bluuebunny/crossref_metadata_2025 huggingface dataset:
Illustrated medication instructions as a strategy to improve medication management among Latinos: A qualitative analysis
Authors: Mohan Arun V. , Riley M. Brian , Boyington Dane R. , Kripalani Sunil
Published: March 2012

Although illustrated medication instructions may improve medication management among vulnerable populations, little prior research has evaluated their use among Latinos. We conducted focus groups and interviews with Latino patients with diabetes at two safety net clinics in Tennessee to understand medication taking practices and perceptions of illustrated medication instructions. Patients reported confidence in being able to take medications, but demonstrated a lack of understanding of medication instructions. On further probing, they described several barriers to effective medication management rooted in poor communication. Patients expressed preference for illustrated medication instructions which could address several of the challenges raised by patients.
L2 effects on the perception and production of a native vowel contrast in early bilinguals
Authors: Mora Joan C. , Nadeu Marianna
Published: March 2012

This study investigates the effect of L2 (Spanish) use on Catalan–Spanish bilinguals’ ability to accurately perceive and produce two contrastive native Catalan vowel categories, /e/ and /ε/. Participants were L1 Catalan highly proficient Catalan–Spanish bilinguals differing in amount of daily exposure/use of Catalan (low: 40%–70% vs. high: 80%–100%). Perceptual accuracy was assessed through speeded categorization and AXB discrimination tasks based on a 10-step vowel continuum (/e/–/ε/). Production accuracy was assessed by eliciting /ε/ tokens in Catalan cognate and noncognate words. The results indicated that participants using Spanish more frequently discriminated Catalan vowels /e/ and /ε/ less accurately and significantly more slowly and had a more Spanish-like acoustic target in the production of Catalan /ε/, particularly in cognate words. These results are consistent with the view that, in a language contact context, extensive L2 experience affects L1 sound categories.
‘One participant said …’: the implications of quotations from biographical talk
Authors: Taylor Stephanie
Published: March 2012

Quotations from biographical talk are widely used in the presentation and writing up of qualitative research. This article discusses the unintended implications that such quotations can carry, partly as a result of the conventions for introducing them and because the basis for their selection is often unclear. These implications are discussed in terms of consistency. An assumption of consistency as an aspect of the talk or the person speaking is problematic because it disregards the situated and variable nature of talk, including talk about memory, and can invoke an over-simple model of the speaker. The article proposes that consistency should not be assumed but become a focus for analysis. An example is presented of an analysis of biographical talk about creative work, following an approach derived from social and discursive psychology. Consistencies in a speaker’s repeated accounts of the same job are interpreted in terms of both discursive resources around contemporary creative working, and ‘local resources’, which are derived from the speaker’s ‘discursive apprenticeship’ with his own family.
Blurring the boundaries between Standard General Sky types due to multiple scattering of light
Authors: Kocifaj M
Published: March 2012

The diffuse light reaching the ground varies with instantaneous physical state of the atmosphere, specifically with atmospheric turbidity, vertical stratification of attenuating and scattering constituents, cloud coverage and many others. Despite this complexity, a set of empirical models based on so-called homogeneous sky types is widely used to simulate the real lighting conditions. However, the sky type classification can be influenced by multiple scattering of light. Even if multiple scattering is essentially important under low elevation angles and high turbidity conditions, it is quite often ignored – e.g. when modelling the luminance patterns. As a consequence, the interpretation of experimental data can suffer from the omission of multiple scattering effects. Since multiple scattering smoothes the luminance patterns, the neighbouring sky types may be subject to blurring, and thus it might be difficult to distinguish them in automated data processing. In this paper we introduce a model that lowers the uncertainties caused by multiple scattering, so the subsequent numerical routines will definitely profit from more accurate identification of sky types.
Ambulatory oxygen improves the effectiveness of pulmonary rehabilitation in selected patients with chronic obstructive pulmonary disease
Authors: Dyer F , Callaghan J , Cheema K , Bott J
Published: March 2012

The effect of ambulatory oxygen use during pulmonary rehabilitation (PR) has not yet been clearly established, but many studies have shown benefit from oxygen acutely. Two small studies to date demonstrated no clear benefit when oxygen was used in patients who desaturated on exertion during a PR programme. One study showed the benefit of using oxygen during PR in patients who were normoxic at rest and desaturated to a minimum of 88% on exertion. We conducted a single-blind, randomised controlled trial comparing PR undertaken either with or without ambulatory oxygen, in those with demonstrable benefit from oxygen at baseline. Subjects from three PR services were recruited who, during baseline assessment, desaturated by more than 4% and to less than 90% on exertion, and walked 10% or more further with ambulatory oxygen on endurance shuttle walk test. Patients were randomised to either room air or oxygen via portable cylinder, titrated to optimise pulse oxygen saturation but up to a maximum flow rate of 6 L/min. All patients then completed a twice weekly, 6- to 7-week PR programme. Data were analysed as per protocol. Totally 51 patients completed the study. At the end of PR, both groups improved with PR, with patients in the oxygen group demonstrating a highly statistically significantly greater mean improvement in endurance walking distance than the controls, 490 m (95% confidence interval 228–750; p ≤ 0.001), as well as clinically, although not statistically, significant changes in quality of life. The use of ambulatory oxygen during a 6- to 7-week PR programme greatly improved endurance walking distance in patients who desaturated on exertion with a positive acute response to ambulatory oxygen at baseline.
The Veil of Esteem
Authors: Hoffer Melba
Published: March 2012

