer the stoichiometry of entry. By fitting our simplest model to previously published data (X. Yang, S. Kurteva, X. Ren, S. Lee, and J. Sodroski, J. Virol. 79: 12132-12147, 2005), we estimated that the number of trimer-receptor interactions required for HIV to infect a target cell is approximately eight, which is higher than previous estimates. We also consider model extensions that explain some systematic deviations of the data from the prediction of the simplest model. However, these extended models yield very different estimates of the stoichiometry of entry ranging from 2 to 19. These results strongly suggest that, based on our present knowledge of HIV entry, the stoichiometry of this process cannot be reliably estimated. Our study identifies parameters that need to be defined to render the estimation of the stoichiometry of HIV entry possible.
Mechanism of mda-5 Inhibition by Paramyxovirus V Proteins
Authors: Childs K. S. , Andrejeva J. , Randall R. E. , Goodbourn S. 
Published: November 2008

ABSTRACT
The RNA helicases encoded by melanoma differentiation-associated gene 5 (mda-5) and retinoic acid-inducible gene I (RIG-I) detect foreign cytoplasmic RNA molecules generated during the course of a virus infection, and their activation leads to induction of type I interferon synthesis. Paramyxoviruses limit the amount of interferon produced by infected cells through the action of their V protein, which binds to and inhibits mda-5. Here we show that activation of both mda-5 and RIG-I by double-stranded RNA (dsRNA) leads to the formation of homo-oligomers through self-association of the helicase domains. We identify a region within the helicase domain of mda-5 that is targeted by all paramyxovirus V proteins and demonstrate that they inhibit activation of mda-5 by blocking dsRNA binding and consequent self-association. In addition to this commonly targeted domain, some paramyxovirus V proteins target additional regions of mda-5. In contrast, V proteins cannot bind to RIG-I and consequently have no effect on the ability of RIG-I to bind dsRNA or to form oligomers.
Neutralization-Sensitive R5-Tropic Simian-Human Immunodeficiency Virus SHIV-2873Nip, Which Carries
env
Isolated from an Infant with a Recent HIV Clade C Infection
Authors: Siddappa Nagadenahalli B. , Song Ruijiang , Kramer Victor G. , Chenine Agnès-Laurence , Velu Vijayakumar , Ong Helena , Rasmussen Robert A. , Grisson Ricky D. , Wood Charles , Zhang Hong , Kankasa Chipeppo , Amara Rama Rao , Else James G. , Novembre Francis J. , Montefiori David C. , Ruprecht Ruth M. 
Published: November 2008

ABSTRACT

Human immunodeficiency virus clade C (HIV-C) accounts for >56% of all HIV infections worldwide. To investigate vaccine safety and efficacy in nonhuman primates, a pathogenic, R5-tropic, neutralization-sensitive simian-human immunodeficiency virus (SHIV) carrying HIV-C
env
would be desirable. We have constructed SHIV-2873Ni, an R5-tropic SHIV carrying a primary pediatric HIV-C
env
gene isolated from a 2-month-old Zambian infant, who died within 1 year of birth. SHIV-2873Ni was constructed using SHIV-1157ipd3N4 (R. J. Song, A. L. Chenine, R. A. Rasmussen, C. R. Ruprecht, S. Mirshahidi, R. D. Grisson, W. Xu, J. B. Whitney, L. M. Goins, H. Ong, P. L. Li, E. Shai-Kobiler, T. Wang, C. M. McCann, H. Zhang, C. Wood, C. Kankasa, W. E. Secor, H. M. McClure, E. Strobert, J. G. Else, and R. M. Ruprecht. J. Virol. 80:8729-8738, 2006) as the backbone, since the latter contains additional NF-κB sites in the long terminal repeats to enhance viral replicative capacity. The parental virus, SHIV-2873Ni, was serially passaged through five rhesus monkeys (RMs); SHIV-2873Nip, the resulting passaged virus, was reisolated from the fourth recipient about 1 year postinoculation. SHIV-2873Nip was replication competent in RM peripheral blood mononuclear cells of all random donors tested and was exclusively R5 tropic, and its
env
gene clustered with HIV-C by phylogenetic analysis; its high sensitivity to neutralization led to classification as a tier 1 virus. Indian-origin RMs were inoculated by different mucosal routes, resulting in high peak viral RNA loads. Signs of virus-induced disease include depletion of gut CD4
+
T lymphocytes, loss of memory T cells in blood, and thrombocytopenia that resulted in fatal cerebral hemorrhage. SHIV-2873Nip is a highly replication-competent, mucosally transmissible, pathogenic R5-tropic virus that will be useful to study viral pathogenesis and to assess the efficacy of immunogens targeting HIV-C Env.
Repair of the U
L
21 Locus in Pseudorabies Virus Bartha Enhances the Kinetics of Retrograde, Transneuronal Infection In Vitro and In Vivo
Authors: Curanović D. , Lyman M. G. , Bou-Abboud C. , Card J. P. , Enquist L. W. 
Published: November 2008

