bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Interacting Cra and KdpE Regulators Are Involved in the Expression of Multiple Virulence Factors in Enterohemorrhagic Escherichia coli
Authors: Njoroge Jacqueline W. , Gruber Charley , Sperandio Vanessa 
Published: March 2013

ABSTRACT

The human pathogen enterohemorrhagic
Escherichia coli
(EHEC) O157:H7 codes for two interacting DNA binding proteins, Cra and KdpE, that coregulate expression of the locus of enterocyte effacement (LEE) genes in a metabolite-dependent manner. Cra is a transcription factor that uses fluctuations in the concentration of carbon metabolism intermediates to positively regulate virulence of EHEC. KdpE is a response regulator that activates the transcription of homeostasis genes in response to salt-induced osmolarity and virulence genes in response to changes in metabolite concentrations. Here, we probed the transcriptional profiles of the Δ
cra
, Δ
kdpE
, and Δ
cra
Δ
kdpE
mutant strains and show that Cra and KdpE share several targets besides the LEE, but both Cra and KdpE also have independent targets. Several genes within O-islands (genomic islands present in EHEC but absent from
E. coli
K-12), such as
Z0639
,
Z0640
,
Z3388
,
Z4267
, and
espFu
(encoding an effector necessary for formation of attaching and effacing lesions on epithelial cells), were directly regulated by both Cra and KdpE, while
Z2077
was only regulated by Cra. These studies identified and confirmed new direct targets for Cra and KdpE that included putative virulence factors as well as characterized virulence factors, such as EspFu and EspG. These results map out the role of the two interacting regulators, Cra and KdpE, in EHEC pathogenesis and global gene regulation.
Factors associated with illness in athletes participating in the London 2012 Paralympic Games: a prospective cohort study involving 49 910 athlete-days
Authors: Schwellnus Martin , Derman Wayne , Jordaan Esme , Blauwet Cheri A , Emery Carolyn , Pit-Grosheide Pia , Patino Marques Norma-Angelica , Martinez-Ferrer Oriol , Stomphorst Jaap , Van de Vliet Peter , Webborn Nick , Willick Stuart E 
Published: March 2013

BackgroundThe incidence and factors associated with illness in Paralympic athletes have not been documented.AimTo determine the factors associated with illness in athletes participating in the London 2012 Paralympic Games.MethodsA cohort of 3565 athletes from 160 of the 164 participating countries in the London 2012 Paralympic Games were followed over a 14-day period (precompetition period=3 days, competition period=11 days; 49 910 athlete-days). Daily illness data were obtained from (1) teams with their own medical support who completed a daily illness log (78 teams, 3329 athletes) on a novel web-based system and (2) teams without their own medical support through the local organising committee database (82 teams, 236 athletes). Illness information from all athletes included age, gender, type of sport and the main system affected.Main outcome measurementIncidence rate (IR) of illness (illness per 1000 athlete-days) and factors associated with IR (time period, gender, age and sport).ResultsThe IR of illness was 13.2 (95% CI 12.2 to 14.2). The highest IR of illness was in the respiratory system, followed by the skin, digestive, nervous and genitourinary systems. The IR in the precompetition period was similar to that in the competition period, but the IR was significantly higher in athletics compared with other sports. Age and gender were not independent predictors of illness.ConclusionsIllness is common in Paralympic athletes and the main factor associated with higher IR of illness was the type of sport (athletics).
Psychiatric disorders among women and men in assisted reproductive technology (ART) treatment. The Danish National ART-Couple (DANAC) cohort: protocol for a longitudinal, national register-based cohort study
Authors: Schmidt Lone , Hageman Ida , Hougaard Charlotte Ørsted , Sejbaek Camilla Sandal , Assens Maria , Ebdrup Ninna Hinchely , Pinborg Anja 
Published: March 2013