This article is the second of a three-part series entitled: The Veil of Esteem: On Seeing Oneself Being Seen. Inspired by Walter Benjamin’s “reflection through vignette” method, the author inquires into the notions and interconnections between memory and esteem. Esteem is the truth of oneself through the eyes of the other, and any truth of esteem must be told from the perspective of that other, through the spectating other. Thus, the author finds that any story of esteem is veiled. This second part, Riddle and Accident, explores unconditional love as maintained without the merit-worthy, yet it is its esteem that catalyzes it. The story is narrated not as a representation of a person or of people but the discourse through which the author has been lent her voice. The author is the translator through whom she is now speaking. The translator is the producer of the discourse that suffocates her and allows her to breathe in gasped breaths, the producer of the discourse that both takes away her voice and gives her voice. The first part of this series, Fragment/Never Thinking of Tomorrow, appears in International Review of Qualitative Research, Volume 5, Issue 1; the third part, A Loan, appears in Qualitative Inquiry, Volume 18, Issue 4.
My Fair Physicist? Feminine Math and Science Role Models Demotivate Young Girls
Authors: Betz Diana E. , Sekaquaptewa Denise
Published: March 2012

Women in science, technology, engineering, and mathematics (STEM) are labeled unfeminine, a costly social label that may discourage female students from pursuing these fields. Challenges to this stereotype include feminine STEM role models, but their counterstereotypic-yet-feminine success may actually be demotivating, particularly to young girls. Study 1 showed that feminine STEM role models reduced middle school girls’ current math interest, self-rated ability, and success expectations relative to gender-neutral STEM role models and depressed future plans to study math among STEM-disidentified girls. These results did not extend to feminine role models displaying general (not STEM-specific) school success, indicating that feminine cues were not driving negative outcomes. Study 2 suggested that feminine STEM role models’ combination of femininity and success seemed particularly unattainable to STEM-disidentified girls. The results call for a better understanding of feminine STEM figures aimed at motivating young girls.
Metyrapone in treatment-resistant depression
Authors: Sigalas Paul David , Garg Himanshu , Watson Stuart , McAllister-Williams Richard Hamish , Ferrier I. Nicol
Published: March 2012

Depression affects a significant proportion of the population, with 1-year and lifetime prevalence of 3–5% and 10–30% respectively. Full remission is achieved in only a third of patients following treatment with first-line antidepressant. There is a need for novel treatments for treatment-resistant depression (TRD). Dysregulation of the hypothalamic–pituitary–adrenal (HPA) axis has been described in patients with depression. There is persistent rise in the levels of cortisol (end product of the HPA axis) and impairment of the negative feedback inhibition mechanism of the HPA axis. Dysregulation of the HPA axis has been found to be linked to nonresponse to antidepressants and relapse following successful treatment. The efficacy of pharmacological agents that intervene with the mechanisms involved in dysregulation of cortisol synthesis and release are being explored in depression, particularly in TRD. Studies have been carried out with these drugs as augmenting agents for antidepressants or as monotherapy. The strongest evidence has come from studies using metyrapone, a cortisol synthesis inhibitor, and this has been described in detail in this review. The most robust evidence for its antidepressant efficacy in depression comes from a double-blind, randomized, placebo-controlled study of augmentation of serotonergic antidepressants with metyrapone. A 3-week augmentation of serotonergic antidepressants with 1 g metyrapone daily was shown to be superior to placebo in reducing the Montgomery–Asberg Depression Rating Scale by 50%, 5 weeks following initiation of treatment. The mechanism of the antidepressant action of metyrapone is not clear but the evidence for various potential mechanisms is discussed.
Demography and national security: The politics of population shifts in contemporary Israel
Authors: Toft Monica Duffy
Published: March 2012

Israel perceives itself to be under a constant and general threat to its existence. Like many other aspects of its security, Israel’s small size relative to its neighbors means that even relatively small demographic shifts may have unexpected and threatening political consequences. Israel’s struggles with security, identity, and demography therefore serve to highlight a relationship not unique to Israel but particularly intense there: a relationship between demographic shifts and state, regional, and interstate security. This article demonstrates that Israel’s demographic shifts have come to be regarded as an existential threat by Israel, and the contemporary salience of demography in Israel explains both (1) Israel’s decision to build a ‘security fence’ between it and the Palestinian Occupied Territories in the West Bank, and (2) the timing of that decision. The article examines Israel’s historical demographic trends and discourse and makes the case that this high-level national policy was a response to the perception among Israel’s leaders that demographic threats to both the Jewish and democratic character of Israel were more grave even than the physical threat of terrorism.
Comparison on genomic predictions using three GBLUP methods and two single-step blending methods in the Nordic Holstein population
Authors: Gao Hongding , Christensen Ole F , Madsen Per , Nielsen Ulrik S , Zhang Yuan , Lund Mogens S , Su Guosheng
Published: March 2012

Background

A single-step blending approach allows genomic prediction using information of genotyped and non-genotyped animals simultaneously. However, the combined relationship matrix in a single-step method may need to be adjusted because marker-based and pedigree-based relationship matrices may not be on the same scale. The same may apply when a GBLUP model includes both genomic breeding values and residual polygenic effects. The objective of this study was to compare single-step blending methods and GBLUP methods with and without adjustment of the genomic relationship matrix for genomic prediction of 16 traits in the Nordic Holstein population.

