bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of Metformin on Metabolic Improvement and Gut Microbiota
Authors: Lee Heetae , Ko GwangPyo 
Published: July 2014

ABSTRACT

Metformin is commonly used as the first line of medication for the treatment of metabolic syndromes, such as obesity and type 2 diabetes (T2D). Recently, metformin-induced changes in the gut microbiota have been reported; however, the relationship between metformin treatment and the gut microbiota remains unclear. In this study, the composition of the gut microbiota was investigated using a mouse model of high-fat-diet (HFD)-induced obesity with and without metformin treatment. As expected, metformin treatment improved markers of metabolic disorders, including serum glucose levels, body weight, and total cholesterol levels. Moreover,
Akkermansia muciniphila
(12.44% ± 5.26%) and
Clostridium cocleatum
(0.10% ± 0.09%) abundances increased significantly after metformin treatment of mice on the HFD. The relative abundance of
A. muciniphila
in the fecal microbiota was also found to increase in brain heart infusion (BHI) medium supplemented with metformin
in vitro
. In addition to the changes in the microbiota associated with metformin treatment, when other influences were controlled for, a total of 18 KEGG metabolic pathways (including those for sphingolipid and fatty acid metabolism) were significantly upregulated in the gut microbiota during metformin treatment of mice on an HFD. Our results demonstrate that the gut microbiota and their metabolic pathways are influenced by metformin treatment.
Carbohydrate Coating Reduces Adhesion of Biofilm-Forming Bacillus subtilis to Gold Surfaces
Authors: Kesel S. , Mader A. , Seeberger P. H. , Lieleg O. , Opitz M. 
Published: July 2014

ABSTRACT

The growth of bacterial biofilms in pipes and food tanks causes severe problems in industry. Biofilms growing on medical implants or catheters are of great concern, as they can cause serious infections and decrease the functionality of the medical device. The prevention of bacterial adhesion—the first step in colonization and biofilm formation—is therefore very important. Current research comprises alterations in surface properties, the prevention of adhesin biosynthesis, inhibition with receptor analogs, or the development of anti-adhesive vaccines. We present a new approach that allows us to study bacterial adhesion with high sensitivity in real-time while testing several different surfaces in parallel. Using the cantilever-array technique we demonstrate that coating of gold surfaces with mono- or disaccharides results in a reduction of the bacterial adhesion of the biofilm-forming bacterium
Bacillus subtilis
NCIB 3610 to these gold surfaces. This reduction in bacterial adhesion is independent of the studied carbohydrate. Using several mutant strains, we investigate the underlying molecular interactions, and our results suggest that adhesion to gold surfaces is mediated by thiol groups present in proteins of the bacterial cell membrane or biofilm matrix proteins expressed at low levels by the wild-type strain. Furthermore, our data indicate that the adhesion of
B. subtilis
NCIB 3610 to carbohydrate-coated gold surfaces is facilitated by interactions between carbohydrates installed on the cantilever gold surface and an exopolysaccharide expressed by this strain. Understanding general and specific contributions of molecular interactions mediating bacterial adhesion will enable its prevention in the future.
Decoration of Outer Membrane Vesicles with Multiple Antigens by Using an Autotransporter Approach
Authors: Daleke-Schermerhorn Maria H. , Felix Tristan , Soprova Zora , ten Hagen-Jongman Corinne M. , Vikström David , Majlessi Laleh , Beskers Joep , Follmann Frank , de Punder Karin , van der Wel Nicole N. , Baumgarten Thomas , Pham Thang V. , Piersma Sander R. , Jiménez Connie R. , van Ulsen Peter , de Gier Jan-Willem , Leclerc Claude , Jong Wouter S. P. , Luirink Joen 
Published: July 2014

