bluuebunny/crossref_metadata_2025 huggingface dataset:
Do Genetic Modifiers of High-Density Lipoprotein Cholesterol and Triglyceride Levels Also Modify Their Response to a Lifestyle Intervention in the Setting of Obesity and Type-2 Diabetes Mellitus?
Authors: Huggins Gordon S. , Papandonatos George D. , Erar Bahar , Belalcazar L. Maria , Brautbar Ariel , Ballantyne Christie , Kitabchi Abbas E. , Wagenknecht Lynne E. , Knowler William C. , Pownall Henry J. , Wing Rena R. , Peter Inga , McCaffery Jeanne M.
Published: July 2013

Background—

High-density lipoprotein cholesterol (HDL-C) and triglycerides are cardiovascular risk factors susceptible to lifestyle behavior modification and genetics. We hypothesized that genetic variants identified by genome-wide association studies as associated with HDL-C or triglyceride levels modify 1-year treatment response to an intensive lifestyle intervention, relative to a usual care of diabetes mellitus support and education.

Methods and Results—

We evaluated 82 single-nucleotide polymorphisms, which represent 31 loci demonstrated by genome-wide association studies to be associated with HDL-C and triglycerides, in 3561 participants who consented for genetic studies and met eligibility criteria. Variants associated with higher baseline HDL-C levels, cholesterol ester transfer protein (
CETP
) rs3764261 and hepatic lipase (
LIPC
) rs8034802, were found to be associated with HDL-C increases with intensive lifestyle intervention (
P
=0.0038 and 0.013, respectively) and had nominally significant treatment interactions (
P
=0.047 and 0.046, respectively). The fatty acid desaturase-2 rs1535 variant, associated with low baseline HDL-C (
P
=0.017), was associated with HDL-C increases with intensive lifestyle intervention (0.0037) and had a nominal treatment interaction (
P
=0.035). Apolipoprotein B (rs693) and
LIPC
(rs8034802) single-nucleotide polymorphisms showed nominally significant associations with HDL-C and triglyceride changes with intensive lifestyle intervention and a treatment interaction (
P
<0.05). Phosphatidylglycerophosphate synthase-1 single-nucleotide polymorphisms (rs4082919) showed the most significant triglyceride treatment interaction in the full cohort (
P
=0.0009).

Conclusions—

This is the first study to identify genetic variants modifying lipid responses to a randomized lifestyle behavior intervention in overweight or obese individuals with diabetes mellitus. The effects of genetic factors on lipid changes may differ from the effects on baseline lipids and are modifiable by behavioral intervention.
Cardiac Insulin-Resistance and Decreased Mitochondrial Energy Production Precede the Development of Systolic Heart Failure After Pressure-Overload Hypertrophy
Authors: Zhang Liyan , Jaswal Jagdip S. , Ussher John R. , Sankaralingam Sowndramalingam , Wagg Cory , Zaugg Michael , Lopaschuk Gary D.
Published: July 2013

Background—

Cardiac hypertrophy is accompanied by significant alterations in energy metabolism. Whether these changes in energy metabolism precede and contribute to the development of heart failure in the hypertrophied heart is not clear.

Methods and Results—

Mice were subjected to cardiac hypertrophy secondary to pressure-overload as a result of an abdominal aortic constriction (AAC). The rates of energy substrate metabolism were assessed in isolated working hearts obtained 1, 2, and 3 weeks after AAC. Mice subjected to AAC demonstrated a progressive development of cardiac hypertrophy. In vivo assessment of cardiac function (via echocardiography) demonstrated diastolic dysfunction by 2 weeks (20% increase in E/E′), and systolic dysfunction by 3 weeks (16% decrease in % ejection fraction). Marked cardiac insulin-resistance by 2 weeks post-AAC was evidenced by a significant decrease in insulin-stimulated rates of glycolysis and glucose oxidation, and plasma membrane translocation of glucose transporter 4. Overall ATP production rates were decreased at 2 and 3 weeks post-AAC (by 37% and 47%, respectively) because of a reduction in mitochondrial oxidation of glucose, lactate, and fatty acids that was not accompanied by an increase in myocardial glycolysis rates. Reduced mitochondrial complex V activity was evident at 3 weeks post-AAC, concomitant with a reduction in the ratio of phosphocreatine to ATP.

Conclusions—

The development of cardiac insulin-resistance and decreased mitochondrial oxidative metabolism are early metabolic changes in the development of cardiac hypertrophy, which create an energy deficit that may contribute to the progression from hypertrophy to heart failure.
Ceruloplasmin and Heart Failure in the Atherosclerosis Risk in Communities Study
Authors: Dadu Razvan T. , Dodge Rhiannon , Nambi Vijay , Virani Salim S. , Hoogeveen Ron C. , Smith Nicholas L. , Chen Fengju , Pankow James S. , Guild Cameron , Tang W.H. Wilson , Boerwinkle Eric , Hazen Stanley L. , Ballantyne Christie M.
Published: July 2013

Background—

Ceruloplasmin (Cp) decreases nitric oxide bioavailability in blood and has been associated with cardiovascular disease (CVD) in clinical studies. We assessed the associations between Cp and incident heart failure (HF), death, and CVD in the Atherosclerosis Risk in Communities (ARIC) study.

