bluuebunny/crossref_metadata_2025 huggingface dataset:
Equilibrium and Kinetic Aspects in the Sensitization of Monolayer Transparent TiO2Thin Films with Porphyrin Dyes for DSSC Applications
Authors: Giovannetti Rita , Zannotti Marco , Alibabaei Leila , Ferraro Stefano
Published: January 2014

Free base, Cu(II) and Zn(II) complexes of the 2,7,12,17-tetrapropionic acid of 3,8,13,18-tetramethyl-21H,23H porphyrin (CPI) in solution and bounded to transparent monolayer TiO2nanoparticle films were studied to determine their adsorption on TiO2surface, to measure the adsorption kinetics and isotherms, and to use the results obtained to optimize the preparation of DSSC photovoltaic cells. Adsorption studies were carried out on monolayer transparent TiO2films of a known thickness. Langmuir and Frendlich adsorption constants of CPI-dyes on TiO2monolayer surface have been calculated as a function of the equilibrium concentrations in the solutions. The amount of these adsorbed dyes showed the accordance with Langmuir isotherm. Kinetic data on the adsorption of dyes showed significantly better fits to pseudo-first-order model and the evaluated rate constants linearly increased with the grow of initial dye concentrations. The stoichiometry of the adsorption of CPI-dyes into TiO2and the influence of presence of coadsorbent (chenodeoxycholic acid) have been established. The DSSC obtained in the similar conditions showed that the best efficiency can be obtained in the absence of coadsorbent with short and established immersion times.
On an Interpolation Based Spectral Homotopy Analysis Method for PDE Based Unsteady Boundary Layer Flows
Authors: Motsa S. S.
Published: January 2014

This work presents a new approach to the application of the spectral homotopy analysis method (SHAM) in solving non-linear partial differential equations (PDEs). The proposed approach is based on an innovative idea of seeking solutions that obey a rule of solution expression that is defined in terms of bivariate Lagrange interpolation polynomials. The applicability and effectiveness of the expanded SHAM approach are tested on a non-linear PDE that models the problem of unsteady boundary layer flow caused by an impulsively stretching plate. Numerical simulations are conducted to generate results for the important flow properties such as the local skin friction. The accuracy of the present results is validated against existing results from the literature and against results generated using the Keller-box method. The preliminary results from the proposed study indicate that the present method is more accurate and computationally efficient than more traditional methods used for solving PDEs that describe nonsimilar boundary layer flow.
Anharmonic Spectroscopic Investigation of Tellurophene and Its Perdeuterated Isotopomer: Application of Second-Order Perturbation Theory
Authors: Alparone Andrea
Published: January 2014

Vibrational spectra of tellurophene and of its perdeuterated isotopomer were computed using the DFT-B3LYP functional with the LANL2DZ(d,p) basis set. The frequencies of fundamental and overtone transitions were obtained in vacuum under the harmonic approximation and anharmonic second-order perturbation theory (PT2). On the whole the anharmonic corrections reduce the harmonic wavenumber values, in many cases better reproducing the observed fundamental frequencies. The largest anharmonic effects are found for the C–H and C–D stretching vibrations, characterized by relatively high anharmonic coupling constants (up to ca. 120 cm−1). For the C–H/C–D stretches, the harmonic H→D isotopic frequency red-shifts overestimate the observed data by 47–63 cm−1 (5.9–8.1%), whereas the PT2 computations exhibit significantly better performances, predicting the experimental data within 1–19 cm−1 (0.1–2.4%).
Combinatorial Interpretation of General Eulerian Numbers
Authors: Xiong Tingyao , Hall Jonathan I. , Tsao Hung-Ping
Published: January 2014

Since the 1950s, mathematicians have successfully interpreted the traditional Eulerian numbers and q-Eulerian numbers combinatorially. In this paper, the authors give a combinatorial interpretation to the general Eulerian numbers defined on general arithmetic progressions a,a+d,a+2d,….
Association between Argyrophilic Proteins of Nucleolar Organizer Regions, Clinicomorphological Parameters, and Survival in Non-Small-Cell Lung Cancer
Authors: Kobyakov Dmitriy , Klimachev Vladimir , Avdalyan Ashot , Bobrov Igor , Bychkova Elena , Kruglova Natalia , Lazarev Aleksandr , Lushnikova Elena , Nepomnyashchikh Lev
Published: January 2014

We studied argyrophilic proteins associated with nucleolar organizer regions (AgNOR) in non-small-cell cancer. We determined the area index (AI) and coefficient of variation (CV) of AgNOR. AI is associated with the key clinicomorphological parameters within the TNM system: T and N values, greatest tumor dimension up to 3 cm and more, disease stage, histogenesis, and tumor differentiation. CV is associated with T value, greatest tumor dimension up to 3 cm and more, histogenesis, and tumor differentiation. Survival of patients is longer in low AI or CV values versus high AI or CV values, longer in low AI and CV values (−AI/−CV type), shorter in high AI and CV values (+AI/+CV type), and intermediate in opposite AI and CV values (−AI/+CV and +AI/−CV types). Independent predictors in non-small-cell lung cancer include N value, greatest tumor dimension, histogenesis, and CV. Assessment of quantitative values and heterogeneity of AgNOR is important for differential diagnosis and prognosis of non-small-cell lung cancer.
Compound Specific Extraction of Camptothecin fromNothapodytes nimmonianaand Piperine fromPiper nigrumUsing Accelerated Solvent Extractor
Authors: Upadhya Vinayak , Pai Sandeep R. , Sharma Ajay K. , Hegde Harsha V. , Kholkute Sanjiva D. , Joshi Rajesh K.
Published: January 2014

