bluuebunny/crossref_metadata_2025 huggingface dataset:
Hygrothermoelastic analysis of multilayered composite and sandwich shells
Authors: Brischetto Salvatore
Published: February 2013

Refined two-dimensional models are proposed for the static hygrothermoleastic analysis of multilayered composite and sandwich shells. These shell models are developed in the framework of the Carrera's unified formulation (in a general and unified manner) by considering both equivalent single layer and layerwise multilayer description. The principle of virtual displacements contains elastic, thermal and hygroscopic strains. The governing equations allow mechanical, thermal and hygroscopic loads to be applied and they are solved in a closed-form solution. Thermal and hygroscopic loads are defined by means of appropriate temperature and moisture content profiles through the thickness of the shell, such profiles can ‘a priori’ be assumed or they can be calculated by solving the Fourier heat conduction equation and the Fick's moisture diffusion law. Such equations are solved in steady-state conditions and in curvilinear coordinates for the shell geometries. The presence of loads due to hygroscopic and thermal effects (in addition to the mechanical load) modifies the bending response of multilayered shells. Comparisons between classical and refined models, and between assumed and calculated temperature and moisture content profiles are proposed in the cases of composite and sandwich shells. The use of refined models combined with calculated temperature and moisture content profiles through the thickness is mandatory for a correct elasto-thermo-hygroscopic analysis of multilayered structures.
Application of the Model of Allostasis to Older Women’s Relocation to Senior Housing
Authors: Ewen Heidi H. , Kinney Jennifer
Published: February 2013

Objectives:

Adjustment to senior housing entails significant lifestyle changes and is a stressful process. The adaptation process is dynamic and has yet to be studied using the conceptual model of allostasis. This article presents exemplars of women whose profiles represent three allostatic states: successful adaptation (homeostasis), ongoing adaptation (allostasis), and maladaptation (allostatic load).

Method:

Older women who had relocated to senior housing participated in three interviews and monthly saliva sample collection over a 6-month period. Saliva was assayed for diurnal cortisol secretion. Triangulation of mixed methods was used to analyze data, and psychosocial data were mapped onto the cortisol graphs to illustrate changes in stress reactivity and well-being.

Results:

Coping abilities, perceptions of stressors, and cortisol measures provide a detailed picture of the interplay among events and perceptions and the effects of both on well-being.

Discussion:

The case exemplars provide detailed information on the complexity of psychosocial and physiological components of the model of allostasis. This study also fills a gap in knowledge on negative relocation outcomes using the allostatic model.
A new direction for general lighting practice
Authors: Cuttle C
Published: February 2013

The currently accepted notion that the basic purpose of general lighting practice is to enable performance of visual tasks is examined and found to be lacking in substance. It is proposed that the purpose of lighting should be redefined in terms of the visual experience of illuminated surroundings, and two criteria are proposed for this purpose, both of which represent significant departures from conventional practice. The first assesses the adequacy of illumination for an activity in terms of the density of reflected light from surrounding room surfaces and the second is concerned with how the luminaire luminous flux is directed onto selected target surfaces. Taken together, these criteria offer a quite new approach for designing lighting installations for general practice.
Cognitive Rehabilitation Changes Memory-Related Brain Activity in People With Alzheimer Disease
Authors: van Paasschen Jorien , Clare Linda , Yuen Kenneth S. L. , Woods Robert T. , Evans Suzannah J. , Parkinson Caroline H. , Rugg Michael D. , Linden David E. J.
Published: February 2013

Background. People with Alzheimer disease (AD) are capable of new learning when cognitive support is provided, suggesting that there is plasticity even in a degenerating brain. However, it is unclear how a cognition-focused intervention operates on a neural level. Objective. The present study examined the effects of cognitive rehabilitation (CR) on memory-related brain activation in people with early-stage AD, as measured by functional magnetic resonance imaging (fMRI). Methods. A total of 19 participants either received 8 weeks of CR treatment (n = 7) or formed a control group (n = 12). We scanned participants pretreatment and posttreatment while they learned and recognized unfamiliar face-name pairs. Results. Following treatment, the CR group showed higher brain activation during recognition of face-name pairs in the left middle and inferior frontal gyri, the left insula, and 2s regions in the right medial parietal cortex. The control group showed decreased activation in these areas during recognition after the intervention period. Neither group showed an activation change during encoding. Behavioral performance on face-name learning did not improve for either group. Conclusions. We suggest that CR may have operated on the process of recognition through partial restoration of function in frontal brain areas that are less compromised in early-stage AD and that physiological markers may be more sensitive indicators of brain plasticity than behavioral performance.
Emotion in Aging and Bipolar Disorder: Similarities, Differences, and Lessons for Further Research
Authors: Isaacowitz Derek M. , Gershon Anda , Allard Eric S. , Johnson Sheri L.
Published: February 2013

In this article, we consider similarities and differences in emotion research on older adults and individuals with bipolar disorder (BD). Recent research and theory within both areas has focused on the importance of positive emotion, but the case of older adults is generally considered a case of “adaptive” positivity whereas BD is usually considered maladaptive positivity. We explore the paradox of the same phenomenon being labeled as adaptive in one group and yet maladaptive in another, with attention to commonalities and distinctions between these two groups. We identify only limited areas of overlap, and suggest a refinement of models of positive emotionality in the two populations.
A case of delayed vesical pancreatic adenocarcinoma metastasis
Authors: Petrides N , Singh R , Hodgson D
Published: February 2013

We report the first case of a pancreatic-vesical metastasis presenting with haematuria as the initial symptom of a previously thought to be completely excised pancreatic primary four years earlier.
Urology on the inside: managing the needs of the incarcerated
Authors: Floyd MS , Mistry R , Williamson EPM , Machin DG , Baird AD
Published: February 2013

Objective:

Despite a substantial body of literature on prisoner health and the management of specific conditions that affect incarcerated persons, there remains a paucity of data pertaining to the specific urological needs of prisoners. Additionally, no study has documented the impact of prison referrals on a department of urology.