ABSTRACT

The attenuated pseudorabies virus (PRV) strain Bartha contains several characterized mutations that affect its virulence and ability to spread through neural circuits. This strain contains a small genomic deletion that abrogates anterograde spread and is widely used as a retrograde-restricted neural circuit tracer. Previous studies showed that the retrograde-directed spread of PRV Bartha is slower than that of wild-type PRV. We used compartmented neuronal cultures to characterize the retrograde defect and identify the genetic basis of the phenotype. PRV Bartha is not impaired in retrograde axonal transport, but transneuronal spread among neurons is diminished. Repair of the U
L
21 locus with wild-type sequence restored efficient transneuronal spread both in vitro and in vivo. It is likely that mutations in the Bartha U
L
21 gene confer defects that affect infectious particle production, causing a delay in spread to presynaptic neurons and amplification of infection. These events manifest as slower kinetics of retrograde viral spread in a neural circuit.
Inactivated Simian Immunodeficiency Virus-Pulsed Autologous Fresh Blood Cells as an Immunotherapy Strategy
Authors: Mason Rosemarie D. , Alcantara Sheilajen , Peut Viv , Loh Liyen , Lifson Jeffrey D. , De Rose Robert , Kent Stephen J. 
Published: November 2008

ABSTRACT

Practical immunotherapies for human immunodeficiency virus infection are needed. We evaluated inactivated simian immunodeficiency virus (SIV) pulsed onto fresh peripheral blood mononuclear cells in 12 pigtail macaques with chronic SIV
mac251
infection for T-cell immunogenicity in a randomized cross-over design study. The immunotherapy was safe and convincingly induced high levels of SIV-specific CD4
+
T-cell responses (mean, 5.9% ± 1.3% of all CD4
+
T cells) and to a lesser extent SIV-specific CD8
+
T-cell responses (mean, 0.7% ± 0.4%). Responses were primarily directed toward Gag and less frequently toward Env but not Pol or regulatory/accessory SIV proteins. T-cell responses against Gag were generally broad and polyfunctional, with a mean of 2.7 CD4
+
T-cell epitopes mapped per animal and more than half of the SIV Gag-specific CD4
+
T cells expressing three or more effector molecules. The immunogenicity was comparable to that found in previous studies of peptide-pulsed blood cells. Despite the high-level immunogenicity, no reduction in viral load was observed in the chronically viremic macaques. This contrasts with our studies of immunization with peptide-pulsed blood cells during early SIV infection in macaques. Future studies of inactivated virus-pulsed blood cell immunotherapy during early infection of patients receiving antiretroviral therapy are warranted.
Posterior lamellar keratoplasty—comparison of deep lamellar endothelial keratoplasty and Descemet stripping automated endothelial keratoplasty in the same patients: a patient’s perspective
Authors: Bahar I , Sansanayudh W , Levinger E , Kaiserman I , Srinivasan S , Rootman D 
Published: November 2008