ABSTRACTOuter membrane vesicles (OMVs) are spherical nanoparticles that naturally shed from Gram-negative bacteria. They are rich in immunostimulatory proteins and lipopolysaccharide but do not replicate, which increases their safety profile and renders them attractive vaccine vectors. By packaging foreign polypeptides in OMVs, specific immune responses can be raised toward heterologous antigens in the context of an intrinsic adjuvant. Antigens exposed at the vesicle surface have been suggested to elicit protection superior to that from antigens concealed inside OMVs, but hitherto robust methods for targeting heterologous proteins to the OMV surface have been lacking. We have exploited our previously developed hemoglobin protease (Hbp) autotransporter platform for display of heterologous polypeptides at the OMV surface. One, two, or three of theMycobacterium tuberculosisantigens ESAT6, Ag85B, and Rv2660c were targeted to the surface ofEscherichia coliOMVs upon fusion to Hbp. Furthermore, a hypervesiculating ΔtolRΔtolAderivative of attenuatedSalmonella entericaserovar Typhimurium SL3261 was generated, enabling efficient release and purification of OMVs decorated with multiple heterologous antigens, exemplified by theM. tuberculosisantigens and epitopes fromChlamydia trachomatismajor outer membrane protein (MOMP). Also, we showed that delivery ofSalmonellaOMVs displaying Ag85B to antigen-presenting cellsin vitroresults in processing and presentation of an epitope that is functionally recognized by Ag85B-specific T cell hybridomas. In conclusion, the Hbp platform mediates efficient display of (multiple) heterologous antigens, individually or combined within one molecule, at the surface of OMVs. Detection of antigen-specific immune responses upon vesicle-mediated delivery demonstrated the potential of our system for vaccine development.
Estimating daily salt intake based on 24 h urinary sodium excretion in adults aged 18–69 years in Shandong, China
Authors: Zhang Ji-yu , Yan Liu-xia , Tang Jun-li , Ma Ji-xiang , Guo Xiao-lei , Zhao Wen-hua , Zhang Xiao-fei , Li Jian-hong , Chu Jie , Bi Zhen-qiang 
Published: July 2014

Objective24 h urinary sodium extretion was used to estimate the daily salt intake of shandong residents aged from 18 to 69 years in China.Setting20 selected counties/districts in Shandong stratified by geographic region (Eastern, Central Southern and North Western) and residence type (urban vs rural).ParticipantsAmong 2184 randomly selected adults, 2061 provided usable 24 h urine samples. Urine volume <500 mL or male creatinine <3.81 (female creatinine <4.57) are not included in the analysis.ResultsThe mean sodium level excreted over 24 h was 237.61 mmol (95% CI 224.77 to 250.44) mmol. Overall, the estimated mean salt intake was 13.90 g/day (95% CI 13.15 to 14.65). The mean salt intake among rural residents was higher than that among urban residents (14.00 vs 13.68 g; p<0.01). Salt intake in men was higher than that in women (14.40 vs 13.37 g; p<0.01). Approximately 96% of the survey participants had a dietary salt intake of ≥6 g/day.ConclusionsThe salt intake in Shandong is alarmingly higher than the current recommended amount (6 g/day). Thus, effective interventions to reduce salt intake levels to combat the increasing burden of non-communicable diseases need to be developed and implemented.
Pop, heavy metal and the blues: secondary analysis of persistent organic pollutants (POP), heavy metals and depressive symptoms in the NHANES National Epidemiological Survey
Authors: Berk Michael , Williams Lana J , Andreazza Ana C , Pasco Julie A , Dodd Seetal , Jacka Felice N , Moylan Steven , Reiner Eric J , Magalhaes Pedro V S 
Published: July 2014

ObjectivesPersistent environmental pollutants, including heavy metals and persistent organic pollutants (POPs), have a ubiquitous presence. Many of these pollutants affect neurobiological processes, either accidentally or by design. The aim of this study was to explore the associations between assayed measures of POPs and heavy metals and depressive symptoms. We hypothesised that higher levels of pollutants and metals would be associated with depressive symptoms.SettingNational Health and Nutrition Examination Survey (NHANES).ParticipantsA total of 15 140 eligible people were included across the three examined waves of NHANES.Primary and secondary outcome measuresDepressive symptoms were assessed using the nine-item version of the Patient Health Questionnaire (PHQ-9), using a cut-off point of 9/10 as likely depression cases. Organic pollutants and heavy metals, including cadmium, lead and mercury, as well as polyfluorinated compounds (PFCs), pesticides, phenols and phthalates, were measured in blood or urine.ResultsHigher cadmium was positively associated with depression (adjusted Prevalence Ratios (PR)=1.48, 95% CI 1.16 to 1.90). Higher levels of mercury were negatively associated with depression (adjusted PR=0.62, 95% CI 0.50 to 0.78), and mercury was associated with increased fish consumption (n=5500, r=0.366, p<0.001). In addition, several PFCs (perfluorooctanoic acid, perfluorohexane sulfonic acid, perfluorodecanoic acid and perfluorononanoic acid) were negatively associated with the prevalence of depression.ConclusionsCadmium was associated with an increased likelihood of depression. Contrary to hypotheses, many of persistent environmental pollutants were not associated or negatively associated with depression. While the inverse association between mercury and depressive symptoms may be explained by a protective role for fish consumption, the negative associations with other pollutants remains unclear. This exploratory study suggests the need for further investigation of the role of various agents and classes of agents in the pathophysiology of depression.
The morbidity and mortality conference as an adverse event surveillance tool in a paediatric intensive care unit
Authors: Cifra Christina L , Jones Kareen L , Ascenzi Judith , Bhalala Utpal S , Bembea Melania M , Fackler James C , Miller Marlene R 
Published: July 2014