Materials and methods:

A year-long prospective study was performed in a university hospital recording all contact made by detained persons with the department of urology.

Results:

A total of 77 clinical encounters were made by 47 detained patients from seven different institutions over 12 months. All patients were male. The most common reason for urological consultation was investigation of lower tract symptoms, but a total of 18 separate complaints were recorded, including acute trauma.

Conclusions:

The presence of several places of detention impacts significantly on a department’s workload. Management of persons detained under Home Office Licence in a general hospital poses several challenges, including confidentiality and security issues, privacy and patient concerns and prison personnel secondments. The transient nature of the prisoner population can pose difficulties for planned admissions and outpatient follow-up.
Using Mechanical Turk to Study Clinical Populations
Authors: Shapiro Danielle N. , Chandler Jesse , Mueller Pam A.
Published: February 2013

Although participants with psychiatric symptoms, specific risk factors, or rare demographic characteristics can be difficult to identify and recruit for participation in research, participants with these characteristics are crucial for research in the social, behavioral, and clinical sciences. Online research in general and crowdsourcing software in particular may offer a solution. However, no research to date has examined the utility of crowdsourcing software for conducting research on psychopathology. In the current study, we examined the prevalence of several psychiatric disorders and related problems, as well as the reliability and validity of participant reports on these domains, among users of Amazon’s Mechanical Turk. Findings suggest that crowdsourcing software offers several advantages for clinical research while providing insight into potential problems, such as misrepresentation, that researchers should address when collecting data online.
Development and validation of a prognostic scoring system for patients with chronic myelomonocytic leukemia
Authors: Such Esperanza , Germing Ulrich , Malcovati Luca , Cervera José , Kuendgen Andrea , Della Porta Matteo G. , Nomdedeu Benet , Arenillas Leonor , Luño Elisa , Xicoy Blanca , Amigo Mari L. , Valcarcel David , Nachtkamp Kathrin , Ambaglio Ilaria , Hildebrandt Barbara , Lorenzo Ignacio , Cazzola Mario , Sanz Guillermo
Published: February 2013

Key Points

CMML is a heterogeneous disorder with a highly variable prognosis that clearly requires a specific and widely accepted prognostic scoring system. CPSS is a powerful prognostic score that defines 4 risk groups for survival and AML evolution, developed and validated in the largest CMML series to date.
Sickle cell vaso-occlusion causes activation of iNKT cells that is decreased by the adenosine A2A receptor agonist regadenoson
Authors: Field Joshua J. , Lin Gene , Okam Maureen M. , Majerus Elaine , Keefer Jeffrey , Onyekwere Onyinye , Ross Ainsley , Campigotto Federico , Neuberg Donna , Linden Joel , Nathan David G.
Published: February 2013

Key Points

The fraction of invariant NKT cells demonstrating activation is increased during painful crises compared with steady state. Regadenoson, an adenosine A2A receptor agonist, decreases the fraction of activated invariant NKT cells during painful crises.
Glycosylphosphatidylinositol-specific, CD1d-restricted T cells in paroxysmal nocturnal hemoglobinuria
Authors: Gargiulo Lucia , Papaioannou Maria , Sica Michela , Talini Giulia , Chaidos Aristeidis , Richichi Barbara , Nikolaev Andrei V. , Nativi Cristina , Layton Mark , de la Fuente Josu , Roberts Irene , Luzzatto Lucio , Notaro Rosario , Karadimitris Anastasios
Published: February 2013

Key Points

The mechanism of bone marrow failure (BMF) in PNH is not known. Novel CD1d-restricted, GPI-specific T cells are present in PNH patients and might be responsible for BMF.
Stability results in ℒ-fuzzy normed spaces for a cubic functional equation
Authors: Lee Sang-Baek , Park Won-Gil , Bae Jae-Hyeong
Published: February 2013

We establish some stability results concerning the functional equation

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=

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]

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where

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is a fixed integer, in the setting of ℒ-fuzzy normed spaces that in turn generalize a Hyers-Ulam stability result in the framework of classical normed spaces.