Aim:To evaluate patients’ perspectives on endothelial keratoplasty and to compare the outcomes of deep lamellar endothelial keratoplasty (DLEK) and Descemet stripping automated endothelial keratoplasty (DSAEK), performed in the same patients.Methods:A fellow eye, comparative retrospective case series. The records of 14 patients (28 eyes) who underwent DLEK in one eye and DSAEK surgery in their fellow eye between 2003 and 2007 were reviewed. Two patients were excluded from the study. Both these techniques were compared for intra- and postoperative complications, visual and refractive outcomes including higher-order ocular aberrations (HOA). Patient satisfaction for both procedures was prospectively evaluated using a subjective questionnaire.Results:Nine (75%) of the 12 patients perceived better vision in the DSAEK operated eye. Eight (66.6%) of the patients reported faster recovery following DSAEK. Ten (83%) of them preferred the outcomes of the DSAEK surgery. The intra- and postoperative complications were comparable between both procedures. There was no significant difference in visual outcomes between the procedures. However, the DLEK procedure was associated with a significantly higher degree (p<0.05) of HOA. Endothelial cell loss was similar following DLEK and DSAEK.Conclusions:We conclude that most patients prefer the DSAEK operation, although there are no differences in visual outcomes between DLEK and DSAEK. Avoidance of surgery-induced hyperopia and HOA is the main benefit of the DSAEK technique.
Recovery of corneal irregular astigmatism, ocular higher-order aberrations, and contrast sensitivity after discontinuation of overnight orthokeratology
Authors: Hiraoka T , Okamoto C , Ishii Y , Okamoto F , Oshika T 
Published: November 2008

Aims:To examine prospectively the recovery of various parameters after discontinuation of overnight orthokeratology.Methods:Seventeen subjects undergoing orthokeratology for 12 months were examined. Refraction, corneal topography, wavefront aberrometry, a visual acuity test and a contrast sensitivity test were performed at baseline, 12 months after commencement of the procedure, and 1 week and 1 month after discontinuation of the treatment. Asymmetry and higher-order irregularity components were calculated using a Fourier analysis of the corneal topography data. Contrast sensitivity was assessed at four spatial frequencies, and the area under the log contrast sensitivity function (AULCSF) was calculated.Results:Orthokeratology significantly reduced manifest refraction (p<0.0001, Dunnett test) and significantly improved uncorrected visual acuity (UCVA) at 12 months after commencement of the procedure (p<0.0001). Asymmetry and higher-order irregularity components increased significantly (p<0.0001, p = 0.0032, respectively), and third- and fourth-order aberrations also increased significantly (p<0.0001). The treatment resulted in significant decreases in AULCSF (p = 0.0004). After discontinuing lens wear, all parameters, such as refraction, UCVA, asymmetry, higher-order irregularity, third-order aberration, fourth-order aberration and AULCSF, returned to the baseline level at 1 week.Conclusion:This study confirmed that the effect of orthokeratology is completely reversible in light of optical quality of the eye and quality of vision as well as refraction and visual acuity.
Recurrent ectasia in corneal grafts and outcomes of repeat keratoplasty for keratoconus
Authors: Patel S V , Malta J B , Banitt M R , Mian S I , Sugar A , Elner V M , Tester R A , Farjo Q A , Soong H K 
Published: November 2008

Aim:To analyse cases of recurrent ectasia in donor corneas after penetrating keratoplasty (PK) for keratoconus.Methods:Data on 25 patients (36 eyes) with recurrent ectasia were retrospectively analysed in this study. The main outcome measures were time to development of recurrent ectasia after first PK for keratoconus, change in keratometric sphere and astigmatism between final suture removal and development of recurrent ectasia, status of regrafts for recurrent ectasia, and histopathology of grafts excised for recurrent ectasia.Results:The age at first PK was 32.6 (SD 8.5) years, and ectasia developed 21.9 (7.0) years after PK. The mean keratometric sphere and cylinder increased by 4.2 D and 3.0 D, respectively, between final suture removal and diagnosis of recurrent ectasia. Ectasia was often preceded by thinning without bulging of the recipient stroma at the graft–host junction. Fifteen eyes (13 patients) were regrafted for recurrent ectasia, and histopathology of the excised grafts showed changes characteristic of keratoconus in the donor tissue in all cases. Two regrafts (two eyes of one patient) developed ectasia again, with one eye requiring a third PK to improve vision.Conclusions:Recurrent ectasia was diagnosed on average two decades after PK. Ectatic changes were often bilateral and occasionally recurred after regrafting, suggesting that host cellular and/or biochemical factors may be responsible. Repeat PK for recurrent ectasia is successful in the intermediate term.
The gluteal triangle: a clinical patho-anatomical approach to the diagnosis of gluteal pain in athletes
Authors: Franklyn-Miller A , Falvey E , McCrory P 
Published: November 2008

