bluuebunny/crossref_metadata_2025_split huggingface dataset:
Multidrug Therapy and Evolution of Antibiotic Resistance: When Order Matters
Authors: Perron Gabriel G. , Kryazhimskiy Sergey , Rice Daniel P. , Buckling Angus 
Published: June 2012

ABSTRACT

The evolution of drug resistance among pathogenic bacteria has led public health workers to rely increasingly on multidrug therapy to treat infections. Here, we compare the efficacy of combination therapy (i.e., using two antibiotics simultaneously) and sequential therapy (i.e., switching two antibiotics) in minimizing the evolution of multidrug resistance. Using
in vitro
experiments, we show that the sequential use of two antibiotics against
Pseudomonas aeruginosa
can slow down the evolution of multiple-drug resistance when the two antibiotics are used in a specific order. A simple population dynamics model reveals that using an antibiotic associated with high costs of resistance first minimizes the chance of multidrug resistance evolution during sequential therapy under limited mutation supply rate. As well as presenting a novel approach to multidrug therapy, this work shows that costs of resistance not only influences the persistence of antibiotic-resistant bacteria but also plays an important role in the emergence of resistance.
N-Glycosylation of Haloferax volcanii Flagellins Requires Known Agl Proteins and Is Essential for Biosynthesis of Stable Flagella
Authors: Tripepi Manuela , You Jason , Temel Sevcan , Önder Özlem , Brisson Dustin , Pohlschröder Mechthild 
Published: June 2012

ABSTRACTN-glycosylation, a posttranslational modification required for the accurate folding and stability of many proteins, has been observed in organisms of all domains of life. Although the haloarchaeal S-layer glycoprotein was the first prokaryotic glycoprotein identified, little is known about the glycosylation of other haloarchaeal proteins. We demonstrate here that the glycosylation ofHaloferax volcaniiflagellins requires archaeal glycosylation (Agl) components involved in S-layer glycosylation and that the deletion of anyHfx. volcaniiaglgene impairs its swimming motility to various extents. A comparison of proteins in CsCl density gradient centrifugation fractions from supernatants of wild-typeHfx. volcaniiand deletion mutants lacking the oligosaccharyltransferase AglB suggests that when the Agl glycosylation pathway is disrupted, cells lack stable flagella, which purification studies indicate consist of a major flagellin, FlgA1, and a minor flagellin, FlgA2. Mass spectrometric analyses of FlgA1 confirm that its three predicted N-glycosylation sites are modified with covalently linked pentasaccharides having the same mass as that modifying its S-layer glycoprotein. Finally, the replacement of any of three predicted N-glycosylated asparagines of FlgA1 renders cells nonmotile, providing direct evidence for the first time that the N-glycosylation of archaeal flagellins is critical for motility. These results provide insight into the role that glycosylation plays in the assembly and function ofHfx. volcaniiflagella and demonstrate thatHfx. volcaniiflagellins are excellent reporter proteins for the study of haloarchaeal glycosylation processes.
The MerR-Like Transcriptional Regulator BrlR Contributes to Pseudomonas aeruginosa Biofilm Tolerance
Authors: Liao Julie , Sauer Karin 
Published: June 2012

ABSTRACTBiofilms are composed of surface-attached microbial communities. A hallmark of biofilms is their profound tolerance of antimicrobial agents. While biofilm drug tolerance has been considered to be multifactorial, our findings indicate, instead, that bacteria within biofilms employ a classical regulatory mechanism to resist the action of antimicrobial agents. Here we report that the transcriptional regulator BrlR, a member of the MerR family of multidrug transport activators, plays a role in the high-level drug tolerance of biofilms formed byPseudomonas aeruginosa. Expression ofbrlRwas found to be biofilm specific, withbrlRinactivation not affecting biofilm formation, motility, orpslAexpression but increasingndvBexpression. Inactivation ofbrlRrendered biofilms but not planktonic cells grown to exponential or stationary phase significantly more susceptible to hydrogen peroxide and five different classes of antibiotics by affecting the MICs and the recalcitrance of biofilms to killing by microbicidal antimicrobial agents. In contrast, overexpression ofbrlRrendered both biofilms and planktonic cells more tolerant to the same compounds.brlRexpression in three cystic fibrosis (CF) isolates was elevated regardless of the mode of growth, suggesting a selection for constitutivebrlRexpression uponin vivobiofilm formation associated with chronic infections. Despite increasedbrlRexpression, however, isolate CF1-8 was as susceptible to tobramycin as was a ΔbrlRmutant because of a nonsense mutation inbrlR. Our results indicate for the first time that biofilms employ a specific regulatory mechanism to resist the action of antimicrobial agents in a BrlR-dependent manner which affects MIC and recalcitrance to killing by microbicidal antimicrobial agents.
Effects of Potyvirus Effective Population Size in Inoculated Leaves on Viral Accumulation and the Onset of Symptoms
Authors: Zwart Mark P. , Daròs José-Antonio , Elena Santiago F. 
Published: June 2012