IntroductionThere are complex causal associations between mental disorders, fertility treatment, fertility treatment outcome and infertility per se. Eating disorders cause endocrine disturbances, anovulation and thereby infertility, and research has shown that infertility as well as unsuccessful assisted reproductive technology (ART) treatment are potential risk factors for developing a depression on a long-term basis. Despite the fact that worldwide more than 400 000 ART treatment cycles are performed every year, the causal associations between mental disorders, use of medication for mental disorders and ART treatment in both sexes have only been sparsely explored.Method and analysisThe main objective of this national register-based cohort study is to assess women's and men's mental health before, during, and after ART treatment in comparison with the mental health in an age-matched population-based cohort of couples with no history of ART treatment. Furthermore, the objective is to study the reproductive outcome of ART treatment among women who have a registered diagnosis of a mental disorder or have used medication for mental disorders prior to ART treatment compared with women in ART treatment without a mental disorder. We will establish the Danish National ART-Couple (DANAC) cohort including all women registered with ART treatment in the Danish in vitro fertilisation Register during 1994–2009 (N=42 915) and their partners. An age-matched population-based comparison cohort of women without ART treatment (n=215 290) and their partners will be established. Data will be cross-linked with data from national registers on psychiatric disorders, medical prescriptions for mental disorders, births, causes of deaths and sociodemographic data. Survival analyses and other statistical analyses will be conducted on the development of mental disorders and use of medication for mental disorders for women and men both prior to and after ART treatment.
Reduction in arterial stiffness and vascular age by naltrexone-induced interruption of opiate agonism: a cohort study
Authors: Reece Albert Stuart , Hulse Gary Kenneth 
Published: March 2013

ObjectiveTo prospectively assess if opiate antagonist treatment or the opiate-free status could reverse opiate-related vasculopathy.DesignLongitudinal Open Observational, Serial ‘N of One’, over 6.5 years under various treatment conditions: opiate dependence, naltrexone and opiate-free.SettingPrimary care, Australia.Participants20 opiate-dependent patients (16 males: 16 cases of buprenorphine 4.11±1.17 mg, two of methadone 57.5±12.5 mg and two of heroin 0.75±0.25 g).InterventionStudies of central arterial stiffness and vascular reference age (RA) were performed longitudinally by SphygmoCor Pulse Wave Analysis (AtCor, Sydney).Primary outcomesPrimary outcome was vascular age and arterial stiffness accrual under different treatment conditions.ResultsThe mean chronological age (CA) was 33.62±2.03 years. The opiate-free condition was associated with a lower apparent vascular age both in itself (males: p=0.0402 and females: p=0.0360) and in interaction with time (males: p=0.0001 and females: p=0.0004), and confirmed with other measures of arterial stiffness. The mean modelled RA was 38.82, 37.73 and 35.05 years in the opiate, naltrexone and opiate-free conditions, respectively. The opiate-free condition was superior to opiate agonism after full multivariate adjustment (p=0.0131), with modelled RA/CA of 1.0173, 0.9563 and 0.8985 (reductions of 6.1% and 11.9%, respectively).ConclusionsData demonstrate that opiate-free status improves vascular age and arterial stiffness in previous chronic opiate users. The role of opiate antagonist treatment in achieving these outcomes requires future clarification and offers hope of novel therapeutic remediation.
TeamGAINS: a tool for structured debriefings for simulation-based team trainings
Authors: Kolbe Michaela , Weiss Mona , Grote Gudela , Knauth Axel , Dambach Micha , Spahn Donat R , Grande Bastian 
Published: March 2013