MSC:39B22, 39B52, 39B72, 46S40, 47S40.
New insights into the cardiovascular risk of migraine and the role of white matter hyperintensities: is gold all that glitters?
Authors: Tana Claudio , Tafuri Emmanuele , Tana Marco , Martelletti Paolo , Negro Andrea , Affaitati Giannapia , Fabrizio Alessandra , Costantini Raffaele , Mezzetti Andrea , Giamberardino Maria Adele
Published: February 2013

The role of migraine as an independent risk factor for cardiovascular events has been debated for several years, while it is more established for ischemic stroke. Recently, new studies have examined the likelihood of migraine to determine cardiovascular events, supporting the hypothesis of a predominant role in patients with migraine with aura, the risk including both sexes. In the literature, multiple pathophysiological mechanisms are described to explain this association, and are here discussed. Furthermore, the emerging evidence that a higher headache frequency and long-term migraine may worsen the cardio-metabolic profile in migraineurs (e.g. with a higher Framingham risk score and risk of developing atherosclerosis, insulin resistance and metabolic syndrome) makes it increasingly necessary to reduce the number and severity of attacks, not only to alleviate the painful symptoms, but also to improve the prognosis in these patients.
The evolutionary rate of antibacterial drug targets
Authors: Gladki Arkadiusz , Kaczanowski Szymon , Szczesny Pawel , Zielenkiewicz Piotr
Published: February 2013

Background

One of the major issues in the fight against infectious diseases is the notable increase in multiple drug resistance in pathogenic species. For that reason, newly acquired high-throughput data on virulent microbial agents attract the attention of many researchers seeking potential new drug targets. Many approaches have been used to evaluate proteins from infectious pathogens, including, but not limited to, similarity analysis, reverse docking, statistical 3D structure analysis, machine learning, topological properties of interaction networks or a combination of the aforementioned methods. From a biological perspective, most essential proteins (knockout lethal for bacteria) or highly conserved proteins (broad spectrum activity) are potential drug targets. Ribosomal proteins comprise such an example. Many of them are well-known drug targets in bacteria. It is intuitive that we should learn from nature how to design good drugs. Firstly, known antibiotics are mainly originating from natural products of microorganisms targeting other microorganisms. Secondly, paleontological data suggests that antibiotics have been used by microorganisms for million years. Thus, we have hypothesized that good drug targets are evolutionary constrained and are subject of evolutionary selection. This means that mutations in such proteins are deleterious and removed by selection, which makes them less susceptible to random development of resistance. Analysis of the speed of evolution seems to be good approach to test this hypothesis.

Results

In this study we show that pN/pS ratio of genes coding for known drug targets is significantly lower than the genome average and also lower than that for essential genes identified by experimental methods. Similar results are observed in the case of dN/dS analysis. Both analyzes suggest that drug targets tend to evolve slowly and that the rate of evolution is a better predictor of drugability than essentiality.

Conclusions

Evolutionary rate can be used to score and find potential drug targets. The results presented here may become a useful addition to a repertoire of drug target prediction methods. As a proof of concept, we analyzed GO enrichment among the slowest evolving genes. These may become the starting point in the search for antibiotics with a novel mechanism.
Use of digital gene expression to discriminate gene expression differences in early generations of resynthesized Brassica napus and its diploid progenitors
Authors: Jiang Jinjin , Shao Yanlin , Du Kun , Ran Liping , Fang Xiaoping , Wang Youping
Published: February 2013

Background

Polyploidy is an important evolutionary mechanism in flowering plants that often induces immediate extensive changes in gene expression through genomic merging and doubling. Brassica napus L. is one of the most economically important polyploid oil crops and has been broadly studied as an example of polyploid crop. RNA-seq is a recently developed technique for transcriptome study, which could be in choice for profiling gene expression pattern in polyploids.

Results

We examined the global gene expression patterns of the first four generations of resynthesized B. napus (F1–F4), its diploid progenitors B. rapa and B. oleracea, and natural B. napus using digital gene expression analysis. Almost 42 million clean tags were generated using Illumina technology to produce the expression data for 25959 genes, which account for 63% of the annotated B. rapa genome. More than 56% of the genes were transcribed from both strands, which indicate the importance of RNA-mediated gene regulation in polyploidization. Tag mapping of the B. rapa genome generated 19023, 18547, 24383, 20659, 18881, 20692, and 19955 annotated genes for the B. rapa, B. oleracea, F1–F4 of synthesized B. napus, and natural B. napus libraries, respectively. The unambiguous tag-mapped genes in the libraries were functionally categorized via gene ontological analysis. Thousands of differentially expressed genes (DEGs) were identified and revealed the substantial changes in F1–F4. Among the 20 most DEGs are DNA binding/transcription factor, cyclin-dependent protein kinase, epoxycarotenoid dioxygenase, and glycine-rich protein. The Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis of the DEGs suggested approximately 120 biological pathways.

Conclusions

The systematic deep sequencing analysis provided a comprehensive understanding of the transcriptome complexity of early generations of synthesized B. napus. This information broadens our understanding of the mechanisms of B. napus polyploidization and contributes to molecular and genetic research by enriching the Brassica database.
Genomic analysis of the regulatory elements and links with intrinsic DNA structural properties in the shrunken genome of Buchnera
Authors: Brinza Lilia , Calevro Federica , Charles Hubert
Published: February 2013

Background

Buchnera aphidicola is an obligate symbiotic bacterium, associated with most of the aphididae, whose genome has drastically shrunk during intracellular evolution. Gene regulation in Buchnera has been a matter of controversy in recent years as the combination of genomic information with the experimental results has been contradictory, refuting or arguing in favour of a functional and responsive transcription regulation in Buchnera.