Methods and Results—

Cp was measured at ARIC visit 4 (1996–1998). We studied 9240 individuals without HF or CVD at ARIC visit 4 and followed them for a mean of 10.5 years. Genome-wide association study was performed to identify genetic determinants of Cp levels and evaluate their association with incident HF in ARIC participants. Cp levels (mean±SD) were higher in women versus men (335±79 versus 258±44 mg/L;
P
<0.0001), women on versus not on hormone-replacement therapy (398±89 versus 291±60 mg/L;
P
<0.0001), and African Americans versus whites (299±63 versus 293±74 mg/L;
P
=0.0005). After adjusting for traditional risk factors, high-sensitivity C-reactive protein, N-terminal pro–B-type natriuretic peptide, and high-sensitivity cardiac troponin T, higher levels of Cp were associated with HF (hazard ratio, 1.44; 95% confidence interval, 1.13–1.83) and mortality (hazard ratio, 1.38; 95% confidence interval, 1.11–1.63). A locus on the ceruloplasmin gene on chromosome 3 was significantly associated with Cp levels (normal 295.56±77.60 mg/L; heterozygote 316.72±88.02 mg/L; homozygote 331.04±85.40 mg/L;
P
=8.3×10
–13
) but not with incident HF. After adjustment for traditional risk factors, Cp levels were also weekly associated with CVD.

Conclusions—

Cp was associated with incident HF, mortality, and CVD in the ARIC population. A single locus on chromosome 3 was associated with Cp levels but not with HF.
Bypassing the Emergency Department and Time to Reperfusion in Patients With Prehospital ST-Segment–Elevation
Authors: Bagai Akshay , Al-Khalidi Hussein R. , Muñoz Daniel , Monk Lisa , Roettig Mayme L. , Corbett Claire C. , Garvey J. Lee , Wilson B. Hadley , Granger Christopher B. , Jollis James G.
Published: July 2013

Background—

Among patients identified prehospital with ST-segment–elevation myocardial infarction, emergency medical service transport from the field directly to the catheterization laboratory, thereby bypassing the emergency department (ED), may shorten time to reperfusion.

Methods and Results—

We studied 1687 patients identified prehospital with ST-segment–elevation myocardial infarction from the Reperfusion in Acute Myocardial Infarction in Carolina Emergency Departments (RACE) project, transported via emergency medical service directly to 21 North Carolina hospitals for primary percutaneous coronary intervention between July 2008 and December 2009. Treatment time intervals were compared between patients evaluated in the ED (ED evaluation) and those transported directly to the catheterization laboratory (ED bypass). Emergency medical service transported 1401 (83.0%) patients to the ED, whereas the ED was bypassed for 286 (17.0%) patients. Overall, first medical contact to device activation within 90 minutes was achieved in 913 (54.1%) patients. Among patients evaluated in the ED, median time (25th–75th percentiles) from ED arrival to catheterization laboratory arrival was 30 (20–41) minutes. First medical contact to device activation occurred faster (75 [59–93] versus 90 [76–109] minutes;
P
<0.001) and was more frequently achieved within 90 minutes (74.1% versus 50.1%;
P
<0.001) among ED bypass patients.

Conclusions—

Among patients identified prehospital with ST-segment–elevation myocardial infarction and transported directly to a percutaneous coronary intervention hospital, only 1 in 2 achieve device activation within 90 minutes. A median of 30 minutes is spent in the ED, contributing significantly to the failure to achieve timely reperfusion. The strategy to bypass the ED is used infrequently and represents a potential opportunity to improve reperfusion times.
Cerebellar Atrophy in Childhood Arterial Ischemic Stroke
Authors: Mah Sarah , deVeber Gabrielle , Wei Xing-Chang , Liapounova Natalia , Kirton Adam
Published: July 2013

Background and Purpose—

Crossed cerebellar atrophy is uncommon in childhood arterial ischemic stroke. Acute corticospinal tract diffusion–weighted imaging (CST-DWI) changes occur in stroke of all ages. Contralateral CST-DWI is unexplained but approximates corticopontocerebellar pathways. We hypothesized that cerebellar atrophy can be quantified on clinical neuroimaging in childhood arterial ischemic stroke and is predicted by contralesional CST-DWI.

Methods—

Consecutive children (>28 days–18 years) were included with the following features: (1) acute, unilateral, middle cerebral artery arterial ischemic stroke, (2) DWI <14 days from stroke onset, (3) anatomic T1 MRI >6 months, and (4) Pediatric Stroke Outcome Measure >12 months. Blinded scorers measured cerebellar volumes (left/right/hemisphere/vermis/total) using Osirix software. Cerebellar volumes ratios (nonstroke/stroke) were expressed as asymmetry indices (AI), with chronic/acute ratio <1.0 suggesting crossed atrophy. Acute brain stem and cerebellum (peduncle, hemisphere) DWI ratios were scored. Software measures were compared with visual inspection. Associations between AI, motor outcome (good/poor), and contralesional CST-DWI were sought. Rater reliabilities were assessed.

Results—

Twenty-three children were studied (median age, 6.3±4.4 years; 62% male). Baseline cerebellar volumes were comparable (right=56.9 cm
3
, left=57.1 cm
3
). Cerebellar atrophy was suggested across the sample with overall AI <1.0 (0.973±0.05;
P
=0.009). Visual atrophy detection was specific (≈100%) but insensitive (54%). Children with poor motor outcome did not have lower AI (0.983±0.027 versus 0.965±0.068;
P
=0.40); however, children with acute contralesional CST-DWI did (0.928±0.078 versus 986±0.040;
P
=0.03). Acute cerebellar DWI did not predict atrophy. Rater reliabilities were excellent (>0.92).

