bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification of Bacillus subtilis SipW as a Bifunctional Signal Peptidase That Controls Surface-Adhered Biofilm Formation
Authors: Terra Rebecca , Stanley-Wall Nicola R. , Cao Guoqiang , Lazazzera Beth A. 
Published: February 2012

ABSTRACT

Biofilms of microbial cells encased in an exopolymeric matrix can form on solid surfaces, but how bacteria sense a solid surface and upregulate biofilm genes is largely unknown. We investigated the role of the
Bacillus subtilis
signal peptidase, SipW, which has a unique role in forming biofilms on a solid surface and is not required at an air-liquid interface. Surprisingly, we found that the signal peptidase activity of SipW was not required for solid-surface biofilms. Furthermore, a SipW mutant protein was constructed that lacks the ability to form a solid-surface biofilm but still retains signal peptidase activity. Through genetic and gene expression tests, the non-signal peptidase role of SipW was found to activate biofilm matrix genes specifically when cells were on a solid surface. These data provide the first evidence that a signal peptidase is bifunctional and that SipW has a regulatory role in addition to its role as a signal peptidase.
Evaluation of a novel nutrition education intervention for medical students from across England
Authors: Ray Sumantra , Udumyan Ruzan , Rajput-Ray Minha , Thompson Ben , Lodge Keri-Michele , Douglas Pauline , Sharma Poonam , Broughton Rachel , Smart Sandra , Wilson Rick , Gillam Stephen , van der Es Mike J , Fisher Ilana , Gandy Joan 
Published: February 2012

ObjectivesProblems such as hospital malnutrition (∼40% prevalence in the UK) may be managed better by improving the nutrition education of ‘tomorrow's doctors’. The Need for Nutrition Education Programme aimed to measure the effectiveness and acceptability of an educational intervention on nutrition for medical students in the clinical phase of their training.DesignAn educational needs analysis was followed by a consultative process to gain consensus on a suitable educational intervention. This was followed by two identical 2-day educational interventions with before and after analyses of Knowledge, Attitudes and Practices (KAP). The 2-day training incorporated six key learning outcomes.SettingTwo constituent colleges of Cambridge University used to deliver the above educational interventions.ParticipantsAn intervention group of 100 clinical medical students from 15 medical schools across England were recruited to attend one of two identical intensive weekend workshops.Primary and secondary outcome measuresThe primary outcome measure consisted of change in KAP scores following intervention using a clinical nutrition questionnaire. Secondary outcome measures included change in KAP scores 3 months after the intervention as well as a student-led semiqualitative evaluation of the educational intervention.ResultsStatistically significant changes in KAP scores were seen immediately after the intervention, and this was sustained for 3 months. Mean differences and 95% CIs after intervention were Knowledge 0.86 (0.43 to 1.28); Attitude 1.68 (1.47 to 1.89); Practice 1.76 (1.11 to 2.40); KAP 4.28 (3.49 to 5.06). Ninety-seven per cent of the participants rated the overall intervention and its delivery as ‘very good to excellent’, reporting that they would recommend this educational intervention to colleagues.ConclusionNeed for Nutrition Education Programme has highlighted the need for curricular innovation in the area of clinical health nutrition in medical schools. This project also demonstrates the effectiveness and acceptability of such a curriculum intervention for ‘tomorrow's doctors’. Doctors, dietitians and nutritionists worked well in an effective interdisciplinary partnership when teaching medical students, providing a good model for further work in a healthcare setting.
Benefits and risks of structuring and/or coding the presenting patient history in the electronic health record: systematic review
Authors: Fernando Bernard , Kalra Dipak , Morrison Zoe , Byrne Emma , Sheikh Aziz 
Published: February 2012