The goal of this study was to describe the gene transcription regulation capabilities of Buchnera based on the inventory of cis- and trans-regulators encoded in the genomes of five strains from different aphids (Acyrthosiphon pisum, Schizaphis graminum, Baizongia pistacea, Cinara cedri and Cinara tujafilina), as well as on the characterisation of some intrinsic structural properties of the DNA molecule in these bacteria.

Results

Interaction graph analysis shows that gene neighbourhoods are conserved between E. coli and Buchnera in structures called transcriptons, interactons and metabolons, indicating that selective pressures have acted on the evolution of transcriptional, protein-protein interaction and metabolic networks in Buchnera. The transcriptional regulatory network in Buchnera is composed of a few general DNA-topological regulators (Nucleoid Associated Proteins and topoisomerases), with the quasi-absence of any specific ones (except for multifunctional enzymes with a known gene expression regulatory role in Escherichia coli, such as AlaS, PepA and BolA, and the uncharacterized hypothetical regulators YchA and YrbA). The relative positioning of regulatory genes along the chromosome of Buchnera seems to have conserved its ancestral state, despite the genome erosion. Sigma-70 promoters with canonical thermodynamic sequence profiles were detected upstream of about 94% of the CDS of Buchnera in the different aphids. Based on Stress-Induced Duplex Destabilization (SIDD) measurements, unstable σ70 promoters were found specifically associated with the regulator and transporter genes.

Conclusions

This genomic analysis provides supporting evidence of a selection of functional regulatory structures and it has enabled us to propose hypotheses concerning possible links between these regulatory elements and the DNA-topology (i.e., supercoiling, curvature, flexibility and base-pair stability) in the regulation of gene expression in the shrunken genome of Buchnera.
A predictive signature gene set for discriminating active from latent tuberculosis in Warao Amerindian children
Authors: Verhagen Lilly M , Zomer Aldert , Maes Mailis , Villalba Julian A , del Nogal Berenice , Eleveld Marc , van Hijum Sacha AFT , de Waard Jacobus H , Hermans Peter WM
Published: February 2013

Background

Tuberculosis (TB) continues to cause a high toll of disease and death among children worldwide. The diagnosis of childhood TB is challenged by the paucibacillary nature of the disease and the difficulties in obtaining specimens. Whereas scientific and clinical research efforts to develop novel diagnostic tools have focused on TB in adults, childhood TB has been relatively neglected. Blood transcriptional profiling has improved our understanding of disease pathogenesis of adult TB and may offer future leads for diagnosis and treatment. No studies applying gene expression profiling of children with TB have been published so far.

Results

We identified a 116-gene signature set that showed an average prediction error of 11% for TB vs. latent TB infection (LTBI) and for TB vs. LTBI vs. healthy controls (HC) in our dataset. A minimal gene set of only 9 genes showed the same prediction error of 11% for TB vs. LTBI in our dataset. Furthermore, this minimal set showed a significant discriminatory value for TB vs. LTBI for all previously published adult studies using whole blood gene expression, with average prediction errors between 17% and 23%. In order to identify a robust representative gene set that would perform well in populations of different genetic backgrounds, we selected ten genes that were highly discriminative between TB, LTBI and HC in all literature datasets as well as in our dataset. Functional annotation of these genes highlights a possible role for genes involved in calcium signaling and calcium metabolism as biomarkers for active TB. These ten genes were validated by quantitative real-time polymerase chain reaction in an additional cohort of 54 Warao Amerindian children with LTBI, HC and non-TB pneumonia. Decision tree analysis indicated that five of the ten genes were sufficient to classify 78% of the TB cases correctly with no LTBI subjects wrongly classified as TB (100% specificity).

Conclusions

Our data justify the further exploration of our signature set as biomarkers for potential childhood TB diagnosis. We show that, as the identification of different biomarkers in ethnically distinct cohorts is apparent, it is important to cross-validate newly identified markers in all available cohorts.
Prevalence and risk factors of Hepatitis C virus infection in Brazil, 2005 through 2009: a cross-sectional study
Authors: Pereira Leila MMB , Martelli Celina MT , Moreira Regina C , Merchan-Hamman Edgar , Stein Airton T , Cardoso Regina Maria A , Figueiredo Gerusa M , Montarroyos Ulisses R , Braga Cynthia , Turchi Marília D , Coral Gabriela , Crespo Deborah , Lima Maria Luiza C , Alencar Luis Claudio A , Costa Marcelo , dos Santos Alex A , Ximenes Ricardo AA
Published: February 2013

Background

Hepatitis C chronic liver disease is a major cause of liver transplant in developed countries. This article reports the first nationwide population-based survey conducted to estimate the seroprevalence of HCV antibodies and associated risk factors in the urban population of Brazil.

Methods

The cross sectional study was conducted in all Brazilian macro-regions from 2005 to 2009, as a stratified multistage cluster sample of 19,503 inhabitants aged between 10 and 69 years, representing individuals living in all 26 State capitals and the Federal District. Hepatitis C antibodies were detected by a third-generation enzyme immunoassay. Seropositive individuals were retested by Polymerase Chain Reaction and genotyped. Adjusted prevalence was estimated by macro-regions. Potential risk factors associated with HCV infection were assessed by calculating the crude and adjusted odds ratios, 95% confidence intervals (95% CI) and p values. Population attributable risk was estimated for multiple factors using a case–control approach.