Conclusions—

Cerebellar atrophy can be demonstrated on MRI in childhood arterial ischemic stroke. Association with acute contralesional pontine DWI signal suggests early degeneration of corticopontocerebellar connections. The clinical significance of cerebellar atrophy in childhood stroke remains to be determined.
Possible Improvements to the Framework of International Investment Arbitration
Authors: Butler Nicolette
Published: July 2013

The framework of international investment arbitration has attracted an increasing amount of criticism in recent years; academics have contended that the system is suffering a ‘crisis of consistency’ brought about primarily through inconsistent decisions. This problem is exacerbated by the fact that the system of international investment arbitration does not utilise a single hierarchical court-like system. Rather, there are hundreds of institutions settling investment disputes, as well as ad hoc tribunals. Furthermore, arbitral decisions do not carry any precedential value. With these problems in mind, the objective of this work is to examine how the framework of international investment arbitration could be reformed in order that it may operate in the most efficient and effective manner.
Bilateral Investment Rule-Making: BITs or FTAs with Investment Rules?
Authors: Qingjiang Kong
Published: July 2013

China is upgrading its bilateral investment treaties (BITs), and in the meantime embracing free trade agreements (FTAs), which can be accommodated to offer international investment rules (IIRs). A specific question in this regard will be: shall the investment issues be left to the upgraded BIT or proposed FTA? Given the trend that the investment rules embodied in the FTAs are increasingly intended to replace BITs between contracting states, this question, which poses a preliminary issue to the trade policy-makers of China and its partners, must be addressed from the public policy choice point of view. The paper argues for a sequencing of bilateral investment rule-making and proposes that unless the proposed FTA with investment rules is to leave policy space for the government, the BIT shall be given a due role to play in the course of economic integration between China and its partners.
Pleasures of Ambiguity: the Case of Piranesi’s Carceri
Authors: Wagemans Johan , Koenderink Jan , van Doorn Andrea
Published: July 2013

Are pictorial spaces evoked by intentionally ambiguous pictures internally coherent? If so, then we expect these to be idiosyncratic. We addressed this issue empirically. Three sheets from the second edition of Piranesi’s Carceri d’Inventione were selected for the experiment. These were compared with a conventional landscape drawing (after a Capriccio by Guardi) as a base line. The pictorial spaces were probed by way of pairwise depth-order judgments. In each image about fifty landmarks were selected, thus yielding over a thousand binary depth-order judgments per image. From such a full set of pairwise comparisons one obtains a linear depth order. This linear order again yields postdictions for the individual pairwise judgments. Actual judgments differ from these postdictions, thereby yielding a convenient handle on the coherence of the pictorial space. Since the Piranesi Carceri are generally considered to be ‘difficult’, ‘ambiguous’ or ‘labyrinthine’, whereas a conventional landscape as the Guardi is designed for its well-defined depth structure, it is expected that they will give rise to very distinct degrees of coherence. This is indeed what we find. We studied the variation of coherence over observers and images in detail. The pictorial locations that are heavily involved in incoherent responses were identified, and the reason for their ambiguous nature traced in the structure of the depth cues provided by the artist (Piranesi). We speculate that the Carceri manage to strike just the right level of ambiguity (between total chaos and obvious structure) so as to render them visually attractive.
Far and Yet Close: Multiple Viewpoints for the Perfect Portrait
Authors: Perona Pietro
Published: July 2013

Realistic pictures, whether paintings, photographs or rendered images of models, are traditionally obtained using classical perspective projection. Here I focus on pictures of people and discuss evidence suggesting that, for best results, full-length realistic-looking portraits should be produced by combining multiple viewpoints. I test this prediction experimentally and find that full-length portraits look more compelling if appropriate multiple viewpoints are chosen. I notice that multi-viewpoint portraiture has likely been used since the Renaissance, although no explicit mention of it is found in the literature.
Revision of Notoglanidium and related genera (Siluriformes: Claroteidae) based on morphology and osteology
Authors: GEERINCKX TOM , VREVEN EMMANUEL , DIERICK MANUEL , HOOREBEKE LUC VAN , ADRIAENS DOMINIQUE
Published: July 2013

Apart from the well-demarcated genera Auchenoglanis and Parauchenoglanis, Auchenoglanidinae, one of the two subfamilies of the African catfish family Claroteidae, suffers from poor resolution at the generic level. For the remaining genera, Notoglanidium, Liauchenoglanis, Platyglanis and Anaspidoglanis, generic discriminations are rudimentary. In addition, several included species are poorly defined and barely represented in scientific collections. Until now, no study has included morphological data for all currently known species, and for many species osteological data were non-existent. Molecular data for most species are lacking as well. Here, a comprehensive account of the morphology and osteology is given of all species included in these four genera. Using computed tomography (CT scanning) as well as clearing and staining, osteological characters were combined with biometric, meristic and other morphological data to revise the status of these genera and included species. Morphological and osteological data, submitted to a phylogenetic analysis, agree with metric and meristic data that all Liauchenoglanis, Platyglanis and Anaspidoglanis cannot be discerned from Notoglanidium; their genus and type species descriptions fail to be distinguished from Notoglanidium. Here their synonymy is proposed, resulting in a single valid genus, including nine species of which the validity is confirmed. A key to the genus and included species, as well as a diagnosis and description for each of them, are provided.
Bilateral atrial appendage aneurysms associated with atrial fibrillation
Authors: Nakahara Takahiro , Minakata Kenji , Yamazaki Kazuhiro , Funamoto Masaki , Sakata Ryuzo
Published: July 2013