BackgroundPatient histories in electronic health records currently exist mainly in free text format thereby limiting the possibility that decision support technology may contribute to the accuracy and timeliness of clinical diagnoses. Structuring and/or coding make patient histories potentially computable.MethodsA systematic review was undertaken of the benefits and risks of structuring and/or coding patient history by searching nine international databases for published and unpublished studies over the period 1990–2010. The focus was on the current patient history, defined as information reported by a patient or the patient's caregiver about the patient's present health situation and health status. Findings were synthesised through a theoretically based textural analysis.FindingsOf the 9207 potentially eligible papers identified, 10 studies satisfied the eligibility criteria. There was evidence of a modest number of benefits associated with structuring the current patient history, including obtaining more complete clinical histories, improved accuracy of patient self-documented histories, and better associated decision-making by professionals. However, no studies demonstrated any resulting improvements in patient care or outcomes. When more detailed records were obtained through the use of a structured format no attempt was made to confirm if this additional information was clinically useful. No studies investigated possible risks associated with structuring the patient history. No studies examined coding of the patient history.ConclusionsThere is an insufficient evidence base for sound policy making on the benefits and risks of structuring and/or coding patient history. The authors suggest this field of enquiry warrants further investigation given the interest in use of decision support technology to aid diagnoses.
Deliberate self-poisoning: characteristics of patients and impact on the emergency department of a large university hospital
Authors: Hendrix Lotte , Verelst Sandra , Desruelles Didier , Gillet Jean-Bernard 
Published: February 2012

Study objectiveThe epidemiology, management and cost of emergency department (ED) visits for deliberate self-poisoning (DSP) are described.MethodsIn a retrospective study, the medical records of all DSP patients older than 16 years, who presented to the ED from 1 January 2009 to 31 December 2009, were reviewed.Results312 episodes of DSP were included, accounting for 0.6% of all ED visits. 190 patients were women, with a female to male ratio of 1.56:1. Mean patient age was 37 years. More than 60% (n=190) of DSP patients were <40 years of age. Most patients presented to the ED between 18:00 and 23:00. A single drug was ingested in 39% (n=121) of patients. Alcohol was co-ingested by 36% of patients who were mostly middle-aged men. Of the overdoses, 50.8% were due to benzodiazepines, 23.2% were due to antidepressants and 16.4% were due to antipsychotics. Two-thirds of patients were treated with oral activated charcoal and 89% were seen by a psychiatrist. Nearly 90% of patients were admitted to the ED observation ward, with a mean length of stay of 16.7 h. The estimated total cost was €;266 134.89, with an average of €;872.57 per patient.ConclusionSelf-poisoning cases in Belgium are grossly similar to those in other Western countries. Supportive treatment alone should be considered in the majority of patients presenting with oral drug overdose. Overall, DSP leads to a significant financial burden on the community.
Pedestrians' perceptions of walkability and safety in relation to the built environment in Cali, Colombia, 2009–10
Authors: Villaveces Andrés , Nieto Luis Alfonso , Ortega Delia , Ríos José Fernando , Medina John Jairo , Gutiérrez María Isabel , Rodríguez Daniel 
Published: February 2012

ObjectiveTo assess pedestrians' perceptions of the walkability of the urban environment and pedestrian safety in Cali, Colombia.DesignStandardised intercept interviews were conducted of 400 pedestrians walking in 20 randomly selected urban zones to ascertain frequency of walking, and perceptions of safety, the built environment and security. Four focus group meetings were held with community members and students addressing these issues in an open-ended forum. The study analysed quantitative data collected in street interviews and qualitative information from focus groups addressing respondents' views on problems for pedestrians, how the built environment affects walking and ideal walking conditions.ResultsAccess to public transportation was deemed the most positive characteristic of the built environment and 61% of respondents liked walking in the street. When disaggregating street conditions, the majority of pedestrians were dissatisfied with their walking experiences. Pedestrians cited lack of respect for norms, personal safety and built environment characteristics as their main concerns. Among frequent walkers, residents tended to rate their neighbourhoods more negatively compared with non-residents. Through qualitative interviews it became apparent that narrow sidewalks that are frequently obstructed by motor vehicles are a key reason for pedestrian dissatisfaction. A perception of overall insecurity further determines how pedestrians assess or modulate their walking in this city.ConclusionsOverall, walking in Cali was perceived negatively by pedestrians because of built environment characteristics and perceptions of insecurity. Qualitative information used to complement intercept surveys can provide a better way to identify pedestrian-specific transport-related problems.
Telecenter for secure, remote, collaborative child fatality review
Authors: Zonfrillo Mark R , Kumar Mahendra , Fortes Jose A , Winston Flaura K 
Published: February 2012