ObjectiveTo determine if standardised chart review applied to records of patients discussed at a paediatric intensive care unit (PICU) morbidity and mortality conference (MMC) yields additional or different information regarding safety event occurrence and characteristics.DesignRetrospective record review.SettingSingle tertiary referral PICU in Baltimore, Maryland, USA.Participants96 patients discussed at the PICU MMC over 14 months (November 2011–December 2012).Main outcome measuresSafety events and their characteristics (medical error category, severity and preventability).ResultsA total of 275 safety events were identified through the MMC and/or chart review. The MMC identified 131 (48%) events, 53 (19%) of which were identified through the MMC alone. After chart review was performed, an additional 144 (52%) events were identified. 78 (28%) events were identified through both. High severity adverse events potentially contributing to permanent harm or death were more likely to be identified through both the MMC and chart review (47%) compared with either alone. The MMC alone identified more near-misses (21%) and preventable events (96%) compared with chart review alone or both MMC and chart review. Although chart review alone helped to identify many healthcare-associated infections, medication errors and sedation/pain control issues not elicited through the MMC, the MMC alone identified more communication errors and workflow problems. The MMC alone also identified 40% of all diagnostic errors, which would not have been discovered otherwise despite chart review by itself identifying 50% of such misdiagnoses.ConclusionsStandardised chart review applied to records of patients discussed at a PICU MMC identified significantly more safety events not initially discovered through the MMC. However, the MMC was superior to chart review in identifying broader problems such as communication errors, workflow issues and certain diagnostic errors not captured by chart review, which can potentially affect many aspects of care.
Review of performance-based incentives in community-based family planning programmes
Authors: Bellows Nicole M , Askew Ian , Bellows Benjamin 
Published: July 2014

BackgroundOne strategy for improving family planning (FP) uptake at the community level is the use of performance-based incentives (PBIs), which offer community distributors financial incentives to recruit more users of FP. This article examines the use of PBIs in community-based FP programmes via a literature search of the peer-reviewed and grey literature conducted in April 2013.ResultsA total of 28 community-based FP programmes in 21 countries were identified as having used PBIs. The most common approach was a sales commission model where distributors received commission for FP products sold, while a referral payment model for long-term methods was also used extensively. Six evaluations were identified that specifically examined the impact of the PBI in community-based FP programmes. Overall, the results of the evaluations are mixed and more research is needed; however, the findings suggest that easy-to-understand PBIs can be successful in increasing the use of FP at the community level.ConclusionFor future use of PBIs in community-based FP programmes it is important to consider the ethics of incentivising FP and ensuring that PBIs are non-coercive and choice-enhancing.
Macrophage Inflammatory Protein Derivative ECI301 Enhances the Alarmin-Associated Abscopal Benefits of Tumor Radiotherapy
Authors: Kanegasaki Shiro , Matsushima Kouji , Shiraishi Kenshiro , Nakagawa Keiichi , Tsuchiya Tomoko 
Published: July 2014

Abstract
Radiotherapy can produce antitumor benefits beyond the local site of irradiation, an immune-based phenomenon known as the abscopal effect, but the mechanisms underlying these benefits are poorly understood. Preclinical studies of ECI301, a mutant derivative of macrophage inhibitory protein-1α, have shown that its administration can improve the antitumor effects of radiotherapy in a manner associated with a tumor-independent abscopal effect. In this article, we report that i.v. administration of ECI301 after intratumoral injection of tumor cell lysates can inhibit tumor growth, not only at the site of injection but also at nontreated sites. Effects of the tumor lysate were further recapitulated by i.v. administration of the alarmins HSP70 or HMGB1, but not HSP60, and combinations of ECI301 + HSP70 were sufficient to inhibit tumor growth. Although injection of ECI301 + HMGB1 did not inhibit tumor growth, we found that administration of a neutralizing HMGB1 antibody neutralized the cooperative effects of ECI301 on tumor irradiation. Moreover, mice genetically deficient in TLR4, an immune pattern receptor that binds alarmins, including HMGB1 and HSP70, did not exhibit antitumor responses to irradiation with ECI301 administration. Although ECI301 was cleared rapidly from peripheral blood, it was found to bind avidly to HSP70 and HMGB1 in vitro. Our results suggest a model in which sequential release of the alarmins HSP70 and HMGB1 from a tumor by irradiation may trap circulating ECI301, thereby licensing or restoring tumor immunosurveillance capabilities of natural killer cells or CD4+ and CD8+ T cells against tumor cells that may evade irradiation. Cancer Res; 74(18); 5070–8. ©2014 AACR.
NACK Is an Integral Component of the Notch Transcriptional Activation Complex and Is Critical for Development and Tumorigenesis
Authors: Weaver Kelly L. , Alves-Guerra Marie-Clotilde , Jin Ke , Wang Zhiqiang , Han Xiaoqing , Ranganathan Prathibha , Zhu Xiaoxia , DaSilva Thiago , Liu Wei , Ratti Francesca , Demarest Renee M. , Tzimas Cristos , Rice Meghan , Carpio Rodrigo Vasquez-Del , Dahmane Nadia , Robbins David J. , Capobianco Anthony J. 
Published: July 2014

