bluuebunny/crossref_metadata_2025 huggingface dataset:
Health strategies and reservoirs of knowledge among adolescents in Denmark
Authors: Wistoft Karen
Published: June 2010

This article presents selected results of qualitative research into perceptions of health among adolescents. Pupils ( N = 108) in the age 13—15 years from nine schools in four different municipalities in Denmark have been interviewed. An analytic strategy that combines knowledge research with systems theory is developed and used for the empirical analyses. The conclusions are focused on health-identities and health-strategies. Young people live their lives ‘here and now’ and it is hard for them to imagine how damaging the consequences of not taking risk-factors seriously can be. They cannot really relate to the diseases and it is therefore difficult for them to actively affect the different determinants. The adolescents feel that a lot of information and teaching is being directed towards them. They face an abundance of communication about health and information directed at their presumed risk-behaviour. They often experience saturation and lose both interest and focus. They reject patronizing or negative knowledge and generally express a desire to know more about the things that make life fun and positive. They feel that the knowledge directed at them must be more concrete and personally relevant for them. Finally, the adolescents are aware that they are influenced by their friends both positively and negatively. Indeed, they are concerned about the way they are being taught about health in school and desirous to learn more.
Programa educacional efectivo en la formación de agentes comunitarios de salud voluntarios en Lima, Perú
Authors: Galvez Cesar Augusto , Neish Christine , Balabarca Yvan , Rojas Leonardo , Serrano Celia
Published: June 2010

Con el propósito de forenar los primeros agentes comunitarios de salud (ACES) del Centro Poblado Virgen del Carmen La Era, Lima, Perú, se realizó un programa de entrenamiento educacional en las áreas de prevención de enfermedades diarreicas agudas (EDAS) infantiles, sexualidad saludable para adolescentes y autocuidado de la salud del adulto mayor. Un grupo de 32 ciudadanos fueron seleccionados por el Ministerio de Salud y la directiva del poblado en el 2006, y capacitados por un equipo interdisciplinario de profesionales de la Universidad Peruana Unión (UPeU) de Lima y Loma Linda University de California, con la finalidad de mejorar el acceso de 5,248 habitantes a la promoción y cuidado de salud. El Programa educacional “Por una Era Saludable” empleó técnicas educativas como rescate de saberes previos, dinámicas de autoestima, demostraciones de actividad física y juego de roles, y culminó con una visita domiciliaria por los ACES para aplicar sus nuevas destrezas. El resultado fue evaluado a través de un cuestionario de conocimientos, actitudes y prácticas para averiguar su progreso y cambio, y una ficha de observación. En el área de autocuidado del adulto mayor, el programa educativo incrementó los conocimientos en 26.46%, las actitudes en 10.12% y las habilidades en 20.13%. En sexualidad saludable, los ACES mejoraron sus conocimientos de 12.3 a 14.4 en la escala vigesimal, sus actitudes de 16.7 a 18.2, y sus destrezas de 13.1 a 15.8. Respecto a EDAS, los conocimientos y actitudes se fortalecieron y sus prácticas fueron incrementadas de 26.52% a 54.55%, desarraigando prácticas de higiene deficientes. A la fecha de entrega de esta publicación, a pedido del puesto de salud del Ministerio de Salud, los ACES, se encuentran terminando una nueva jornada de capacitación por la UPeU para promover salud bucal infantil en La Era.
Opioids in chronic musculoskeletal conditions
Authors: Calvo-Alén Jaime
Published: June 2010

The use of opioids for benign disorders has been limited by concerns about these compounds’ potential adverse events and their possible misuse. However, during the last few years an increased use in nonmalignant disorders, including rheumatologic diseases, has been observed. Herein, we review the scientific evidence for opioid therapy in three common scenarios in clinical rheumatology. Low back pain is a very frequent reason for consultation. Overall, the large majority of studies show a positive, yet rather moderate, effect of opioids in pain control, as well as in other outcomes including mood, work disability and anxiety. Similarly, opioids seem to have a role in the management of hip and knee osteoarthritis; indeed, they have been included in all international guidelines for the treatment of these conditions. However, clinical studies addressing opioid use in clinical situations are plagued by methodological limitations; furthermore, the large majority of these studies only provide short-term information about opiod utilization in these patients. Finally, opioids are currently being used as complementary therapy in inflammatory joint conditions whereby they may significantly improve the quality of life of some of these patients. Regarding their safety, severe adverse events, including abnormal drug-seeking behaviour, are very rare, but mild adverse events are frequent leading to drug discontinuation in a significant number of cases.
The carboxyterminal EF domain of erythroid α-spectrin is necessary for optimal spectrin-actin binding
Authors: Korsgren Catherine , Lux Samuel E.
Published: June 2010

