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1.
Crystal Structure of Escherichia coli CusC,the Outer Membrane Component of a Heavy Metal Efflux Pump
Background
While copper has essential functions as an enzymatic co-factor, excess copper ions are toxic for cells, necessitating mechanisms for regulating its levels. The cusCBFA operon of E. coli encodes a four-component efflux pump dedicated to the extrusion of Cu(I) and Ag(I) ions.Methodology/Principal Findings
We have solved the X-ray crystal structure of CusC, the outer membrane component of the Cus heavy metal efflux pump, to 2.3 Å resolution. The structure has the largest extracellular opening of any outer membrane factor (OMF) protein and suggests, for the first time, the presence of a tri-acylated N-terminal lipid anchor.Conclusions/Significance
The CusC protein does not have any obvious features that would make it specific for metal ions, suggesting that the narrow substrate specificity of the pump is provided by other components of the pump, most likely by the inner membrane component CusA. 相似文献2.
Objectives
To quantify the proportion of adverse pregnancy outcome attributable to maternal obesity.Design
Cross sectional analysis of routine obstetric dataset.Setting
Guy’s and St Thomas’s NHS Foundation Trust (GSTFT).Population
23,668 women who had singleton deliveries at GSTFT between 2004 and 2008.Methods
Logistic regression was used to estimate the association between BMI and outcome in different ethnic groups. Adjusted odds ratios, and the proportions of obese women, were used to calculate population attributable risk fractions (PAFs).Main Outcome Measures
(i) Maternal outcomes: diabetes, type of delivery, post-partum haemorrhage, and preterm delivery. (ii) Perinatal outcomes: macrosomia, low birth weight, admission to neonatal intensive care/special care baby unit, and perinatal death.Results
The prevalence of maternal obesity was 14%. Increasing BMI was independently associated with increasing risk of adverse obstetric and neonatal outcome. At the individual level, the effect of obesity on diabetes was highest in Asian women compared to white women (p for interaction = 0.03). Calculation of population attributable risk fractions demonstrated that one third of diabetes cases and one in six Caesarean sections could be avoided in this population if all obese women were of normal BMI. At the population level, the contribution of obesity to diabetes was highest for Black women (42%), and lowest for oriental women (8%). Seven percent of neonatal macrosomia in all the population, and 13% in Black mothers, were attributable to obesity.Conclusions
Preventing obesity prior to pregnancy will substantially reduce the burden of obstetric and neonatal morbidity in this population. This reduction will be higher in Black women. 相似文献3.
Background
Despite the high prevalence and major public health ramifications, obstructive sleep apnea syndrome (OSAS) remains underdiagnosed. In many developed countries, because community pharmacists (CP) are easily accessible, they have been developing additional clinical services that integrate the services of and collaborate with other healthcare providers (general practitioners (GPs), nurses, etc.). Alternative strategies for primary care screening programs for OSAS involving the CP are discussed.Objective
To estimate the quality of life, costs, and cost-effectiveness of three screening strategies among patients who are at risk of having moderate to severe OSAS in primary care.Design
Markov decision model.Data Sources
Published data.Target Population
Hypothetical cohort of 50-year-old male patients with symptoms highly evocative of OSAS.Time Horizon
The 5 years after initial evaluation for OSAS.Perspective
Societal.Interventions
Screening strategy with CP (CP-GP collaboration), screening strategy without CP (GP alone) and no screening.Outcomes measures
Quality of life, survival and costs for each screening strategy.Results of base-case analysis
Under almost all modeled conditions, the involvement of CPs in OSAS screening was cost effective. The maximal incremental cost for “screening strategy with CP” was about 455€ per QALY gained.Results of sensitivity analysis
Our results were robust but primarily sensitive to the treatment costs by continuous positive airway pressure, and the costs of untreated OSAS. The probabilistic sensitivity analysis showed that the “screening strategy with CP” was dominant in 80% of cases. It was more effective and less costly in 47% of cases, and within the cost-effective range (maximum incremental cost effectiveness ratio at €6186.67/QALY) in 33% of cases.Conclusions
CP involvement in OSAS screening is a cost-effective strategy. This proposal is consistent with the trend in Europe and the United States to extend the practices and responsibilities of the pharmacist in primary care. 相似文献4.