Aneurysm of the left atrial appendage is an extremely rare anomaly. We describe the case of a 68-year-old man who presented with palpitation and was found to have a very large aneurysm located near the left atrial appendage on routine echocardiography. During surgery, an additional small aneurysm of the right atrial appendage was found. Both atrial aneurysms were resected in addition to mitral annuloplasty and a maze procedure.
‘Prisoners of the Peace’: German Prisoners-of-War in Rural France 1944–48
Authors: Diamond Hanna
Published: July 2013

Historians have paid little attention to the over half a million German prisoners-of-war who were deployed for the purposes of reconstruction in France between 1944 and 1948. In an effort to contain the rural labour crisis over half were allocated to agriculture. Despite an initially hostile reception by the French, this article argues that moving the prisoners into farms marked the beginning of a strikingly rapid process of acceptance by these local communities. Farmers led the way to broader acceptance by refusing to enforce the rules and granting prisoners more freedom than the authorities intended. It shows how, despite opposition from some quarters, in a process of growing normalization, rural populations gradually came to identify the Germans less as prisoners and more as foreign workers living amongst them.
Correlative analysis of social support with anxiety and depression in men undergoing in vitro fertilization embryo transfer for the first time
Authors: Dong Yue-Zhi , Yang Xiao-Xia , Sun Ying-Pu
Published: July 2013

Objective

To explore the correlation between the level of social support and the extent of anxiety and depression in Chinese men undergoing in vitro fertilization embryo transfer (IVF-ET) for the first time, in order to provide a basis for male mental health counselling.

Methods

Self-administered questionnaires covering general health status, anxiety (self-rating anxiety scale), depression (self-rating depression scale) and social support (social support rating scale) were completed by men undergoing their first round of IVF-ET.

Results

A total of 502 completed questionnaires were considered valid and were analysed. The anxiety, depression and social support scores for men undergoing their first round of IVF-ET were significantly higher than those for Chinese normative data. Social support was inversely correlated with anxiety and depression.

Conclusions

These findings suggest that health care professionals should provide specific psychological counselling to Chinese men undergoing their first round of IVF-ET, in order to improve their psychological health and to facilitate increased levels of social support.
The role of school librarians in enhancing science learning
Authors: Subramaniam Mega , Ahn June , Waugh Amanda , Taylor Natalie Greene , Druin Allison , Fleischmann Kenneth R. , Walsh Greg
Published: July 2013

School librarians play a pivotal role in facilitating learning of all subjects in primary and secondary schools in the United States, but their potential contributions to science have not been explored. In this paper, we show how school librarian practices can directly enhance aspects of science education by providing concrete examples from a study where we engaged school librarians to co-design and co-implement a science-infused after-school program. We found that librarians are a strong asset in science learning, as they foster youth engagement in authentic inquiry practices and engage young people’s everyday life interests in science learning. This study contributes new insight into how librarians can use their expertise to enhance science education efforts in schools.
The Role of Customer Orientation in the Relationship Between Manager Communications and Customer Satisfaction
Authors: Mathe Kimberly , Scott-Halsell Sheila , Roseman Mary
Published: July 2013

Within the restaurant and hospitality industry, employee behaviors and relationships are important in determining customer satisfaction. The present study extended the hospitality literature regarding customer satisfaction in three ways using a cross-sectional survey design. First, the relationship between manager communications and customer orientation was explored, and results supported a positive, significant relationship. Second, this study helped confirm past studies that have tested the relationship between customer orientation and customer satisfaction using a single-item customer response measure. Finally, a meditational test examined whether customer orientation carries the full influence of a manager’s communication and the resulting customer satisfaction. Results supported the meditational test. Practical and theoretical implications are explored for both hospitality researchers and practitioners.
Does Danish Football Club Brøndby Swim With the Fishes? An Application of the Reversed News Model
Authors: Croonenbroeck Carsten , Monaco Fabrizio Leonardo , Christensen Mads Julius
Published: July 2013

We complement a former study by Jørgensen, Moritzen, and Stadtmann and estimate a reversed news model for the Danish publicly listed football club Brøndby. In addition to match outcome (as in Jørgensen et al.), news related to corporate governance and the financial status are important.
Expression profiling of TCR-engineered T cells demonstrates overexpression of multiple inhibitory receptors in persisting lymphocytes
Authors: Abate-Daga Daniel , Hanada Ken-ichi , Davis Jeremy L. , Yang James C. , Rosenberg Steven A. , Morgan Richard A.
Published: July 2013

Key Points

Gene expression in TCR-engineered cells resembles that of virus-reactive cells more than native tumor antigen-reactive cells. Persisting TCR gene–engineered T cells are sensitive to PD-L1–PD-1 interaction but CD160-associated impairment is ligand-independent.
An outbreak of feline infectious peritonitis in a Taiwanese shelter: epidemiologic and molecular evidence for horizontal transmission of a novel type II feline coronavirus
Authors: Wang Ying-Ting , Su Bi-Ling , Hsieh Li-En , Chueh Ling-Ling
Published: July 2013