Gluteal pain is a common presentation in sports medicine. The aetiology of gluteal pain is varied, it may be referred from the lower back, mimic other pathology and refer to the hip or the groin. The complex anatomy of the buttock and pelvis, variability of presentation and non specific nature of signs and symptoms make the diagnostic process difficult. To date the approaches to this problem have focused on individual pathologies.The paper proposes a novel educational system based on patho-anatomic concepts. Anatomical reference points were selected to form a diagnostic triangle, which provides the discriminative power to restrict the differential diagnosis, and form the basis of ensuing investigation.This paper forms part of a series addressing the three dimensional nature of proximal lower limb pathology. The 3G approach (groin, gluteal and greater trochanter triangles) acknowledges this, permitting the clinician to move throughout the region, considering pathologies appropriately. These papers should be read in conjunction with one another in order to fully understand the conceptual approach.
The greater trochanter triangle; a pathoanatomic approach to the diagnosis of chronic, proximal, lateral, lower pain in athletes
Authors: Falvey E C , Franklyn-Miller A , McCrory P R 
Published: November 2008

Chronic pain experienced in the proximal, lateral, lower limb may arise from the femoro-acetabular joint, from the muscles and tendons that act upon it, from any of the structures that traverse the area, and from more remote structures such as the lumbar spine.The aetiology of pathology in this area is not confined to either trauma or overuse. As a result many different sporting activities may have a causal role.Without a clear clinical/pathological diagnosis, the subsequent management of chronic groin pain is difficult. The combination of complex anatomy, variability of presentation and the non-specific nature of the signs and symptoms makes the diagnostic process problematic.The paper proposes a novel educational model based on pathoanatomic concepts. Anatomical reference points were selected to form a triangle, which provides the discriminative power to restrict the differential diagnosis, and form the basis of ensuing investigation.This paper forms part of a series addressing the three-dimensional nature of proximal lower limb pathology. The 3G approach (groin, gluteal, and greater trochanter triangles) acknowledges this, permitting the clinician to move throughout the region, considering pathologies appropriately.
Sonographically guided intratendinous injections of hyperosmolar dextrose/lidocaine: a pilot study for the treatment of chronic plantar fasciitis
Authors: Ryan M B , Wong A D , Gillies J H , Wong J , Taunton J E 
Published: November 2008

Objective:To report on the effectiveness of sonographically guided injections of hyperosmolar dextrose at reducing the pain associated with chronic plantar fasciitis.Design:Case series.Setting:Ultrasound division of St Paul’s Hospital.Patients:20 referrals (3 men, 17 women; age 51 (SD 13) years) from local sports medicine primary care practitioners who had failed previous conservative treatments.Interventions:A 27-gauge needle administered a 25% dextrose/lidocaine solution under sonographic guidance at 6 week intervals returning for a median of three consultations.Main outcome measures:Visual analogue scale (VAS) items for pain levels at rest (VAS1), activities of daily living (VAS2), and during or after physical activity (VAS3) were recorded at baseline and at the final treatment consultation (post-test). A telephone interview conducted an average of 11.8 months after the post-test consultation provided a measure of long-term follow-up.Results:16 patients reported a good to excellent outcome, while the symptoms in 4 patients were unchanged. There was a significant decrease (p<0.001) in all mean VAS items from pre-test to post-test: VAS1 (36.8 (SD 25.6) to 10.3 (10.9)), VAS2 (74.7 (20.8) to 25.0 (27.7)) and VAS3 (91.6 (9.2) to 38.7 (35.1)) and there were no apparent changes after the follow-up interview.Conclusions:Sonographically guided dextrose injections showed a good clinical response in patients with chronic plantar fasciitis insofar as pain was reduced during rest and activity. Further studies including a control group are needed to validate these outcomes.
State anxiety and subjective well-being responses to acute bouts of aerobic exercise in patients with depressive and anxiety disorders
Authors: Knapen J , Sommerijns E , Vancampfort D , Sienaert P , Pieters G , Haake P , Probst M , Peuskens J 
Published: November 2008