Effects of varying temperatures with constant pressure of solvent on extraction efficiency of two chemically different alkaloids were studied. Camptothecin (CPT) from stem ofNothapodytes nimmoniana(Grah.) Mabb. and piperine from the fruits ofPiper nigrumL. were extracted using Accelerated Solvent Extractor (ASE). Three cycles of extraction for a particular sample cell at a given temperature assured complete extraction. CPT and piperine were determined and quantified by using a simple and efficient UFLC-PDA (245 and 343 nm) method. Temperature increased efficiency of extraction to yield higher amount of CPT, whereas temperature had diminutive effect on yield of piperine. Maximum yield for CPT was achieved at80∘Cand for piperine at40∘C. Thus, the study determines compound specific extraction of CPT fromN. nimmonianaand piperine fromP. nigrumusing ASE method. The present study indicates the use of this method for simple, fast, and accurate extraction of the compound of interest.
Use and Diversity of Palm (Arecaceae) Resources in Central Western Brazil
Authors: Martins Renata Corrêa , Filgueiras Tarciso de Sousa , Albuquerque Ulysses Paulino
Published: January 2014

Arecaceae Schultz-Sch. (Palmae Juss.), a member of the monocotyledon group, is considered one of the oldest extant angiosperm families on Earth. This family is highly valuable because of its species diversity, its occurrence in a wide range of habitats, and its status as an integral part of the culture and the family-based economy of many traditional and nontraditional communities. The main objectives of this study were to perform an ethnobotanical study involving these palms and a “Quilombola” (Maroon) community in the municipality of Cavalcante, GO, Brazil. The variables gender, age, and formal schooling had no influence on the number of species recognized and used by the Kalungas. Ethnobotanical studies based on traditional knowledge in addition to use and management of palms are fundamental aspects for planning and appliance of public policies directed to the use of natural resources and improvement of life quality.
Orthopedic Management of Patients with Pompe Disease: A Retrospective Case Series of 8 Patients
Authors: Haaker Gerrit , Forst Jürgen , Forst Raimund , Fujak Albert
Published: January 2014

Introduction.Pompe disease (PD), a lysosomal storage disease as well as a neuromuscular disorder, is a rare disease marked by progressive muscle weakness. Enzyme replacement therapy (ERT) in recent years allowed longer survival but brought new problems to the treatment of PD with increasing affection of the musculoskeletal system, particularly with a significantly higher prevalence of scoliosis. The present paper deals with the orthopedic problems in patients with PD and is the first to describe surgical treatment of scoliosis in PD patients.Patients and Methods.The orthopedic problems and treatment of eight patients with PD from orthopedic consultation for neuromuscular disorders are retrospectively presented. We analyzed the problems of scoliosis, hip dysplasia, feet deformities, and contractures and presented the orthopedic treatment options.Results.Six of our eight PD patients had scoliosis and two young patients were treated by operative spine stabilization with benefits for posture and sitting ability. Hip joint surgery, operative contracture release, and feet deformity correction were performed with benefits for independent activity.Conclusion.Orthopedic management gains importance due to extended survival and musculoskeletal involvement under ERT. Surgical treatment is indicated in distinct cases. Further investigation is required to evidence the effect of surgical spine stabilization in PD.
Performance Analysis of the Sleep Mode in WiMAX 2 Networks with Multimedia Application
Authors: Jin Shunfu , Yue Wuyi , Zhang Xiaofei
Published: January 2014

We consider the sleep mode with multimedia application in WiMAX 2 networks, where the real-time traffic includes the real-time and the best-effort traffic mixed. We present a queueing model with multiple heterogeneous vacations to characterize the system probability behavior in the networks with multimedia application. Taking into account the correlation of the real-time traffic, we assume the arrival process as a discrete-time Markovian arrival process (D-MAP) and analyze this queueing model by using the method of an embedded Markov chain. Then, we present the probability distribution for the number of data packets. Accordingly, we give the formulas for the performance measures in terms of the average response time of data packets, the energy saving ratio, and the standard deviation of the number of data packets. We also develop a cost function to determine the optimal length of the sleep cycle in order to maximize the energy saving ratio while satisfying the Quality of Service (QoS) constraint on the average response time of data packets. Finally, we provide numerical results to investigate the influence of the system parameters on the system performance.
Incidence of and Risk Factors for Catheterization-Induced Complete Heart Block in the Pediatric Cardiac Catheterization Laboratory
Authors: Mah Douglas Y. , Porras Diego , Bergersen Lisa , Marshall Audrey C. , Walsh Edward P. , Triedman John K.
Published: January 2014

Background—

The majority of the literature on catheterization-induced heart block (CIHB) was published >30 years ago. The field of cardiac catheterization has evolved, performing more interventional compared with diagnostic cases. We sought to determine the incidence and risk factors of CIHB.