ObjectivesChild fatality review (CFR) is the systematic, interdisciplinary, multi-agency examination of paediatric deaths. While CFR findings may influence policies and reduce preventable fatalities, limited resources challenge accurate CFR data collection and prevention recommendations. Therefore, using technology to improve efficiency of reviews and access to remote participants could enhance the CFR experience. This project aimed to adapt a previously developed collaborative web-based appliance for remote, secure, collaborative review of crash investigations for use with CFR.MethodsThe user-centred design and evaluation process included: (1) key informant interviews and visits to CFR sessions to determine current practices, (2) an anonymous, qualitative, internet-based survey of 64 Pennsylvania CFR team leaders, (3) redesign and adaptation of the Telecenter appliance based on survey results and team feedback and (4) pilot-testing of the adapted Telecenter application at an actual local CFR.ResultsThe qualitative informant interviews identified facilitators and barriers for adoption of the Telecenter. Facilitators included: team member training, improved communication and collaboration, more efficient reviews, and enhanced preventive efforts. Barriers identified included: concern for confidentiality and security, concern about accepting a novel CFR method, low interest in using technology, cost and maintenance. The survey of CFR team leaders identified themes for improving CFR team functioning including the need for evidence-based prevention resources, increased team training and efficient information gathering. The Telecenter was redesigned and adapted based on the information gathered and was successfully piloted for use with CFR.ConclusionsTelecenter met the design goal to improve information dissemination and identification of fatality prevention strategies for CFR.
Macrophage Imaging Within Human Cerebral Aneurysms Wall Using Ferumoxytol-Enhanced MRI: A Pilot Study
Authors: Hasan David M. , Mahaney Kelly B. , Magnotta Vincent A. , Kung David K. , Lawton Michael T. , Hashimoto Tomoki , Winn H. Richard , Saloner David , Martin Alastair , Gahramanov Seymur , Dósa Edit , Neuwelt Edward , Young William L. 
Published: February 2012

Objective—
Macrophages play a critical role in cerebral aneurysm formation and rupture. The purpose of this study is to demonstrate the feasibility and optimal parameters of imaging macrophages within human cerebral aneurysm wall using ferumoxytol-enhanced MRI.

Methods and Results—
Nineteen unruptured aneurysms in 11 patients were imaged using T2*-GE–MRI sequence. Two protocols were used. Protocol A was an infusion of 2.5 mg/kg of ferumoxytol and imaging at day 0 and 1. Protocol B was an infusion of 5 mg/kg of ferumoxytol and imaging at day 0 and 3. All images were reviewed independently by 2 neuroradiologists to assess for ferumoxytol-associated loss of MRI signal intensity within aneurysm wall. Aneurysm tissue was harvested for histological analysis. Fifty percent (5/10) of aneurysms in protocol A showed ferumoxytol-associated signal changes in aneurysm walls compared to 78% (7/9) of aneurysms in protocol B. Aneurysm tissue harvested from patients infused with ferumoxytol stained positive for both CD68+, demonstrating macrophage infiltration, and Prussian blue, demonstrating uptake of iron particles. Tissue harvested from controls stained positive for CD68 but not Prussian blue.

Conclusion—
Imaging with T2*-GE–MRI at 72 hours postinfusion of 5 mg/kg of ferumoxytol establishes a valid and useful approximation of optimal dose and timing parameters for macrophages imaging within aneurysm wall. Further studies are needed to correlate these imaging findings with risk of intracranial aneurysm rupture.
Intercellular Adhesion Molecule 1 Engagement Modulates Sphingomyelinase and Ceramide, Supporting Uptake of Drug Carriers by the Vascular Endothelium
Authors: Serrano Daniel , Bhowmick Tridib , Chadha Rishi , Garnacho Carmen , Muro Silvia 
Published: February 2012

Objective—

Engagement of intercellular adhesion molecule 1 (ICAM-1) on endothelial cells by ICAM-1-targeted carriers induces cell adhesion molecule–mediated endocytosis, providing intraendothelial delivery of therapeutics. This pathway differs from classical endocytic mechanisms and invokes aspects of endothelial signaling during inflammation. ICAM-1 interacts with Na
+
/H
+
exchanger NHE1 during endocytosis, but it is unclear how this regulates plasmalemma and cytoskeletal changes. We studied such aspects in this work.