Methods

The data consisted of de-regressed proofs (DRP) for 5 214 genotyped and 9 374 non-genotyped bulls. The bulls were divided into a training and a validation population by birth date, October 1, 2001. Five approaches for genomic prediction were used: 1) a simple GBLUP method, 2) a GBLUP method with a polygenic effect, 3) an adjusted GBLUP method with a polygenic effect, 4) a single-step blending method, and 5) an adjusted single-step blending method. In the adjusted GBLUP and single-step methods, the genomic relationship matrix was adjusted for the difference of scale between the genomic and the pedigree relationship matrices. A set of weights on the pedigree relationship matrix (ranging from 0.05 to 0.40) was used to build the combined relationship matrix in the single-step blending method and the GBLUP method with a polygenetic effect.

Results

Averaged over the 16 traits, reliabilities of genomic breeding values predicted using the GBLUP method with a polygenic effect (relative weight of 0.20) were 0.3% higher than reliabilities from the simple GBLUP method (without a polygenic effect). The adjusted single-step blending and original single-step blending methods (relative weight of 0.20) had average reliabilities that were 2.1% and 1.8% higher than the simple GBLUP method, respectively. In addition, the GBLUP method with a polygenic effect led to less bias of genomic predictions than the simple GBLUP method, and both single-step blending methods yielded less bias of predictions than all GBLUP methods.

Conclusions

The single-step blending method is an appealing approach for practical genomic prediction in dairy cattle. Genomic prediction from the single-step blending method can be improved by adjusting the scale of the genomic relationship matrix.
Tandem repeats discovery service (TReaDS) applied to finding novel cis-acting factors in repeat expansion diseases
Authors: Pellegrini Marco , Renda Maria Elena , Vecchio Alessio
Published: March 2012

Background

Tandem repeats are multiple duplications of substrings in the DNA that occur contiguously, or at a short distance, and may involve some mutations (such as substitutions, insertions, and deletions). Tandem repeats have been extensively studied also for their association with the class of repeat expansion diseases (mostly affecting the nervous system). Comparative studies on the output of different tools for finding tandem repeats highlighted significant differences among the sets of detected tandem repeats, while many authors pointed up how critical it is the right choice of parameters.

Results

In this paper we present TReaDS - Tandem Repeats Discovery Service, a tandem repeat meta search engine. TReaDS forwards user requests to several state of the art tools for finding tandem repeats and merges their outcome into a single report, providing a global, synthetic, and comparative view of the results. In particular, TReaDS allows the user to (i) simultaneously run different algorithms on the same data set, (ii) choose for each algorithm a different setting of parameters, and (iii) obtain a report that can be downloaded for further, off-line, investigations. We used TReaDS to investigate sequences associated with repeat expansion diseases.

Conclusions

By using the tool TReaDS we discover that, for 27 repeat expansion diseases out of a currently known set of 29, long fuzzy tandem repeats are covering the expansion loci. Tests with control sets confirm the specificity of this association. This finding suggests that long fuzzy tandem repeats can be a new class of cis-acting elements involved in the mechanisms leading to the expansion instability.

We strongly believe that biologists can be interested in a tool that, not only gives them the possibility of using multiple search algorithm at the same time, with the same effort exerted in using just one of the systems, but also simplifies the burden of comparing and merging the results, thus expanding our capabilities in detecting important phenomena related to tandem repeats.
GIDL: a rule based expert system for GenBank Intelligent Data Loading into the Molecular Biodiversity database
Authors: Pannarale Paolo , Catalano Domenico , De Caro Giorgio , Grillo Giorgio , Leo Pietro , Pappadà Graziano , Rubino Francesco , Scioscia Gaetano , Licciulli Flavio
Published: March 2012

Background

In the scientific biodiversity community, it is increasingly perceived the need to build a bridge between molecular and traditional biodiversity studies. We believe that the information technology could have a preeminent role in integrating the information generated by these studies with the large amount of molecular data we can find in bioinformatics public databases. This work is primarily aimed at building a bioinformatic infrastructure for the integration of public and private biodiversity data through the development of GIDL, an Intelligent Data Loader coupled with the Molecular Biodiversity Database. The system presented here organizes in an ontological way and locally stores the sequence and annotation data contained in the GenBank primary database.

Methods

The GIDL architecture consists of a relational database and of an intelligent data loader software. The relational database schema is designed to manage biodiversity information (Molecular Biodiversity Database) and it is organized in four areas: MolecularData, Experiment, Collection and Taxonomy. The MolecularData area is inspired to an established standard in Generic Model Organism Databases, the Chado relational schema. The peculiarity of Chado, and also its strength, is the adoption of an ontological schema which makes use of the Sequence Ontology.

The Intelligent Data Loader (IDL) component of GIDL is an Extract, Transform and Load software able to parse data, to discover hidden information in the GenBank entries and to populate the Molecular Biodiversity Database. The IDL is composed by three main modules: the Parser, able to parse GenBank flat files; the Reasoner, which automatically builds CLIPS facts mapping the biological knowledge expressed by the Sequence Ontology; the DBFiller, which translates the CLIPS facts into ordered SQL statements used to populate the database. In GIDL Semantic Web technologies have been adopted due to their advantages in data representation, integration and processing.