ABSTRACT

Effective population size (

N
e

) is a key parameter for understanding evolutionary processes, but it is generally not considered in epidemiological studies or in studying infections of individual hosts. Whether

N
e

has an effect on the onset of symptoms and viral accumulation in
Tobacco etch virus
(TEV) infection of
Nicotiana tabacum
plants is considered here. Using mixtures of TEV variants carrying fluorescent markers, the dose dependence of

N
e

was confirmed, and the inoculation procedure was found to be the main source of variation in these experiments. Whereas the onset of symptoms was independent of

N
e

, there was less and more variable accumulation at 6 days postinoculation for small

N
e

values (

N
e

< 5). The observed variation in accumulation was not heritable, however, suggesting that this variation was not due to the fixation of deleterious mutations in the small founder populations. On the other hand, virus-induced fluorescence and accumulation in the inoculated leaf were strongly

N
e

dependent. Systemic accumulation was independent of

N
e

, although removal of the inoculated leaf led to a small reduction in systemic accumulation for small

N
e

values. For whole plants,

N
e

-dependent effects on accumulation were no longer observed at 9 days postinoculation. Therefore, the effects of

N
e

on accumulation are due mainly to limited expansion in the inoculated leaf and are transient. In this system,

N
e

-dependent effects will be strongest at low doses and early in infection. We conclude that

N
e

can have implications for epidemiology and infection at the individual host level, beyond determining the rate of mixed-genotype infection.
Effects of Auricular Acupressure Combined with Low-Calorie Diet on the Leptin Hormone in Obese and Overweight Iranian Individuals
Authors: Darbandi Mahsa , Darbandi Sara , Mobarhan Majid Ghayor , Owji Ali Akbar , Zhao Baxiao , Iraji Kambiz , Abdi Hamid , Saberfiroozi Mehdi , Nematy Mohsen , Safarian Mohammad , Parizadeh Mohammad Reza , Abbasi Parisa , Salehmoghadam Masoud , Fardaei Majid , Dabbaghmanesh Mohammad Hossein , Ferns Gordon , Mokarram Pooneh 
Published: June 2012

Background Human leptin is a peptide hormone that is released from white adipocytes. The absence of leptin or its receptor leads to uncontrolled food intake, leading to obesity. In the present work, the effects of auricular acupressure combined with low-calorie diet on the leptin hormone level were investigated. Methods Volunteers (n=86) with body mass indices (BMI) between 25 and 45 kg/m2 were randomised into a case (n=43) or a control (n=43) group. Participants in each group received a low-calorie diet for 6 weeks. The case group was treated with auricular acupressure and the control group received a sham procedure. Plasma leptin levels, body fat mass, body weight and BMI were measured before and after treatment. Results Participants who received auricular acupressure showed significant reductions in their plasma leptin levels (18.57%, p<0.01) as well as in their body fat mass (4%, p<0.05). These changes were not observed in the control group. The reduction in leptin was significantly greater in the acupressure group than the controls. Conclusions Auricular acupressure combined with a low-calorie diet significantly reduced plasma levels of leptin. However, the mechanism of this reduction is not clear.
Influence of Acupuncture on Leptin, Ghrelin, Insulin and Cholecystokinin in Obese Women: A Randomised, Sham-Controlled Preliminary Trial
Authors: Güçel Funda , Bahar Burak , Demirtas Canan , Mit Setenay , Çevik Cemal 
Published: June 2012