BackgroundImproving patient safety by training teams to successfully manage emergencies is a major concern in healthcare. Most current trainings use simulation of emergency situations to practice and reflect on relevant clinical and behavioural skills. We developed TeamGAINS, a hybrid, structured debriefing tool for simulation-based team trainings in healthcare that integrates three different debriefing approaches: guided team self-correction, advocacy-inquiry and systemic-constructivist techniques.MethodsTeamGAINS was administered during simulation-based trainings for clinical and behavioural skills for anaesthesia staff. One of the four daily scenarios involved all trainees, whereas the remaining three scenarios each involved only two trainees with the others observing them. Training instructors were senior anaesthesiologists and psychologists. To determine debriefing quality, we used a post-test-only (debriefing quality) and a pre-post-test (psychological safety, leader inclusiveness), no-control-group design. After each debriefing all trainees completed a self-report debriefing quality scale which we developed based on the Debriefing Assessment for Simulation in Healthcare and the Observational Structured Assessment of Debriefing. Perceived psychological safety and leader inclusiveness were measured before trainees’ first (premeasure) and after their last debriefing (postmeasure) at which time trainees’ reactions to the overall training were measured as well.ResultsFour senior anaesthetists, 29 residents and 28 nurses participated in a total of 40 debriefings resulting in 235 evaluations. Utility of debriefings was evaluated as highly positive. Pre-post comparisons revealed that psychological safety and leader inclusiveness significantly increased after the debriefings.ConclusionsThe results indicate that TeamGAINS could provide a useful debriefing tool for training anaesthesia staff on all levels of work experience. By combining state-of-the-art debriefing methods and integrating systemic-constructivist techniques, TeamGAINS has the potential to allow for a surfacing, reflecting on and changing of the dynamics of team interactions. Further research is necessary to systematically compare the effects of TeamGAINS’ components on the debriefing itself and on trainees’ changes in attitudes and behaviours.
Trans-jugular intrahepatic porto-systemic shunt placement for refractory ascites: a ‘real-world’ UK health economic evaluation
Authors: Parker Matthew J , Guha Neil , Stedman Brian , Hacking Nigel , Wright Mark 
Published: March 2013

ObjectiveTo assess the benefit of trans-jugular intrahepatic porto-systemic shunt (TIPS) placement for refractory ascites.DesignA retrospective observational study of all patients undergoing TIPS for refractory ascites in our hospital between 2003 and 2012.SettingSecondary care.PatientsCirrhotic patients with refractory ascites.Main outcome measuresWe examined direct real-world (National Health Service) health related costs in the year before and after the TIPS procedure took place. Data were collected relating to the need for reintervention and hepatic encephalopathy.ResultsData were available for 24 patients who underwent TIPS for refractory ascites (86% of eligible patients). TIPS was technically successful in all cases. Mean number of bed days in the year prior to TIPS was 30.3 and 14.3 in the year following (p=0.005). No patient had ascites at the end of the year after the TIPS with less requirement for paracentesis over the course of the year (p<0.001). Mean reduction in cost was £2759 per patient. TIPS was especially cost-effective in patients requiring between 6 and 12 drains per year with a mean saving of £9204 per patient.ConclusionsTIPS is both a clinically effective and economically advantageous therapeutic option for selected patients with refractory ascites.
Failure to improve door-to-needle time by switching to emergency physician-initiated thrombolysis for ST elevation myocardial infarction
Authors: Loch Alexander , Lwin Tint , Zakaria Idzwan Mohd , Abidin Imran Zainal , Wan Ahmad Wan Azman , Hautmann Oliver 
Published: March 2013

Abstract

Introduction
Achieving target door–needle times for ST elevation myocardial infarction remains challenging. Data on emergency department (ED) doctor-led thrombolysis in developing countries and factors causing delay are limited.

Objectives
To assess the effect on door–needle times by transferring responsibility for thrombolysis to the ED doctors and to identify predictors of prolonged door–needle times.

Methodology
Data on medical on-call team-led thrombolysis at a tertiary Asian hospital were prospectively collected from May 2007 to Aug 2008 (1st study period). In September 2008, ED doctors were empowered to perform thrombolysis. The practice change was accompanied by new guidelines, tick chart implementation, and training sessions. Data were then consecutively collected from September 2008 to May 2009 (2nd study period). Door-to-needle times for the 1st and 2nd study periods were compared. All cases were analysed for factors of delay by multiple logistic regression.

Results
297 patients were thrombolysed, 169 by the medical on-call team during the 1st study period and 128 by the ED doctors during the 2nd study period. Median door–needle times were 54 and 48 min, respectively (p=0.76). Significant delays were predicted by ‘incorrect initial ECG interpretation’ (adjusted OR (aOR) 14.3), ‘inappropriate triage’ (aOR 10.4) and ‘multiple referrals’ (aOR 5.9). No cases of inappropriate thrombolysis were recorded.