Methods and Results—

A catheterization database that records the occurrence of adverse events on all cases was queried for heart block. Additional retrospective data on event outcome were collected on patients who developed CIHB. Multivariable logistic regression modeling was used to identify risk factors of CIHB (odds ratio, 95% confidence interval). In a 6-year period, 6183 cases were performed. The median weight was 15.0 (7.0–47.0) kg, with 29% consisting of infants <1 year. A total of 72% involved complex congenital heart disease. One hundred thirty-five cases were complicated by CIHB (2.2%; 95% confidence interval, 1.9–2.6). Age <1 year (3.0; 2.2–4.3) and case duration ≥2 hours (3.4; 2.0–6.0) were risk factors of CIHB; cardiac anatomy and intervention performed were not. A total of 96% of CIHB recovered within 1 week but 6 patients underwent pacemaker placement (3 L-loop ventricles, 2 intracardiac devices, 1 double inlet-double outlet RV). Of these, 50% recovered atrioventricular nodal conduction within 1 month; 2 patients with L-loop ventricles and 1 patient with a left ventricular-to-right atrial device did not recover.

Conclusions—

The incidence of CIHB in the pediatric cardiac catheterization laboratory is low at 2.2%. Risk factors include young age and long case duration. The recovery of atrioventricular nodal function after CIHB is high and follows a similar time course to that of postsurgical heart block.
High-Density Mapping of Ventricular Scar
Authors: Nayyar Sachin , Wilson Lauren , Ganesan Anand N. , Sullivan Thomas , Kuklik Pawel , Chapman Darius , Brooks Anthony G. , Mahajan Rajiv , Baumert Mathias , Young Glenn D. , Sanders Prashanthan , Roberts-Thomson Kurt C.
Published: January 2014

Background—

Surviving myocytes within scar may form channels that support ventricular tachycardia (VT) circuits. There are little data on the properties of channels that comprise VT circuits and those that are non-VT supporting channels.

Methods and Results—

In 22 patients with ischemic cardiomyopathy and VT, high-density mapping was performed with the PentaRay catheter and Ensite NavX system during sinus rhythm. A channel was defined as a series of matching pace-maps with a stimulus (S) to QRS time of ≥40 ms. Sites were determined to be part of a VT channel if there were matching pace-maps to the VT morphology. This was confirmed with entrainment mapping when possible. Of the 238 channels identified, 57 channels corresponded to an inducible VT. Channels that were part of a VT circuit were more commonly located within dense scar than non-VT channels (97% versus 82%;
P
=0.036). VT supporting channels were of greater length (mean±SEM, 53±5 versus 33±4 mm), had higher longest S-QRS (130±12 versus 82±12 ms), longer conduction time (103±14 versus 43±13 ms), and slower conduction velocity (0.87±0.23 versus 1.39±0.21 m/s) than non-VT channels (
P
<0.001). Of all the fractionated, late, and very late potentials located in scar, only 21%, 26%, and 29%, respectively, were recorded within VT channels.

Conclusions—

High-density mapping shows substantial differences among channels in ventricular scar. Channels supporting VT are more commonly located in dense scar, longer than non-VT channels, and have slower conduction velocity. Only a minority of scar-related potentials participate in the VT supporting channels.
Mendelian Disorders of High-Density Lipoprotein Metabolism
Authors: Oldoni Federico , Sinke Richard J. , Kuivenhoven Jan Albert
Published: January 2014

High-density lipoproteins (HDLs) are a highly heterogeneous and dynamic group of the smallest and densest lipoproteins present in the circulation. This review provides the current molecular insight into HDL metabolism led by articles describing mutations in genes that have a large affect on HDL cholesterol levels through their roles in HDL and triglyceride metabolism. Using this information from both human and animal studies, it is discussed how HDL is produced, remodeled in the circulation, affected by factors that control the metabolism of triglyceride-rich lipoproteins, how it helps maintain cellular cholesterol homeostasis, and, finally, how it is catabolized. It can be concluded that HDL cholesterol as a trait is genetically heterogeneous, with as many as 40 genes involved. In most cases, only heterozygotes of gene variants are known, and HDL cholesterol as a trait is inherited in an autosomal-dominant manner. Only 3 Mendelian disorders of HDL metabolism are currently known, which are inherited in an autosomal-recessive mode.
Regulation of High-Density Lipoprotein Metabolism
Authors: Rye Kerry-Anne , Barter Philip J.
Published: January 2014

There is compelling evidence from human population studies that plasma levels of high-density lipoprotein (HDL) cholesterol correlate inversely with cardiovascular risk. Identification of this relationship has stimulated research designed to understand how HDL metabolism is regulated. The ultimate goal of these studies has been to develop HDL-raising therapies that have the potential to decrease the morbidity and mortality associated with atherosclerotic cardiovascular disease. However, the situation has turned out to be much more complex than originally envisaged. This is partly because the HDL fraction consists of multiple subpopulations of particles that vary in terms of shape, size, composition, and surface charge, as well as in their potential cardioprotective properties. This heterogeneity is a consequence of the continual remodeling and interconversion of HDL subpopulations by multiple plasma factors. Evidence that the remodeling of HDLs may impact on their cardioprotective properties is beginning to emerge. This serves to highlight the importance of understanding not only how the remodeling and interconversion of HDL subpopulations is regulated but also how these processes are affected by agents that increase HDL levels. This review provides an overview of what is currently understood about HDL metabolism and how the subpopulation distribution of these lipoproteins is regulated.
ATP-Binding Cassette Transporters, Atherosclerosis, and Inflammation
Authors: Westerterp Marit , Bochem Andrea E. , Yvan-Charvet Laurent , Murphy Andrew J. , Wang Nan , Tall Alan R.
Published: January 2014