Background Obesity is an energy balance problem caused by overeating. Obesity treatment includes diet, exercise, behaviour treatment, pharmacotherapy and surgery; in addition, acupuncture is also an option. Objective To investigate the effect of acupuncture on weight loss and whether a brief acupuncture treatment of 5 weeks can change circulating levels of leptin, ghrelin, insulin and cholecystokinin (CCK) in obese women. Methods 40 women with a body mass index (BMI)>30 kg/m2 were equally randomised to either an acupuncture group or a sham (non-penetrating) acupuncture group and received treatment at LI4, HT7, ST36, ST44 and SP6 bilaterally. Both groups had two sessions of 20 min/week for a total of 10 sessions. Serum insulin, leptin, plasma ghrelin and CCK levels were measured by ELISA. Results Acupuncture treatment decreased insulin and leptin levels and induced weight loss, together with a decrease in BMI compared with sham acupuncture. Furthermore, between-group analyses demonstrated increases in plasma ghrelin and CCK levels in subjects who received acupuncture treatment. Conclusion These findings suggest that acupuncture may help to regulate weight owing to its beneficial effects on hormones such as insulin, leptin, ghrelin and CCK in obese subjects even after a few weeks of treatment.
‘Is he awake?’: dialogues between callers and call handlers about consciousness during emergency calls for suspected acute stroke
Authors: Gibson Josephine M E , Bullock Mike , Ford Gary A , Jones Stephanie P , Leathley Michael J , McAdam Joanna J , Quinn Tom , Watkins Caroline L ,   on behalf of the ESCORTT group
Published: June 2012

BackgroundAltered consciousness is an important symptom of acute stroke but assessment may be challenging when cognitive or language deficits are present. Callers are routinely questioned about conscious level by emergency medical services (EMS) call handlers for any presenting problem.ObjectiveThis study aimed to identify and compare how patients' conscious level was questioned, described and interpreted by callers and call handlers during acute stroke calls.MethodAudio recordings of 643 EMS calls for patients with suspected or confirmed acute stroke, admitted to one hospital in North West England over a 12-month period were retrieved from EMS recordings. Calls from primary care physicians were excluded. The caller's response to two standard questions was coded: ‘Is the patient conscious?’ and ‘Is he/she completely awake?’, and other relevant dialogue. Responses which suggested misinterpretation of terms relating to conscious level, or where the call handler used additional clarifying questions, were analysed in detail.Results109/643 (17%) of the calls had an altered level of consciousness recorded on the ambulance report form. Calls often contained unscripted, protracted dialogue about conscious level. Conscious level was difficult for the caller to determine, miscommunicated, or conflated with breathing difficulties.ConclusionAmbiguities and contradictions in dialogue about conscious level arise during ambulance calls for suspected and confirmed stroke. Further study is needed to identify whether these issues also arise in non-stroke calls, and which terms are best understood by the public in describing conscious level.
Pedestrian crossing location influences injury severity in urban areas
Authors: Rothman Linda , Howard Andrew William , Camden Andi , Macarthur Colin 
Published: June 2012

BackgroundPedestrian incidents represent an increasing proportion of serious injuries resulting from motor vehicle collisions in Canada. However, few studies have examined the effect of pedestrian crossing location in urban areas on injury severity. The objective of this study was to investigate the relationship between pedestrian–motor vehicle collision injury severity and crossing location.MethodsThis study was a population-based analysis of police-reported pedestrian collision data. The study group was pedestrian collisions from 1 January 2000 to 31 December 2009 in Toronto. Main outcome measures were a binary indicator of severe injury, and a four-level categorical variable of injury severity. The exposure variable was crossing at mid-block with no traffic control compared to signalised intersection. Analysis was via binary and multinomial logistic regression models to estimate ORs of injury severity with 95% CIs.ResultsThe analysis included 9575 pedestrian–motor vehicle collisions, of which 7325 occurred at signalised intersections when crossing and 2230 occurred at uncontrolled mid-block locations when crossing without right of way. Uncontrolled mid-block collisions resulted in greater injury severity when controlling for road type. The odds of severe injury were 1.75 (95% CI 1.07 to 2.86) for children, 2.55 (95% CI 2.13 to 3.05) for adults and 1.68 (95% CI 1.23 to 2.28) for older adults. The odds of death at uncontrolled mid-block crossings were 4.97 (95% CI 3.11 to 7.94) in adults and 3.49 (95% CI 2.07 to 5.89) in older adults.ConclusionsCrossing at uncontrolled mid-block locations resulted in greater injury severity compared with crossing at signalised intersections. This has important implications for pedestrian behaviour and traffic environment design and emphasises the need for safe pedestrian crossings on urban roads.
Translating road safety into health outcomes using a quantitative impact assessment model
Authors: Dhondt Stijn , Pirdavani Ali , Macharis Cathy , Bellemans Tom , Putman Koen 
Published: June 2012