Abstract
The Notch signaling pathway governs many distinct cellular processes by regulating transcriptional programs. The transcriptional response initiated by Notch is highly cell context dependent, indicating that multiple factors influence Notch target gene selection and activity. However, the mechanism by which Notch drives target gene transcription is not well understood. Herein, we identify and characterize a novel Notch-interacting protein, Notch activation complex kinase (NACK), which acts as a Notch transcriptional coactivator. We show that NACK associates with the Notch transcriptional activation complex on DNA, mediates Notch transcriptional activity, and is required for Notch-mediated tumorigenesis. We demonstrate that Notch1 and NACK are coexpressed during mouse development and that homozygous loss of NACK is embryonic lethal. Finally, we show that NACK is also a Notch target gene, establishing a feed-forward loop. Thus, our data indicate that NACK is a key component of the Notch transcriptional complex and is an essential regulator of Notch-mediated tumorigenesis and development. Cancer Res; 74(17); 4741–51. ©2014 AACR.
Survival After Primary Prevention Implantable Cardioverter-Defibrillator Placement Among Patients With Chronic Kidney Disease
Authors: Hess Paul L. , Hellkamp Anne S. , Peterson Eric D. , Sanders Gillian D. , Al-Khalidi Hussein R. , Curtis Lesley H. , Hammill Bradley G. , Pun Patrick H. , Curtis Jeptha P. , Anstrom Kevin J. , Hammill Stephen C. , Al-Khatib Sana M. 
Published: July 2014

Background—
Guidelines recommend that implantable cardioverter-defibrillator (ICD) candidates have an estimated longevity of ≥1 year. Longevity can be affected by chronic kidney disease (CKD).

Methods and Results—

Using the National Cardiovascular Data Registry ICD registry linked with the Social Security Death Master File, we assessed the rate of death after primary prevention ICD placement between January 1, 2006, and December 31, 2007, according to CKD stage. Using Cox models, we identified factors associated with death among patients with CKD. Compared with patients without CKD (n=26 056), those with CKD (n=21 226) were older, less commonly men, more often white, and more frequently had comorbid illness. Compared with patients without CKD, patients with a glomerular filtration rate 30 to 60, glomerular filtration rate <30, and end-stage renal disease on dialysis had a higher risk of death after ICD placement (hazard ratio, 2.08; 95% confidence interval, 1.99–2.18;
P
<0.0001; hazard ratio, 4.20; 95% confidence interval, 3.92–4.50;
P
<0.0001; and hazard ratio, 4.80; 95% confidence interval, 4.46–5.17;
P
<0.0001, respectively). Corresponding 1-year death rates were 4.4%, 9.1%, 20.2%, and 22.4%. Among patients with CKD, factors associated with increased risk of death included CKD severity, age >65 years, heart failure symptoms, diabetes mellitus, lung disease, serum sodium <140 mEq/L, atrial fibrillation or flutter, and a lower ejection fraction.

Conclusions—
The risk of death after primary prevention ICD placement is proportional to CKD severity. Among patients with CKD, several factors are prognostically significant and could inform clinical decision making on primary prevention ICD candidacy.
Percutaneous Ventricular Restoration Using the Parachute Device in Patients With Ischemic Heart Failure
Authors: Costa Marco A. , Mazzaferri Ernest L. , Sievert Horst , Abraham William T. , Gradinac Sinisa , Sagic Dragan , Otasevic Petar , Hasan Ayesha K. , Goff Thomas L. , Wunderlich Nina , DePuy Venita , Smart Frank 
Published: July 2014

Background—
Left ventricle remodeling after anterior wall myocardial infarction leads to increased left ventricle volumes, myocardial stress, and ultimately heart failure (HF). Treatment options are limited for these high-risk HF patients. A study was conducted to assess safety and feasibility of a percutaneous ventricular restoration therapy using the Parachute device in subjects with HF because of a cardiac ischemic event.