Results

The overall weighted prevalence of hepatitis C antibodies was 1.38% (95% CI: 1.12%–1.64%). Prevalence of infection increased in older groups but was similar for both sexes. The multivariate model showed the following to be predictors of HCV infection: age, injected drug use (OR = 6.65), sniffed drug use (OR = 2.59), hospitalization (OR = 1.90), groups socially deprived by the lack of sewage disposal (OR = 2.53), and injection with glass syringe (OR = 1.52, with a borderline p value). The genotypes 1 (subtypes 1a, 1b), 2b and 3a were identified. The estimated population attributable risk for the ensemble of risk factors was 40%. Approximately 1.3 million individuals would be expected to be anti-HCV-positive in the country.

Conclusions

The large estimated absolute numbers of infected individuals reveals the burden of the disease in the near future, giving rise to costs for the health care system and society at large. The known risk factors explain less than 50% of the infected cases, limiting the prevention strategies. Our findings regarding risk behaviors associated with HCV infection showed that there is still room for improving strategies for reducing transmission among drug users and nosocomial infection, as well as a need for specific prevention and control strategies targeting individuals living in poverty.
Defining the mid-diastolic imaging period for cardiac CT – lessons from tissue Doppler echocardiography
Authors: Otton James M , Phan Justin , Feneley Michael , Yu Chung-yao , Sammel Neville , McCrohon Jane
Published: February 2013

Background

Aggressive dose reduction strategies for cardiac CT require the prospective selection of limited cardiac phases. At lower heart rates, the period of mid-diastole is typically selected for image acquisition. We aimed to identify the effect of heart rate on the optimal CT acquisition phase within the period of mid-diastole.

Methods

We utilized high temporal resolution tissue Doppler to precisely measure coronary motion within diastole. Tissue-Doppler waveforms of the myocardium corresponding to the location of the circumflex artery (100 patients) and mid-right coronary arteries (50 patients) and the duration and timing of coronary motion were measured. Using regression analysis an equation was derived for the timing of the period of minimal coronary motion within the RR interval. In a validation set of 50 clinical cardiac CT examinations, we assessed coronary motion artifact and the effect of using a mid-diastolic imaging target that was adjusted according to heart rate vs a fixed 75% phase target.

Results

Tissue Doppler analysis shows the period of minimal cardiac motion suitable for CT imaging decreases almost linearly as the RR interval decreases, becoming extinguished at an average heart rate of 91 bpm for the circumflex (LCX) and 78 bpm for the right coronary artery (RCA). The optimal imaging phase has a strong linear relationship with RR duration (R2 = 0.92 LCX, 0.89 RCA). The optimal phase predicted by regression analysis of the tissue-Doppler waveforms increases from 74% at a heart rate of 55 bpm to 77% at 75 bpm. In the clinical CT validation set, the optimal CT acquisition phase similarly occurred later with increasing heart rate. When the selected cardiac phase was adjusted according to heart rate the result was closer to the optimal phase than using a fixed 75% phase. While this effect was statistically significant (p < 0.01 RCA/LCx), the mean effect of heart-rate adjustment was minor relative to typical beat-to-beat variability and available precision of clinical phase selection.

Conclusion

High temporal resolution imaging of coronary motion can be used to predict the optimal acquisition phase in cardiac CT. The optimal phase for cardiac CT imaging within mid-diastole increases with increasing heart rate although the magnitude of change is small.
Analysis of the contribution of FTO, NPC1, ENPP1, NEGR1, GNPDA2 and MC4Rgenes to obesity in Mexican children
Authors: Mejía-Benítez Aurora , Klünder-Klünder Miguel , Yengo Loic , Meyre David , Aradillas Celia , Cruz Esperanza , Pérez-Luque Elva , Malacara Juan Manuel , Garay Maria Eugenia , Peralta-Romero Jesús , Flores-Huerta Samuel , García-Mena Jaime , Froguel Philippe , Cruz Miguel , Bonnefond Amélie
Published: February 2013

Background

Recent genome wide association studies (GWAS) and previous positional linkage studies have identified more than 50 single nucleotide polymorphisms (SNPs) associated with obesity, mostly in Europeans. We aimed to assess the contribution of some of these SNPs to obesity risk and to the variation of related metabolic traits, in Mexican children.

Methods

The association of six European obesity-related SNPs in or near FTO, NPC1, ENPP1, NEGR1, GNPDA2 and MC4R genes with risk of obesity was tested in 1,463 school-aged Mexican children (N

cases
 = 514; N

controls
 = 949). We also assessed effects of these SNPs on the variation of body mass index (BMI), fasting serum insulin levels, fasting plasma glucose levels, total cholesterol and triglyceride levels, in a subset of 1,171 nonobese Mexican children.

Results

We found a significant effect of GNPDA2 rs10938397 on risk of obesity (odds ratio [OR] = 1.30; P = 1.34 × 10-3). Furthermore, we found nominal associations between obesity risk or BMI variation and the following SNPs: ENPP1 rs7754561, MC4R rs17782313 and NEGR1 rs2815752. Importantly, the at-risk alleles of both MC4R rs17782313 and NPC1 rs1805081 showed significant effect on increased fasting glucose levels (β = 0.36 mmol/L; P = 1.47 × 10-3) and decreased fasting serum insulin levels (β = −0.10 μU/mL; P = 1.21 × 10-3), respectively.