Results and conclusions

Entries coming from Virus (814,122), Plant (1,365,360) and Invertebrate (959,065) divisions of GenBank rel.180 have been loaded in the Molecular Biodiversity Database by GIDL. Our system, combining the Sequence Ontology and the Chado schema, allows a more powerful query expressiveness compared with the most commonly used sequence retrieval systems like Entrez or SRS.
Nosocomial acquisition of methicillin-resistant Staphyloccocus aureus (MRSA) and extended-spectrum beta-lactamase (ESBL) Enterobacteriaceae in hospitalised patients: a prospective multicenter study
Authors: De Angelis Giulia , Restuccia Giovanni , Venturiello Silvia , Cauda Roberto , Malhotra-Kumar Surbhi , Goossens Herman , Schrenzel Jacques , Tacconelli Evelina
Published: March 2012

Background

The risk of acquisition of antibiotic resistant-bacteria during or shortly after antibiotic therapy is still unclear and it is often confounded by scarce data on antibiotic usage.

Primary objective of the study is to compare rates of acquisition of methicillin-resistant Staphylococcus aureus and extended spectrum beta-lactamase-producing Enterobacteriaceae in hospitalised patients, after starting antibiotic therapy.

Methods/Design

The study, running in three European hospitals, is a multicenter, prospective, longitudinal, observational cohort study funded from the European Community's Seventh Framework Programme [FP7/2007-2013] within the project 'Impact of Specific Antibiotic Therapies on the prevalence of hUman host ResistaNt bacteria' (acronym SATURN). Nasal and rectal screening for methicillin-resistant Staphylococcus aureus and extended spectrum beta-lactamase-producing Enterobacteriaceae will be obtained at hospital admission, discharge, at antibiotic start (t0, within one hour) and at the following intervals: day 3 (t1), 7 (t2), 15 (t3), and 30 (t4). Two nested case-control studies will be performed. The objective of the first study will be to define individual level of risk related to specific antibiotics. Patients acquiring methicillin-resistant Staphylococcus aureus and extended spectrum beta-lactamase-producing Enterobacteriaceae (cases) will be compared with patients not acquiring antibiotic-resistant strains after starting antibiotic therapy (controls; ratio 1:4). To define the impact of antibiotics on new acquisition of target antibiotic-resistant bacteria, a second nested case-control study will be done (ratio 1:4). Control group will be selected among patients not receiving antibiotics, admitted in the same ward on the day of the corresponding case, with negative cultures at admission. Epidemiological, clinical and microbiological data will be prospective collected.

Discussion

The rationale of this study is to better understand the impact of antibiotic use on acquisition, selection and transmission of antimicrobial resistant-bacteria in European hospitals.

Trial registration

ClinicalTrials.gov NCT01208519.
The absence of dystrophin brain isoform expression in healthy human heart ventricles explains the pathogenesis of 5' X-linked dilated cardiomyopathy
Authors: Neri Marcella , Valli Emanuele , Alfano Giovanna , Bovolenta Matteo , Spitali Pietro , Rapezzi Claudio , Muntoni Francesco , Banfi Sandro , Perini Giovanni , Gualandi Francesca , Ferlini Alessandra
Published: March 2012

Background

In X-linked dilated cardiomyopathy due to dystrophin mutations which abolish the expression of the M isoform (5'-XLDC), the skeletal muscle is spared through the up-regulation of the Brain (B) isoform, a compensatory mechanism that does not appear to occur in the heart of affected individuals.

Methods

We quantitatively studied the expression topography of both B and M isoforms in various human heart regions through in-situ RNA hybridization, Reverse-Transcriptase and Real-Time PCR experiments. We also investigated the methylation profile of the B promoter region in the heart and quantified the B isoform up regulation in the skeletal muscle of two 5'-XLDC patients.

Results

Unlike the M isoform, consistently detectable in all the heart regions, the B isoform was selectively expressed in atrial cardiomyocytes, but absent in ventricles and in conduction system structures. Although the level of B isoform messenger in the skeletal muscle of 5'-XLDC patients was lower that of the M messenger present in control muscle, it seems sufficient to avoid an overt muscle pathology. This result is consistent with the protein level in XLDC patients muscles we previously quantified. Methylation studies revealed that the B promoter shows an overall low level of methylation at the CG dinucleotides in both atria and ventricles, suggesting a methylation-independent regulation of the B promoter activity.

Conclusions

The ventricular dilatation seen in 5'-XLDC patients appears to be functionally related to loss of the M isoform, the only isoform transcribed in human ventricles; in contrast, the B isoform is well expressed in heart but confined to the atria. Since the B isoform can functionally replace the M isoform in the skeletal muscle, its expression in the heart could potentially exert the same rescue function. Methylation status does not seem to play a role in the differential B promoter activity in atria and ventricles, which may be governed by other regulatory mechanisms. If these mechanisms could be deduced, de-silencing of the B isoform may represent a therapeutic strategy in 5'-XLDC patients.
Genetic polymorphisms in MMP 2, 9 and 3genes modify lung cancer risk and survival
Authors: González-Arriaga Patricia , Pascual Teresa , García-Alvarez Arturo , Fernández-Somoano Ana , López-Cima M Felicitas , Tardón Adonina
Published: March 2012

Background

Matrix metalloproteases (MMPs) are proteolytic enzymes that contribute to all stages of tumour progression, including the later stages of invasion and metastasis. Genetic variants in theMMPgenes may influence the biological function of these enzymes and change their role in carcinogenesis and progression. We have investigated the association between the -735 C/T, the -1171 5A/6A, and the -1562 C/T polymorphisms in theMMP2, MMP3andMMP9genes, respectively, and the risk and survival of lung cancer.