Feline infectious peritonitis (FIP) is a fatal disease caused by feline coronavirus (FCoV) infection. FCoV can be divided into serotypes I and II. The virus that causes FIP (FIPV) is believed to occur sporadically and spread infrequently from cat to cat. Recently, an FIP outbreak from an animal shelter was confirmed in Taiwan. FCoV from all the cats in this shelter were analyzed to determine the epidemiology of this outbreak. Thirteen of 46 (28.2%) cats with typical signs of FIP were identified. Among them, seven cats were confirmed by necropsy and/or histopathological examinations. Despite the fact that more than one FCoV was identified in this multi-cat environment, the eight FIP cats were invariably found to be infected with a type II FCoV. Sequence analysis revealed that the type II FIPV detected from fecal samples, body effusions and granulomatous tissue homogenates from the cats that succumbed to FIP all harbored an identical recombination site in theirSgene. Two of the cats that succumbed to FIP were found to harbor an identical nonsense mutation in the3cgene. Fecal shedding of this type II virus in the effusive form of FIP can be detected up to six days before death. Taken together, our data demonstrate that horizontal transmission of FIPV is possible and that FIP cats can pose a potential risk to other cats living in the same environment.
Genomic characterization provides new insight into Salmonella phage diversity
Authors: Moreno Switt Andrea I , Orsi Renato H , den Bakker Henk C , Vongkamjan Kitiya , Altier Craig , Wiedmann Martin
Published: July 2013

Background

Salmonella is a widely distributed foodborne pathogen that causes tens of millions of salmonellosis cases globally every year. While the genomic diversity of Salmonella is increasingly well studied, our knowledge of Salmonella phage genomic diversity is still rather limited, despite the contributions of both lysogenic and lytic phages to Salmonella virulence, diversity and ecology (e.g., through horizontal gene transfer and Salmonella lysis). To gain a better understanding of phage diversity in a specific ecological niche, we sequenced 22 Salmonella phages isolated from a number of dairy farms from New York State (United States) and analyzed them using a comparative genomics approach.

Results

Classification of the 22 phages according to the presence/absence of orthologous genes allowed for classification into 8 well supported clusters. In addition to two phage clusters that represent novel virulent Salmonella phages, we also identified four phage clusters that each contained previously characterized phages from multiple continents. Our analyses also identified two clusters of phages that carry putative virulence (e.g., adhesins) and antimicrobial resistance (tellurite and bicyclomycin) genes as well as virulent and temperate transducing phages. Insights into phage evolution from our analyses include (i) identification of DNA metabolism genes that may facilitate nucleotide synthesis in phages with a G+C % distinct from Salmonella, and (ii) evidence of Salmonella phage tailspike and fiber diversity due to both single nucleotide polymorphisms and major re-arrangements, which may affect the host specificity of Salmonella phages.

Conclusions

Genomics-based characterization of 22 Salmonella phages isolated from dairy farms allowed for identification of a number of novel Salmonella phages. While the comparative genomics analyses of these phages provide a number of new insights in the evolution and diversity of Salmonella phages, they only represent a first glimpse into the diversity of Salmonella phages that is likely to be discovered when phages from different environments are characterized.
Conservation of the genes for HC-toxin biosynthesis in Alternaria jesenskae
Authors: Wight Wanessa D , Labuda Roman , Walton Jonathan D
Published: July 2013

Background

HC-toxin, a cyclic tetrapeptide, is a virulence determinant for the plant pathogenic fungus Cochliobolus carbonum. It was recently discovered that another fungus, Alternaria jesenskae, also produces HC-toxin.

Results

The major genes (collectively known as AjTOX2) involved in the biosynthesis of HC-toxin were identified from A. jesenskae by genomic sequencing. The encoded orthologous proteins share 75-85% amino acid identity, and the genes for HC-toxin biosynthesis are duplicated in both fungi. The genomic organization of the genes in the two fungi show a similar but not identical partial clustering arrangement. A set of representative housekeeping proteins show a similar high level of amino acid identity between C. carbonum and A. jesenskae, which is consistent with the close relatedness of these two genera within the family Pleosporaceae (Dothideomycetes).

Conclusions

This is the first report that the plant virulence factor HC-toxin is made by an organism other than C. carbonum. The genes may have moved by horizontal transfer between the two species, but it cannot be excluded that they were present in a common ancestor and lost from other species of Alternaria and Cochliobolus.
Baseline characteristics and prevalence of cardiovascular disease in newly visiting or referred chronic kidney disease patients to nephrology centers in Japan: a prospective cohort study
Authors: Iimori Soichiro , Noda Yumi , Okado Tomokazu , Naito Shotaro , Toda Takayuki , Chida Yoshiko , Kuwahara Michio , Ando Ryoichi , Nishio Yasuhide , Maeda Yoshitaka , Tanaka Hiroyuki , Tamura Teiichi , Kimoto Shigeaki , Kanda Eiichiro , Inoshita Seiji , Yoshikawa Momono , Okutsu Rie , Tajima Masato , Kusaura Takashi , Kobayashi Katsuki , Rai Tatemitsu , Uchida Shinichi , Sasaki Sei
Published: July 2013

Background

About 39,000 patients were newly prescribed renal replacement therapy in Japan in 2011, resulting in a total of more than 300,000 patients being treated with dialysis. This high prevalence of treated end stage kidney disease (ESKD) patients is an emergent problem that requires immediate attention. We launched a prospective cohort study to evaluate population specific characteristics of the progression of chronic kidney disease (CKD). In this report, we describe the baseline characteristics and risk factors for cardiovascular disease (CVD) prevalence among this cohort.