Although recent genome-wide association studies have called into question the causal relationship between high-density lipoprotein (HDL) cholesterol levels and cardiovascular disease, ongoing research in animals and cells has produced increasing evidence that cholesterol efflux pathways mediated by ATP-binding cassette (ABC) transporters and HDL suppress atherosclerosis. These differing perspectives may be reconciled by a modified HDL theory that emphasizes the antiatherogenic role of cholesterol flux pathways, initiated in cells by ABC transporters. ABCA1 and ABCG1 control the proliferation of hematopoietic stem and multipotential progenitor cells in the bone marrow and hematopoietic stem and multipotential progenitor cell mobilization and extramedullary hematopoiesis in the spleen. Thus, activation of cholesterol efflux pathways by HDL infusions or liver X receptor activation results in suppression of hematopoietic stem and multipotential progenitor cell mobilization and extramedullary hematopoiesis, leading to decreased production of monocytes and neutrophils and suppression of atherosclerosis. In addition, macrophage-specific knockout of transporters has confirmed their role in suppression of inflammatory responses in the arterial wall. Recent studies have also shown that ABCG4, a close relative of ABCG1, controls platelet production, atherosclerosis, and thrombosis. ABCG4 is highly expressed in megakaryocyte progenitors, where it promotes cholesterol efflux to HDL and controls the proliferative responses to thrombopoietin. Reconstituted HDL infusions act in an ABCG4-dependent fashion to limit hypercholesterolemia-driven excessive platelet production, thrombosis, and atherogenesis, as occurs in human myeloproliferative syndromes. Activation of ABC transporter–dependent cholesterol efflux pathways in macrophages, hematopoietic stem and multipotential progenitor cells, or platelet progenitors by reconstituted HDL infusion or liver X receptor activation remain promising approaches to the treatment of human atherothrombotic diseases.
Atherosclerotic Plaque Destabilization
Authors: Silvestre-Roig Carlos , de Winther Menno P. , Weber Christian , Daemen Mat J. , Lutgens Esther , Soehnlein Oliver
Published: January 2014

Understanding the pathophysiology of atherogenesis and the progression of atherosclerosis have been major goals of cardiovascular research during the previous decades. However, the complex molecular and cellular mechanisms underlying plaque destabilization remain largely obscure. Here, we review how lesional cells undergo cell death and how failed clearance exacerbates necrotic core formation. Advanced atherosclerotic lesions are further weakened by the pronounced local activity of matrix-degrading proteases as well as immature neovessels sprouting into the lesion. To stimulate translation of the current knowledge of molecular mechanisms of plaque destabilization into clinical studies, we further summarize available animal models of plaque destabilization. Based on the molecular mechanisms leading to plaque instability, we outline the current status of clinical and preclinical trials to induce plaque stability with a focus on induction of dead cell clearance, inhibition of protease activity, and dampening of inflammatory cell recruitment.
The Impact of Armed Conflict on Economic Performance
Authors: Serneels Pieter , Verpoorten Marijke
Published: January 2014

Important gaps remain in the understanding of the economic consequences of civil war. Focusing on the conflict in Rwanda in the early 1990s, and using micro data, this article finds that households and localities that experienced more intense conflict are lagging behind in terms of consumption six years after the conflict, a finding that is robust to taking into account the endogeneity of violence. Significantly different returns to land and labor are observed between zones that experienced low- and high-intensity conflict which is consistent with the ongoing recovery. Distinguishing between civil war and genocide, the findings also provide evidence that these returns, and by implication the process of recovery, depend on the form of violence.
Mediators of the Association Between Driving Cessation and Mortality Among Older Adults
Authors: O’Connor Melissa L. , Edwards Jerri D. , Waters Martinique P. , Hudak Elizabeth M. , Valdés Elise G.
Published: January 2014

Objective: The present study examined health and physical performance as mediators of the association between driving cessation and mortality among older residents of small and large cities. Method: Participants ( N = 2,793) were from the Advanced Cognitive Training for Independent and Vital Elderly (ACTIVE) study. Participants’ driving status and health were measured at baseline, and mortality rates were observed across the subsequent 5 years. Results: Overall, mortality risk was 1.68 times higher for nondrivers versus drivers; this relationship was significantly mediated by physical performance and social, physical, and general health. For large-city residents, mediation effects for all mediators were significant and complete. For small-city residents, only physical and general health were significant mediators, and these effects were partial. Discussion: Health difficulties that accompany or follow driving cessation may explain the association between driving cessation and mortality, particularly for residents of large cities, where alternative transportation options may be more numerous.
Relationship of Demographic and Health Factors to Cognition in Older Adults in the ACTIVE Study
Authors: Rexroth Daniel F. , Tennstedt Sharon L. , Jones Richard N. , Guey Lin T. , Rebok George W. , Marsiske Michael M. , Xu Yan , Unverzagt Frederick W.
Published: January 2014

Objective: Examine the relationship of demographics and health conditions, alone and in combination, on objective measures of cognitive function in a large sample of community-dwelling older adults. Method: Baseline data from 2,782 participants in the Advanced Cognitive Training in Independent and Vital Elderly (ACTIVE) study were used to examine relationships of demographics and health conditions with composite scores of memory, reasoning, and speed of processing. Results: Younger age, increased education, and White race were independently associated with better performance in each cognitive domain after adjusting for gender and health conditions. Male gender, diabetes, and suspected clinical depression were associated with poorer cognitive functioning; suspected clinical depression was associated with lower reasoning and diabetes and history of stroke with slower speed of processing. Discussion: Age, education, and race are consistently associated with cognitive performance in this sample of older community-dwelling adults. Diabetes, stroke, and suspected clinical depression had independent but weaker effects on cognition.
The Influence of Cognitive Training on Older Adults’ Recall for Short Stories
Authors: Sisco Shannon M. , Marsiske Michael , Gross Alden L. , Rebok George W.
Published: January 2014