Methods

The case-control study includes 879 lung cancer patients and 803 controls from a Caucasian population in Spain (CAPUA study). Genotypes were determined by PCR-RFLP. Odds ratios (OR) and 95% confidence intervals (CI) were calculated using unconditional logistic regression. The Kaplan-Meier method, long-rank test and Cox's were used for the survival analysis.

Results

TheMMP9-1562 T/T genotype was associated with a statistically significant decreased risk of developing lung cancer (OR = 0.23; 95% CI: 0.06-0.85), whereas no association was found for theMMP2-735 C/T andMMP3-1171 5A/6A polymorphisms. TheMMP2-735 T/T genotype was statistically significantly associated with a decreased survival in non-small cell lung cancer (NSCLC) patients, identified as an independent prognosis factor of survival (hazard ratio (HR) = 1.79; 95% CI: 1.00-3.20). In contrast, no association was found between theMMP3-1171 5A/6A and theMMP9-1562 C/T polymorphisms and survival.

Conclusions

These findings support the hypothesis that theMMP9-1562 C/T polymorphism is associated with a protective effect against the development of lung cancer and suggest that theMMP2-735 C/T polymorphism modify the length of survival in NSCLC patients.
Relationship of metabolic syndrome and its components with -844 G/A and HindIII C/G PAI-1 gene polymorphisms in Mexican children
Authors: De la Cruz-Mosso Ulises , Muñoz-Valle José F , Salgado-Goytia Lorenzo , García-Carreón Adrián , Illades-Aguiar Berenice , Castañeda-Saucedo Eduardo , Parra-Rojas Isela
Published: March 2012

Background

Several association studies have shown that -844 G/A andHindIIIC/GPAI-1polymorphisms are related with increase of PAI-1 levels, obesity, insulin resistance, glucose intolerance, hypertension and dyslipidemia, which are components of metabolic syndrome. The aim of this study was to analyze the allele and genotype frequencies of these polymorphisms inPAI-1gene and its association with metabolic syndrome and its components in a sample of Mexican mestizo children.

Methods

This study included 100 children with an age range between 6-11 years divided in two groups: a) 48 children diagnosed with metabolic syndrome and b) 52 children metabolically healthy without any clinical and biochemical alteration. Metabolic syndrome was defined as the presence of three or more of the following criteria: fasting glucose levels ≥ 100 mg/dL, triglycerides ≥ 150 mg/dL, HDL-cholesterol < 40 mg/dL, obesity BMI ≥ 95thpercentile, systolic blood pressure (SBP) and diastolic blood pressure (DBP) ≥ 95thpercentile and insulin resistance HOMA-IR ≥ 2.4. The -844 G/A andHindIIIC/GPAI-1polymorphisms were analyzed by PCR-RFLP.

Results

For the -844 G/A polymorphism, the G/A genotype (OR = 2.79; 95% CI, 1.11-7.08;p= 0.015) and the A allele (OR = 2.2; 95% CI, 1.10-4.43;p= 0.015) were associated with metabolic syndrome. The -844 G/A and A/A genotypes were associated with increase in plasma triglycerides levels (OR = 2.6; 95% CI, 1.16 to 6.04;p= 0.02), decrease in plasma HDL-cholesterol levels (OR = 2.4; 95% CI, 1.06 to 5.42;p= 0.03) and obesity (OR = 2.6; 95% CI, 1.17-5.92;p= 0.01). The C/G and G/G genotypes of theHindIIIC/G polymorphism contributed to a significant increase in plasma total cholesterol levels (179 vs. 165 mg/dL;p= 0.02) in comparison with C/C genotype.

Conclusions

The -844 G/APAI-1polymorphism is related with the risk of developing metabolic syndrome, obesity and atherogenic dyslipidemia, and theHindIIIC/GPAI-1polymorphism was associated with the increase of total cholesterol levels in Mexican children.
Use of the internet by Italian pediatricians: habits, impact on clinical practice and expectations
Authors: Romano Mariateresa , Gesualdo Francesco , Pandolfi Elisabetta , Tozzi Alberto E , Ugazio Alberto G
Published: March 2012

Background

Medical professionals go online for literature searches and communication with families.

We administered a questionnaire to members of the Italian Society of Pediatrics to assess determinants of their use of the Internet, of social platforms and of personal health records during clinical practice.

Methods

All the 9180 members of the Italian Society of Pediatrics were invited to fill in a questionnaire concerning use of the Internet and usefulness of Internet-based tools during clinical practice. The questionnaire was administered through the SurveyMonkey® web platform. Logistic regression analysis was used to study factors affecting use and influence of the Internet in clinical practice.

Results

A total of 1335 (14.5%) members returned the questionnaire. Mean age was 49.2 years, 58.6% were female. 32.3% had access to the Internet through a Smartphone. 71.9% of respondents used the Internet during clinical practice, mainly searching for guidelines and drug references. Use of the Internet during clinical practice was more frequent among younger pediatricians (OR 0.964; 95% CI 0.591-0.978), males (OR 1.602; 95% CI 1.209-2.123) and those living in Northern and Central Italy (OR 1.441; 95% CI 1.111-1.869), while it was lower among family pediatricians. 94.6% of respondents were influenced in their clinical practice by information found on the Internet, in particular younger pediatricians (OR 0.96, 95% CI 0.932-0.989), hospital pediatricians (OR 2.929, 95% CI 1.708-5.024), and other pediatric profiles (OR 6.143, 95%CI 1.848-20.423). 15.9% of respondents stated that social networks may be useful in pediatric practice. Slightly more than half (50.5%) of respondents stated that personal health records may be clinically relevant. Registrars and hospital pediatricians were more likely to perceive personal health records as useful tools for clinical practice. Additional resources pediatricians would like to access were free bibliographic databases and tools for interacting with families.

