bluuebunny/crossref_metadata_2025 huggingface dataset:
Congruent Evolution of Fitness and Genetic Robustness in Vesicular Stomatitis Virus
Authors: Novella Isabel S. , Presloid John B. , Beech Cameron , Wilke Claus O.
Published: February 2013

Quasispecies theory is a case of mutation-selection balance for evolution at high mutation rates, such as those observed in RNA viruses. One of the main predictions of this model is the selection for robustness, defined as the ability of an organism to remain phenotypically unchanged in the face of mutation. We have used a collection of vesicular stomatitis virus strains that had been evolving either under positive selection or under random drift. We had previously shown that the former increase in fitness while the latter have overall fitness decreases (I. S. Novella, J. B. Presloid, T. Zhou, S. D. Smith-Tsurkan, B. E. Ebendick-Corpus, R. N. Dutta, K. L. Lust, and C. O. Wilke, J. Virol.
84:
4960–4968, 2010). Here, we determined the robustness of these strains and demonstrated that strains under positive selection not only increase in fitness but also increase in robustness. In contrast, strains under drift not only decreased in fitness but also decreased in robustness. There was a good overall correlation between fitness and robustness. We also tested whether there was a correlation between fitness and thermostability, and we observed that the correlation was imperfect, indicating that the fitness effects of mutations are exerted in part at a level other than changing the resistance of the protein to temperature.
Multiple Independent Emergences of Type 2 Vaccine-Derived Polioviruses during a Large Outbreak in Northern Nigeria
Authors: Burns Cara C. , Shaw Jing , Jorba Jaume , Bukbuk David , Adu Festus , Gumede Nicksy , Pate Muhammed Ali , Abanida Emmanuel Ade , Gasasira Alex , Iber Jane , Chen Qi , Vincent Annelet , Chenoweth Paul , Henderson Elizabeth , Wannemuehler Kathleen , Naeem Asif , Umami Rifqiyah Nur , Nishimura Yorihiro , Shimizu Hiroyuki , Baba Marycelin , Adeniji Adekunle , Williams A. J. , Kilpatrick David R. , Oberste M. Steven , Wassilak Steven G. , Tomori Oyewale , Pallansch Mark A. , Kew Olen
Published: February 2013

Since 2005, a large poliomyelitis outbreak associated with type 2 circulating vaccine-derived poliovirus (cVDPV2) has occurred in northern Nigeria, where immunization coverage with trivalent oral poliovirus vaccine (tOPV) has been low. Phylogenetic analysis of P1/capsid region sequences of isolates from each of the 403 cases reported in 2005 to 2011 resolved the outbreak into 23 independent type 2 vaccine-derived poliovirus (VDPV2) emergences, at least 7 of which established circulating lineage groups. Virus from one emergence (lineage group 2005-8; 361 isolates) was estimated to have circulated for over 6 years. The population of the major cVDPV2 lineage group expanded rapidly in early 2009, fell sharply after two tOPV rounds in mid-2009, and gradually expanded again through 2011. The two major determinants of attenuation of the Sabin 2 oral poliovirus vaccine strain (A
481
in the 5′-untranslated region [5′-UTR] and VP1-Ile
143
) had been replaced in all VDPV2 isolates; most A
481
5′-UTR replacements occurred by recombination with other enteroviruses. cVDPV2 isolates representing different lineage groups had biological properties indistinguishable from those of wild polioviruses, including efficient growth in neuron-derived HEK293 cells, the capacity to cause paralytic disease in both humans and PVR-Tg21 transgenic mice, loss of the temperature-sensitive phenotype, and the capacity for sustained person-to-person transmission. We estimate from the poliomyelitis case count and the paralytic case-to-infection ratio for type 2 wild poliovirus infections that ∼700,000 cVDPV2 infections have occurred during the outbreak. The detection of multiple concurrent cVDPV2 outbreaks in northern Nigeria highlights the risks of cVDPV emergence accompanying tOPV use at low rates of coverage in developing countries.
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