Objective: This article investigated how a multicomponent memory intervention affected memory for prose. We compared verbatim and paraphrased recall for short stories immediately and 1, 2, 3, and 5 years post-intervention in the Advanced Cognitive Training for Independent and Vital Elderly (ACTIVE) sample. Method: We studied 1,912 ACTIVE participants aged 65 to 91. Participants were randomized into one of three training arms (Memory, Reasoning, Speed of Processing) or a no-contact Control group; about half of the trained participants received additional booster training 1 and 3 years post-intervention. Results: Memory-trained participants showed higher verbatim recall than non-memory-trained participants. Booster-memory training led to higher verbatim recall. Memory training effects were evident immediately following training and not after 1 year following training. Discussion: Results suggest that multifactorial memory training can improve verbatim recall for prose, but the effect does not last without continued intervention.
Reasoning Training in the ACTIVE Study
Authors: Willis Sherry L. , Caskie Grace I. L.
Published: January 2014

Objective: To characterize change through 5-year follow-up, associated with training, booster, adherence, and other characteristics. Methods: Sample included all individuals randomly assigned to reasoning training (N = 699). Piecewise latent growth modeling was used to examine trajectory of performance on outcome measures. Results: Training resulted in improved reasoning performance through Year 5. A significant third annual booster effect was one-half the size of the training effect. Training adherence resulted in greater training effects. Higher education, Mini-Mental State Exam (MMSE), better health, and younger age related to higher baseline performance. Higher MMSE was related to larger training effects, larger linear slopes, and smaller booster effects. Significant functional outcomes included a training effect for complex reaction time (CRT), and first annual booster effects for the CRT and observed tasks of daily living. Discussion: Initial training gain was comparable with magnitude of age-related cognitive decline over 5 years with no training. Neither age nor gender predicted training or booster effects, indicating the generality of training effects across age (65-90 years).
Gender and Racial Disparities in Driving Cessation Among Older Adults
Authors: Choi Moon , Mezuk Briana , Lohman Matthew C. , Edwards Jerri D. , Rebok George W.
Published: January 2014

Objectives: To longitudinally examine gender and racial disparities in driving cessation among older adults. Methods: Data came from the Advanced Cognitive Training for Independent and Vital Elderly (ACTIVE) Study ( N = 1,789). Logistic generalized estimating equations (GEE) were used to identify predictors of driving cessation; stratified analysis and interaction terms were used to determine whether factors differed by gender and race. Results: Two hundred and five (11.5%) participants stopped driving over the study period. Education was associated with increased risk of cessation for men (adjusted odds ratio [AOR] =1.40, 95% confidence interval [CI] =1.10 to 1.78), but decreased risk for women (AOR = 0.90, 95% CI = 0.82-0.98). Being married was associated with lower risk of cessation for men (AOR = 0.18, 95% CI = 0.06-0.56) but was unrelated to cessation for women (AOR = 1.00, 95% CI = 0.56-1.80). Results were consistent with the hypothesis that racial disparities in cessation widen with increasing age. Discussion: Factors predictive of driving cessation vary by gender. Racial disparities in cessation are wider at older ages. Transportation policies and programs should account for social determinants and aim to address social disparities in driving mobility among older adults.
Cardiovascular risk in patients with hemophilia
Authors: Kamphuisen Pieter W. , ten Cate Hugo
Published: January 2014

Patients with hemophilia, who have a lifelong hypocoagulability, seem to have a lower cardiovascular mortality than the general population. Nevertheless, the prevalence of cardiovascular risk factors in patients with hemophilia is as prevalent as in the general population, and hypertension is even more common. Furthermore, hemophiliacs have the same degree of atherosclerosis as the general population. The reduced cardiovascular mortality may be explained by reduced thrombus formation resulting from hypocoagulability. On the other hand, hemophilia, which is associated with reduced thrombin generation, may also increase atherosclerotic plaque stability, as has been shown in mice. Because treatment of these events is extremely challenging in patients with increased bleeding tendency, detection and aggressive treatment of risk factors is mandatory.
A genome-wide association study of seed protein and oil content in soybean
Authors: Hwang Eun-Young , Song Qijian , Jia Gaofeng , Specht James E , Hyten David L , Costa Jose , Cregan Perry B
Published: January 2014

Background

Association analysis is an alternative to conventional family-based methods to detect the location of gene(s) or quantitative trait loci (QTL) and provides relatively high resolution in terms of defining the genome position of a gene or QTL. Seed protein and oil concentration are quantitative traits which are determined by the interaction among many genes with small to moderate genetic effects and their interaction with the environment. In this study, a genome-wide association study (GWAS) was performed to identify quantitative trait loci (QTL) controlling seed protein and oil concentration in 298 soybean germplasm accessions exhibiting a wide range of seed protein and oil content.