Conclusions

Italian pediatricians frequently use the Internet during their practice. One-third of them access the Internet through a Smartphone. Interaction with families and their empowerment can be improved by the use of Internet tools, including personal health records, toward which respondents show a significant interest. Though, they show a general resistance to the introduction of social networks in clinical practice.
Large-scale survey for novel genotypes of Plasmodium falciparum chloroquine-resistance gene pfcrt
Authors: Takahashi Nobuyuki , Tanabe Kazuyuki , Tsukahara Takahiro , Dzodzomenyo Mawuli , Dysoley Lek , Khamlome Boualam , Sattabongkot Jetsumon , Nakamura Masatoshi , Sakurai Miki , Kobayashi Jun , Kaneko Akira , Endo Hiroyoshi , Hombhanje Francis , Tsuboi Takafumi , Mita Toshihiro
Published: March 2012

Background

In Plasmodium falciparum, resistance to chloroquine (CQ) is conferred by a K to T mutation at amino acid position 76 (K76T) in the P. falciparum CQ transporter (PfCRT). To date, at least 15 pfcrt genotypes, which are represented by combinations of five amino acids at positions 72-76, have been described in field isolates from various endemic regions. To identify novel mutant pfcrt genotypes and to reveal the genetic relatedness of pfcrt genotypes, a large-scale survey over a wide geographic area was performed.

Methods

Sequences for exon 2 in pfcrt, including known polymorphic sites at amino acid positions 72, 74, 75 and 76, were obtained from 256 P. falciparum isolates collected from eight endemic countries in Asia (Bangladesh, Cambodia, Lao P.D.R., the Philippines and Thailand), Melanesia (Papua New Guinea and Vanuatu) and Africa (Ghana). A haplotype network was constructed based on six microsatellite markers located -29 kb to 24 kb from pfcrt in order to examine the genetic relatedness among mutant pfcrt genotypes.

Results

In addition to wild type (CVMNK at positions 72-76), four mutant pfcrt were identified; CVIET, CVIDT, S VMNT and CVMNT (mutated amino acids underlined). Haplotype network revealed that there were only three mutant pfcrt lineages, originating in Indochina, Philippines and Melanesia. Importantly, the Indochina lineage contained two mutant pfcrt genotypes, CVIET (n = 95) and CVIDT (n = 14), indicating that CVIDT shares a common origin with CVIET. Similarly, one major haplotype in the Melanesian lineage contained two pfcrt genotypes; S VMNT (n = 71) and CVMNT (n = 3). In Africa, all mutant pfcrt genotypes were the CVIET of the Indochina lineage, probably resulting from the intercontinental migration of CQ resistance from Southeast Asia.

Conclusions

The number of CQ-mutant lineages observed in this study was identical to that found in previous studies. This supports the hypothesis that the emergence of novel CQ resistance is rare. However, in the mutant pfcrt genotypes, amino acid changes at positions 72, 74 and 75 appear to have recently been generated at least several times, producing distinct pfcrt mutant genotypes. The occurrence of new mutations flanking K76T may yield stronger resistance to CQ and/or a higher fitness than the original pfcrt mutant.
Fuzheng Huayu recipe prevents nutritional fibrosing steatohepatitis in mice
Authors: Jia Yan-Hong , Wang Rong-Qi , Mi Hong-Mei , Kong Ling-Bo , Ren Wei-Guang , Li Wen-Cong , Zhao Su-Xian , Zhang Yu-Guo , Wu Wen-Juan , Nan Yue-Min , Yu Jun
Published: March 2012

Background

Fuzheng Huayu recipe (FZHY), a compound of Chinese herbal medicine, was reported to improve liver function and fibrosis in patients with hepatitis B virus infection. However, its effect on nutritional fibrosing steatohepatitis is unclear. We aimed to elucidate the role and molecular mechanism of FZHY on this disorder in mice.

Methods

C57BL/6 J mice were fed with methionine-choline deficient (MCD) diet for 8 weeks to induce fibrosing steatohepatitis. FZHY and/or heme oxygenase-1 (HO-1) chemical inducer (hemin) were administered to mice, respectively. The effect of FZHY was assessed by comparing the severity of hepatic injury, levels of hepatic lipid peroxides, activation of hepatic stellate cells (HSCs) and the expression of oxidative stress, inflammatory and fibrogenic related genes.

Results

Mice fed with MCD diet for 8 weeks showed severe hepatic injury including hepatic steatosis, necro-inflammation and fibrosis. Administration of FZHY or hemin significantly lowered serum levels of alanine aminotransferase, aspartate aminotransferase, reduced hepatic oxidative stress and ameliorated hepatic inflammation and fibrosis. An additive effect was observed in mice fed MCD supplemented with FZHY or/and hemin. These effects were associated with down-regulation of pro-oxidative stress gene cytochrome P450 2E1, up-regulation of anti-oxidative gene HO-1; suppression of pro-inflammation genes tumor necrosis factor alpha and interleukin-6; and inhibition of pro-fibrotic genes including α-smooth muscle actin, transforming growth factor beta 1, collagen type I (Col-1) and Col-3.

