bluuebunny/crossref_metadata_2025_split huggingface dataset:
Characteristics of the Cellular Receptor Influence the Intracellular Fate and Efficiency of Virus Infection
Authors: Krueger Robin L. , Albritton Lorraine M. 
Published: March 2013

ABSTRACT
The intracellular fate of internalized virus-receptor complexes is suspected of influencing the efficiency of virus infection. However, direct evidence of a link between infection and the fate of internalized virus has been difficult to obtain. To directly address this question, we generated human 293 cell lines stably expressing comparable cell surface levels of three different members of the somatostatin receptor family (SSTR) which have natural differences in intracellular trafficking. Utilizing a glycoprotein that recognizes SSTR, we found that distinctive receptor subtype-specific destinations correlated with observable differences in the level of infection. Infection via SSTR-2 and -3 is restricted at a point after receptor binding and endocytosis but prior to penetration into the host cytoplasm. In contrast, entry via SSTR-5 featured a slower internalization with greater dependence on cholesterol. Quantitative real-time PCR showed that virus bound to SSTR-5 was directed to an intracellular environment that allowed near-wild-type (WT) levels of penetration, possibly due to a more favorable complement of host cell proteases, whereas SSTR-2 and -3 directed virions to a degradative compartment in which cytosol penetration was less efficient. Taken together, the results support that the superior receptor capacity of SSTR-5 results from its internalization into a cellular compartment that is more favorable to the cytoplasmic penetration of viral cores and reverse transcription. They suggest that the intracellular destination of internalized complexes is an important characteristic of a virus receptor and may have exerted a selective pressure on the choice of an entry receptor during evolution of viral glycoproteins.
A Tyrosine-to-Histidine Switch at Position 18 of the Ross River Virus E2 Glycoprotein Is a Determinant of Virus Fitness in Disparate Hosts
Authors: Jupille Henri J. , Medina-Rivera Melisa , Hawman David W. , Oko Lauren , Morrison Thomas E. 
Published: March 2013

ABSTRACT

Arthritogenic alphaviruses are human pathogens maintained in nature through alternating replication in vertebrates and mosquitoes. Using chimeric viruses, we previously reported that replacement of the PE2 coding region of the T48 strain of Ross River virus (RRV-T48) with that from the attenuated DC5692 strain, which differ by 7 amino acids, resulted in an attenuated disease phenotype in a mouse model of RRV-induced rheumatic disease. Here, we demonstrate that introduction of one of these amino acid differences, a tyrosine (Y)-to-histidine (H) change at position 18 of the E2 glycoprotein (E2 Y18H), into the RRV-T48 genetic background was sufficient to generate a virus that caused dramatically less severe musculoskeletal disease in mice. The attenuated phenotype of RRV-T48 E2 Y18H was associated with reduced viral loads in musculoskeletal tissues, reduced viremia, and less efficient virus spread. Consistent with these findings, RRV-T48 E2 Y18H replicated less well in mammalian cells
in vitro
due to significantly reduced PFU released per infected cell. In contrast, RRV-T48 E2 Y18H replicated more efficiently than RRV-T48 in C6/36 mosquito cells. Competition studies confirmed that RRV-T48 E2 Y18H had a fitness advantage in mosquito cells and a fitness disadvantage in mammalian cells. Interestingly, all sequenced Ross River viruses encode either a tyrosine or a histidine at E2 position 18, and this holds true for other alphaviruses in the Semliki Forest antigenic complex. Taken together, these findings suggest that a tyrosine-to-histidine switch at E2 position 18 functions as a regulator of RRV fitness in vertebrate and invertebrate cells.
Categorising sports injuries in epidemiological studies: the subsequent injury categorisation (SIC) model to address multiple, recurrent and exacerbation of injuries
Authors: Finch Caroline F , Cook Jill 
Published: March 2013