Human 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

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

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

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

A 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.
The use of an extract ofHypericum perforatumandAzadirachta indicain advanced diabetic foot: an unexpected outcome
Authors: Iabichella Maria Letizia
Published: February 2013

This is the first case reporting the results of using an extract ofHypericumflowers (Hypericum perforatum) and neem oil (Azadirachta indica) in foot wounds with exposed bone in a patient with bilateral advanced diabetic ulcers. The effective use of this cheap treatment in patients with diabetic lesions on the feet, if confirmed in a wide controlled study, might allow the caregivers to take care of patients at home.
An unusual and deadly cause for massive haemoptysis
Authors: Naha Kushal , Shetty Ranjan K , Vivek G , Magazine Rahul
Published: February 2013

We report a 47-year-old man with diabetics presenting with massive haemoptysis. Physical examination showed moderate pallor, but was otherwise normal. Evaluation showed normal bleeding and clotting parameters. Aerobic cultures of sputum samples and acid-fast staining were negative. CT showed fusiform aneurysmal dilation of the descending thoracic aorta compressing the left main bronchus with secondary collapse of the left lower and lingular lobes. Massive haemoptysis was attributed to probable erosion of the aneurysm into the left main bronchus. Retrospective questioning failed to elicit pathognomic symptoms of aortic aneurysm including chest pain. While in the hospital, the patient had another bout of massive haemoptysis, requiring endotracheal intubation for airway protection. Chest x-ray revealed homogeneous opacification of the left hemithorax. The patient was treated with antitussives and blood transfusions and referred to a higher centre for endovascular stent grafting of the aneurysm and simultaneous surgical repair of the left main bronchus. Aortic aneurysm is a rare but deadly cause for haemoptysis, as rapid exsanguination can lead to cardiovascular collapse and death.
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

Objective

The 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.

Design

Population-based cohort study.

Setting

Data were obtained from the Regional Hospital Discharge Registry Lazio Region in Central Italy (around 5 million inhabitants) in 2007–2008.

Participants

All 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).

Results

13 651 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).

Conclusions

This 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

Objective

To investigate the determinants of specialty choice among graduating medical students in Spain, a country that entered into a severe, ongoing economic crisis in 2008.

Setting

Since 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.

Design

A nationwide cross-sectional survey conducted online in April 2011.

Participants

We invited all students in their final year before graduation from each of Spain's 27 public and private medical schools to participate.

Main outcome measures

Respondents’ 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.

Results

978 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.

Conclusions

In 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

Objective

To examine accounts of medication use in participants with early rheumatoid arthritis (RA) from symptom onset to early postdiagnosis.

Design

Qualitative study with in-depth, personal interviews.

Participants

37 women and one man, aged 30–70s, with a diagnosis of RA <12 months.

Main outcome measure

Participants’ experiences and feelings of medication use in early RA.

Setting

British Columbia, Canada.

Results

Medications 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.

Conclusions

This 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

Introduction

There 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 analysis

A 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 dissemination

The 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 details

Trial 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 objective

The 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).

Methods

This 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.

Results

A 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).

Conclusions

Intravenous 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

Background

Focussed 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).

Methods

Data 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.

Results

166 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%.

Discussion

This 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.
Using the unmatched count technique to improve base rate estimates of risky driving behaviours among veterans of the wars in Iraq and Afghanistan
Authors: Sheppard Sean C , Earleywine Mitch
Published: February 2013

Background

Few studies have investigated base rate estimates of risky driving behaviours among veterans of the wars in Afghanistan and Iraq despite evidence suggesting such behaviours result in increased death rates. In addition, published estimates of driving behaviours may be subject to a significant response bias via the impact of perceived mental health stigma on honest self-reporting.

Aim

The present study compared the unmatched count technique, a form of randomised response technique used to mitigate biased responding, with traditional anonymous self-report to gain information about base rates of risky driving behaviours among combat veterans.

Methods

Cross-sectional data gathered as part of a study of attitudes and behaviours related to military service provided estimates of target activities. Six facets of risky driving (horn honking, carrying firearms in the vehicle, drinking and driving, screaming at other drivers, following other drivers to complain, and tailgating) were assessed.