Results

A total of 55,159 single nucleotide polymorphisms (SNPs) were genotyped using various methods including Illumina Infinium and GoldenGate assays and 31,954 markers with minor allele frequency >0.10 were used to estimate linkage disequilibrium (LD) in heterochromatic and euchromatic regions. In euchromatic regions, the mean LD (r

2
) rapidly declined to 0.2 within 360 Kbp, whereas the mean LD declined to 0.2 at 9,600 Kbp in heterochromatic regions. The GWAS results identified 40 SNPs in 17 different genomic regions significantly associated with seed protein. Of these, the five SNPs with the highest associations and seven adjacent SNPs were located in the 27.6-30.0 Mbp region of Gm20. A major seed protein QTL has been previously mapped to the same location and potential candidate genes have recently been identified in this region. The GWAS results also detected 25 SNPs in 13 different genomic regions associated with seed oil. Of these markers, seven SNPs had a significant association with both protein and oil.

Conclusions

This research indicated that GWAS not only identified most of the previously reported QTL controlling seed protein and oil, but also resulted in narrower genomic regions than the regions reported as containing these QTL. The narrower GWAS-defined genome regions will allow more precise marker-assisted allele selection and will expedite positional cloning of the causal gene(s).
Characterization and resuscitation of ‘non-culturable’ cells of Legionella pneumophila
Authors: Ducret Adrien , Chabalier Maïalène , Dukan Sam
Published: January 2014

Background

Legionella pneumophila is a waterborne pathogen responsible for Legionnaires’ disease, an infection which can lead to potentially fatal pneumonia. After disinfection, L. pneumophila has been detected, like many other bacteria, in a “viable but non culturable” state (VBNC). The physiological significance of the VBNC state is unclear and controversial: it could be an adaptive response favoring long-term survival; or the consequence of cellular deterioration which, despite maintenance of certain features of viable cells, leads to death; or an injured state leading to an artificial loss of culturability during the plating procedure. VBNC cells have been found to be resuscitated by contact with amoebae.

Results

We used quantitative microscopic analysis, to investigate this “resuscitation” phenomenon in L. pneumophila in a model involving amending solid plating media with ROS scavengers (pyruvate or glutamate), and co-culture with amoebae. Our results suggest that the restoration observed in the presence of pyruvate and glutamate may be mostly due to the capacity of these molecules to help the injured cells to recover after a stress. We report evidence that this extracellular signal leads to a transition from a not-culturable form to a culturable form of L. pneumophila, providing a technique for recovering virulent and previously uncultivated forms of L. pneumophila.

Conclusion

These new media could be used to reduce the risk of underestimation of counts of virulent of L. pneumophila cells in environmental samples.
Over-expression of COX-2 mRNA in colorectal cancer
Authors: Roelofs Hennie MJ , te Morsche Rene HM , van Heumen Bjorn WH , Nagengast Fokko M , Peters Wilbert HM
Published: January 2014

Background

Cyclooxygenase-2 (COX-2, PTGS2) is an enzyme involved in the synthesis of prostaglandins and thromboxanes, which are regulators of biologic processes such as inflammation, cell proliferation and angiogenesis. COX-2 over-expression was reported in many (pre) malignant tissues, but data strongly vary and seem to depend on the methodology used.

Methods

Normal colorectal mucosa and paired cancerous tissue from 60 patients with colorectal cancer was investigated for the levels of COX-2 mRNA by real-time quantitative Polymerase Chain Reaction (qPCR). COX-2 levels were expressed relative to either: tissue weight or levels of the housekeeping genes beta-2 microglobulin (B2M) and glyceraldehyde-3-phosphate dehydrogenase (GAPDH).

Results

COX-2 mRNA levels, normalized with respect to tissue weight or mRNA levels of the housekeeping genes B2M or GAPDH, were over-expressed in 80%, 70% and 40% of the colorectal tumor tissues, as compared to the paired adjacent normal colorectal mucosa samples, respectively. Highest mRNA COX-2 ratios tumor/normal were measured when expressed per mg tissue (mean ratio 21.6). When normalized with respect to the housekeeping genes B2M or GAPDH, mean tumor/normal ratios were 16.1 and 7.5, respectively.

Conclusion

Expression of COX-2 mRNA levels per mg tissue is most simple in comparison to normalization with respect to the housekeeping genes B2M or GAPDH. Levels of COX-2 mRNA are found over-expressed in almost 80% of the colorectal tumors, compared to paired adjacent normal colorectal mucosa, suggesting a role of COX-2 as a potential biomarker for cancer risk, whereas inhibitors of COX-2 could be of value in chemoprevention of colon cancer.
Attitudes, practices and information needs regarding novel influenza A (H7N9) among employees of food production and operation in Guangzhou, Southern China: a cross-sectional study
Authors: Li Tiegang , Feng Jing , Qing Pengzhe , Fan Xiaomei , Liu Weisi , Li MeiXia , Wang Ming
Published: January 2014

Background

As of 30 May 2013, 132 human infections with avian influenza A (H7N9) had been reported in 10 Chinese cities. On 17 May 2013, because a chicken infection with H7 subtype avian influenza virus was detected in Guanzhou, Guangzhou became the 11th city to conduct emergency response operations. The goal of this study was to identify attitudes, practices and information needs among employees of food production and operation in Guangzhou.

Methods

A cross-sectional survey of face-to-face interviews was used during 17–24 June 2013. All adults seeking health examination in Guangzhou Center for Disease Control and Prevention who had lived in Guangzhou for at least 3 months, were engaged in food production and operation, and agreed to participate were interviewed.