Background/Objectives
A rare, but life-threatening complication in pancreatitis is a spontaneous bleeding from intestinal vessels with or without previous formation of (pseudo-) aneurysms. And yet, the optimal diagnostic and therapeutic strategies remain unclear.Methods
We performed a retrospective analysis of all patients with pancreatitis and intraabdominal bleeding at a German tertiary referral center between January 2002 and December 2012.Results
Bleeding occurred in <1% (14/3,421) of patients with pancreatitis. Most involved vessels were arteria lienalis, arteria gastroduodenalis, and arteria pancreaticoduodenalis. All bleedings could be stopped by transcatheter arterial coil embolization. Recurrent bleeding after coil embolization occurred in 2/14 (14%) patients.Conclusions
In cases of intraabdominal hemorrhage in patients with pancreatitis, transcatheter arterial coil embolization should be considered as the first interventional procedure. 相似文献5.
Schmidt S Naranjo JR Brenneisen C Gundlach J Schultz C Kaube H Hinterberger T Jeanmonod D 《PloS one》2012,7(3):e31138
Objectives
Several recent studies report the presence of a specific EEG pattern named Thalamocortical Dysrhythmia (TCD) in patients with severe chronic neurogenic pain. This is of major interest since so far no neuroscientific indicator of chronic pain could be identified. We investigated whether a TCD-like pattern could be found in patients with moderate chronic back pain, and we compared patients with neuropathic and non-neuropathic pain components. We furthermore assessed the presence of psychopathology and the degree of psychological functioning and examined whether the strength of the TCD-related EEG markers is correlated with psychological symptoms and pain ratings.Design
Controlled clinical trial with age and sex matched healthy controls.Methods
Spontaneous EEG was recorded in 37 back pain patients and 37 healthy controls.Results
We were not able to observe a statistically significant TCD effect in the EEG data of the whole patient group, but a subsample of patients with evidence for root damage showed a trend in this direction. Pain patients showed markedly increased psychopathology. In addition, patients'' ratings of pain intensity within the last 1 to 12 months showed strong correlations with EEG power, while psychopathology was correlated to the peak frequency.Conclusion
Out of several possible interpretations the most likely conclusion is that only patients with severe pain as well as root lesions with consecutive thalamic deafferentation develop the typical TCD pattern. Our primary method of defining ‘neuropathic pain’ could not reliably determine if such a deafferentation was present. Nevertheless the analysis of a specific subsample as well as correlations between pain ratings, psychopathology and EEG power and peak frequency give some support to the TCD concept.Trial Registration
ClinicalTrials.gov NCT00744575相似文献6.
Ma?gorzata Wierzbicka Mariola Popko Karolina Piskad?o Rafa? Czepczyński Aleksandra Stankowska Tomasz Pi?tka Miros?aw Dziuk Witold Szyfter 《Reports of Practical Oncology and Radiotherapy》2011,16(5):184-188
Background
Posttreatment surveillance for the local and regional recurrence of the head and neck squamous cell carcinoma often requires a multimodality techniques that include PET combined with CT, MRI, US.Aim
The purpose of this study is to compare the diagnostic performance of two imaging techniques (PET/CT and US), and their combined use for the detection of a subclinical regional recurrence in patients after HNSCC treatment.Materials and methods
83 patients after completion of the HNSCC treatment underwent both US and PET/CT on the mean follow-up of 14 months after initial treatment.Results
The sensitivity and specificity of PET/CT were 86% and 82%, respectively; US values reached 81% and 87%, respectively. PPV was 79% for PET/CT, and 83% for US. NPV was 89% for PET/CT, and 85% for US. The overall accuracy for PET/CT and US was 84% for both methods.Conclusion
US could be regarded as complementary to PET/CT as the procedures with highest sensitivity, specificity and NPV for detecting subclinical regional recurrences after HNSCC treatment. 相似文献7.