Spectrin and protein 4.1R crosslink F-actin, forming the membrane skeleton. Actin and 4.1R bind to one end of β-spectrin. The adjacent end of α-spectrin, called the EF domain, is calmodulin-like, with calcium-dependent and calcium-independent EF hands. The severely anemic sph1J/sph1J mouse has very fragile red cells and lacks the last 13 amino acids in the EF domain, implying that the domain is critical for skeletal integrity. To test this, we constructed a minispectrin heterodimer from the actin-binding domain, the EF domain, and 4 adjacent spectrin repeats in each chain. The minispectrin bound to F-actin in the presence of native human protein 4.1R. Formation of the spectrin-actin-4.1R complex was markedly attenuated when the minispectrin contained the shortened sph1J α-spectrin. The α-spectrin deletion did not interfere with spectrin heterodimer assembly or 4.1R binding but abolished the binary interaction between spectrin and F-actin. The data show that the α-spectrin EF domain greatly amplifies the function of the β-spectrin actin-binding domain (ABD) in forming the spectrin-actin-4.1R complex. A model, based on the structure of α-actinin, suggests that the EF domain modulates the function of the ABD and that the C-terminal EF hands (EF34) may bind to the linker that connects the ABD to the first spectrin repeat.
A novel histidine tyrosine phosphatase, TULA-2, associates with Syk and negatively regulates GPVI signaling in platelets
Authors: Thomas Dafydd H. , Getz Todd M. , Newman Tiffanny N. , Dangelmaier Carol A. , Carpino Nick , Kunapuli Satya P. , Tsygankov Alexander Y. , Daniel James L.
Published: June 2010

T-cell ubiquitin ligand-2 (TULA-2) is a recently discovered histidine tyrosine phosphatase thought to be ubiquitously expressed. In this work, we have investigated whether TULA-2 has a key role in platelet glycoprotein VI (GPVI) signaling. This study indicates that TULA-2 is expressed in human and murine platelets and is able to associate with Syk and dephosphorylate it. Ablation of TULA-2 resulted in hyperphosphorylation of Syk and its downstream effector phospholipase C-γ2 as well as enhanced GPVI-mediated platelet functional responses. In addition, shorter bleeding times and a prothrombotic phenotype were observed in mice lacking TULA-2. We therefore propose that TULA-2 is the primary tyrosine phosphatase mediating the dephosphorylation of Syk and thus functions as a negative regulator of GPVI signaling in platelets.
Depletion of L3MBTL1 promotes the erythroid differentiation of human hematopoietic progenitor cells: possible role in 20q− polycythemia vera
Authors: Perna Fabiana , Gurvich Nadia , Hoya-Arias Ruben , Abdel-Wahab Omar , Levine Ross L. , Asai Takashi , Voza Francesca , Menendez Silvia , Wang Lan , Liu Fan , Zhao Xinyang , Nimer Stephen D.
Published: June 2010

L3MBTL1, the human homolog of the Drosophila L(3)MBT polycomb group tumor suppressor gene, is located on chromosome 20q12, within the common deleted region identified in patients with 20q deletion-associated polycythemia vera, myelodysplastic syndrome, and acute myeloid leukemia. L3MBTL1 is expressed within hematopoietic CD34+ cells; thus, it may contribute to the pathogenesis of these disorders. To define its role in hematopoiesis, we knocked down L3MBTL1 expression in primary hematopoietic stem/progenitor (ie, CD34+) cells isolated from human cord blood (using short hairpin RNAs) and observed an enhanced commitment to and acceleration of erythroid differentiation. Consistent with this effect, overexpression of L3MBTL1 in primary hematopoietic CD34+ cells as well as in 20q− cell lines restricted erythroid differentiation. Furthermore, L3MBTL1 levels decrease during hemin-induced erythroid differentiation or erythropoietin exposure, suggesting a specific role for L3MBTL1 down-regulation in enforcing cell fate decisions toward the erythroid lineage. Indeed, L3MBTL1 knockdown enhanced the sensitivity of hematopoietic stem/progenitor cells to erythropoietin (Epo), with increased Epo-induced phosphorylation of STAT5, AKT, and MAPK as well as detectable phosphorylation in the absence of Epo. Our data suggest that haploinsufficiency of L3MBTL1 contributes to some (20q−) myeloproliferative neoplasms, especially polycythemia vera, by promoting erythroid differentiation.
Comparing the retention mechanisms of tandem duplicates and retrogenes in human and mouse genomes
Authors: Wang Zhen , Dong Xiao , Ding Guohui , Li Yixue
Published: June 2010