Conclusions
Transfer of responsibility for thrombolysis to the ED doctors did not improve door–needle times despite measures introduced to facilitate this change. Key causative factors for this failure were identified.
Restless legs syndrome: pathophysiology and modern management
Authors: Nagandla Kavitha , De Somsubhra 
Published: March 2013

Abstract
Restless legs syndrome (RLS) is a common sensory motor neurological disorder that is characterised by an irresistible urge to move the legs that significantly affects the quality of life of the patient. Prevalence in the general population is 5–25% and it is twice as prevalent in women as in men. RLS is the most common movement disorder in pregnancy with a fourfold increased risk of developing this disorder later in life. The pathophysiology of RLS is centred on dopaminergic dysfunction, reduced central nervous system iron, genetic linkages, or alteration in neurotransmitters such as hypocretins, endorphins levels and immune dysfunction and inflammatory mechanisms. With the emergence of new evidence, there are changes to the previous treatment recommendations for RLS. There is sufficient evidence to conclude that dopamine agonists such as rotigotine transdermal patch, pramipexole, ropinirole, gabapentin enacarbil, pregabalin and gabapentin are effective in the short-term treatment of RLS and rotigotine, followed by gabapentin enacarbil, ropinirole, pramipexole and gabapentin for long-term treatment. Based on expert consensus, the recommendation for daily RLS is dopamine agonists or gabapentin or low-potency opioids. Levodopa is less preferred for treating daily RLS due to its high risk of augmentation. For intermittent RLS, it is levodopa or dopamine agonists or low-potency opioids or benzodiazepines. For refractory RLS, the choice is to change to gabapentin or a different dopamine agonist, addition of a second agent like gabapentin or benzodiazepine to the existing drug or changing to a high-potency opioid or tramadol. Medications with safety record in pregnancy include opioids and antiepileptics such as carbamazepine and gabapentin. There are concerns that patients with RLS are at risk for metabolic deregulation, autonomic dysfunction and cardiovascular morbidity. However, a recent study concluded that RLS is not associated with increased risk of cardiovascular complications.
Noncanonical Regulation of the Hedgehog Mediator GLI1 by c-MYC in Burkitt Lymphoma
Authors: Yoon Joon Won , Gallant Marisa , Lamm Marilyn LG , Iannaccone Stephen , Vieux Karl-Frederic , Proytcheva Maria , Hyjek Elizabeth , Iannaccone Philip , Walterhouse David 
Published: March 2013

Abstract
Although Hedgehog signaling plays a major role in GLI1 transcription, there is now evidence suggesting that other pathways/genes, such as c-MYC, may also regulate GLI1 expression. We initiated studies in Burkitt lymphoma cells, which constitutively express c-MYC due to a chromosomal translocation, to determine whether Hedgehog or c-MYC regulates GLI1 expression. We show that all Burkitt lymphoma cell lines tested express GLI1, PTCH1, and SMO and that five of six Burkitt lymphomas express GLI1. Exposure to Sonic or Indian Hedgehog or cyclopamine (SMO inhibitor) does not modulate GLI1 expression, cell proliferation, or apoptosis in most Burkitt lymphoma cell lines. Sequence analysis of PTCH1, SMO, and SuFu failed to show mutations that might explain the lack of Hedgehog responsiveness, and we did not detect primary cilia, which may contribute to it. We show that c-MYC interacts with the 5′-regulatory region of GLI1, using chromatin immunoprecipitation (ChIP) assay, and E-box–dependent transcriptional activation of GLI1 by c-MYC in NIH3T3 and HeLa cells. The c-MYC small-molecule inhibitor 10058-F4 downregulates GLI1 mRNA and protein and reduces the viability of Burkitt lymphoma cells. Inhibition of GLI1 by GANT61 increases apoptosis and reduces viability of some Burkitt lymphoma cells. Collectively, our data provide evidence that c-MYC directly regulates GLI1 and support an antiapoptotic role for GLI1 in Burkitt lymphoma. Burkitt lymphoma cells do not seem to be Hedgehog responsive. These findings suggest a mechanism for resistance to SMO inhibitors and have implications for using SMO inhibitors to treat human cancers. Mol Cancer Res; 11(6); 604–15. ©2013 AACR.
Right Ventricular Function, Pulmonary Pressure Estimation, and Clinical Outcomes in Cardiac Resynchronization Therapy
Authors: Campbell Patricia , Takeuchi Madoka , Bourgoun Mikhail , Shah Amil , Foster Elyse , Brown Mary W. , Goldenberg Ilan , Huang David T. , McNitt Scott , Hall W. Jackson , Moss Arthur , Pfeffer Marc A. , Solomon Scott D. ,   for the Multicenter Automatic Defibrillator Implantation Trial With Cardiac Resynchronization Therapy (MADIT-CRT) Investigators
Published: March 2013