Vis JC De Bruin-Bon HA Bouma BJ Huisman SA Imschoot L van den Brink K Mulder BJ 《Netherlands heart journal》2012,20(6):264-269
Objective
Physical fitness is reduced in adults with Down syndrome (DS). The present study was conducted to elucidate the exercise response in adults with DS.Design
Case controlled before-after trial.Setting
Residential centre for people with intellectual disabilities.Participants
96 Adults with DS, 25 non-DS adults with an intellectual disability, 33 controls.Interventions
Echocardiography to exclude heart defects and to measure cardiac index (CI) in the supine position, supine position with raised legs, and following ten knee bends.Main outcome measure
Exercise testingResults
At rest, mean CI was not significantly different between persons with DS and controls (2.3 vs. 2.4 l/min/m2, p = 0.3). However, mean CI after exercise was significantly lower in DS (2.9 vs. 3.7 l/min/m2, p < 0.001) and mean CI increase from rest to exercise was more than 50% lower in DS. On the contrary, CI after exercise was similar among controls and non-DS adults with an intellectual disability. Significantly lower stroke volumes in DS were found with insufficient heart rate response.Conclusions
CI at rest was similar in adults with DS and controls; however persons with DS have a diminished cardiac response to exercise. Stroke volumes were significantly lower in DS during exercise and a compensated heightened heart rate was absent. 相似文献8.
Ronan A. Lyons Denise Kendrick Elizabeth M. L. Towner Carol Coupland Mike Hayes Nicola Christie Judith Sleney Sarah Jones Richard Kimberlee Sarah E. Rodgers Samantha Turner Mariana Brussoni Yana Vinogradova Tinnu Sarvotham Steven Macey 《PloS one》2013,8(4)
Objective
To determine whether advocacy targeted at local politicians leads to action to reduce the risk of pedestrian injury in deprived areas.Design
Cluster randomised controlled trial.Setting
239 electoral wards in 57 local authorities in England and Wales.Participants
617 elected local politicians.Interventions
Intervention group politicians were provided with tailored information packs, including maps of casualty sites, numbers injured and a synopsis of effective interventions.Main outcome measures
25–30 months post intervention, primary outcomes included: electoral ward level: percentage of road traffic calmed; proportion with new interventions; school level: percentage with 20 mph zones, Safe Routes to School, pedestrian training or road safety education; politician level: percentage lobbying for safety measures. Secondary outcomes included politicians’ interest and involvement in injury prevention, and facilitators and barriers to implementation.Results
Primary outcomes did not significantly differ: % difference in traffic calming (0.07, 95%CI: −0.07 to 0.20); proportion of schools with 20 mph zones (RR 1.47, 95%CI: 0.93 to 2.32), Safe Routes to School (RR 1.34, 95%CI: 0.83 to 2.17), pedestrian training (RR 1.23, 95%CI: 0.95 to 1.61) or other safety education (RR 1.16, 95%CI: 0.97 to 1.39). Intervention group politicians reported greater interest in child injury prevention (RR 1.09, 95%CI 1.03 to 1.16), belief in potential to help prevent injuries (RR 1.36, 95%CI 1.16 to 1.61), particularly pedestrian safety (RR 1.55, 95%CI 1.19 to 2.03). 63% of intervention politicians reported supporting new pedestrian safety schemes. The majority found the advocacy information surprising, interesting, effectively presented, and could identify suitable local interventions.Conclusions
This study demonstrates the feasibility of an innovative approach to translational public health by targeting local politicians in a randomised controlled trial. The intervention package was positively viewed and raised interest but changes in interventions were not statistically significance. Longer term supported advocacy may be needed.Trial Registration
Current Controlled Trials ISRCTN91381117 相似文献9.
Sietke G. Postema Corry K. van der Sluis Kristina Waldenl?v Liselotte M. Norling Hermansson 《PloS one》2012,7(11)
Objective
To describe upper body structures associated with upper limb reduction deficiency and the development of these structures over time, to examine the presence of physical complaints in this population, and to compare body structures and complaints between groups based on prosthesis use.Design
Prospective cohort study with a follow-up period of 24 years, with matched able-bodied controls.Subjects
Twenty-eight patients with unilateral below-elbow reduction deficiency fitted with myoelectric prostheses, aged 8–18 years at inclusion.Method
Measurements of upper arm, trunk and spine were performed and study-specific questionnaires were answered at baseline and follow-up; the Brief Pain Inventory and the Quick Disability of Arm, Shoulder, and Hand questionnaires were answered at follow-up.Results
Both at baseline and follow-up, within-subjects differences in structures of the arm and trunk were shown in patients but not in controls. Spinal deviations, although small, were greater in patients compared to controls. Self-reported disability was higher in patients compared to controls. Differences in back pain and effect of prostheses use could not be shown.Conclusions
Patients with unilateral below-elbow reduction deficiency have consistent differences in upper body structures. Deviations of the spine, probably of functional origin, do not progress to clinically relevant scoliosis. 相似文献10.
