bluuebunny/crossref_metadata_2025_split huggingface dataset:
Systemic and Local Infection Routes Govern Different Cellular Dissemination Pathways during Gammaherpesvirus InfectionIn Vivo
Authors: Vidy Aurore , Sacher Torsten , Adler Heiko , Jordan Stefan , Koszinowski Ulrich H. , Ruzsics Zsolt 
Published: February 2013

ABSTRACTHuman gammaherpesviruses cause morbidity and mortality associated with infection and transformation of lymphoid and endothelial cells. Knowledge of cell types involved in virus dissemination from primary virus entry to virus latency is fundamental for the understanding of gammaherpesvirus pathogenesis. However, the inability to directly trace cell types with respect to virus dissemination pathways has prevented definitive conclusions regarding the relative contribution of individual cell types. Here, we describe that the route of infection affects gammaherpesvirus dissemination pathways. We constructed a recombinant murine gammaherpesvirus 68 (MHV-68) variant harboring a cassette which switches fluorescent markers in a Cre-dependent manner. Since the recombinant virus which was constructed on the wild-type background was attenuated, in this study we used an M1-deleted version, which infected mice with normal kinetics. Infection of Cre-transgenic mice with this convertible virus was used to estimate the quantitative contribution of defined cell types to virus productivity and dissemination during the acute phase of MHV-68 infection. In systemic infection, we found splenic vascular endothelial cells (EC) among the first and main cells to produce virus. After local infection, the contribution of EC to splenic virus production did not represent such early kinetics. However, at later time points, B cell-derived viruses dominated splenic productivity independently of systemic or local infection. Systemic versus local infection also governed the cell types involved in loading peritoneal exudate cells, leading to latency in F4/80- and CD11b-positive target cells. Systemic infection supported EC-driven dissemination, whereas local infection supported B cell-driven dissemination.
Identification of Critical Residues in the Hemagglutinin and Neuraminidase of Influenza Virus H1N1pdm for Vaccine Virus Replication in Embryonated Chicken Eggs
Authors: Wang Weijia , Lu Janine , Cotter Christopher R. , Wen Katie , Jin Hong , Chen Zhongying 
Published: February 2013

ABSTRACT
In 2009, we successfully produced a high-yield live attenuated H1N1pdm A/California/7/2009 vaccine (CA/09 LAIV) by substitution of three residues (K119E, A186D, and D222G) in the hemagglutinin (HA) protein. Since then, we have generated and evaluated additional H1N1pdm vaccine candidates from viruses isolated in 2010 and 2011. The 2010 strains with the new HA substitutions near the HA receptor binding site (N125D and D127E or D127E and K209E) grew well in eggs and formed large plaques in Madin-Darby canine kidney (MDCK) cells. Introduction of these acidic amino acids into the HA of CA/09 also improved vaccine virus growth in eggs to a titer comparable to that of CA/09 LAIV. However, the high growth of A/Gilroy/231/2011 (Gil/11) vaccine virus required modification in both the HA and the NA segments. The residue at position 369 of the NA was found to be critical for virus replication in MDCK cells and eggs. These HA and NA residues had minimal impact on viral entry but greatly improved viral release from infected cells. Our data implied that the HA receptor binding and NA receptor cleaving function of the poor-growth H1N1pdm virus was not well balanced for virus replication in host cells. The high-growth vaccine candidates described in this study maintained vaccine virus antigenicity and induced high levels of neutralizing antibodies in immunized ferrets, making them suitable for vaccine production. The identification of the amino acids and their roles in viral replication should greatly help vaccine manufacturers to produce high-yield reassortant vaccine viruses against the future drifted H1N1pdm viruses.
Aggresome Formation by the Adenoviral Protein E1B55K Is Not Conserved among Adenovirus Species and Is Not Required for Efficient Degradation of Nuclear Substrates
Authors: Blanchette Paola , Wimmer Peter , Dallaire Frédéric , Cheng Chi Ying , Branton Philip E. 
Published: February 2013