Background

Multiple models have been proposed to interpret the retention of duplicated genes. In this study, we attempted to compare whether the duplicates arising from tandem duplications and retropositions are retained by the same mechanisms in human and mouse genomes.

Results

Both sequence and expression similarity analyses revealed that tandem duplicates tend to be more conserved, whereas retrogenes tend to be more divergent. The duplicability of tandem duplicates is also higher than that of retrogenes. However, positive selection seems to play significant roles in the retention of both types of duplicates.

Conclusions

We propose that dosage effect is more prevalent in the retention of tandem duplicates, while 'escape from adaptive conflict' (EAC) effect is more prevalent in the retention of retrogenes.
Protein complex prediction via verifying and reconstructing the topology of domain-domain interactions
Authors: Ozawa Yosuke , Saito Rintaro , Fujimori Shigeo , Kashima Hisashi , Ishizaka Masamichi , Yanagawa Hiroshi , Miyamoto-Sato Etsuko , Tomita Masaru
Published: June 2010

Background

High-throughput methods for detecting protein-protein interactions enable us to obtain large interaction networks, and also allow us to computationally identify the associations of proteins as protein complexes. Although there are methods to extract protein complexes as sets of proteins from interaction networks, the extracted complexes may include false positives because they do not account for the structural limitations of the proteins and thus do not check that the proteins in the extracted complex can simultaneously bind to each other. In addition, there have been few searches for deeper insights into the protein complexes, such as of the topology of the protein-protein interactions or into the domain-domain interactions that mediate the protein interactions.

Results

Here, we introduce a combinatorial approach for prediction of protein complexes focusing not only on determining member proteins in complexes but also on the DDI/PPI organization of the complexes. Our method analyzes complex candidates predicted by the existing methods. It searches for optimal combinations of domain-domain interactions in the candidates based on an assumption that the proteins in a candidate can form a true protein complex if each of the domains is used by a single protein interaction. This optimization problem was mathematically formulated and solved using binary integer linear programming. By using publicly available sets of yeast protein-protein interactions and domain-domain interactions, we succeeded in extracting protein complex candidates with an accuracy that is twice the average accuracy of the existing methods, MCL, MCODE, or clustering coefficient. Although the configuring parameters for each algorithm resulted in slightly improved precisions, our method always showed better precision for most values of the parameters.

Conclusions

Our combinatorial approach can provide better accuracy for prediction of protein complexes and also enables to identify both direct PPIs and DDIs that mediate them in complexes.
Identifying differentially regulated subnetworks from phosphoproteomic data
Authors: Klammer Martin , Godl Klaus , Tebbe Andreas , Schaab Christoph
Published: June 2010

Background

Various high throughput methods are available for detecting regulations at the level of transcription, translation or posttranslation (e.g. phosphorylation). Integrating these data with protein networks should make it possible to identify subnetworks that are significantly regulated. Furthermore, such integration can support identification of regulated entities from often noisy high throughput data. In particular, processing mass spectrometry-based phosphoproteomic data in this manner may expose signal transduction pathways and, in the case of experiments with drug-treated cells, reveal the drug's mode of action.

Results

Here, we introduce SubExtractor, an algorithm that combines phosphoproteomic data with protein network information from STRING to identify differentially regulated subnetworks and individual proteins. The method is based on a Bayesian probabilistic model combined with a genetic algorithm and rigorous significance testing. The Bayesian model accounts for information about both differential regulation and network topology. The method was tested with artificial data and subsequently applied to a comprehensive phosphoproteomics study investigating the mode of action of sorafenib, a small molecule kinase inhibitor.