Methods and Results—

We used fluorescence and electron microscopy, inhibitors and knockout tools, cell culture, and mouse models. ICAM-1 engagement by anti-ICAM carriers induced sphingomyelin-enriched engulfment structures. Acid sphingomyelinase (ASM), an acidic enzyme that hydrolyzes sphingomyelin into ceramide (involved in plasmalemma deformability and cytoskeletal reorganization), redistributed to ICAM-1-engagement sites at ceramide-enriched areas. This induced actin stress fibers and carrier endocytosis. Inhibiting ASM impaired ceramide enrichment, engulfment structures, cytoskeletal reorganization, and carrier uptake, which was rescued by supplying this enzyme activity exogenously. Interfering with NHE1 rendered similar outcomes, suggesting that Na
+
/H
+
exchange might provide an acidic microenvironment for ASM at the plasmalemma.

Conclusion—
These findings are consistent with the ability of endothelial cells to internalize relatively large ICAM- 1--targeted drug carriers and expand our knowledge on the regulation of the sphingomyelin/ceramide pathway by the vascular endothelium.
Protein Kinase C-Delta Mediates Adventitial Cell Migration Through Regulation of Monocyte Chemoattractant Protein-1 Expression in a Rat Angioplasty Model
Authors: Si Yi , Ren Jun , Wang Pu , Rateri Debra L. , Daugherty Alan , Shi Xu-Dong , Kent K. Craig , Liu Bo 
Published: February 2012

Objective—
The adventitia is increasingly recognized as an important player during the development of intimal hyperplasia. However, the mechanism of adventitial cell recruitment to the subintimal space remains largely undefined. We have shown previously that gene transfer of protein kinase C-delta (PKCδ) increases apoptosis of smooth muscle cells following balloon injury. In the current study, we investigated a potential role of PKCδ in regulating the recruitment of adventitial cells.

Methods and Results—
Conditioned media from PKCδ-overexpressing smooth muscle cells stimulated migration and CCR2 expression of adventitial fibroblasts through a MCP-1 dependent mechanism. Following balloon injury of rat carotid arteries, overexpression of PKCδ in smooth muscle cells significantly increased MCP-1 and CCR2 expression and the number of adventitia-originated cells detected in the neointima. Administration of an anti-MCP–1 antibody markedly diminished the recruitment of adventitial cells. Combined PKCδ overexpression and anti-MCP–1 inhibited intimal hyperplasia more effectively than either approach alone.

Conclusion—
Our data suggest that PKCδ regulates recruitment of adventitial cells to the neointima via a mechanism involving upregulation of the MCP-1/CCR2 signaling axis in injured arteries. Blockage of MCP-1 while enhancing apoptosis may serve as a potential therapeutic strategy to attenuate intimal hyperplasia.
Comparison of Various Niches for Endothelial Progenitor Cell Therapy on Ischemic Myocardial Repair
Authors: Zhang Shaoheng , Zhao Lan , Shen Li , Xu Danling , Huang Bingqing , Wang Qibing , Lin Jinyi , Zou Yunzeng , Ge Junbo 
Published: February 2012

Objective—
Comparative studies are lacking that show the effects of different microenvironments on the activity of engrafted stem cells after myocardial infarction (MI). Here, we analyzed the temporal and spatial variations of angiogenesis, collateralization, and the expression of Akt-related signals after MI to test whether the effects of endothelial progenitor cells (EPCs) were different.

Methods and Results—
After the induction of MI, pigs were selected that did not develop a collateral coronary circulation (R0) or developed a significant collateral coronary circulation (R2). Both sets were allocated randomly to 4 groups: phosphate-buffered saline (intramyocardial injection of phosphate-buffered saline), EPC transplantation, LY294002 (intramyocardial injection of an Akt inhibitor), and EPCs plus LY294002. Infarcted porcine hearts at different time points and under different collateralized conditions exhibited a variety of vascular microenvironments. At 14 days post-MI, angiogenesis and the expression of Akt-mediated angiogenic cytokines predominated in R2 porcine hearts. When grafted into this microenvironment, EPCs induced the greatest effects in impeding the development of heart failure, preserving left ventricular function and dimensions, and inhibiting infarct expansion. LY294002 significantly reduced these effects.

Conclusion—
These findings suggest that the microenvironment that coexists with collateralization and Akt-mediated angiogenesis appears to be more beneficial to cardiac repair induced by EPC therapy than other niches after MI.
Preoperative Serum Brain Natriuretic Peptide and Risk of Acute Kidney Injury After Cardiac Surgery
Authors: Patel Uptal D. , Garg Amit X. , Krumholz Harlan M. , Shlipak Michael G. , Coca Steven G. , Sint Kyaw , Thiessen-Philbrook Heather , Koyner Jay L. , Swaminathan Madhav , Passik Cary S. , Parikh Chirag R. ,   for the Translational Research Investigating Biomarker Endpoints in Acute Kidney Injury (TRIBE-AKI) Consortium
Published: February 2012

Background—
Acute kidney injury (AKI) after cardiac surgery is associated with poor outcomes and is difficult to predict. We conducted a prospective study to evaluate whether preoperative brain natriuretic peptide (BNP) levels predict postoperative AKI among patients undergoing cardiac surgery.