ObjectiveSports injuries are often recurrent and there is wide recognition that a subsequent injury (of either the same or a different type) can be strongly influenced by a previous injury. Correctly categorising subsequent injuries (multiple, recurrent, exacerbation or new) requires substantial clinical expertise, but there is also considerable value in combining this expertise with more objective statistical criteria. This paper presents a new model, the subsequent injury categorisation (SIC) model, for categorising subsequent sports injuries that takes into account the need to include both acute and overuse injuries and ten different dependency structures between injury types.MethodsThe suitability of the SIC model was demonstrated with date ordered sports injury data from a large injury database from community Australian football players over one playing season. A subsequent injury was defined to have occurred in the subset of players with two or more reported injuries.Results282 players sustained 469 subsequent injuries of which 15.6% were coded to categories representing injuries that were directly related to previous index injuries. This demonstrates that players can sustain a number of injuries over one playing season. Many of these will be unrelated to previous injuries but subsequent injuries that are related to previous injury occurrences are not uncommon.ConclusionThe handling of subsequent sports injuries is a substantial challenge for the sports medicine field—both in terms of injury treatment and in epidemiological research to quantify them. Application of the SIC model allows for multiple different injury types and relationships within players, as well as different index injuries.
High ambulatory blood pressure in male professional football players
Authors: Berge Hilde Moseby , Andersen Thor Einar , Solberg Erik E , Steine Kjetil 
Published: March 2013

BackgroundNo data exist on ambulatory blood pressure (ABP) in athletes.ObjectivesTo identify ABP and examine recommended follow-up of high office blood pressure (OBP) in male professional football players and secondary study indicators of sympathetic activity.MethodsPlayers with high OBP (cases) from a previous screening of 594 players (n=28) were matched for age and ethnicity with players with optimal OBP (controls). High ABP was defined as a mean of ≥135/85 mm Hg during daytime and ≥120/75 mm Hg during night-time. The players replied to questions regarding follow-up of high OBP. High night-time ABP and lack of nocturnal dip (≤10% decline in average BP) were taken as indicators of increased sympathetic activity.Results26 cases and 26 controls, mean age 28±4 years, were included. 15 (58%) of the cases had sustained hypertension and 11 (42%) white coat hypertension. Among the controls, 17 (65%) had normotension and 9 (35%) masked hypertension. ABP during night-time was high in 23 (88%) of the cases and in 16 (64%) of the controls, and nocturnal dip was absent in 9 (35%) and 11 (42%), respectively. 10 (38%) of the cases had no follow-up of high OBP.ConclusionsMore than one-third of the players with optimal OBP had masked hypertension during daytime and more than half of all players had high ABP during night-time, which are novel findings in athletes. Together with the reduced nocturnal dip, this might indicate increased sympathetic activity. Follow-up of high OBP after preparticipation screening is random and should be organised.
Survival analysis of HDR brachytherapy versus reoperation versus temozolomide alone: a retrospective cohort analysis of recurrent glioblastoma multiforme
Authors: Archavlis Eleftherios , Tselis Nikolaos , Birn Gerhard , Ulrich Peter , Baltas Dimos , Zamboglou Nikolaos 
Published: March 2013

ObjectivesTumour recurrence of glioblastoma multiforme (GBM) after initial treatment with surgical resection, radiotherapy and chemotherapy is an inevitable phenomenon. This retrospective cohort study compared the efficacy of interstitial high dose rate brachytherapy (HDR-BRT), re-resection and sole dose dense temozolomide chemotherapy (ddTMZ) in the treatment of recurrent glioblastoma after initial surgery and radiochemotherapy.DesignRetropective cohort study.SettingPrimary level of care with two participating centres. The geographical location was central Germany.ParticipantsFrom January 2005 to December 2010, a total of 111 patients developed recurrent GBM after initial surgery and radiotherapy with concomitant temozolomide. The inclusion criteria were as follows: (1) histology-proven diagnosis of primary GBM (WHO grade 4), (2) primary treatment with resection and radiochemotherapy, and (3) tumour recurrence/progression.InterventionsThis study compared retrospectively the efficacy of interstitial HDR-BRT, re-resection and ddTMZ alone in the treatment of recurrent glioblastoma.Primary and secondary outcome measuresMedian survival, progression free survival and complication rate.ResultsMedian survival after salvage therapy of the recurrence was 37, 30 and 26 weeks, respectively. The HDR-BRT group did significantly better than both the reoperation (p<0.05) and the ddTMZ groups (p<0.05). Moderate to severe complications in the HDR-BRT, reoperation and sole chemotherapy groups occurred in 5/50 (10%), 4/36 (11%) and 9/25 (36%) cases, respectively.ConclusionsCT-guided interstitial HDR-BRT attained higher survival benefits in the management of recurrent glioblastoma after initial surgery and radiotherapy with concurrent temozolomide in comparison with the other treatment modalities. The low risk of complications of the HDR-BRT and the fact that it can be delivered percutaneously in local anaesthesia render it a promissing treatment option for selected patients which should be further evaluated.
A cross-sectional study of visual impairment in elderly population in residential care in the South Indian state of Andhra Pradesh: a cross-sectional study
Authors: Marmamula Srinivas , Ravuri Chandra Sekhar L V , Boon Mei Ying , Khanna Rohit C 
Published: March 2013