Results

In our sample of 1351 combat veterans, the unmatched count technique revealed significantly higher rates relative to traditional anonymous assessment specifically for horn honking in anger (22.1% vs 13.6%), carrying firearms (51.1% vs 32.2%), and drinking and driving (77.8% vs 54.0%). There were no significant differences for the remaining three items.

Conclusions

The high level of morbidity associated with risky driving and motor vehicle crashes is a significant concern in the combat veteran population. These data suggest the presence of a strong response bias associated with endorsing certain risky driving behaviours, potentially leading to serious underestimation of these problem behaviours in standard anonymous questionnaires.
Validation of a parent survey for reporting child injuries
Authors: Curry Allison E , Zonfrillo Mark R , Myers Rachel K , Durbin Dennis R
Published: February 2013

Objective

To evaluate the validity of a parent-reported survey to identify children's moderate and serious injuries in seven specific body regions using medical records as the ‘gold standard’.

Methods

A prospective validation study was conducted in three urban paediatric emergency departments (EDs). 798 parents of 859 children treated for injuries at participating EDs between August 2010 and July 2011 completed either a telephone interview or self-administered paper survey at 2 weeks post-ED visit. Parents were asked to report child injuries to seven body regions: head, face, neck/spine/back, thorax, abdomen, upper extremities and lower extremities. Injury data were abstracted from medical records using a standardised protocol. Body region injury severity levels of none/minor, moderate or serious were assigned to each subject based on the Abbreviated Injury Scale.

Results

The overall sensitivity, reflecting parents’ ability to identify a documented moderate or greater severity injury, was 0.95 (95% CI 0.92 to 0.97). Sensitivities were >0.90 for the face, upper extremity and lower extremity regions; 0.80–0.90 for head, abdomen and neck/back/spine regions; and <0.60 for the thorax region. The overall sensitivity for identification of a serious injury was 0.71 (0.60 to 0.80).

Conclusions

This survey enables parents to accurately identify moderate and greater severity injuries to body regions, though it does not accurately identify serious injuries in most body regions except the extremities. The survey could serve as a screening tool to identify moderate and greater severity injuries in population-based surveillance systems, or as the primary outcome of interest in injury prevention studies.
Base stability of multi-propped excavations in soft clay subjected to hydraulic uplift
Authors: Hong Y. , Ng Charles W.W.
Published: February 2013

Excavations in soft clay underlain with an aquifer may be destabilized by hydraulic uplift. Previous studies on this subject are based mainly on field observations. Dewatering from the aquifer is a common method to improve base stability where ground settlement is not a major concern. Alternatively, piles readily installed as part of the top-down construction method for multi-propped excavation may be considered to provide base stability and minimize ground settlement outside the excavation. This paper presents results from two centrifuge tests that were conducted to simulate multi-propped excavations in-flight (with and without piles) in soft clay destabilized by hydraulic pressure from an underlying sand aquifer. Moreover, coupled three-dimensional finite element analyses were carried out to back-analyse the centrifuge tests. Numerical parametric studies were also conducted to study the influence of pile length on the effectiveness of base stabilization. It is revealed that both for excavations with and without piles, the artesian pressure required to initiate uplift inside the excavation is about 1.2 times the overburden pressure of the clay. By using “anti-uplift” piles inside the excavation, the ultimate hydraulic uplift resistance increases by 16%, while the uplift movement can be reduced by 80%. The presence of piles also increases the passive resistance in front of the wall by 70%, but reduces the mobilized undrained shear strength, cu, of clay by 53%.
A review of factors affecting cave climates for hibernating bats in temperate North America
Authors: Perry Roger W.
Published: February 2013