ABSTRACT
Much of the work on the basic molecular biology of human adenoviruses has been carried out on a very limited number of the more than 60 serotypes, primarily the highly related species C viruses adenovirus type 5 (Ad5) and Ad2 and, to some extent, Ad12 of species A. Until recently, it has been widely assumed that insights obtained with these model viruses were representative of all human adenoviruses. Recent studies on the E3 ubiquitin ligase formed by the viral E1B55K and E4orf6 proteins with a cellular Cullin-based complex indicated that although all species form such a functional complex, significant variations exist in terms of complex composition and the substrates that are degraded. In the present report we conducted a comprehensive analysis of the localization of E1B55K products from representatives of six of the seven adenovirus species in the presence and the absence of the corresponding E4orf6 protein. We found that although in some species E1B55K localized in aggresomes, such was not always the case, suggesting that these structures are not necessary for the efficient degradation of substrates. In addition, differences were evident in the localization of E1B55K, although all forms readily associated with PML. Finally, Ad5 E1B55K was seen to localize in close proximity to Rab11, a marker for the endosomal recycling compartment, and both focused at the microtubule organizing center. These findings suggest that E1B55K from some species may employ the transport system utilized by the membrane recycling pathway to assemble aggresomes and the possibility that this structure might then affect recycling of cell surface components.
Diversity of Virophages in Metagenomic Data Sets
Authors: Zhou Jinglie , Zhang Weijia , Yan Shuling , Xiao Jinzhou , Zhang Yuanyuan , Li Bailin , Pan Yingjie , Wang Yongjie 
Published: February 2013

ABSTRACT
Virophages, e.g., Sputnik, Mavirus, and Organic Lake virophage (OLV), are unusual parasites of giant double-stranded DNA (dsDNA) viruses, yet little is known about their diversity. Here, we describe the global distribution, abundance, and genetic diversity of virophages based on analyzing and mapping comprehensive metagenomic databases. The results reveal a distinct abundance and worldwide distribution of virophages, involving almost all geographical zones and a variety of unique environments. These environments ranged from deep ocean to inland, iced to hydrothermal lakes, and human gut- to animal-associated habitats. Four complete virophage genomic sequences (Yellowstone Lake virophages [YSLVs]) were obtained, as was one nearly complete sequence (Ace Lake Mavirus [ALM]). The genomes obtained were 27,849 bp long with 26 predicted open reading frames (ORFs) (YSLV1), 23,184 bp with 21 ORFs (YSLV2), 27,050 bp with 23 ORFs (YSLV3), 28,306 bp with 34 ORFs (YSLV4), and 17,767 bp with 22 ORFs (ALM). The homologous counterparts of five genes, including putative FtsK-HerA family DNA packaging ATPase and genes encoding DNA helicase/primase, cysteine protease, major capsid protein (MCP), and minor capsid protein (mCP), were present in all virophages studied thus far. They also shared a conserved gene cluster comprising the two core genes of MCP and mCP. Comparative genomic and phylogenetic analyses showed that YSLVs, having a closer relationship to each other than to the other virophages, were more closely related to OLV than to Sputnik but distantly related to Mavirus and ALM. These findings indicate that virophages appear to be widespread and genetically diverse, with at least 3 major lineages.
Immunogenicity of a Vaccine Regimen Composed of Simian Immunodeficiency Virus DNA, rMVA, and Viral Particles Administered to Female Rhesus Macaques via Four Different Mucosal Routes
Authors: Manrique Mariana , Kozlowski Pamela A. , Cobo-Molinos Antonio , Wang Shainn-Wei , Wilson Robert L. , Montefiori David C. , Carville Angela , Aldovini Anna 
Published: February 2013