ObjectiveTo assess the prevalence and major causes of visual impairment (VI) in elderly residents of ‘home for the aged’ institutions in the Prakasam district in India.DesignCross-sectional study.Setting‘Home for the aged’ institutions in the Prakasam district in the South Indian state of Andhra Pradesh.ParticipantsAll 524 residents in the 26 ‘homes for aged’ institutions in the district were enumerated.Primary and secondary outcome measuresPrevalence and causes of VI; visual acuity (VA) was assessed using a Snellen chart at a distance of 6 m. Pinhole VA was assessed if presenting VA was <6/18. Torchlight examination and direct ophthalmoscopy were performed. VI was defined as presenting VA <6/18 in the better eye.ResultsOf the 494 participants examined (response rate 94.3%), 78.1% were women, 72.1% had no formal schooling. The mean age of participants was 70 years (SD ±8.6 years). VI was present in 280/494 individuals (56.9%; 95% CI 52.3 to 61.3). Over 80% of the VI was due to avoidable causes including cataract (57.1%) and uncorrected refractive errors (26.4%). Among 134 individuals who had undergone bilateral cataract surgery, only 78 (58.2%) individuals had presenting VA ≥6/18 and 13/134 (9.7%) participants were blind.ConclusionsThere is high prevalence of VI in the institutionalised elderly population in the Prakasam district in India. A significant proportion of this elderly population with VI can benefit from spectacles and cataract surgery. Strategies are required to provide high-quality services to this population.
Injury among a population based sample of career firefighters in the central USA
Authors: Jahnke Sara A , Poston Walker S Carlos , Haddock Christopher Keith , Jitnarin Nattinee 
Published: March 2013

BackgroundRates of occupational injuries among firefighters are high because of the physically demanding and variable tasks required by their job. While descriptive data about injuries exist, few studies have explored individual risk factors and their relationship to occupational injury.MethodsThe current study presents data from a population-based sample of 462 career firefighters from 11 randomly-selected fire departments in the Missouri Valley region of the USA (Kansas, Missouri, Iowa, North Dakota, South Dakota, Colorado, Wyoming, Nebraska) who participated in a study evaluating risks for negative cardiovascular outcomes and injury. Relationships were examined between injury and demographic characteristics, body composition, fitness, and health behaviours.ResultsParticipants were most likely to be injured during physical exercise and those who reported regular on-duty exercise had a fourfold increase in risk for exercise-related injury compared with those who did not exercise on duty (OR=4.06, 95% CI 1.73 to 12.24). However, those who exercised were half as likely to sustain non-exercise injuries (OR=0.53, 95% CI 0.32 to 0.85).ConclusionsFindings highlight the benefit of physical training for firefighters despite the risk of injury during exercise.
Factors associated with non-participation in one or two follow-up phases in a cohort study of injured adults
Authors: Langley John Desmond , Lilley Rebbecca , Wilson Suzanne , Derrett Sarah , Samaranayaka Ari , Davie Gabrielle , Ameratunga Shanthi N , Wyeth Emma H , Hansen Paul , Hokowhitu Brendan 
Published: March 2013