The fungal pathogen Geomyces destructans, which causes white-nose syndrome in bats, thrives in the cold and moist conditions found in caves where bats hibernate. To aid managers and researchers address this disease, an updated and accessible review of cave hibernacula and cave microclimates is presented. To maximize energy savings and reduce evaporative water loss during winter, most temperate vespertilionid bats in North America select caves with temperatures between 2 and 10 °C, with 60%–100% relative humidity. Generally, the temperature in caves is similar to the mean annual surface temperature (MAST) of a region, which varies by latitude, altitude, and topography. However, MAST for most areas where caves are found in eastern North America is well above 10 °C. Thus, various factors cause cold-air infiltration that reduces temperatures of these caves during winter. These factors include depth of cave, topographic setting, airflow patterns, cave configuration, and water infiltration. Factors affecting humidity, condensation, and evaporation are also addressed. In areas where MAST is above or below the thermal requirements of Geomyces destructans, many caves used by bats as hibernacula may still provide favorable sites for optimal growth of this fungus.
The skull anatomy of
Decuriasuchus quartacolonia
(Pseudosuchia: Suchia: Loricata) from the middle Triassic of Brazil
Authors: De França Marco A. G. , Langer Max C. , Ferigolo Jorge
Published: February 2013

Unlike most rauisuchians, which are known based on partially preserved specimens, fossils attributed to
Decuriasuchus quartacolonia
include a monotaxonomic assemblage composed of nine associated individuals (MCN-PV10.105a–i), three with almost complete skulls (MCN-PV10.105a,c,d), and a partial disarticulated skull (MCN-PV10.004) collected in the Middle Triassic (Ladinian,
Dinodontosaurus
Biozone) beds of the Santa Maria Formation, in south Brazil. Because of its completeness and possible phylogenetic position, as one of the most basal loricatans,
D. quartacolonia
is a key taxon for anatomic, evolutionary and biomechanical studies of rauisuchians. The comparative description of its osteology reveals that the skull and mandible of
D
.
quartacolonia
are very similar to those of cf.
Prestosuchus chiniquensis
and
Saurosuchus galilei
, sharing a drop-shaped subnarial fenestra, a subtriangular antorbital fenestra with an elongated and narrow anterior point, a ‘roman nosed’ nasal, and a posteroventrally oriented ridge on the lateral surface of the ventral ramus of the squamosal. Among the differences are the autapomorphies of
D
.
quartacolonia
: numerous maxillary teeth (17), lateral expansion of the nasal/lacrimal covering the antorbital fenestra dorsally, and squamosal and quadratojugal forming a subtriangular projection that invades the lower temporal fenestra.
CREB, NF-κB, and NADPH oxidase coordinately upregulate indoxyl sulfate-induced angiotensinogen expression in proximal tubular cells
Authors: Shimizu Hidehisa , Saito Shinichi , Higashiyama Yukihiro , Nishijima Fuyuhiko , Niwa Toshimitsu
Published: February 2013

In chronic kidney disease (CKD), indoxyl sulfate, a uremic toxin, accumulates in serum, and the expression of angiotensinogen (AGT) is upregulated in renal proximal tubular cells. The present study aimed to determine the relationship between indoxyl sulfate and the upregulation of AGT expression in proximal tubular cells. Indoxyl sulfate induced expression of AGT in rat renal cortex and in cultured human proximal tubular cells (HK-2). In proximal tubular cells, indoxyl sulfate induced phosphorylation of cAMP response element-binding protein (CREB) on Ser-133, and small interfering RNA (siRNA) specific to CREB inhibited indoxyl sulfate-induced AGT expression. Our previous study demonstrated that indoxyl sulfate activated nuclear factor-κB (NF-κB) through reactive oxygen species (ROS) production. NF-κB inhibitors (pyrrolidine dithiocarbamate and isohelenin), NF-κB p65 siRNA, an antioxidant [ N-acetylcysteine (NAC)], and a nicotinamide adenine dinucleotide phosphate (NADPH) oxidase inhibitor [diphenyleneiodonium (DPI)] suppressed indoxyl sulfate-induced AGT expression. Both NAC and DPI suppressed indoxyl sulfate-induced expression of NF-κB p65 and CREB. CREB siRNA suppressed indoxyl sulfate-induced NF-κB p65 expression, whereas both NF-κB inhibitors and NF-κB p65 siRNA prevented indoxyl sulfate-induced CREB expression. Furthermore, we focused on the expression of NADPH oxidase 4 (NOX4), because indoxyl sulfate induced NOX4 expression in vascular smooth muscle cells and vascular endothelial cells. Indoxyl sulfate induced the expression of NOX4 in proximal tubular cells, which was suppressed by NAC, DPI, NF-κB inhibitors, NF-κB p65 siRNA, and CREB siRNA. Taken together, CREB, NF-κB, and NOX4 coordinately upregulate indoxyl sulfate-induced AGT expression in proximal tubular cells.
Voltage dependence of the Ca2+-activated K+ channel KCa3.1 in human erythroleukemia cells
Authors: Stoneking Colin J. , Shivakumar Oshini , Thomas David Nicholson , Colledge William H. , Mason Michael J.
Published: February 2013