Results

Of 1,450 participants, 69.72% worried about being infected with the A/H7N9 and 74.41% stated that they had searched for information about A/H7N9. The internet (76.92%), television (67.56%), and newspapers (56.26%) were the main methods of obtaining information; the use of these methods differed significantly by various demographic variables (P < 0.05). More than one-fifth of participants complained that the information was not timely enough (20.28%) and was intentionally concealed by the government (20.76%). Nearly one-third (32.35%) did not believe that the government could control the A/H7N9 epidemic. Most participants (80.76%) reported washing hands more frequently than before, while over one-third (37.17%) stated no longer buying poultry. A total of 84.00% indicated a willingness to receive an A/H7N9 vaccine, and the primary reason for not being willing was concern about safety (58.19%). A history of influenza vaccination and worry about being infected with the A/H7N9 were significantly associated with intention to receive an A/H7N9 vaccine (P < 0.05).

Conclusions

Our findings provide insight into the attitudes and practices of employees of food production and operation 3 months after the first human A/H7N9 case reported in China, and 1 month after infected chickens were identified in Guangzhou. Distrust in the health department should be addressed, and more effort should be made to improve compliance of proper preventive measures to reduce panic among the public. The information needs should be taken into account in the next step of health education.
The effect of antihypertensive agents on sleep apnea: protocol for a randomized controlled trial
Authors: Cichelero Fábio Tremea , Martinez Denis , Fuchs Sandra Costa , Gus Miguel , Moreira Leila Beltrami , Fuchs Flávio Danni
Published: January 2014

Background

Obstructive sleep apnea (OSA) and hypertension are well-known cardiovascular risk factors. Their control could reduce the burden of heart disease across populations. Several drugs are used to control hypertension, but the only consistently effective treatment of OSA is continuous positive airway pressure. The identification of a drug capable of improving OSA and hypertension simultaneously would provide a novel approach in the treatment of both diseases.

Methods/Design

This is a randomized double-blind clinical trial, comparing the use of chlorthalidone with amiloride versus amlodipine as a first drug option in patients older than 40 years of age with stage I hypertension (140 to 159/90 to 99 mmHg) and moderate OSA (15 to 30 apneas/hour of sleep). The primary outcomes are the variation of the number of apneas per hour and blood pressure measured by ambulatory blood pressure monitoring. The secondary outcomes are adverse events, somnolence scale (Epworth), ventilatory parameters and C reactive protein levels. The follow-up will last 8 weeks. There will be 29 participants per group. The project has been approved by the ethics committee of our institution.

Discussion

The role of fluid retention in OSA has been known for several decades. The use of diuretics are well established in treating hypertension but have never been appropriately tested for sleep apnea. As well as testing the efficacy of these drugs, this study will help to understand the mechanisms that link hypertension and sleep apnea and their treatment.

Trial registration

ClinicalTrials.gov: NCT01896661
Guidance for updating clinical practice guidelines: a systematic review of methodological handbooks
Authors: Vernooij Robin WM , Sanabria Andrea Juliana , Solà Ivan , Alonso-Coello Pablo , Martínez García Laura
Published: January 2014

Background

Updating clinical practice guidelines (CPGs) is a crucial process for maintaining the validity of recommendations. Methodological handbooks should provide guidance on both developing and updating CPGs. However, little is known about the updating guidance provided by these handbooks.

Methods

We conducted a systematic review to identify and describe the updating guidance provided by CPG methodological handbooks and included handbooks that provide updating guidance for CPGs. We searched in the Guidelines International Network library, US National Guidelines Clearinghouse and MEDLINE (PubMed) from 1966 to September 2013. Two authors independently selected the handbooks and extracted the data. We used descriptive statistics to analyze the extracted data and conducted a narrative synthesis.

Results

We included 35 handbooks. Most handbooks (97.1%) focus mainly on developing CPGs, including variable degrees of information about updating. Guidance on identifying new evidence and the methodology of assessing the need for an update is described in 11 (31.4%) and eight handbooks (22.8%), respectively. The period of time between two updates is described in 25 handbooks (71.4%), two to three years being the most frequent (40.0%). The majority of handbooks do not provide guidance for the literature search, evidence selection, assessment, synthesis, and external review of the updating process.

Conclusions

Guidance for updating CPGs is poorly described in methodological handbooks. This guidance should be more rigorous and explicit. This could lead to a more optimal updating process, and, ultimately to valid trustworthy guidelines.
Patients with knee osteoarthritis demonstrate improved gait pattern and reduced pain following a non-invasive biomechanical therapy: a prospective multi-centre study on Singaporean population
Authors: Elbaz Avi , Mor Amit , Segal Ganit , Aloni Yoav , Teo Yee Hong , Teo Yee Sze , Das-De Shamal , Yeo Seng Jin
Published: January 2014

Background

Previous studies have shown the effect of a unique therapy with a non-invasive biomechanical foot-worn device (AposTherapy) on Caucasian western population suffering from knee osteoarthritis. The purpose of the current study was to evaluate the effect of this therapy on the level of symptoms and gait patterns in a multi-ethnic Singaporean population suffering from knee osteoarthritis.

Methods

Fifty-eight patients with bilateral medial compartment knee osteoarthritis participated in the study. All patients underwent a computerized gait test and completed two self-assessment questionnaires (WOMAC and SF-36). The biomechanical device was calibrated to each patient, and therapy commenced. Changes in gait patterns and self-assessment questionnaires were reassessed after 3 and 6 months of therapy.