ABSTRACTA comparative evaluation of the immunity stimulated with a vaccine regimen that includes simian immunodeficiency virus (SIV), interleukin 2 (IL-2), and IL-15 DNAs, recombinant modified vaccinia virus Ankara (rMVA), and inactivated SIVmac239 particles administered into the oral and nasal cavities, small intestine, and vagina was carried out in female rhesus macaques to determine the best route to induce diverse anti-SIV immunity that may be critical to protection from SIV infection and disease. All four immunizations generated mucosal SIV-specific IgA. Oral immunization was as effective as vaginal immunization in inducing SIV-specific IgA in vaginal secretions and generated greater IgA responses in rectal secretions and saliva samples compared to the other immunization routes. All four immunizations stimulated systemic T-cell responses against Gag and Env, albeit to a different extent, with oral immunization providing greater magnitude and nasal immunization providing wider functional heterogeneity. SIV-specific T cells producing gamma interferon (IFN-γ) dominated these responses. Limited levels of SIV-specific IgG antibodies were detected in plasma samples, and no SIV-specific IgG antibodies were detected in secretions. Vaccination also induced CD4+and CD8+T-cell responses in the rectal and vaginal mucosa with greater functional heterogeneity than in blood samples. Rectal T-cell responses were significantly greater in the orally vaccinated animals than in the other animals. The most balanced, diverse, and higher-magnitude vaginal T-cell responses were observed after intestinal vaccination. Significantly higher CD8+granzyme B-positive T-cell responses were observed systemically after intestinal vaccination and in rectal cells after oral immunization. The majority of SIV-specific T cells that produced granzyme B did not produce cytokines. Of the immunization routes tested, oral vaccination provided the most diverse and significant response to the vaccine.
Thirty-day complications after laparoscopic or open cholecystectomy: a population-based cohort study in Italy
Authors: Agabiti Nera , Stafoggia Massimo , Davoli Marina , Fusco Danilo , Barone Anna Patrizia , Perucci Carlo Alberto 
Published: February 2013

ObjectiveThe objective of the study is to evaluate short-term complications after laparoscopic (LC) or open cholecystectomy (OC) in patients with gallstones by using linked hospital discharge data.DesignPopulation-based cohort study.SettingData were obtained from the Regional Hospital Discharge Registry Lazio Region in Central Italy (around 5 million inhabitants) in 2007–2008.ParticipantsAll patients admitted to hospitals of Lazio with symptomatic gallstones (International Classification of disease, 9th Revision, Clinical Modification (ICD-9-CM)=574) who underwent LC (ICD-9-CM 51.23) or OC (ICD-9-CM 51.22).Outcome measures(1)‘30-day surgical-related complications’ defined as any complication of the biliary tract (including postoperative infection, haemorrhage or haematoma or seroma complicating a procedure, persistent postoperative fistula, perforation of bile duct and disruption of wound). (2) ‘30-day systemic complications’ defined as any complications of other organs (including sepsis, infections from other organs, major cardiovascular events and selected adverse events).Results13 651 patients were included; 86.1% had LC, 13.9% OC. 2.0% experienced surgical-related complications (SRC), 2.1% systemic complications (SC). The OR of complications after LC versus OC was 0.60 (p<0.001) for SRC and 0.52 (p<0.001) for SC. In relation to SRC, the advantage of LC was consistent across age categories, severity of gallstones and previous upper abdominal surgery, whereas there was no advantage among people with emergency admission (OR=0.94, p=0.764). For SC, no significant advantage of LC was seen among very old people (OR=0.99, p=0.975) and among those with previous upper abdominal surgery (OR=0.86, p=0.905).ConclusionsThis large observational study confirms that LC is more effective than OC with respect to 30-day complications. Population-based linkage of administrative datasets can enlarge evidence of treatment benefits in clinical practice.
Specialty choice in times of economic crisis: a cross-sectional survey of Spanish medical students
Authors: Harris Jeffrey E , González López-Valcárcel Beatriz , Ortún Vicente , Barber Patricia 
Published: February 2013