Methods and Results—

The Translational Research Investigating Biomarker Endpoints in Acute Kidney Injury (TRIBE-AKI) study enrolled 1139 adults undergoing cardiac surgery at 6 hospitals from 2007 to 2009 who were selected for high AKI risk. Preoperative BNP was categorized into quintiles. AKI was common with the use of Acute Kidney Injury Network definitions; at least mild AKI was a ≥0.3-mg/dL or 50% rise in creatinine (n=407, 36%), and severe AKI was either a doubling of creatinine or the requirement of acute renal replacement therapy (n=58, 5.1%). In analyses adjusted for preoperative characteristics, preoperative BNP was a strong and independent predictor of mild and severe AKI. Compared with the lowest BNP quintile, the highest quintile had significantly higher risk of at least mild AKI (risk ratio, 1.87; 95% confidence interval, 1.40–2.49) and severe AKI (risk ratio, 3.17; 95% confidence interval, 1.06–9.48). After adjustment for clinical predictors, the addition of BNP improved the area under the curve to predict at least mild AKI (0.67–0.69;
P
=0.02) and severe AKI (0.73–0.75;
P
=0.11). Compared with clinical parameters alone, BNP modestly improved risk prediction of AKI cases into lower and higher risk (continuous net reclassification index; at least mild AKI: risk ratio, 0.183; 95% confidence interval, 0.061–0.314; severe AKI: risk ratio, 0.231; 95% confidence interval, 0.067–0.506).

Conclusions—
Preoperative BNP level is associated with postoperative AKI in high-risk patients undergoing cardiac surgery. If confirmed in other types of patients and surgeries, preoperative BNP may be a valuable component of future efforts to improve preoperative risk stratification and discrimination among surgical candidates.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT00774137.
Renal Sympathetic Denervation Suppresses De Novo Podocyte Injury and Albuminuria in Rats With Aortic Regurgitation
Authors: Rafiq Kazi , Noma Takahisa , Fujisawa Yoshihide , Ishihara Yasuhiro , Arai Yoshie , Nabi A.H.M. Nurun , Suzuki Fumiaki , Nagai Yukiko , Nakano Daisuke , Hitomi Hirofumi , Kitada Kento , Urushihara Maki , Kobori Hiroyuki , Kohno Masakazu , Nishiyama Akira 
Published: February 2012

Background—
The presence of chronic kidney disease is a significant independent risk factor for poor prognosis in patients with chronic heart failure. However, the mechanisms and mediators underlying this interaction are poorly understood. In this study, we tested our hypothesis that chronic cardiac volume overload leads to de novo renal dysfunction by coactivating the sympathetic nervous system and renin-angiotensin system in the kidney. We also examined the therapeutic potential of renal denervation and renin-angiotensin system inhibition to suppress renal injury in chronic heart failure.

Methods and Results—
Sprague-Dawley rats underwent aortic regurgitation and were treated for 6 months with vehicle, olmesartan (an angiotensin II receptor blocker), or hydralazine. At 6 months, albuminuria and glomerular podocyte injury were significantly increased in aortic regurgitation rats. These changes were associated with increased urinary angiotensinogen excretion, kidney angiotensin II and norepinephrine (NE) levels, and enhanced angiotensinogen and angiotensin type 1a receptor gene expression and oxidative stress in renal cortical tissues. Aortic regurgitation rats with renal denervation had decreased albuminuria and glomerular podocyte injury, which were associated with reduced kidney NE, angiotensinogen, angiotensin II, and oxidative stress. Renal denervation combined with olmesartan prevented podocyte injury and albuminuria induced by aortic regurgitation.

Conclusions—
In this chronic cardiac volume-overload animal model, activation of the sympathetic nervous system augments kidney renin-angiotensin system and oxidative stress, which act as crucial cardiorenal mediators. Renal denervation and olmesartan prevent the onset and progression of renal injury, providing new insight into the treatment of cardiorenal syndrome.