Conclusions

Our study demonstrated the protective role of FZHY in ameliorating nutritional fibrosing steatohepatitis. The effect was mediated through regulating key genes related to oxidative stress, inflammation and fibrogenesis.
Androgen receptor-beta mRNA levels in different tissues in breeding and post-breeding male and female sticklebacks, Gasterosteus aculeatus
Authors: Hoffmann Erik , Walstad Anders , Karlsson Johnny , Olsson Per-Erik , Borg Bertil
Published: March 2012

Background

Androgens induce male characters by activating androgen receptors (AR). Previous quantitative studies on AR in fishes have been limited to few tissues and/or a single season/reproductive state. The aim of this investigation was to study the possible role of AR-beta expression levels in the control of male traits in the three-spined stickleback. To that end, AR-beta expression levels in major tissues in breeding and post-breeding male and female sticklebacks were examined.

Methods

AR-beta mRNA levels were quantified in ten tissues; eye, liver, axial muscle, heart, brain, intestine, ovary, testis, kidney and pectoral muscle in six breeding and post-breeding males and females using reverse transcription quantitative PCR.

Results

Breeding in contrast to post-breeding males built nests and showed secondary sexual characters (e.g. kidney hypertrophy) and elevated androgen levels. Post-breeding females had lower ovarian weights and testosterone levels than breeding females. AR-beta was expressed in all studied tissues in both sexes and reproductive states with the highest expression in the gonads and in the kidneys. The kidney is an androgen target organ in sticklebacks, from which breeding males produce the protein spiggin, which is used in nest-building. There was also high AR-beta expression in the intestine, an organ that appears to take over hyperosmo-regulation in fresh water when the kidney hypertrophies in mature males and largely loses this function. The only tissue that showed effects of sex or reproductive state on AR-beta mRNA levels was the kidneys, where post-breeding males displayed higher AR-beta mRNA levels than breeding males.

Conclusion

The results indicate that changes in AR-beta mRNA levels play no or little role in changes in androgen dependent traits in the male stickleback.
Host-pathogen interactome mapping for HTLV-1 and -2 retroviruses
Authors: Simonis Nicolas , Rual Jean-François , Lemmens Irma , Boxus Mathieu , Hirozane-Kishikawa Tomoko , Gatot Jean-Stéphane , Dricot Amélie , Hao Tong , Vertommen Didier , Legros Sébastien , Daakour Sarah , Klitgord Niels , Martin Maud , Willaert Jean-François , Dequiedt Franck , Navratil Vincent , Cusick Michael E , Burny Arsène , Van Lint Carine , Hill David E , Tavernier Jan , Kettmann Richard , Vidal Marc , Twizere Jean-Claude
Published: March 2012

Background

Human T-cell leukemia virus type 1 (HTLV-1) and type 2 both target T lymphocytes, yet induce radically different phenotypic outcomes. HTLV-1 is a causative agent of Adult T-cell leukemia (ATL), whereas HTLV-2, highly similar to HTLV-1, causes no known overt disease. HTLV gene products are engaged in a dynamic struggle of activating and antagonistic interactions with host cells. Investigations focused on one or a few genes have identified several human factors interacting with HTLV viral proteins. Most of the available interaction data concern the highly investigated HTLV-1 Tax protein. Identifying shared and distinct host-pathogen protein interaction profiles for these two viruses would enlighten how they exploit distinctive or common strategies to subvert cellular pathways toward disease progression.

Results

We employ a scalable methodology for the systematic mapping and comparison of pathogen-host protein interactions that includes stringent yeast two-hybrid screening and systematic retest, as well as two independent validations through an additional protein interaction detection method and a functional transactivation assay. The final data set contained 166 interactions between 10 viral proteins and 122 human proteins. Among the 166 interactions identified, 87 and 79 involved HTLV-1 and HTLV-2 -encoded proteins, respectively. Targets for HTLV-1 and HTLV-2 proteins implicate a diverse set of cellular processes including the ubiquitin-proteasome system, the apoptosis, different cancer pathways and the Notch signaling pathway.

Conclusions

This study constitutes a first pass, with homogeneous data, at comparative analysis of host targets for HTLV-1 and -2 retroviruses, complements currently existing data for formulation of systems biology models of retroviral induced diseases and presents new insights on biological pathways involved in retroviral infection.
Warmth Suppresses and Desensitizes Damage-Sensing Ion Channel TRPA1
Authors: Wang Sen , Lee Jongseok , Ro Jin Y , Chung Man-Kyo
Published: March 2012

Background:

Acute or chronic tissue damage induces an inflammatory response accompanied by pain and alterations in local tissue temperature. Recent studies revealed that the transient receptor potential A1 (TRPA1) channel is activated by a wide variety of substances that are released following tissue damage to evoke nociception and neurogenic inflammation. Although the effects of a noxious range of cold temperatures on TRPA1 have been rigorously studied, it is not known how agonist-induced activation of TRPA1 is regulated by temperature over an innocuous range centred on the normal skin surface temperature. This study investigated the effect of temperature on agonist-induced currents in human embryonic kidney (HEK) 293 cells transfected with rat or human TRPA1 and in rat sensory neurons.