Methods

New patients from 16 nephrology centers who were older than 20 years of age and who visited or were referred for the treatment of CKD stage 2–5, but were not on dialysis therapy, were recruited in this study. At enrollment, medical history, lifestyle behaviors, functional status and current medications were recorded, and blood and urine samples were collected. Estimated glomerular filtration rate (eGFR) was calculated by a modified three-variable equation.

Results

We enrolled 1138 patients, 69.6% of whom were male, with a mean age of 68 years. Compared with Western cohorts, patients in this study had a lower body mass index (BMI) and higher proteinuria. The prevalence of CVD was 26.8%, which was lower than that in Western cohorts but higher than that in the general Japanese population. Multivariate analysis demonstrated the following association with CVD prevalence: hypertension (adjusted odds ratio (aOR) 3.57; 95% confidence interval (CI) 1.82-7.02); diabetes (aOR 2.45; 95% CI 1.86-3.23); hemoglobin level less than 11 g/dl (aOR 1.61; 95% CI 1.21-2.15); receiving anti-hypertensive agents (aOR 3.54; 95% CI 2.27-5.53); and statin therapy (aOR 2.73; 95% CI 2.04-3.66). The combination of decreased eGFR and increased proteinuria was also associated with a higher prevalence of CVD.

Conclusions

The participants in this cohort had a lower BMI, higher proteinuria and lower prevalence of CVD compared with Western cohorts. Lower eGFR and high proteinuria were associated with CVD prevalence. Prospective follow up of these study patients will contribute to establishment of individual population-based treatment of CKD.
Serum calcium and risk of gastrointestinal cancer in the Swedish AMORIS study
Authors: Wulaningsih Wahyu , Michaelsson Karl , Garmo Hans , Hammar Niklas , Jungner Ingmar , Walldius Göran , Lambe Mats , Holmberg Lars , Van Hemelrijck Mieke
Published: July 2013

Background

Observational studies have indicated that high calcium intake may prevent colorectal cancer, but as for randomized trials the results are inconclusive. Meanwhile, limited data on the link between serum calcium and cancer risk is available. We investigated the relation between serum calcium and risk of different gastrointestinal cancers in a prospective study.

Methods

A cohort based on 492,044 subjects with baseline information on calcium (mmol/L) and albumin (g/L) was selected from the Swedish Apolipoprotein MOrtality RISk (AMORIS) study. Multivariable Cox proportional hazard models were used to analyse associations between standardised levels, quartiles and age/sex-specific categories of serum calcium and risk of oesophageal, stomach, colon, rectal cancer and also colorectal cancer combined, while taking into account serum albumin and other comorbidities.

Results

During 12 years of follow-up, we identified 323 incident oesophageal cancers, 782 stomach cancers, 2519 colon cancers, and 1495 rectal cancers. A positive association was found between albumin-adjusted serum calcium and risk of oesophageal [HR: 4.82 (95% CI: 2.07 – 11.19) for high compared to normal age-specific calcium levels] and colon cancer [e.g. HR: 1.07 (95% CI: 1.00 – 1.14) for every SD increase of calcium] as well as colorectal cancer [e.g. HR: 1.06 (95% CI: 1.02-1.11) for every SD increase of calcium] in women. In men there were similar but weaker non-statistically significant trends.

Conclusion

The positive relation between serum calcium, oesophageal cancer and colorectal cancer calls for further studies including calcium regulators to evaluate whether there is a true link between calcium metabolism and development of gastrointestinal cancer.
Ethyl acetate extract of germinated brown rice attenuates hydrogen peroxide-induced oxidative stress in human SH-SY5Y neuroblastoma cells: role of anti-apoptotic, pro-survival and antioxidant genes
Authors: Azmi Nur Hanisah , Ismail Norsharina , Imam Mustapha Umar , Ismail Maznah
Published: July 2013

Background

There are reports of improved metabolic outcomes due to consumption of germinated brown rice (GBR). Many of the functional effects of GBR can be linked to its high amounts of antioxidants. Interestingly, dietary components with high antioxidants have shown promise in the prevention of neurodegenerative diseases like Alzheimer’s disease (AD). This effect of dietary components is mostly based on their ability to prevent apoptosis, which is believed to link oxidative damage to pathological changes in AD. In view of the rich antioxidant content of GBR, we studied its potential to modulate processes leading up to AD.

Methods

The total phenolic content and antioxidant capacity of the ethyl acetate extract of GBR were compared to that of brown rice (BR), and the cytotoxicity of both extracts were determined on human SH-SY5Y neuronal cells using 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) Assay. Based on its higher antioxidant potentials, the effect of the GBR extract on morphological changes due to hydrogen peroxide (H2O2)-induced oxidative damage in human SH-SY5Y neuronal cells was examined using inverted light microscope and fluorescence microscope by means of acridine orange-propidium iodide (AO/PI) staining. Also, evaluation of the transcriptional regulation of antioxidant and apoptotic genes was carried out using Multiplex Gene Expression System.