Objective
To evaluate the effectiveness of a school-based intervention involving the families and teachers that aimed to promote healthy eating habits in adolescents; the ultimate aim of the intervention was to reduce the increase in body mass index (BMI) of the students.Design
Paired cluster randomized school-based trial conducted with a sample of fifth graders.Setting
Twenty classes were randomly assigned into either an intervention group or a control group.Participants
From a total of 574 eligible students, 559 students participated in the study (intervention: 10 classes with 277 participants; control: 10 classes with 282 participants). The mean age of students was 11 years.Intervention
Students attended 9 nutritional education sessions during the 2010 academic year. Parents/guardians and teachers received information on the same subjects.Main Outcome Measurement
Changes in BMI and percentage of body fat.Results
Intention-to-treat analysis showed that changes in BMI were not significantly different between the 2 groups (β = 0.003; p = 0.75). There was a major reduction in the consumption of sugar-sweetened beverages and cookies in the intervention group; students in this group also consumed more fruits.Conclusion
Encouraging the adoption of healthy eating habits promoted important changes in the adolescent diet, but this did not lead to a reduction in BMI gain. Strategies based exclusively on the quality of diet may not reduce weight gain among adolescents.Trial Registration
Clinicaltrials.gov . NCT01046474相似文献11.
Gina M. Howell Hernando Gomez Richard D. Collage Patricia Loughran Xianghong Zhang Daniel A. Escobar Timothy R. Billiar Brian S. Zuckerbraun Matthew R. Rosengart 《PloS one》2013,8(7)
Objective
To determine that 1) an age-dependent loss of inducible autophagy underlies the failure to recover from AKI in older, adult animals during endotoxemia, and 2) pharmacologic induction of autophagy, even after established endotoxemia, is of therapeutic utility in facilitating renal recovery in aged mice.Design
Murine model of endotoxemia and cecal ligation and puncture (CLP) induced acute kidney injury (AKI).Setting
Academic research laboratory.Subjects
C57Bl/6 mice of 8 (young) and 45 (adult) weeks of age.Intervention
Lipopolysaccharide (1.5 mg/kg), Temsirolimus (5 mg/kg), AICAR (100 mg/kg). Measurements and Main Results: Herein we report that diminished autophagy underlies the failure to recover renal function in older adult mice utilizing a murine model of LPS-induced AKI. The administration of the mTOR inhibitor temsirolimus, even after established endotoxemia, induced autophagy and protected against the development of AKI.Conclusions
These novel results demonstrate a role for autophagy in the context of LPS-induced AKI and support further investigation into like interventions that have potential to alter the natural history of disease. 相似文献12.