Objective:Acute aerobic exercise is associated with a reduction in state anxiety and an improvement in subjective well-being. The objective of the present study was to contrast the effects of aerobic exercise at self-selected intensity versus prescribed intensity on state anxiety and subjective well-being (negative affect, positive well-being and fatigue) in patients with depressive and/or anxiety disorders. In addition, the potential impact of heart rate feedback was assessed.Methods:Nineteen men and 29 women performed three test conditions on a bicycle ergometer during 20 minutes: two tests at self-selected intensity; one with and another without heart rate feedback, and a third test at the prescribed intensity of 50% of the maximal heart rate reserve according to Karvonen. Tests were executed in random order. State anxiety and subjective well-being were evaluated using the state anxiety inventory and the subjective exercise experiences scale.Results:After 20 minutes cycling, patients showed significantly decreased state anxiety and negative affect in the three conditions. The magnitude of the reduction did not differ significantly between the three conditions. Only cycling at self-selected intensity enhanced positive well-being. Cycling at 50% of the maximal heart rate reserve decreased fatigue, whereas cycling at self-selected intensity increased fatigue.Conclusions:The response in state anxiety and negative affect was unaffected by the type of aerobic exercise. Self-selected intensity influenced exercise-induced changes in positive well-being and fatigue in a positive and negative way, respectively.
Eccentric calf muscle exercise produces a greater acute reduction in Achilles tendon thickness than concentric exercise
Authors: Grigg N L , Wearing S C , Smeathers J E 
Published: November 2008

Objective:To investigate the acute effects of isolated eccentric and concentric calf muscle exercise on Achilles tendon sagittal thickness.Design:Within-subject, counterbalanced, mixed design.Setting:Institutional.Participants:11 healthy, recreationally active male adults.Interventions:Participants performed an exercise protocol, which involved isolated eccentric loading of the Achilles tendon of a single limb and isolated concentric loading of the contralateral, both with the addition of 20% bodyweight.Main outcome measurements:Sagittal sonograms were acquired prior to, immediately following and 3, 6, 12 and 24 h after exercise. Tendon thickness was measured 2 cm proximal to the superior aspect of the calcaneus.Results:Both loading conditions resulted in an immediate decrease in normalised Achilles tendon thickness. Eccentric loading induced a significantly greater decrease than concentric loading despite a similar impulse (−0.21 vs −0.05, p<0.05). Post-exercise, eccentrically loaded tendons recovered exponentially, with a recovery time constant of 2.5 h. The same exponential function did not adequately model changes in tendon thickness resulting from concentric loading. Even so, recovery pathways subsequent to the 3 h time point were comparable. Regardless of the exercise protocol, full tendon thickness recovery was not observed until 24 h.Conclusions:Eccentric loading invokes a greater reduction in Achilles tendon thickness immediately after exercise but appears to recover fully in a similar time frame to concentric loading.
Physical activity habits of doctors and medical students influence their counselling practices
Authors: Lobelo F , Duperly J , Frank E 
Published: November 2008

Doctors are well positioned to provide physical activity (PA) counselling to patients. They are a respected source of health-related information and can provide continuing preventive counselling feedback and follow-up; they may have ethical obligations to prescribe PA. Several barriers to PA counselling exist, including insufficient training and motivation of doctors and improvable, personal PA habits. Rates of exercise counselling by doctors remain low; only 34% of US adults report exercise counselling at their last medical visit. In view of this gap, one of the US health objectives for 2010 is increasing the proportion of patients appropriately counselled about health behaviours, including exercise/PA. Research shows that clinical providers who themselves act on the advice they give provide better counselling and motivation of their patients to adopt such health advice.In summary, there is compelling evidence that the health of doctors matters and that doctors’ own PA practices influence their clinical attitudes towards PA. Medical schools need to increase the proportion of students adopting and maintaining regular PA habits to increase the rates and quality of future PA counselling delivered by doctors.