Methods and Results—

Thirty-nine subjects with New York Heart Association class II to IV ischemic HF, ejection fraction between 15% and 40%, and dilated akinetic or dyskinetic anterior-apical wall without the need to be revascularized were enrolled in a prospective, nonrandomized, multicenter investigation testing percutaneous ventricular restoration using the Parachute device. The safety primary end point was defined as successful procedure without device-related major adverse cardiac events during 6 months. Clinical and echocardiographic outcomes were obtained at 6, 12, 24, and 36 months post-treatment. Echocardiographic and end point data were adjudicated independently. Of the 39 subjects enrolled, device implantation was attempted in 34 and successful in 31 patients. Twenty-three subjects reached 3 years post-treatment with the device implanted. New York Heart Association symptom class was improved or maintained in 85% of subjects. Left ventricle end-diastolic volume index and end-systolic volume index were reduced from 128.4±22.1 and 94.9±22.3 mL/m
2
preimplant to 115.2±23.1 and 87.3±18.7 mL/m
2
at 3-year follow-up (end-diastolic volume index,
P
=0.0056; end-systolic volume index,
P
=0.4719). The cumulative incidence of HF hospitalization or death was 16.1%, 32.3%, and 38.7% at 12, 24, and 36 months, respectively. By 3-year follow-up, 2 (6.5%) of 31 patients with successful implant had died from cardiac reasons, with no cardiac deaths occurring past 6 months post-treatment.

Conclusions—
The first series of ischemic HF patients treated with percutaneous ventricular restoration using the Parachute device demonstrates feasibility and safety of the device ≤3 years post-treatment.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifiers: NCT00573560 (US patients) and NCT01286116 (EU patients).
Repeat Coronary Computed Tomographic Angiography in Patients With a Prior Scan Excluding Significant Stenosis
Authors: Kumamaru Kanako K. , Kondo Takeshi , Kumamaru Hiraku , Amanuma Makoto , George Elizabeth , Rybicki Frank J. 
Published: July 2014

Background—
ACCF/SCCT/ACR/AHA/ASE/ASNC/NASCI/SCAI/SCMR 2010 Appropriate Use Criteria for Cardiac Computed Tomography (AUC2010) does not incorporate prior coronary computed tomographic angiography (CCTA) results in the appropriateness of a CCTA examination. The purpose of this study was to explore the criteria for forgoing repeat CCTA among patients with clinical scenarios suggesting CCTA as appropriate after prior CCTA excluding coronary artery disease.

Methods and Results—
Among patients from a single center (February 2006 to April 2013) who underwent appropriate CCTA based on AUC2010, consecutive 555 CCTAs, which had a prior CCTA excluding significant stenosis (>50% stenosis in diameter), were selected. The median time difference between the studies was 34.2 (Q1–Q3, 22.9–50.1) months. Significant stenosis was detected at the time of repeat scan (by CCTA or subsequent catheter angiography) in 13.3% (74 of 555). A multivariable logistic model (C-statistic, 0.74; bootstrapped overfitting bias, 0.8%) identified 3 predictors of significant stenosis: time difference between the studies >3 years (adjusted odds ratio, 2.1; 95% confidence interval, 1.2–3.5), diabetes mellitus (odds ratio, 2.4; 95% confidence interval,1.4–4.3), and 26% to 50% stenosis on the initial CCTA (odds ratio, 5.6; 95% confidence interval, 3.2–9.6). When these 3 factors were all absent (corresponding to 31.9% of the population), the probability of significant stenosis was 4.5% (95% confidence interval, 2.7–7.4%), whereas 17.1% of patients had significant stenosis among those with at least 1 positive variable. When coronary arteries were completely normal at the initial scan, the prevalence of significant stenosis was only 1.8% irrespective of other factors, and no patient underwent revascularization.

Conclusions—
Nondiabetic patients with a prior CCTA <3 years showing no or ≤25% stenosis had a <5% prevalence of significant stenosis. The value of repeat CCTA in this group is likely small, especially when the prior CCTA demonstrated normal coronaries, even if the clinical scenario considered a CCTA appropriate.