Conclusions

SubExtractor reliably identifies differentially regulated subnetworks from phosphoproteomic data by integrating protein networks. The method can also be applied to gene or protein expression data.
Analysis of inhibitor of apoptosis protein family expression during mammary gland development
Authors: Owens Thomas W , Foster Fiona M , Tanianis-Hughes Jolanta , Cheung Julia Y , Brackenbury Lisa , Streuli Charles H
Published: June 2010

Background

Inhibitors-of-Apoptosis-Proteins (IAPs) are an evolutionarily conserved family of proteins capable of regulating several facets of apoptosis. IAPs are frequently dysregulated in cancer, but their role in the regulation of apoptosis during developmental processes is not fully understood. Here we examined the expression of IAPs during the post-natal development of the mouse mammary gland, which is a tissue that exhibits a profound induction of apoptosis during involution.

Results

Six out of eight mammalian IAP family members are expressed in the mammary gland. Notably, quantitative PCR and immunoblotting revealed that XIAP, c-IAP1 and c-IAP2 are down-regulated in pregnancy and lactation, and prior to the onset of involution. In cultured mammary epithelial cells (MECs), XIAP levels decreased in response to inhibition of growth factor signalling. Maintaining XIAP levels in MECs by expressing exogenous XIAP protected them from all apoptotic stimuli tested.

Conclusions

These data suggest that the developmental regulation of IAP expression in vivo contributes to naturally occurring programmes of cell death.
Rampant historical mitochondrial genome introgression between two species of green pond frogs, Pelophylax nigromaculatus and P. plancyi
Authors: Liu Kui , Wang Fang , Chen Wei , Tu Lihong , Min Mi-Sook , Bi Ke , Fu Jinzhong
Published: June 2010

Background

Mitochondrial introgression may result in the mitochondrial genome of one species being replaced by that of another species without leaving any trace of past hybridization in its nuclear genome. Such introgression can confuse the species genealogy estimates and lead to absurd inferences of species history. We used a phylogenetic approach to explore the potential mitochondrial genome introgression event(s) between two closely related green pond frog species,Pelophylax nigromaculatusandP. plancyi.

Results

DNA sequence data of one mitochondrial and two nuclear genes from an extensive sampling of the two species were collected, and the genealogies of the three genes were constructed and compared. While the two nuclear genes congruently showed mutual reciprocal monophyly of both species, the mitochondrial phylogeny separated a KoreanP. nigromaculatusclade, a paraphyletic central ChinaP. plancyiassemblage, and a large well-supported introgression clade. Within the introgression clade, the mitochondrial haplotypes of the two speciesweremixed together. This reticulated pattern can be most parsimoniously explained by an ancient mitochondrial introgression event fromP. plancyitoP. nigromaculatusthat occurred at least 1.36 MYA, followed by multiple recent introgression events fromP. nigromaculatusback toP. plancyiwithin the last 0.63 MY. The re-constitution of previously co-adapted genomes inP. plancyimay be responsible for the recent rampant introgression events. The KoreanP. nigromaculatusclade likely represents the only surviving "true" mitochondrial lineage ofP. nigromaculatus, and the central ChinaP. plancyiassemblage likely represents the "original"P. plancyimitochondrial lineage. Refugia in the Korean Peninsula and central China may have played a significant role in preserving these ancient lineages.

Conclusions

The majority of individuals in the two species have either introgressed (P. nigromaculatus) or reclaimed (P. plancyi) mitochondrial genomes while no trace of past hybridization in their nuclear genomes was detected. Asymmetrical reproductive ability of hybrids and continuous backcrossing are likely responsible for the observed mitochondrial introgression. This case is unique in that it includes an ancient "forward" introgression and many recent "backward" introgressions, which re-constitutes the original nuclear and mitochondrial genomes ofP. plancyi. This hybrid system provides an excellent opportunity to study cyto-nuclear interaction and co-adaptation.
Small RNAs, DNA methylation and transposable elements in wheat
Authors: Cantu Dario , Vanzetti Leonardo S , Sumner Adam , Dubcovsky Martin , Matvienko Marta , Distelfeld Assaf , Michelmore Richard W , Dubcovsky Jorge
Published: June 2010

Background

More than 80% of the wheat genome is composed of transposable elements (TEs). Since active TEs can move to different locations and potentially impose a significant mutational load, their expression is suppressed in the genome via small non-coding RNAs (sRNAs). sRNAs guide silencing of TEs at the transcriptional (mainly 24-nt sRNAs) and post-transcriptional (mainly 21-nt sRNAs) levels. In this study, we report the distribution of these two types of sRNAs among the different classes of wheat TEs, the regions targeted within the TEs, and their impact on the methylation patterns of the targeted regions.