ObjectiveTo identify factors associated with non-participation at the 12-month and 24-month follow-up phases of a prospective cohort study of injury outcomes.MethodsAssociations between non-participation at follow-up phases and a range of sociodemographic, injury, health, outcome and administrative factors were examined.ResultsAn individual's non-participation at 12 months did not necessarily mean non-participation at 24 months. Sociodemographic factors were the most salient for non-participation, regardless of the number of follow-up phases or specific phase considered.ConclusionsRetention rates in prospective cohort studies of injury outcome may be improved by follow-up of everyone irrespective of previous non-participation, focusing resources to retain men, young adults, indigenous people and those living with people other than family members, and by ensuring that multiple alternative participant contacts are obtained. There is sufficient evidence to be concerned about potential bias given that several of the factors we, and others, have identified as associated with non-participation are also associated with various functional and disability outcomes following injury. This suggests detailed investigations are warranted into the effect non-participation may be having on the estimates for various outcomes.
Historical data decrease complete blood count reflex blood smear review rates without missing patients with acute leukaemia
Authors: Rabizadeh Esther , Pickholtz Itay , Barak Mira , Froom Paul 
Published: March 2013

IntroductionThe availability of historical data decreases the rate of blood smear review rates in outpatients, but we are unaware of studies done at referral centres. In the following study, we determined the effect of historical data on the rates of peripheral blood smears over a 3-month period and then the detection rate of patients with acute leukaemia.MethodsAll results of complete blood counts (CBCs) tested on three ADVIA 120 analyzers at the regional Rabin Medical Centre, Beilinson Campus over a 3-month period were accessed on a computerised laboratory information system. Over a 3-month period, we determined the proportion of total CBC and patients with criteria for a manual differential count and the actual number of peripheral blood smears done. Finally, we determined the proportion of 100 consecutive patients with acute leukaemia detected using our criteria that included limiting reflex testing according to historical data.ResultsOver the 3-month period, there were 34 827 tests done in 12 785 patients. Without historical data, our smear rate would have been 24.5%, but with the availability of historical data, the blood smear review rate was 5.6%. The detection rate for cases of acute leukaemia was 100%.ConclusionsWe conclude that the availability of previous test results significantly reduces the need for blood smear review without missing any patients with acute leukaemia.
Social participation and drug use in a cohort of Brazilian sex workers
Authors: Leslie Hannah Hogan , Ahern Jennifer , Chinaglia Magda , Kerrigan Deanna , Lippman Sheri A 
Published: March 2013

BackgroundStructural interventions focused on community mobilisation to engender an enabling social context have reduced sexual risk behaviours among sex workers. Interventions to date have increased social participation and shown an association between participation and safer sex. Social participation could modify risk for other health behaviours, particularly drug use. We assessed social participation and drug use before and after implementation of a clinical, social and structural intervention with sex workers intended to prevent sexually transmitted infections/HIV infection.MethodsWe followed 420 sex workers participating in theEncontrosintervention in Corumbá, Brazil, between 2003 and 2005. We estimated the association of participation in external social groups with drug use at baseline and follow-up using logistic regression and marginal modelling. Follow-up analyses of preintervention/postintervention change in drug use employed inverse probability weighting to account for censoring and were stratified by exposure to the intervention.ResultsSocial participation showed a protective association with drug use at baseline (1 SD higher level of social participation associated with 3.8% lower prevalence of drug use, 95% CI −0.1 to 8.3). Among individuals exposed toEncontros, higher social participation was associated with an 8.6% lower level of drug use (95% CI 0.1 to 23.3). No significant association was found among the unexposed.ConclusionsA structural intervention that modified sex workers’ social environment, specifically participation in external social groups, was associated with reduced drug use. These findings suggest that sexual risk prevention initiatives that enhance social integration among marginalised populations can produce broad health impacts, including reductions in drug use.
A Phase I Trial of Vorinostat and Alvocidib in Patients with Relapsed, Refractory, or Poor Prognosis Acute Leukemia, or Refractory Anemia with Excess Blasts-2
Authors: Holkova Beata , Supko Jeffrey G. , Ames Matthew M. , Reid Joel M. , Shapiro Geoffrey I. , Perkins Edward Brent , Ramakrishnan Viswanathan , Tombes Mary Beth , Honeycutt Connie , McGovern Renee M. , Kmieciak Maciej , Shrader Ellen , Wellons Martha D. , Sankala Heidi , Doyle Austin , Wright John , Roberts John D. , Grant Steven 
Published: March 2013