Maria Fiorella Contarino Paul F. C. Groot Johan N. van der Meer Lo J. Bour Johannes D. Speelman Aart J. Nederveen Pepijn van den Munckhof Marina A. J. Tijssen Peter Rick Schuurman Anne-Fleur van Rootselaar 《PloS one》2012,7(10)
Background
Functional MRI combined with electromyography (EMG-fMRI) is a new technique to investigate the functional association of movement to brain activations. Thalamic stereotactic surgery is effective in reducing tremor. However, while some patients have satisfying benefit, others have only partial or temporary relief. This could be due to suboptimal targeting in some cases. By identifying tremor-related areas, EMG-fMRI could provide more insight into the pathophysiology of tremor and be potentially useful in refining surgical targeting.Objective
Aim of the study was to evaluate whether EMG-fMRI could detect blood oxygen level dependent brain activations associated with tremor in patients with Essential Tremor. Second, we explored whether EMG-fMRI could improve the delineation of targets for stereotactic surgery.Methods
Simultaneous EMG-fMRI was performed in six Essential Tremor patients with unilateral thalamotomy. EMG was recorded from the trembling arm (non-operated side) and from the contralateral arm (operated side). Protocols were designed to study brain activations related to voluntary muscle contractions and postural tremor.Results
Analysis with the EMG regressor was able to show the association of voluntary movements with activity in the contralateral motor cortex and supplementary motor area, and ipsilateral cerebellum. The EMG tremor frequency regressor showed an association between tremor and activity in the ipsilateral cerebellum and contralateral thalamus. The activation spot in the thalamus varied across patients and did not correspond to the thalamic nucleus ventralis intermedius.Conclusion
EMG-fMRI is potentially useful in detecting brain activations associated with tremor in patients with Essential Tremor. The technique must be further developed before being useful in supporting targeting for stereotactic surgery. 相似文献13.
14.
Suzue T Hoshikawa Y Nishihara S Fujikawa A Miyatake N Sakano N Yoda T Yoshioka A Hirao T 《PloS one》2012,7(2):e30639
Objective
To evaluate the new Japanese School Absentees Reporting System for Infectious Disease (SARSID) for pandemic influenza A/H1N1 2009 infection in comparison with the National epidemiological Surveillance of Infectious Disease (NESID).Methods
We used data of 53,223 students (97.7%) in Takamatsu city Japan. Data regarding school absentees in SARSID was compared with that in NESID from Oct 13, 2009 to Jan 12, 2010.Results
Similar trends were observed both in SARSID and NESID. However, the epidemic trend for influenza in SARSID was thought to be more sensitive than that in NESID.Conclusion
The epidemic trend for influenza among school-aged children could be easily and rapidly assessed by SARSID compared to NESID. SARSID might be useful for detecting the epidemic trend of influenza. 相似文献15.
Paula Kuivasaari-Pirinen Heli Koivumaa-Honkanen Maritta Hippel?inen Kaisa Raatikainen Seppo Heinonen 《PloS one》2014,9(11)
Objective
To compare life satisfaction between women with successful or unsuccessful outcome after assisted reproductive treatment (ART) by taking into account the time since the last ART.Design
Cohort study.Setting
Tertiary hospital.Patients
A total of 987 consecutive women who had undergone ART during 1996–2007 were invited and altogether 505 women participated in the study.Interventions
A postal enquiry with a life satisfaction scale.Main Outcome Measure
Self-reported life satisfaction in respect to the time since the last ART.Results
In general, women who achieved a live birth after ART had a significantly higher life satisfaction than those who had unsuccessful ART, especially when compared in the first three years. The difference disappeared in the time period of 6–9 years after ART. The unsuccessfully treated women who had a child by some other means before or after the unsuccessful ART had comparable life satisfaction with successfully treated women even earlier.Conclusions
Even if unsuccessful ART outcome is associated with subsequent lower level of life satisfaction, it does not seem to threaten the long-term wellbeing. 相似文献16.
Background
Desmosine and Isodesmosine (D/I) are cross-linking amino acids which are present only in mature elastin. Changes in their concentration in body fluids indicate changes in elastin degradation and can be a reflection of tissue elastase activity. This study was undertaken to determine whether continuous therapy with the long-acting bronchodilator Tiotropium bromide (TTP) could result in reductions in D/I as measured by mass spectrometry in plasma, urine and sputum.Methods
Twelve not currently smoking patients with chronic obstructive pulmonary disease (COPD), never on TTP, were selected for study. Levels of D/I, along with measurements of FVC, FEV1 and FEV1/FVC. were determined before starting TTP daily, and then one and two months after.Results
D/I decreased in plasma (10 of 12 patients), in sputum all (12 of 12), and in the percentage of free D/I in urine (10 of 12). Most patients showed slight increases in FVC and FEV1 percent predicted over two months.Conclusion
The results are consistent with an effect of prolonged bronchodilitation by anti-cholinergic blockade to also result in reduced lung elastin degradation. 相似文献17.
Student-run clinics increasingly serve as primary care providers for patients of lower socioeconomic status, but studies show that quality of care at student-run clinics has room for improvement.