Results

We constructed an sRNA library from hexaploid wheat and developed a database that included our library and three other publicly available sRNA libraries from wheat. For five completely-sequenced wheat BAC contigs, most perfectly matching sRNAs represented TE sequences, suggesting that a large fraction of the wheat sRNAs originated from TEs. An analysis of all wheat TEs present in the Triticeae Repeat Sequence database showed that sRNA abundance was correlated with the estimated number of TEs within each class. Most of the sRNAs perfectly matching miniature inverted repeat transposable elements (MITEs) belonged to the 21-nt class and were mainly targeted to the terminal inverted repeats (TIRs). In contrast, most of the sRNAs matching class I and class II TEs belonged to the 24-nt class and were mainly targeted to the long terminal repeats (LTRs) in the class I TEs and to the terminal repeats in CACTA transposons. An analysis of the mutation frequency in potentially methylated sites revealed a three-fold increase in TE mutation frequency relative to intron and untranslated genic regions. This increase is consistent with wheat TEs being preferentially methylated, likely by sRNA targeting.

Conclusions

Our study examines the wheat epigenome in relation to known TEs. sRNA-directed transcriptional and post-transcriptional silencing plays important roles in the short-term suppression of TEs in the wheat genome, whereas DNA methylation and increased mutation rates may provide a long-term mechanism to inactivate TEs.
Coordinated transcriptional regulation of two key genes in the lignin branch pathway - CAD and CCR - is mediated through MYB- binding sites
Authors: Rahantamalala Anjanirina , Rech Philippe , Martinez Yves , Chaubet-Gigot Nicole , Grima-Pettenati Jacqueline , Pacquit Valérie
Published: June 2010

Background

Cinnamoyl CoA reductase (CCR) and cinnamyl alcohol dehydrogenase (CAD) catalyze the final steps in the biosynthesis of monolignols, the monomeric units of the phenolic lignin polymers which confer rigidity, imperviousness and resistance to biodegradation to cell walls. We have previously shown that the Eucalyptus gunnii CCR and CAD2 promoters direct similar expression patterns in vascular tissues suggesting that monolignol production is controlled, at least in part, by the coordinated transcriptional regulation of these two genes. Although consensus motifs for MYB transcription factors occur in most gene promoters of the whole phenylpropanoid pathway, functional evidence for their contribution to promoter activity has only been demonstrated for a few of them. Here, in the lignin-specific branch, we studied the functional role of MYB elements as well as other cis-elements identified in the regulatory regions of EgCAD2 and EgCCR promoters, in the transcriptional activity of these gene promoters.

Results

By using promoter deletion analysis and in vivo footprinting, we identified an 80 bp regulatory region in the Eucalyptus gunnii EgCAD2 promoter that contains two MYB elements, each arranged in a distinct module with newly identified cis-elements. A directed mutagenesis approach was used to introduce block mutations in all putative cis-elements of the EgCAD2 promoter and in those of the 50 bp regulatory region previously delineated in the EgCCR promoter. We showed that the conserved MYB elements in EgCAD2 and EgCCR promoters are crucial both for the formation of DNA-protein complexes in EMSA experiments and for the transcriptional activation of EgCAD2 and EgCCR promoters in vascular tissues in planta. In addition, a new regulatory cis-element that modulates the balance between two DNA-protein complexes in vitro was found to be important for EgCAD2 expression in the cambial zone.

Conclusions

Our assignment of functional roles to the identified cis-elements clearly demonstrates the importance of MYB cis-elements in the transcriptional regulation of two genes of the lignin-specific pathway and support the hypothesis that MYB elements serve as a common means for the coordinated regulation of genes in the entire lignin biosynthetic pathway.
Comparing large-scale computational approaches to epidemic modeling: Agent-based versus structured metapopulation models
Authors: Ajelli Marco , Gonçalves Bruno , Balcan Duygu , Colizza Vittoria , Hu Hao , Ramasco José J , Merler Stefano , Vespignani Alessandro
Published: June 2010

Background

In recent years large-scale computational models for the realistic simulation of epidemic outbreaks have been used with increased frequency. Methodologies adapt to the scale of interest and range from very detailed agent-based models to spatially-structured metapopulation models. One major issue thus concerns to what extent the geotemporal spreading pattern found by different modeling approaches may differ and depend on the different approximations and assumptions used.