We have isolated a K+-selective, Ca2+-dependent whole cell current and single-channel correlate in the human erythroleukemia (HEL) cell line. The whole cell current was inhibited by the intermediate-conductance KCa3.1 inhibitors clotrimazole, TRAM-34, and charybdotoxin, unaffected by the small-conductance KCa2 family inhibitor apamin and the large-conductance KCa1.1 inhibitors paxilline and iberiotoxin, and augmented by NS309. The single-channel correlate of the whole cell current was blocked by TRAM-34 and clotrimazole, insensitive to paxilline, and augmented by NS309 and had a single-channel conductance in physiological K+ gradients of ∼9 pS. RT-PCR revealed that the KCa3.1 gene, but not the KCa1.1 gene, was expressed in HEL cells. The KCa3.1 current, isolated in HEL cells under whole cell patch-clamp conditions, displayed an activated current component during depolarizing voltage steps from hyperpolarized holding potentials and tail currents upon repolarization, consistent with voltage-dependent modulation. This activated current increased with increasing voltage steps above −40 mV and was sensitive to inhibition by clotrimazole, TRAM-34, and charybdotoxin and insensitive to apamin, paxilline, and iberiotoxin. In single-channel experiments, depolarization resulted in an increase in open channel probability ( Po) of KCa3.1, with no increase in channel number. The voltage modulation of Po was an increasing monotonic function of voltage. In the absence of elevated Ca2+, voltage was ineffective at inducing channel activity in whole cell and single-channel experiments. These data indicate that KCa3.1 in HEL cells displays a unique form of voltage dependence modulating Po.
Fish oil and neurovascular reactivity to mental stress in humans
Authors: Carter Jason R. , Schwartz Christopher E. , Yang Huan , Joyner Michael J.
Published: February 2013

Omega-3 fatty acids found in fish oil have been suggested to protect against cardiovascular disease, yet underlying mechanisms remain unclear. Despite the well-documented link between mental stress and cardiovascular risk, no study has examined neural cardiovascular reactivity to mental stress after fish oil supplementation. We hypothesized that fish oil would blunt the blood pressure, heart rate (HR), and muscle sympathetic nerve activity (MSNA) responsiveness to mental stress and/or augment limb vasodilation associated with mental stress. Blood pressure, HR, MSNA, forearm vascular conductance (FVC), and calf vascular conductance (CVC) responses were recorded during a 5-min mental stress protocol in 67 nonhypertensive subjects before and after 8 wk of fish oil ( n = 34) or placebo supplementation ( n = 33). Fish oil blunted HR reactivity to mental stress (group × condition × time interactions, P = 0.012) but did not alter blood pressure reactivity to mental stress (interactions, P > 0.05). Fish oil blunted total MSNA reactivity to mental stress (interaction, P = 0.039) but did not alter MSNA burst frequency and burst incidence reactivity (interactions, P > 0.05). Finally, fish oil significantly blunted CVC reactivity to mental stress (interaction, P = 0.013) but did not alter FVC reactivity (interaction, P > 0.05). In conclusion, 8 wk of fish oil supplementation significantly attenuated both HR and total MSNA reactivity to mental stress and elicited a paradoxical blunting of calf vascular conductance. These findings support and extend the growing evidence that fish oil may have positive health benefits regarding neural cardiovascular control in humans.
Reversal of mitochondrial proteomic loss in Type 1 diabetic heart with overexpression of phospholipid hydroperoxide glutathione peroxidase
Authors: Baseler Walter A. , Dabkowski Erinne R. , Jagannathan Rajaganapathi , Thapa Dharendra , Nichols Cody E. , Shepherd Danielle L. , Croston Tara L. , Powell Matthew , Razunguzwa Trust T. , Lewis Sara E. , Schnell David M. , Hollander John M.
Published: February 2013