IntroductionThe majority of traffic safety policies are limited to preventing mortality. However, non-fatal injuries also impose a significant risk of adverse health. Therefore, both mortality and morbidity outcomes should be included in the evaluation of traffic safety policies. The authors propose a method to evaluate different policy options taking into account both fatalities and serious injuries.MethodsA health impact model was developed and aligned with a transport and road safety model, calculating the health impact of fatalities and seriously injured traffic victims for two transport scenarios in Flanders and Brussels (Belgium): a base scenario and a fuel price increase of 20% as an alternative. Victim counts were expressed as disability adjusted life years, using a combination of police and medical data. Seriously injured victims were assigned an injury, using injury distributions derived from hospital data, to estimate the resulting health impact from each crash. Health impact of fatalities was taken as the remaining life expectancy at the moment of the fatal crash.ResultsThe fuel price scenario resulted in a decrease of health impact due to fatalities of 5.53%–5.85% and 3.37%–3.88% for severe injuries. This decrease was however not equal among all road users.ConclusionsWith this method, the impact of traffic polices can be evaluated on both mortality and morbidity, while taking into account the variability of different injuries following a road crash. This model however still underestimates the impact due to non-fatal injuries.
Transarterial balloon assisted Onyx embolization of pericallosal arteriovenous malformations
Authors: Orozco Ludwig D , Luzardo Gustavo D , Buciuc Razvan F 
Published: June 2012

SummaryPreliminary experience using a balloon assisted technique (BAT) for embolization of arteriovenous malformations (AVM) is reported. Two patients with large pericallosal AVMs were successfully embolized with Onyx under Scepter C balloon catheter flow arrest.Clinical presentationOne patient presented with a large intraventricular hemorrhage and hydrocephalus. The second patient presented with a long history of seizures and a small intracerebral hemorrhage. Both patients demonstrated extensive interhemispheric AVMs with multiple arterial feeders, predominantly from the pericallosal arteries.InterventionA Marathon microcatheter was navigated into the target arterial feeders and a Scepter C occlusion balloon catheter was inflated immediately proximal. Under flow arrest, Onyx was injected via the microcatheter with excellent nidal penetration. In both cases, there was complete angiographic obliteration of the treated component of the AVM.ConclusionsOnyx embolization under balloon catheter flow arrest allows for greater nidal penetration of embolic material and improved reflux control. The technique is limited by the current deliverability of balloon catheters and the potential risk for earlier embolization of dangerous anastomosis.
Gaseous Galaxy Halos
Authors: Putman M.E. , Peek J.E.G. , Joung M.R. 
Published: June 2012