Results

The ethyl acetate extract of GBR had higher total phenolic content and antioxidant capacity compared to BR. The cytotoxicity results showed that GBR extract did not cause any damage to the human SH-SY5Y neuronal cells at concentrations of up to 20 ppm, and the morphological analyses showed that the GBR extract (up to 10 ppm) prevented H2O2-induced apoptotic changes in the cells. Furthermore, multiplex gene expression analyses showed that the protection of the cells by the GBR extract was linked to its ability to induce transcriptional changes in antioxidant (SOD 1, SOD 2 and catalase) and apoptotic (AKT, NF-Kβ, ERK1/2, JNK, p53 and p38 MAPK) genes that tended towards survival.

Conclusions

Taken together, the results of our study showed that the ethyl acetate extract of GBR, with high antioxidant potentials, could prevent H2O2-induced oxidative damage in SH-SY5Y cells. The potential of GBR and its neuroprotective mechanism in ameliorating oxidative stress-related cytotoxicity is therefore worth exploring further.
The benefits of psychosocial interventions for cancer patients undergoing radiotherapy
Authors: Guo Zhen , Tang Hua-ying , Li Hao , Tan Sheng-kui , Feng Kai-hua , Huang Yin-chun , Bu Qing , Jiang Wei
Published: July 2013

Background

Many patients with cancer experience depression and anxiety, and an associated decrease in quality of life (QOL) during radiation therapy (RT). The main objective of the study was to determine the benefits of psychosocial interventions for cancer patients who received RT.

Methods

Patients with cancer (n = 178) who agreed to participate in the study were randomized to the intervention arm (n = 89) or the control arm (n = 89). Patients in the intervention group received psychosocial care during RT, whereas the control group received RT only. The benefits of the intervention were evaluated using the Zung Self-rating Depression Scale (SDS) to measure depression, the Self-rating Anxiety Scale (SAS) to assess anxiety, and the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) to survey health-related QOL. The association between intervention and survival was also assessed.

Results

Patients randomly assigned to the intervention arm showed significant improvements on symptoms of depression (p < 0.05) and anxiety (p < 0.05), health-related QOL (p < 0.05) (i.e. better global health status, and physical and emotional functioning, and less insomnia) when compared with controls. In the subset analysis, female patients, those that received high dose irradiation, and those that underwent adjuvant chemotherapy could benefit more from psychosocial intervention. There was no difference between the two groups in disease-free survival (DFS) (2-year DFS 79.8% in the intervention arm and 76.4% in the control arm; p = 0.527) and overall survival (OS) (2-year OS 83.1% in the intervention arm and 84.3% in the control arm; p = 0.925)

Conclusions

Psychosocial intervention is a cost-effective approach that can improve a patient’s mood and QOL both during and after RT. However, the intervention was not found to reduce the risk of cancer recurrence and death.

Trial registration

ChiCTR-TRC-12002438
Automethylation of protein arginine methyltransferase 6 (PRMT6) regulates its stability and its anti-HIV-1 activity
Authors: Singhroy Diane N , Mesplède Thibault , Sabbah Arielle , Quashie Peter K , Falgueyret Jean-Pierre , Wainberg Mark A
Published: July 2013

Background

Protein arginine methyltransferase 6 (PRMT6) is a nuclear enzyme that methylates arginine residues on histones and transcription factors. In addition, PRMT6 inhibits HIV-1 replication in cell culture by directly methylating and interfering with the functions of several HIV-1 proteins, i.e. Tat, Rev and nucleocapsid (NC). PRMT6 also displays automethylation capacity but the role of this post-translational modification in its antiretroviral activity remains unknown.

Results

Here we report the identification by liquid chromatography-mass spectrometry of R35 within PRMT6 as the target residue for automethylation and have confirmed this by site-directed mutagenesis and in vitro and in vivo methylation assays. We further show that automethylation at position 35 greatly affects PRMT6 stability and is indispensable for its antiretroviral activity, as demonstrated in HIV-1 single-cycle TZM-bl infectivity assays.

Conclusion

These results show that PRMT6 automethylation plays a role in the stability of this protein and that this event is indispensible for its anti-HIV-1 activity.
Psychological advocacy toward healing (PATH): study protocol for a randomized controlled trial
Authors: Brierley Gwen , Agnew-Davies Roxane , Bailey Jayne , Evans Maggie , Fackrell Morgan , Ferrari Giulia , Hollinghurst Sandra , Howard Louise , Howarth Emma , Malpass Alice , Metters Carol , Peters Tim J , Saeed Fayeza , Sardhina Lynnmarie , Sharp Debbie , Feder Gene S
Published: July 2013

Background

Domestic violence and abuse (DVA), defined as threatening behavior or abuse by adults who are intimate partners or family members, is a key public health and clinical priority. The prevalence of DVA in the United Kingdom and worldwide is high, and its impact on physical and mental health is detrimental and persistent. There is currently little support within healthcare settings for women experiencing DVA. Psychological problems in particular may be difficult to manage outside specialist services, as conventional forms of therapy such as counseling that do not address the violence may be ineffective or even harmful. The aim of this study is to assess the overall effectiveness and cost-effectiveness of a novel psychological intervention tailored specifically for survivors of DVA and delivered by domestic violence advocates based in third-sector organizations.