Mitochondrial dysfunction is a contributor to diabetic cardiomyopathy. Previously, we observed proteomic decrements within the inner mitochondrial membrane (IMM) and matrix of diabetic cardiac interfibrillar mitochondria (IFM) correlating with dysfunctional mitochondrial protein import. The goal of this study was to determine whether overexpression of mitochondria phospholipid hydroperoxide glutathione peroxidase 4 (mPHGPx), an antioxidant enzyme capable of scavenging membrane-associated lipid peroxides in the IMM, could reverse proteomic alterations, dysfunctional protein import, and ultimately, mitochondrial dysfunction associated with the diabetic heart. MPHGPx transgenic mice and controls were made diabetic by multiple low-dose streptozotocin injections and examined after 5 wk of hyperglycemia. Five weeks after hyperglycemia onset, in vivo analysis of cardiac contractile function revealed decreased ejection fraction and fractional shortening in diabetic hearts that was reversed with mPHGPx overexpression. MPHGPx overexpression increased electron transport chain function while attenuating hydrogen peroxide production and lipid peroxidation in diabetic mPHGPx IFM. MPHGPx overexpression lessened proteomic loss observed in diabetic IFM. Posttranslational modifications, including oxidations and deamidations, were attenuated in diabetic IFM with mPHGPx overexpression. Mitochondrial protein import dysfunction in diabetic IFM was reversed with mPHGPx overexpression correlating with protein import constituent preservation. Ingenuity Pathway Analyses indicated that oxidative phosphorylation, tricarboxylic acid cycle, and fatty acid oxidation processes most influenced in diabetic IFM were preserved by mPHGPx overexpression. Specific mitochondrial networks preserved included complex I and II, mitochondrial ultrastructure, and mitochondrial protein import. These results indicate that mPHGPx overexpression can preserve the mitochondrial proteome and provide cardioprotective benefits to the diabetic heart.
Asymmetry in the control of cardiac performance by dorsomedial hypothalamus
Authors: Xavier Carlos Henrique , Beig Mirza Irfan , Ianzer Danielle , Fontes Marco Antônio Peliky , Nalivaiko Eugene
Published: February 2013

Dorsomedial hypothalamus (DMH) plays a key role in integrating cardiovascular responses to stress. We have recently reported greater heart rate responses following disinhibition of the right side of the DMH (R-DMH) in anesthetized rats and greater suppression of stress-induced tachycardia following inhibition of the R-DMH in conscious rats [both compared with similar intervention in the left DMH (L-DMH)], suggesting existence of right/left side asymmetry in controlling cardiac chronotropic responses by the DMH. The aim of the present study was to determine whether similar asymmetry is present for controlling cardiac contractility. In anesthetized rats, microinjections of the GABAA antagonist bicuculline methiodide (BMI; 40 pmol/100 nl) into the DMH-evoked increases in heart rate (HR), left ventricular pressure (LVP), myocardial contractility (LVdP/d t), arterial pressure, and respiratory rate. DMH disinhibition also precipitated multiple ventricular and supraventricular ectopic beats. DMH-induced increases in HR, LVP, LVdP/d t, and in the number of ectopic beats dependent on the side of stimulation, with R-DMH provoking larger responses. In contrast, pressor and respiratory responses did not depend on the side of stimulation. Newly described DMH-induced inotropic responses were rate-, preload- and (largely) afterload-independent; they were mediated by sympathetic cardiac pathway, as revealed by their sensitivity to β-adrenergic blockade. We conclude that recruitment of DMH neurons causes sympathetically mediated positive chronotropic and inotropic effects, and that there is an asymmetry, at the level of the DMH, in the potency to elicit these effects, with R-DMH > L-DMH.