ObjectiveTo investigate the determinants of specialty choice among graduating medical students in Spain, a country that entered into a severe, ongoing economic crisis in 2008.SettingSince 2008, the percentage of Spanish medical school graduates electing Family and Community Medicine (FCM) has experienced a reversal after more than a decade of decline.DesignA nationwide cross-sectional survey conducted online in April 2011.ParticipantsWe invited all students in their final year before graduation from each of Spain's 27 public and private medical schools to participate.Main outcome measuresRespondents’ preferred specialty in relation to their perceptions of: (1) the probability of obtaining employment; (2) lifestyle and work hours; (3) recognition by patients; (4) prestige among colleagues; (5) opportunity for professional development; (6) annual remuneration and (7) the proportion of the physician's compensation from private practice.Results978 medical students (25% of the nationwide population of students in their final year) participated. Perceived job availability had the largest impact on specialty preference. Each 10% increment in the probability of obtaining employment increased the odds of preferring a specialty by 33.7% (95% CI 27.2% to 40.5%). Job availability was four times as important as compensation from private practice in determining specialty choice (95% CI 1.7 to 6.8). We observed considerable heterogeneity in the influence of lifestyle and work hours, with students who preferred such specialties as Cardiovascular Surgery and Obstetrics and Gynaecology valuing longer rather than shorter workdays.ConclusionsIn the midst of an ongoing economic crisis, job availability has assumed critical importance as a determinant of specialty preference among Spanish medical students. In view of the shortage of practitioners of FCM, public policies that take advantage of the enhanced perceived job availability of FCM may help steer medical school graduates into this specialty.
A qualitative interview study: patient accounts of medication use in early rheumatoid arthritis from symptom onset to early postdiagnosis
Authors: Townsend Anne , Backman Catherine L , Adam Paul , Li Linda C 
Published: February 2013

ObjectiveTo examine accounts of medication use in participants with early rheumatoid arthritis (RA) from symptom onset to early postdiagnosis.DesignQualitative study with in-depth, personal interviews.Participants37 women and one man, aged 30–70s, with a diagnosis of RA <12 months.Main outcome measureParticipants’ experiences and feelings of medication use in early RA.SettingBritish Columbia, Canada.ResultsMedications were central to how people managed symptoms and disease. Two main themes were identified, showing that optimum medication use was hampered, and how this related to delayed diagnosis and effective care. The first theme, ‘paradox of prediagnosis reliance on over the counter (OTC) medications’, describes how people's self-management with OTC medications was ‘effective’. Participants relied extensively on OTC medications for pain relief and to maintain ‘normal life’. However, as this contributed to delayed medical consultation, diagnosis and effective treatment, OTC medication was also potentially detrimental to disease outcome. The second theme, ‘ambivalence around prescription medications post diagnosis’, describes how adherence was hindered by patient beliefs, priorities and ambivalence towards medications.ConclusionsThis study highlights how people use medications in early RA and contributes to a better understanding of medication use that may transfer to other conditions. Given the drive towards active self-management in healthcare and patients’ ambivalence about using strong medications, an in-depth understanding of how these combined factors impact patient experiences will help healthcare providers to support effective medication practices. The reported extensive reliance on OTC medications may speak to a care gap needing further investigation in the context of health behaviours and outcomes of patient self-management.
A randomised controlled non-inferiority trial of primary care-based facilitated access to an alcohol reduction website (EFAR-FVG): the study protocol
Authors: Struzzo Pierluigi , Scafato Emanuele , McGregor Richard , Della Vedova Roberto , Verbano Lisa , Lygidakis Charilaos , Tersar Costanza , Crapesi Lucia , Tubaro Gianni , Freemantle Nick , Wallace Paul 
Published: February 2013

IntroductionThere is a strong body of evidence demonstrating the effectiveness of brief interventions by primary care professionals for risky drinkers. However, implementation levels remain low because of time constraints and other factors. Facilitated access to an alcohol reduction website offers primary care professionals a time-saving alternative to standard face-to-face intervention, but it is not known whether it is as effective.Methods and analysisA randomised controlled non-inferiority trial for risky drinkers comparing facilitated access to a dedicated website with standard face-to-face brief intervention to be conducted in primary care settings in the Region of Friuli Giulia Venezia, Italy. Adult patients will be given a leaflet inviting them to log on to a website to complete the Alcohol Use Disorders Identification Test (AUDIT-C) alcohol screening questionnaire. Screen positives will be requested to complete an online trial module including consent, baseline assessment and randomisation to either standard intervention by the practitioner or facilitated access to an alcohol reduction website. Follow-up assessment of risky drinking will be undertaken online at 1 month, 3 months and 1 year using the full AUDIT questionnaire. Proportions of risky drinkers in each group will be calculated and non-inferiority assessed against a specified margin of 10%. Assuming a reduction of 30% of risky drinkers receiving standard intervention, 1000 patients will be required to give 90% power to reject the null hypothesis.Ethics and disseminationThe protocol was approved by the Isontina Independent Local Ethics Committee on 14 June 2012. The findings of the trial will be disseminated through peer-reviewed journals, national and international conference presentations and public events involving the local administrations of the towns where the trial participants are resident.Registration detailsTrial registration number NCT: 01638338.
Intravenous paracetamol versus dexketoprofen versus morphine in acute mechanical low back pain in the emergency department: a randomised double-blind controlled trial
Authors: Eken Cenker , Serinken Mustafa , Elicabuk Hayri , Uyanik Emrah , Erdal Muhammed 
Published: February 2013