Methods and study design

This study is an open, pragmatic, parallel group, individually randomized controlled trial. Women ages 16 years and older experiencing domestic violence are being enrolled and randomly allocated to receive usual DVA agency advocacy support (control) or usual DVA agency support plus psychological intervention (intervention). Those in the intervention group will receive eight specialist psychological advocacy (SPA) sessions weekly or fortnightly, with two follow-up sessions, 1 month and then 3 months later. This will be in addition to any advocacy support sessions each woman receives. Women in the control group will receive usual DVA agency support but no additional SPA sessions. The aim is to recruit 250 women to reach the target sample size. The primary outcomes are psychological well-being and depression severity at 1 yr from baseline, as measured by the Clinical Outcomes in Routine Evaluation–Outcome Measure (CORE-OM) and the Patient Health Questionnaire (PHQ-9), respectively. Secondary outcome measures include anxiety, posttraumatic stress, severity and frequency of abuse, quality of life and cost-effectiveness of the intervention. Data from a subsample of women in both groups will contribute to a nested qualitative study with repeat interviews during the year of follow-up.

Discussion

This study will contribute to the evidence base for management of the psychological needs of women experiencing DVA. The findings will have important implications for healthcare commissioners and providers, as well as third sector specialist DVA agencies providing services to this client group.

Trial registration

ISRCTN58561170
Validation of the English version of the UNESP-Botucatu multidimensional composite pain scale for assessing postoperative pain in cats
Authors: Brondani Juliana T , Mama Khursheed R , Luna Stelio P L , Wright Bonnie D , Niyom Sirirat , Ambrosio Jennifer , Vogel Pamela R , Padovani Carlos R
Published: July 2013

Background

A scale validated in one language is not automatically valid in another language or culture. The purpose of this study was to validate the English version of the UNESP-Botucatu multidimensional composite pain scale (MCPS) to assess postoperative pain in cats. The English version was developed using translation, back-translation, and review by individuals with expertise in feline pain management. In sequence, validity and reliability tests were performed.

Results

Of the three domains identified by factor analysis, the internal consistency was excellent for ‘pain expression’ and ‘psychomotor change’ (0.86 and 0.87) but not for ‘physiological variables’ (0.28). Relevant changes in pain scores at clinically distinct time points (e.g., post-surgery, post-analgesic therapy), confirmed the construct validity and responsiveness (Wilcoxon test, p < 0.001). Favorable correlation with the IVAS scores (p < 0.001) and moderate to very good agreement between blinded observers and ‘gold standard’ evaluations, supported criterion validity. The cut-off point for rescue analgesia was > 7 (range 0–30 points) with 96.5% sensitivity and 99.5% specificity.

Conclusions

The English version of the UNESP-Botucatu-MCPS is a valid, reliable and responsive instrument for assessing acute pain in cats undergoing ovariohysterectomy, when used by anesthesiologists or anesthesia technicians. The cut-off point for rescue analgesia provides an additional tool for guiding analgesic therapy.
Evaluation of immune and stress status in harbour porpoises (Phocoena phocoena): can hormones and mRNA expression levels serve as indicators to assess stress?
Authors: Müller Sabine , Lehnert Kristina , Seibel Henrike , Driver Jörg , Ronnenberg Katrin , Teilmann Jonas , van Elk Cornelius , Kristensen Jakob , Everaarts Eligius , Siebert Ursula
Published: July 2013

Background

The harbour porpoise is exposed to increasing pressure caused by anthropogenic activities in its marine environment. Numerous offshore wind farms are planned or under construction in the North and Baltic Seas, which will increase underwater noise during both construction and operation. A better understanding of how anthropogenic impacts affect the behaviour, health, endocrinology, immunology and physiology of the animals is thus needed. The present study compares levels of stress hormones and mRNA expression of cytokines and acute-phase proteins in blood samples of harbour porpoises exposed to different levels of stress during handling, in rehabilitation or permanent human care.

Free-ranging harbour porpoises, incidentally caught in pound nets in Denmark, were compared to harbour porpoises in rehabilitation at SOS Dolfijn in Harderwijk, the Netherlands, and individuals permanently kept in human care in the Dolfinarium Harderwijk and Fjord & Belt Kerteminde, Denmark. Blood samples were investigated for catecholamines, adrenaline, noradrenaline and dopamine, as well as for adrenocorticotropic hormone (ACTH), cortisol, metanephrine and normetanephrine. mRNA expression levels of relevant cell mediators (cytokines IL-10 and TNFα, acute-phase proteins haptoglobin and C-reactive protein and the heat shock protein HSP70) were measured using real-time PCR.

Results

Biomarker expression levels varied between free-ranging animals and porpoises in human care. Hormone and cytokine ranges showed correlations to each other and to the health status of investigated harbour porpoises. Hormone concentrations were higher in free-ranging harbour porpoises than in animals in human care. Adrenaline can be used as a parameter for the initial reaction to acute stress situations; noradrenaline, dopamine, ACTH and cortisol are more likely indicators for the following minutes of acute stress. There is evidence for different correlations between production of normetanephrine, metanephrine, cortisol and the expression of IL-10, HSP70 and haptoglobin.

Conclusions

The expression patterns of the selected molecular biomarkers of the immune system are promising to reflect the health and immune status of the harbour porpoise under different levels of stress.