Results:

Agonist-induced TRPA1 currents in HEK293 cells were strongly suppressed by warm temperatures, and almost abolished at 39°C. Such inhibition occurred when TRPA1 was activated by either electrophilic or non-electrophilic agonists. Warming not only decreased the apparent affinity of TRPA1 for mustard oil (MO), but also greatly enhanced the desensitization and tachyphylaxis of TRPA1. Warming also attenuated MO-induced ionic currents in sensory neurons. These results suggest that the extent of agonist-induced activity of TRPA1 may depend on surrounding tissue temperature, and local hyperthermia during acute inflammation could be an endogenous negative regulatory mechanism to attenuate persistent pain at the site of injury.

Conclusion:

These results indicate that warmth suppresses and desensitizes damage-sensing ion channel TRPA1. Such warmth-induced suppression of TRPA1 may also explain, at least in part, the mechanistic basis of heat therapy that has been widely used as a supplemental anti-nociceptive approach.
Prevalence and molecular characterization of Clostridium difficileisolated from feedlot beef cattle upon arrival and mid-feeding period
Authors: Costa Marcio C , Reid-Smith Richard , Gow Sheryl , Hannon Sherry J , Booker Calvin , Rousseau Joyce , Benedict Katharine M , Morley Paul S , Weese J Scott
Published: March 2012

Background

The presence of indistinguishable strains of Clostridium difficile in humans, food animals and food, as well as the apparent emergence of the food-animal-associated ribotype 078/toxinotype V as a cause of community-associated C. difficile infection have created concerns about the potential for foodborne infection. While studies have reported C. difficile in calves, studies of cattle closer to the age of harvest are required. Four commercial feedlots in Alberta (Canada) were enrolled for this study. Fecal samples were collected at the time of arrival and after acclimation (< 62, 62-71 or > 71 days on feed). Selective culture for Clostridium difficile was performed, and isolates were characterized by ribotyping and pulsed-field gel electrophoresis. A logistic regression model was built to investigate the effect of exposure to antimicrobial drugs on the presence of C. difficile.

Results

Clostridium difficile was isolated from 18 of 539 animals at the time of feedlot arrival (CI = 2.3-6.1) and from 18 of 335 cattle at mid-feeding period (CI = 2.9-13.1). Overall, there was no significant difference in the prevalence of C. difficile shedding on arrival versus mid-feeding period (P = 0.47). No association between shedding of the bacterium and antimicrobial administration was found (P = 0.33). All the isolates recovered were ribotype 078, a toxinotype V strain with genes encoding toxins A, B and CDT. In addition, all strains were classified as NAP7 by pulsed field gel electrophoresis (PFGE) and had the characteristic 39 base pairs deletion and upstream truncating mutation on the tcdC gene.

Conclusions

It is apparent that C. difficile is carried in the intestinal tracts of a small percentage of feedlot cattle arriving and later in the feeding period and that ribotype 078/NAP7 is the dominant strain in these animals. Herd management practices associated with C. difficile shedding were not identified, however further studies of the potential role of antimicrobials on C. difficile acquisition and shedding are required.
Complex effects of flavopiridol on the expression of primary response genes
Authors: Keskin Havva , Garriga Judit , Georlette Daphne , Graña Xavier
Published: March 2012

Background

The Positive Transcription Elongation Factor b (P-TEFb) is a complex of Cyclin Dependent Kinase 9 (CDK9) with either cyclins T1, T2 or K. The complex phosphorylates the C-Terminal Domain of RNA polymerase II (RNAPII) and negative elongation factors, stimulating productive elongation by RNAPII, which is paused after initiation. P-TEFb is recruited downstream of the promoters of many genes, including primary response genes, upon certain stimuli. Flavopiridol (FVP) is a potent pharmacological inhibitor of CDK9 and has been used extensively in cells as a means to inhibit CDK9 activity. Inhibition of P-TEFb complexes has potential therapeutic applications.

Results

It has been shown that Lipopolysaccharide (LPS) stimulates the recruitment of P-TEFb to Primary Response Genes (PRGs) and proposed that P-TEFb activity is required for their expression, as the CDK9 inhibitor DRB prevents localization of RNAPII in the body of these genes. We have previously determined the effects of FVP in global gene expression in a variety of cells and surprisingly observed that FVP results in potent upregulation of a number of PRGs in treatments lasting 4-24 h. Because inhibition of CDK9 activity is being evaluated in pre-clinical and clinical studies for the treatment of several pathologies, it is important to fully understand the short and long term effects of its inhibition. To this end, we determined the immediate and long-term effect of FVP in the expression of several PRGs. In exponentially growing normal human fibroblasts, the expression of several PRGs including FOS, JUNB, EGR1 and GADD45B, was rapidly and potently downregulated before they were upregulated following FVP treatment. In serum starved cells re-stimulated with serum, FVP also inhibited the expression of these genes, but subsequently, JUNB, GADD45B and EGR1 were upregulated in the presence of FVP. Chromatin Immunoprecipitation of RNAPII revealed that EGR1 and GADD45B are transcribed at the FVP-treatment time points where their corresponding mRNAs accumulate. These results suggest a possible stress response triggered by CDK9 inhibition than ensues transcription of certain PRGs.

Conclusions

We have shown that certain PRGs are transcribed in the presence of FVP in a manner that might be independent of CDK9, suggesting a possible alternative mechanism for their transcription when P-TEFb kinase activity is pharmacologically inhibited. These results also show that the sensitivity to FVP is quite variable, even among PRGs.