Purpose
To examine change in provision of preventive services in a student-run free clinic after implementation of a student-led QI intervention involving prompting.Method
Review of patient charts pre- and post-intervention, examining adherence to screening guidelines for diabetes, dyslipidemia, HIV, and cervical cancer.Results
Adherence to guidelines among eligible patients increased after intervention in 3 of 4 services examined. Receipt of HIV testing increased from 33% (80/240) to 48% (74/154; p = 0.004), fasting lipid panel increased from 53% (46/86) to 72% (38/53; p = 0.033), and fasting blood glucose increased from 59% (27/46) to 82% (18/22; p = 0.059).Conclusions
This student-run free clinic implemented a student-led QI intervention that increased provision of prevention. Such a model for QI could extend to other student-run clinics nationally. 相似文献18.
Maria Giné-Garriga Carme Martin-Borràs Anna Puig-Ribera Carlos Martín-Cantera Mercè Solà Antonio Cuesta-Vargas 《PloS one》2013,8(6)
Background
Effective promotion of exercise could result in substantial savings in healthcare cost expenses in terms of direct medical costs, such as the number of medical appointments. However, this is hampered by our limited knowledge of how to achieve sustained increases in physical activity.Objectives
To assess the effectiveness of a Primary Health Care (PHC) based physical activity program in reducing the total number of visits to the healthcare center among inactive patients, over a 15-month period.Research Design
Randomized controlled trial.Subjects
Three hundred and sixty-two (n = 362) inactive patients suffering from at least one chronic condition were included. One hundred and eighty-three patients (n = 183; mean (SD); 68.3 (8.8) years; 118 women) were randomly allocated to the physical activity program (IG). One hundred and seventy-nine patients (n = 179; 67.2 (9.1) years; 106 women) were allocated to the control group (CG). The IG went through a three-month standardized physical activity program led by physical activity specialists and linked to community resources.Measures
The total number of medical appointments to the PHC, during twelve months before and after the program, was registered. Self-reported health status (SF-12 version 2) was assessed at baseline (month 0), at the end of the intervention (month 3), and at 12 months follow-up after the end of the intervention (month 15).Results
The IG had a significantly reduced number of visits during the 12 months after the intervention: 14.8 (8.5). The CG remained about the same: 18.2 (11.1) (P = .002).Conclusions
Our findings indicate that a 3-month physical activity program linked to community resources is a short-duration, effective and sustainable intervention in inactive patients to decrease rates of PHC visits.Trial Registration
ClinicalTrials.gov NCT00714831相似文献19.
Ponce J Calvet X Gallach M Ponce M;Esophagitis Study Group of the Asociación Española de Gastroenterología 《PloS one》2011,6(10):e25051
Background
Few data are available on the prevalence of erosive and severe esophagitis in Western countries.Objective
To retrospectively determine the prevalence and the factors predicting erosive esophagitis and severe esophagitis in a large series of endoscopies in Spain.Design
Retrospective observational study. A multivariate analysis was performed to determine variables predicting severe esophagitis.Setting
Databases of 29 Spanish endoscopy units.Patients
Patients submitted to a diagnostic endoscopy during the year 2005.Interventions
Retrospective review of the databases.Main Outcome Measurements
Esophagitis severity (graded according to the Los Angeles classification) and associated endoscopic findings.Results
Esophagitis was observed in 8.7% of the 93,699 endoscopies reviewed. Severe esophagitis (LA grade C or D) accounted for 22.5% of cases of the disease and was found in 1.9% of all endoscopies. Incidences of esophagitis and those of severe esophagitis were 86.2 and 18.7 cases per 100,000 inhabitants per year respectively. Male sex (OR 1.89) and advanced age (OR 4.2 for patients in the fourth age quartile) were the only variables associated with severe esophagitis. Associated peptic ulcer was present in 8.8% of cases.Limitations
Retrospective study, no data on individual proton pump inhibitors use.Conclusions
Severe esophagitis is an infrequent finding in Spain. It occurs predominantly in males and in older individuals. Peptic ulcer disease is frequently associated with erosive esophagitis. 相似文献20.