Methods

We provide for the first time a side-by-side comparison of the results obtained with a stochastic agent-based model and a structured metapopulation stochastic model for the progression of a baseline pandemic event in Italy, a large and geographically heterogeneous European country. The agent-based model is based on the explicit representation of the Italian population through highly detailed data on the socio-demographic structure. The metapopulation simulations use the GLobal Epidemic and Mobility (GLEaM) model, based on high-resolution census data worldwide, and integrating airline travel flow data with short-range human mobility patterns at the global scale. The model also considers age structure data for Italy. GLEaM and the agent-based models are synchronized in their initial conditions by using the same disease parameterization, and by defining the same importation of infected cases from international travels.

Results

The results obtained show that both models provide epidemic patterns that are in very good agreement at the granularity levels accessible by both approaches, with differences in peak timing on the order of a few days. The relative difference of the epidemic size depends on the basic reproductive ratio, R
0, and on the fact that the metapopulation model consistently yields a larger incidence than the agent-based model, as expected due to the differences in the structure in the intra-population contact pattern of the approaches. The age breakdown analysis shows that similar attack rates are obtained for the younger age classes.

Conclusions

The good agreement between the two modeling approaches is very important for defining the tradeoff between data availability and the information provided by the models. The results we present define the possibility of hybrid models combining the agent-based and the metapopulation approaches according to the available data and computational resources.
Novel deletion alleles carrying CYP21A1P/A2chimeric genes in Brazilian patients with 21-hydroxylase deficiency
Authors: Coeli Fernanda B , Soardi Fernanda C , Bernardi Renan D , de Araújo Marcela , Paulino Luciana C , Lau Ivy F , Petroli Reginaldo J , de Lemos-Marini Sofia HV , Baptista Maria TM , Guerra-Júnior Gil , de-Mello Maricilda P
Published: June 2010

Background

Congenital adrenal hyperplasia due to 21-hydroxylase deficiency is caused by deletions, large gene conversions or mutations in CYP21A2 gene. The human gene is located at 6p21.3 within a locus containing the genes for putative serine/threonine Kinase RP, complement C4, steroid 21-hydroxylase CYP21 tenascin TNX, normally, in a duplicated cluster known as RCCX module. The CYP21 extra copy is a pseudogene (CYP21A1P). In Brazil, 30-kb deletion forming monomodular alleles that carry chimeric CYP21A1P/A2 genes corresponds to ~9% of disease-causing alleles. Such alleles are considered to result from unequal crossovers within the bimodular C4/CYP21 locus. Depending on the localization of recombination breakpoint, different alleles can be generated conferring the locus high degree of allelic variability. The purpose of the study was to investigate the variability of deleted alleles in patients with 21-hydroxylase deficiency.

Methods

We used different techniques to investigate the variability of 30-kb deletion alleles in patients with 21-hydroxylase deficiency. Alleles were first selected after Southern blotting. The composition of CYP21A1P/A2 chimeric genes was investigated by ASO-PCR and MLPA analyses followed by sequencing to refine the location of recombination breakpoints. Twenty patients carrying at least one allele with C4/CYP21 30-kb deletion were included in the study.

Results

An allele carrying a CYP21A1P/A2 chimeric gene was found unusually associated to a C4B/C4A
Taq I 6.4-kb fragment, generally associated to C4B and CYP21A1P deletions. A novel haplotype bearing both p.P34L and p.H62L, novel and rare mutations, respectively, was identified in exon 1, however p.P30L, the most frequent pseudogene-derived mutation in this exon, was absent. Four unrelated patients showed this haplotype. Absence of p.P34L in CYP21A1P of normal controls indicated that it is not derived from pseudogene. In addition, the combination of different approaches revealed nine haplotypes for deleted 21-hydroxylase deficiency alleles.

Conclusions

This study demonstrated high allelic variability for 30-kb deletion in patients with 21-hydroxylase deficiency indicating that a founder effect might be improbable for most monomodular alleles carrying CYP21A1P/A2 chimeric genes in Brazil.
Home-based chlamydia testing of young people attending a music festival - who will pee and post?
Authors: Sacks-Davis Rachel , Gold Judy , Aitken Campbell K , Hellard Margaret E
Published: June 2010

Background

Chlamydia is most common among young people, but only a small proportion of Australian young people are tested annually. Home-based chlamydia testing has been piloted in several countries to increase testing rates, but uptake has been low. We aimed to identify predictors of uptake of home-based chlamydia testing to inform future testing programs.