Results

A significant improvement was seen in all of the gait parameters following 6 months of therapy. Specifically, gait velocity increased by 15.9%, step length increased by 10.3%, stance phase decreased by 5.9% and single limb support phase increased by 2.7%. In addition, pain, stiffness and functional limitation significantly decreased by 68.3%, 66.7% and 75.6%, respectively. SF-36 physical score and mental score also increased significantly following 6 months of therapy (46.1% and 22.4%, respectively) (P < 0.05 for all parameters).

Conclusions

Singaporean population with medial compartment knee osteoarthritis demonstrated improved gait patterns, reported alleviation in symptoms and improved function and quality of life following 6 months of therapy with a unique biomechanical device.

Trial registration

Registration number NCT01562652.
Trans-cranial focused ultrasound without hair shaving: feasibility study in an ex vivo cadaver model
Authors: Eames Matthew DC , Hananel Arik , Snell John W , Kassell Neal F , Aubry Jean-Francois
Published: January 2014

In preparing a patient for a trans-cranial magnetic resonance (MR)-guided focused ultrasound procedure, current practice is to shave the patient’s head on treatment day. Here we present an initial attempt to evaluate the feasibility of trans-cranial focused ultrasound in an unshaved, ex vivo human head model. A human skull filled with tissue-mimicking phantom and covered with a wig made of human hair was sonicated using 220- and 710-kHz head transducers to evaluate the feasibility of acoustic energy transfer. Heating at the focal point was measured by MR proton resonance shift thermometry. Results showed that the hair had a negligible effect on focal spot thermal rise at 220 kHz and a 17% drop in temperature elevation when using 710 kHz.
Long fasting is effective in inhibiting physiological myocardial 18F-FDG uptake and for evaluating active lesions of cardiac sarcoidosis
Authors: Morooka Miyako , Moroi Masao , Uno Kimiichi , Ito Kimiteru , Wu Jin , Nakagawa Takashi , Kubota Kazuo , Minamimoto Ryogo , Miyata Yoko , Okasaki Momoko , Okazaki Osamu , Yamada Yoshihito , Yamaguchi Tetsuo , Hiroe Michiaki
Published: January 2014

Background

F-fluorodeoxyglucose (FDG) positron emission tomography (PET) is a promising modality for detecting active lesions of cardiac sarcoidosis (CS). However, determining whether 18F-FDG uptake in the myocardium is physiological is challenging due to metabolic shift in myocardial cells. Although methods for inhibiting physiological myocardial 18F-FDG uptake have been proposed, no standard methods exist. This study therefore aimed to compare the effect of an 18-h fast (long fasting (LF)) with heparin loading plus a 12-h fast (HEP) before 18F-FDG PET scan.

Methods

We analyzed the effects of LF and HEP on the inhibition of physiological myocardial 18F-FDG uptake in healthy subjects (18 in HEP and 19 in LF) and in patients with known or suspected CS (96 in HEP and 69 in LF). In CS, the lower uptake of 18F-FDG in the myocardium was evaluated. A visual four-point scale was used to assess myocardial 18F-FDG uptake in comparison with hepatic uptake (1 lower, 2 similar, 3 somewhat higher, 4 noticeably higher).

Results

Myocardial 18F-FDG uptake was 1.68 ± 1.06 in LF and 3.17 ± 1.16 in HEP in healthy subjects (p < 0.0001), whereas it was 1.48 ± 0.99 in LF and 2.48 ± 1.33 in HEP in CS patients (p < 0.0001). Logistic regression and regression trees revealed the LF was the most effective in inhibiting myocardial 18F-FDG uptake. In addition, serum free fatty acid levels on intravenous 18F-FDG injection were a possible biomarker.

Conclusions

LF is effective in inhibiting myocardial 18F-FDG uptake, and consequently, it could be useful for evaluating active lesions of CS in 18F-FDG PET images.
Fibroblast growth factor-21 enhances mitochondrial functions and increases the activity of PGC-1α in human dopaminergic neurons via Sirtuin-1
Authors: Mäkelä Johanna , Tselykh Timofey V. , Maiorana Francesca , Eriksson Ove , Do Hai Thi , Mudò Giuseppa , Korhonen Laura T. , Belluardo Natale , Lindholm Dan
Published: January 2014

Mitochondrial dysfunctions accompany several neurodegenerative disorders and contribute to disease pathogenesis among others in Parkinson’s disease (PD). Peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α) is a major regulator of mitochondrial functions and biogenesis, and was suggested as a therapeutic target in PD. PGC-1α is regulated by both transcriptional and posttranslational events involving also the action of growth factors. Fibroblast growth factor-21 (FGF21) is a regulator of glucose and fatty acid metabolism in the body but little is known about its action in the brain. We show here that FGF21 increased the levels and activity of PGC-1α and elevated mitochondrial antioxidants in human dopaminergic cells in culture. The activation of PGC-1α by FGF21 occurred via the NAD+-dependent deacetylase Sirtuin-1 (SIRT1) subsequent to an increase in the enzyme, nicotinamide phosphoribosyltransferase (Nampt). FGF21 also enhanced mitochondrial respiratory capacity in human dopaminergic neurons as shown in real-time analyses of living cells. FGF21 is present in the brain including midbrain and is expressed by glial cells in culture. These results show that FGF21 activates PGC-1α and increases mitochondrial efficacy in human dopaminergic neurons suggesting that FGF21 could potentially play a role in dopaminergic neuron viability and in PD.