Background—
Right ventricular function (RVF) is an important determinant of outcome in patients with heart failure, and those with severe RV dysfunction have worse outcome after cardiac resynchronization therapy (CRT). We used data from the Multicenter Automatic Defibrillator Implantation Trial with Cardiac Resynchronization Therapy (MADIT-CRT) Trial to determine whether therapy with CRT is influenced by or affects RV function and to define the relationship between RV function and outcomes.

Methods and Results—

A total of 1820 patients were randomly assigned to CRT plus implantable cardioverter defibrillator or implantable cardioverter defibrillator-only in a 3:2 ratio. We assessed RVF as RV fractional area change by echocardiography at baseline and after 1 year of therapy (n=1511 and 1273, respectively). The median RV fractional area change was 41%, with 10.9% of patients <35% at baseline. Baseline RVF did not modify the treatment effect of CRT on the primary outcome (interaction
P
=0.19). Randomization to CRT-implantable cardioverter defibrillator was associated with a greater improvement in RVF (ΔRV fractional area change 8.1% versus 5.4%;
P
<0.001), and improvement in RVF was related to subsequent outcomes. Every 5-point increase in RV fractional area change was associated with a 22% reduction in event rates (hazard ratio, 0.78; 95% confidence interval, 0.66–0.92;
P
=0.003), although this was not independent of the concurrent improvement in left ventricular function. Baseline tricuspid regurgitant velocity, a measure of pulmonary systolic pressure, was predictive of events in a multivariate analysis (hazard ratio, 1.86; 95% confidence interval, 1.24–2.8;
P
=0.003).

Conclusions—
In this population with mild heart failure symptoms, CRT was associated with improvement in RVF, which improved in parallel with improvement in left ventricular function. Patients with the best RVF at 1 year demonstrated the lowest subsequent event rates.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT01294449.
Armenian Demonology: A Critical Overview
Authors: Asatrian Garnik 
Published: March 2013

The paper is a critical study of the Armenian demonic nomenclature of the ancient and later periods, covering the Classical and Middle Armenian texts and modern dialects, including Western Armenian traditions, which were alive until the first decades of the 20th century among the population of the Armenian provinces of the Ottoman Empire.
The author presents a full list of the Armenian demons of different periods, critically revising the origin of their names and functions on a comparative background.
Obesity and the relationship with positive and negative affect
Authors: Pasco Julie A , Williams Lana J , Jacka Felice N , Brennan Sharon L , Berk Michael 
Published: March 2013

Objective: To examine the cross-sectional association between overweight and obesity and positive and negative affect. Method: Participants included 273 women, aged 29–84 years, who were enrolled in the Geelong Osteoporosis Study (GOS). Weight and height were measured and overweight and obesity determined from body mass index (BMI; kg/m2) according to WHO criteria. Medical history and lifestyle exposures were assessed by questionnaire. Positive and negative affect scores were derived using the validated 20-item Positive and Negative Affect Schedule (PANAS) and categorised into tertiles. Results: A pattern of greater negative affect scores was observed for increasing levels of BMI. Setting normal weight as the referent category, the odds for having a negative affect score in the highest tertile were sequentially increased for women who were overweight (OR = 1.31, 95% CI: 0.72–2.40) and obese (OR = 1.95, 95% CI: 1.02–3.73). The association between obesity and increased negative affect was diminished by adjusting for physical illness (adjusted OR = 1.76, 95% CI: 0.91–3.42). These associations were not substantially influenced by positive affect score or other exposures. No association was detected between BMI categories and positive affect scores. Conclusions: We report data suggesting that obesity is associated with greater negative affect scores, reflecting emotions such as distress, anger, disgust, fear and shame, and that this association is attenuated by physical illness. Further investigations are now warranted to explore possible mechanistic interplay between pathological, neurobiological and psychosocial factors.