Conclusion

Our present results suggest that some obesity-associated SNPs previously reported in Europeans also associate with risk of obesity, or metabolic quantitative traits, in Mexican children. Importantly, we found new associations between MC4R and fasting glucose levels, and between NPC1 and fasting insulin levels.
Prognostic factors of all-cause mortalities in continuous ambulatory peritoneal dialysis: a cohort study
Authors: Vejakama Phisitt , Thakkinstian Ammarin , Ingsathit Atiporn , Dhanakijcharoen Prateep , Attia John
Published: February 2013

Background

The role of small solute clearance on mortalities in patients with CAPD has been controversial. We therefore conducted a study with 3 years' follow up in adult patients who participated in the CAPD-first policy.

Methods

There were 11,523 patients with end-stage renal disease who participated in the CAPD-first policy between 2008 and 2011. Among them, 1,177 patients were included in the retrospective cohort study. A receiver operating characteristic curve was applied to calibrate the cutoffs of tKt/V, rKt/V and tCrcl. Kaplan-Meier and Cox-regression models with time varying covariates were applied to estimate overall death rate, probability of death and prognosis, respectively.

Results

The cutoffs of rKt/V and tKt/V were 0.25 and 1.75, respectively. The Cox regression suggested that the higher these clearance parameters, the lower the risks of death after adjusting for covariables. The risks of death for those above these cutoffs were 57% (HR = 0.43, 95% CI: 0.31, 0.60) and 29% (HR = 0.71, 95% CI: 0.52, 0.98) lower for rKt/V and tKt/V, respectively. Age, serum albumin, hemoglobin, systolic blood pressure, and ultra-filtration volume significantly affected the mortality outcome.

Conclusions

Our study suggested that the cutoffs of 0.25 and 1.75 for rKt/V and tKt/V might be associated with mortality in CAPD patients. A minimum tKt/V of 1.75 should be targeted, but increased dialysis dosage to achieve tKt/V > 2.19 adds no further benefit. Serum albumin, hemoglobin, SBP, and UF volume are also associated with mortality. However, our study may face with selection and other unobserved confounders, so further randomized controlled trials are required to confirm these cutoffs.
Does phosphorylation of cofilin affect the progression of human bladder cancer?
Authors: Chung Hong , Kim Bokyung , Jung Seung-Hyo , Won Kyung-Jong , Jiang Xiaowen , Lee Chang-Kwon , Lim So Dug , Yang Sang-Kuk , Song Ki Hak , Kim Hong Sup
Published: February 2013

Background

We determined the differently expressed protein profiles and their functions in bladder cancer tissues with the aim of identifying possible target proteins and underlying molecular mechanisms for taking part in their progression.

Methods

We examined the expression of proteins by proteomic analysis and western blot in normal urothelium, non-muscle-invasive bladder cancers (NMIBCs), and muscle-invasive bladder cancers (MIBCs). The function of cofilin was analyzed using T24 human bladder cancer cells.

Results

The expression levels of 12 proteins were altered between bladder cancers and normal bladder tissues. Of these proteins, 14-3-3σ was upregulated in both NMIBCs and MIBCs compared with controls. On the other hand, myosin regulatory light chain 2, galectin-1, lipid-binding AI, annexin V, transthyretin, CARD-inhibitor of NF-κB-activating ligand, and actin prepeptide were downregulated in cancer samples. Cofilin, an actin-depolymerizing factor, was prominent in both NMIBCs and MIBCs compared with normal bladder tissues. Furthermore, we confirmed that cofilin phosphorylation was more prominent in MIBCs than in NMIBCs using immunoblotting and immunohistochemcal analyses. Epidermal growth factor (EGF) increased the phosphorylation of cofilin and elevated the migration in T24 cells. Knockdown of cofilin expression with small interfering RNA attenuated the T24 cell migration in response to EGF.

Conclusions

These results demonstrate that the increased expression and phosphorylation of cofilin might play a role in the occurrence and invasiveness of bladder cancer. We suspected that changes in cofilin expression may participate in the progression of the bladder cancer.
Parents’ expectations of staff in the early bonding process with their premature babies in the intensive care setting: a qualitative multicenter study with 60 parents
Authors: Guillaume Sonia , Michelin Natacha , Amrani Elodie , Benier Brigitte , Durrmeyer Xavier , Lescure Sandra , Bony Charlotte , Danan Claude , Baud Olivier , Jarreau Pierre-Henri , Zana-Taïeb Elodie , Caeymaex Laurence
Published: February 2013

Background

During the first weeks of hospitalization, premature babies and their parents encounter difficulties in establishing early bonds and interactions. Only a few studies have explored what caregivers can do to meet parents' needs in relation to these interactions and help optimize them. This study sought to explore parents' perception of these first interactions and to identify the actions of caregivers that help or hinder its development.

Methods

Prospective study, qualitative discourse analysis of 60 face-to-face interviews conducted with 30 mothers and 30 fathers of infants born before 32 weeks of gestation (mean ± SD: 27 ± 2 weeks of gestational age), during their child's stay in one out of three NICUs in France. Interviews explored parental experience, from before birth up to the first month of life.