Study objectiveThe objective of this study was to determine the analgesic efficacy and safety of intravenous, single-dose paracetamol versus dexketoprofen versus morphine in patients presenting with mechanical low back pain (LBP) to the emergency department (ED).MethodsThis randomised double-blind study compared the efficacy of intravenous 1 gm paracetamol, 50 mg dexketoprofen and 0.1 mg/kg morphine in patients with acute mechanical LBP. Visual analogue scale (VAS) was used for pain measurement at baseline, after 15 and after 30 min.ResultsA total of 874 patients were eligible for the study, and 137 of them were included in the final analysis: 46 patients from the paracetamol group, 46 patients in the dexketoprofen group and 45 patients in the morphine group. The mean age of study subjects was 31.5±9.5 years, and 60.6% (n=83) of them were men. The median reduction in VAS score at the 30th minute for the paracetamol group was 65 mm (95% CI 58 to 72), 67 mm (95% CI 60 to 73) for the morphine group and 58 mm (95% CI 50 to 64) for the dexketoprophen group. Although morphine was not superior to paracetamol at 30 min (difference: 3.8±4.9 (95% CI −6 to 14), the difference between morphine and dexketoprofen in reducing pain was 11.2±4.7 (95% CI 2 to 21). At least one adverse effect occurred in 8.7% (n=4) of the cases in the paracetamol group, 15.5% (n=7) of the morphine group, and 8.7% (n=4) of the dexketoprophen group (p=0.482).ConclusionsIntravenous paracetamol, dexketoprofen and morphine are not superior to each other for the treatment of mechanical LBP in ED.
Emergency focussed assessment with sonography in trauma (FAST) and haemodynamic stability
Authors: Smith Zoë A , Wood Darryl 
Published: February 2013

BackgroundFocussed assessment with sonography in trauma (FAST) has assumed a key role in the rapid non-invasive assessment of thoracoabdominal trauma and assists in decreasing disposition time. This study evaluates FAST's efficacy with respect to haemodynamic stability in a South African emergency department (ED).MethodsData were collected prospectively by four emergency medicine doctors trained in emergency ultrasonography. FAST scans were performed by one ED doctor and timings, scan result and disposition were recorded. Patient haemodynamic stability was assessed by the emergency doctor performing the scan; subjectively at the time of scanning and objectively using calculation of the shock index. All scan results were subsequently verified by a second ED doctor in a blinded fashion and by CT scanning or operative intervention when clinically indicated.Results166 FAST scans were conducted of which 36 (21.7%) were positive. Mean age was 30.6 years (SD 12.8). 74.1% of patients sustained blunt traumatic injury. Doctors’ subjective haemodynamic stability assessments had higher specificity, sensitivity and predictive values than shock index alone. Haemodynamic instability and a positive FAST result were significantly related (p=0.004). Sensitivities and specificities of FAST scans for blunt and penetrating trauma were 93.1% and 100%, and 90.0% and 100%, respectively. Corresponding values for pneumothoraces were 84.6% and 100%.DiscussionThis study showed a valuable role for FAST in all traumas, particularly in haemodynamic compromise. As an addition to the physician's repertoire of bedside assessment tools, it improves diagnostic capabilities in comparison with simple haemodynamic assessments alone.