Galactic halo gas traces inflowing star-formation fuel and feedback from a galaxy's disk and is therefore crucial to our understanding of galaxy evolution. In this review, we summarize the multiwavelength observational properties and origin models of Galactic and low-redshift spiral galaxy halo gas. Galactic halos contain multiphase gas flows that are dominated in mass by the ionized component and extend to large radii. The densest, coldest halo gas observed in neutral hydrogen (Hi) is generally closest to the disk (<20 kpc), and absorption line results indicate warm and warm-hot diffuse halo gas is present throughout a galaxy's halo. The hot halo gas detected is not a significant fraction of a galaxy's baryons. The disk-halo interface is where the multiphase flows are integrated into the star-forming disk, and there is evidence for both feedback and fueling at this interface from its temperature and kinematic gradients, and Hi structures. The origin and fate of halo gas are considered in the context of cosmological and idealized local simulations. Accretion along cosmic filaments occurs in both hot (>105.5 K) and cold modes in simulations, with the compressed material close to the disk being the coldest and densest, in agreement with observations. There is evidence in halo gas observations for radiative and mechanical feedback mechanisms, including escaping photons from the disk, supernova-driven winds, and a galactic fountain. Satellite accretion also leaves behind abundant halo gas. This satellite gas interacts with the existing halo medium, and much of this gas will become part of the diffuse halo before it reaches the disk. The accretion rate from cold and warm halo gas is generally below a galaxy disk's star-formation rate, but gas at the disk-halo interface and stellar feedback may be important additional fuel sources.
Stat3 Inhibition Augments the Immunogenicity of B-cell Lymphoma Cells, Leading to Effective Antitumor Immunity
Authors: Cheng Fengdong , Wang Hongwei , Horna Pedro , Wang Zi , Shah Bijal , Sahakian Eva , Woan Karrune V. , Villagra Alejandro , Pinilla-Ibarz Javier , Sebti Said , Smith Mitchell , Tao Jianguo , Sotomayor Eduardo M. 
Published: June 2012

AbstractMantle cell lymphoma (MCL) is an aggressive and incurable subtype of B-cell non–Hodgkin lymphomas. Although patients often respond initially to first-line treatment with chemotherapy plus monoclonal antibodies, relapse and decreased response to further lines of treatment eventually occurs. Harnessing the immune system to elicit its exquisite specificity and long-lasting protection might provide sustained MCL immunity that could potentially eradicate residual malignant cells responsible for disease relapse. Here, we show that genetic or pharmacologic disruption of Stat3 in malignant B cells augments their immunogenicity leading to better activation of antigen-specific CD4+ T cells and restoration of responsiveness of tolerized T cells. In addition, treatment of MCL-bearing mice with a specific Stat3 inhibitor resulted in decreased Stat3 phosphorylation in malignant B cells and anti-lymphoma immunity in vivo. Our findings therefore indicate that Stat3 inhibition may represent a therapeutic strategy to overcome tolerance to tumor antigens and elicit a strong immunity against MCL and other B-cell malignancies. Cancer Res; 72(17); 4440–8. ©2012 AACR.
Antitumor Action of the MET Tyrosine Kinase Inhibitor Crizotinib (PF-02341066) in Gastric Cancer Positive for MET Amplification
Authors: Okamoto Wataru , Okamoto Isamu , Arao Tokuzo , Kuwata Kiyoko , Hatashita Erina , Yamaguchi Haruka , Sakai Kazuko , Yanagihara Kazuyoshi , Nishio Kazuto , Nakagawa Kazuhiko 
Published: June 2012

Abstract
Therapeutic strategies that target the tyrosine kinase MET hold promise for gastric cancer, but the mechanism underlying the antitumor activity of such strategies remains unclear. We examined the antitumor action of the MET tyrosine kinase inhibitor crizotinib (PF-02341066) in gastric cancer cells positive or negative for MET amplification. Inhibition of MET signaling by crizotinib or RNA interference–mediated MET depletion resulted in induction of apoptosis accompanied by inhibition of AKT and extracellular signal–regulated kinase phosphorylation in gastric cancer cells with MET amplification but not in those without it, suggesting that MET signaling is essential for the survival of MET amplification–positive cells. Crizotinib upregulated the expression of BIM, a proapoptotic member of the Bcl-2 family, as well as downregulated that of survivin, X-linked inhibitor of apoptosis protein (XIAP), and c-IAP1, members of the inhibitor of apoptosis protein family, in cells with MET amplification. Forced depletion of BIM inhibited crizotinib-induced apoptosis, suggesting that upregulation of BIM contributes to the proapoptotic effect of crizotinib. Crizotinib also exhibited a marked antitumor effect in gastric cancer xenografts positive for MET amplification, whereas it had little effect on those negative for this genetic change. Crizotinib thus shows a marked antitumor action both in vitro and in vivo specifically in gastric cancer cells positive for MET amplification. Mol Cancer Ther; 11(7); 1557–64. ©2012 AACR.