Results

Data analysis uncovered two main themes, which were independent of parents' geographical or cultural origin but differed between mothers and fathers. First, fathers described the bond with their child as composed more of words and looks and involving distance, while mothers experienced the bond more physically. Secondly, two aspects of the caregivers' influence were decisive: nurses' caring attitude towards baby and parents, and their communication with parents, which reduced stress and made interactions with the baby possible. This communication appeared to be the locus of a supportive and fulfilling encounter between parents and caregivers that reinforced parents' perception of a developing bond.

Conclusions

At birth and during the first weeks in the NICU, the creation of a bond between mothers and fathers and their premature baby is rooted in their relationship with the caregivers. Nurses' caring attitude and regular communication adapted to specific needs are perceived by parents as necessary preconditions for parents' interaction and development of a bond with their baby. These results might allow NICU staff to provide better support to parents and facilitate the emergence of a feeling of parenthood.
Nondisclosure prosecutions and population health outcomes: examining HIV testing, HIV diagnoses, and the attitudes of men who have sex with men following nondisclosure prosecution media releases in Ottawa, Canada
Authors: O’Byrne Patrick , Willmore Jacqueline , Bryan Alyssa , Friedman Dara S , Hendriks Andrew , Horvath Cynthia , Massenat Dominique , Bouchard Christiane , Remis Robert S , Etches Vera
Published: February 2013

Background

During the past decade, the intersection of HIV and criminal law has become increasingly discussed. The majority of studies to date have approached this topic from a sociological or legal perspective. As a result, the potential effect of nondisclosure prosecutions on population health and HIV prevention work remains mostly unknown.

Methods

A descriptive quantitative-qualitative study was undertaken to examine HIV testing, HIV diagnoses, and the attitudes of men who have sex with men following regional media releases about a local nondisclosure prosecution. As part of this study, first, we reviewed the trends in HIV testing and HIV diagnoses from 2008 through 2011 in Ottawa, Canada. Second, we explored the attitudes and beliefs of local MSM about HIV, HIV prevention, HIV serostatus disclosure, nondisclosure prosecutions, and public health.

Results

Quantitatively, the findings of this study revealed that, in comparison to the period preceding the media releases about a local nondisclosure prosecution, HIV testing and HIV diagnoses among men who have sex with men did not significantly change after the media releases of interest. Qualitatively, a subgroup of 27 men who have sex with men (12 HIV-positive, 15 HIV-negative) noted their beliefs that the local public health department openly shares information about people living with HIV with the police. Moreover, some HIV-positive participants stated that this perceived association between the local public health department and police services caused them to not access public health department services, notwithstanding their desires to seek assistance in maintaining safer sexual practices.

Conclusions

Nondisclosure prosecutions likely undermine HIV prevention efforts.
Synoviocytes protect cartilage from the effects of injury in vitro
Authors: Lee Christina M , Kisiday John D , McIlwraith C Wayne , Grodzinsky Alan J , Frisbie David D
Published: February 2013

Background

It is well documented that osteoarthritis (OA) can develop following traumatic joint injury and is the leading cause of lameness and subsequent wastage of equine athletes. Although much research of injury induced OA has focused on cartilage, OA is a disease that affects the whole joint organ.

Methods

In this study, we investigated the impact of synovial cells on the progression of an OA phenotype in injured articular cartilage. Injured and control cartilage were cultured in the presence of synoviocytes extracted from normal equine synovium. Synoviocytes and cartilage were evaluated for catabolic and anabolic gene expression. The cartilage was also evaluated histologically for loss of extracellular matrix molecules, chondrocyte cell death and chondrocyte cluster formation.

Results

The results indicate synoviocytes exert both positive and negative effects on injured cartilage, but ultimately protect injured cartilage from progressing toward an OA phenotype. Synoviocytes cultured in the presence of injured cartilage had significantly reduced expression of aggrecanase 1 and 2 (ADAMTS4 and 5), but also had increased expression of matrix metalloproteinase (MMP) -1 and reduced expression of tissue inhibitor of metalloproteinases 1 (TIMP-1). Injured cartilage cultured with synoviocytes had increased expression of both collagen type 2 and aggrecanase 2. Histologic examination of cartilage indicated that there was a protective effect of synoviocytes on injured cartilage by reducing the incidence of both focal cell loss and chondrocyte cluster formation, two major hallmarks of OA.

Conclusions

These results support the importance of evaluating more than one synovial joint tissue when investigating injury induced OA.
Characterisation of Walker 256 breast carcinoma cells from two tumour cell banks as assessed using two models of secondary brain tumours
Authors: Lewis Kate M , Harford-Wright Elizabeth , Vink Robert , Ghabriel Mounir N
Published: February 2013

Background

Metastatic brain tumours are a common end stage of breast cancer progression, with significant associated morbidity and high mortality. Walker 256 is a rat breast carcinoma cell line syngeneic to Wistar rats and commonly used to induce secondary brain tumours. Previously there has been the assumption that the same cancer cell line from different cell banks behave in a similar manner, although recent studies have suggested that cell lines may change their characteristics over time in vitro.