Abstract
Purpose: This phase I study was conducted to identify the maximum-tolerated dose (MTD) of alvocidib when combined with vorinostat in patients with relapsed, refractory, or poor prognosis acute leukemia, or refractory anemia with excess blasts-2. Secondary objectives included investigating the pharmacokinetic and pharmacodynamic effects of the combination.
Experimental Design: Patients received vorinostat (200 mg orally, three times a day, for 14 days) on a 21-day cycle, combined with 2 different alvocidib administration schedules: a 1-hour intravenous infusion, daily × 5; or a 30-minute loading infusion followed by a 4-hour maintenance infusion, weekly × 2. The alvocidib dose was escalated using a standard 3+3 design.
Results: Twenty-eight patients were enrolled and treated. The alvocidib MTD was 20 mg/m2 (30-minute loading infusion) followed by 20 mg/m2 (4-hour maintenance infusion) on days one and eight, in combination with vorinostat. The most frequently encountered toxicities were cytopenias, fatigue, hyperglycemia, hypokalemia, hypophosphatemia, and QT prolongation. Dose-limiting toxicities (DLT) were cardiac arrhythmia-atrial fibrillation and QT prolongation. No objective responses were achieved although 13 of 26 evaluable patients exhibited stable disease. Alvocidib seemed to alter vorinostat pharmacokinetics, whereas alvocidib pharmacokinetics were unaffected by vorinostat. Ex vivo exposure of leukemia cells to plasma obtained from patients after alvocidib treatment blocked vorinostat-mediated p21CIP1 induction and downregulated Mcl-1 and p-RNA Pol II for some specimens, although parallel in vivo bone marrow responses were infrequent.
Conclusions: Alvocidib combined with vorinostat is well tolerated. Although disease stabilization occurred in some heavily pretreated patients, objective responses were not obtained with these schedules. Clin Cancer Res; 19(7); 1873–83. ©2013 AACR.
ERK Phosphorylation Is Predictive of Resistance to IGF-1R Inhibition in Small Cell Lung Cancer
Authors: Zinn Rebekah L. , Gardner Eric E. , Marchionni Luigi , Murphy Sara C. , Dobromilskaya Irina , Hann Christine L. , Rudin Charles M. 
Published: March 2013

AbstractNew therapies are critically needed to improve the outcome for patients with small cell lung cancer (SCLC). Insulin-like growth factor 1 receptor (IGF-1R) inhibition is a potential treatment strategy for SCLC: the IGF-1R pathway is commonly upregulated in SCLC and has been associated with inhibition of apoptosis and stimulation of proliferation through downstream signaling pathways, including phosphatidylinositol-3-kinase-Akt and mitogen-activated protein kinase. To evaluate potential determinants of response to IGF-1R inhibition, we assessed the relative sensitivity of 19 SCLC cell lines to OSI-906, a small molecule inhibitor of IGF-1R, and the closely related insulin receptor. Approximately one third of these cell lines were sensitive to OSI-906, with an IC50 &lt; 1 μmol/L. Cell line expression of IGF-1R, IR, IGF-1, IGF-2, IGFBP3, and IGFBP6 did not correlate with sensitivity to OSI-906. Interestingly, OSI-906 sensitive lines expressed significantly lower levels of baseline phospho-ERK relative to resistant lines (P = 0.006). OSI-906 treatment resulted in dose-dependent inhibition of phospho-IGF-1R and phospho-Akt in both sensitive and resistant cell lines, but induced apoptosis and cell-cycle arrest only in sensitive lines. We tested the in vivo efficacy of OSI-906 using an NCI-H187 xenograft model and two SCLC patient xenografts in mice. OSI-906 treatment resulted in 50% tumor growth inhibition in NCI-H187 and 30% inhibition in the primary patient xenograft models compared with mock-treated animals. Taken together our data support IGF-1R inhibition as a viable treatment strategy for a defined subset of SCLC and suggest that low pretreatment levels of phospho-ERK may be indicative of sensitivity to this therapeutic approach. Mol Cancer Ther; 12(6); 1131–9. ©2013 AACR.