Methods

In this study internal carotid artery injection and direct cerebral inoculation models of secondary brain tumours were used to determine the tumorigenicity of Walker 256 cells obtained from two cell banks, the American Type Culture Collection (ATCC), and the Cell Resource Centre for Medical Research at Tohoku University (CRCTU).

Results

Tumour incidence and volume, plus immunoreactivity to albumin, IBA1 and GFAP, were used as indicators of tumorigenicity and tumour interaction with the host brain microenvironment. CRCTU Walker 256 cells showed greater incidence, larger tumour volume, pronounced blood–brain barrier disruption and prominent glial response when compared to ATCC cell line.

Conclusions

These findings indicate that immortalised cancer cell lines obtained from different cell banks may have diverse characteristics and behaviour in vivo.
Combining the negative lymph nodes count with the ratio of positive and removed lymph nodes can better predict the postoperative survival in cervical cancer patients
Authors: Chen Ying , Zhang Lei , Tian Jing , Ren Xiubao , Hao Quan
Published: February 2013

Background

To evaluate the impacts of the negative lymph nodes (NLNs) count on the prognostic prediction of the ratio of positive and removed lymph nodes (RPL) in cervical cancer patients after radical hysterectomy and pelvic lymphadenectomy (RHPL).

Methods

The positive and negative lymph node counts were calculated for 609 postoperative cervical cancer patients. The 5-year survival rate (5-YSR) was examined according to clinicopathologic variables. Cox regression was used to identify independent prognostic factors.

Results

The NLNs count cutoffs were determined to be 10 and 25 with 5-YSR of 62.8% and 80.5%. The RPL of 13 patients who had the NLNs count of 10 or fewer was >20%. Among 242 patients who had 10 < NLNs count ≤ 25, 194 without positive nodes had the 5-YSR of 77.8%, 31 with 0% < RPL ≤ 5% had the 5-YSR of 3.2%, 15 with RPL > 20% had died when follow-up was completed. Among 354 patients who had NLNs count >25, 185 without positive nodes had the 5-YSR of 87.6%, 6 with 0% < RPL ≤ 5% had the 5-YSR of 25%, 15 with 5% < RPL ≤ 20% had the 5-YSR of 4.5%, and 2 with RPL >20% had died when follow-up was completed. Furthermore, stage, histologic grade and RPL were independently correlated with overall survival of cervical cancer patients after RHPL in the multivariate analysis.

Conclusions

RPL was an independent prognostic factor. The NLNs count is a key factor for improvement of survival prediction of RPL in cervical cancer.
MiRNA-26b inhibits proliferation by targeting PTGS2 in breast cancer
Authors: Li Jia , Kong Xiangjie , Zhang Junfeng , Luo Qifeng , Li Xiaoyu , Fang Lin
Published: February 2013

Background

MicroRNAs (miRNAs) are small, non-coding RNAs (20–24 nucleotides) that post-transcriptionally modulate gene expression by negatively regulating the stability or translational efficiency of their target mRNAs. The aim of this study was to investigate the expression pattern of microRNA-26b (miR-26b) in human breast cancer, and its potential role in disease pathogenesis.

Methods

Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was performed to determine the expression level of miR-26b in 38 breast cancer specimens and adjacent normal breast tissues. MTT assays were conducted to explore the impact of miR-26b overexpression on the proliferation of human MDA-MB-231 breast cancer cells. Luciferase reporter assays were employed to validate regulation of a putative target of miR-26b. The effect of modulating miR-26b on endogenous levels of this target were subsequently confirmed via qRT-PCR and Western blot.

Results

MiR-26b expression was relatively decreased in breast cancer specimens compared with adjacent normal tissues (P<0.01). Overexpression of miR-26b suppressed MDA-MB-231 cell growth. Luciferase assays using a reporter carrying a putative miR-26b target site in the 3' untranslated region of PTGS2 revealed that miR-26b directly targets PTGS2. Overexpression of miR-26b led to downregulation of PTGS2 at the mRNA and protein level, as assessed by qRT-PCR and Western blot. Targeted knockdown of PTGS2 by siRNA significantly inhibited the proliferation of MDA-MB-231 breast cancer cells.

Conclusions

MiR-26b may act as a tumor suppressor in breast cancer. The overexpression of miR-26b inhibits cellular growth by targeting PTGS2, suggesting its use as a potential therapeutic target for breast cancer.
M48U1 CD4 mimetic has a sustained inhibitory effect on cell-associated HIV-1 by attenuating virion infectivity through gp120 shedding
Authors: Selhorst Philippe , Grupping Katrijn , Tong Tommy , Crooks Ema T , Martin Loïc , Vanham Guido , Binley James M , Ariën Kevin K
Published: February 2013

Background

HIV-1 infected cells can establish new infections by crossing the vaginal epithelia and subsequently producing virus in a milieu that avoids the high microbicide concentrations of the vaginal lumen.

Findings

To address this problem, here, we report that pretreatment of HIV-infected peripheral blood mononuclear cells (PBMCs) with a 27 amino acid CD4-mimetic, M48U1, causes dramatic and prolonged reduction of infectious virus output, due to its induction of gp120 shedding.

Conclusions

M48U1 may, therefore, be valuable for prophylaxis of mucosal HIV-1 transmission.