Methods

We offered home-based chlamydia testing kits to participants in a sexual behaviour cross-sectional survey conducted at a music festival in Melbourne, Australia. Those who consented received a testing kit and were asked to return their urine or vaginal swab sample via post.

Results

Nine hundred and two sexually active music festival attendees aged 16-29 completed the survey; 313 (35%) opted to receive chlamydia testing kits, and 67 of 313 (21%) returned a specimen for testing. One participant was infected with chlamydia (1% prevalence). Independent predictors of consenting to receive a testing kit included older age, knowing that chlamydia can make women infertile, reporting more than three lifetime sexual partners and inconsistent condom use. Independent predictors of returning a sample to the laboratory included knowing that chlamydia can be asymptomatic, not having had an STI test in the past six months and not living with parents.

Conclusions

A low proportion of participants returned their chlamydia test, suggesting that this model is not ideal for reaching young people. Home-based chlamydia testing is most attractive to those who report engaging in sexual risk behaviours and are aware of the often asymptomatic nature and potential sequelae of chlamydia infection.
Knowledge of human papillomavirus infection and its prevention among adolescents and parents in the greater Milan area, Northern Italy
Authors: Pelucchi Claudio , Esposito Susanna , Galeone Carlotta , Semino Margherita , Sabatini Caterina , Picciolli Irene , Consolo Silvia , Milani Gregorio , Principi Nicola
Published: June 2010

Background

In order to be widely accepted by users, the implementation of a new health intervention requires them to be adequately informed about its clinical importance, benefits and risks. The aim of this study was to provide data on the knowledge of Italian adolescents and parents concerning human papillomavirus (HPV) infection and its prevention in order to allow the development of adequate training programmes.

Methods

Between 2 May and 15 June 2008, we made a cross-sectional survey of 863 high school students and 2,331 parents of middle and high school students using two anonymously completed questionnaires covering the knowledge of HPV infection and related diseases, and attitudes to vaccinations. The approached schools were a convenience sample of the schools of the greater Milan area, Northern Italy.

Results

More mothers than fathers were aware that HPV infection could concern their children (58% vs 53%; p = 0.004) and were favourable towards vaccinating their children against HPV (68% vs 65%; p = 0.03); among the students, more females than males were aware that HPV infection could concern themselves (45% vs 26%; p < 0.001) and would undergo vaccination against HPV (68% vs 40%; p < 0.001). The parents' propensity to vaccinate their children against HPV was significantly associated with professing the Catholic religion (odds ratio - OR = 0.61, 95% confidence interval - CI 0.46-0.82, being atheist), the gender of the offspring (OR = 1.88, 95% CI 1.53-2.30, having at least one daughter), a propensity to vaccinations in general (OR = 23.1, 95% CI 13.7-38.8), a knowledge that HPV vaccine is aimed at preventing cervical cancer (OR = 2.31, 95% CI 1.69-3.16), and an awareness that HPV could affect their own children (OR = 3.52, 95% CI 2.89-4.29). The students who were aware that HPV infection could affect themselves were more in favour of to HPV vaccination, regardless of whether they were male (OR = 5.73, 95% CI 2.85-11.5) or female (OR = 2.39, 95% CI 1.66-3.46).

Conclusions

Both students and parents seem to underestimate the likelihood of HPV infection, and this is associated with a lower propensity for vaccination. This is an important indication for future training programmes concerning HPV prevention designed to increase the acceptance of HPV vaccine in families.
Supplementation of diet with krill oil protects against experimental rheumatoid arthritis
Authors: Ierna Michelle , Kerr Alison , Scales Hannah , Berge Kjetil , Griinari Mikko
Published: June 2010

Background

Although the efficacy of standard fish oil has been the subject of research in arthritis, the effect of krill oil in this disease has yet to be investigated. The objective of the present study was to evaluate a standardised preparation of krill oil and fish oil in an animal model for arthritis.

Methods

Collagen-induced arthritis susceptible DBA/1 mice were provided ad libitum access to a control diet or diets supplemented with either krill oil or fish oil throughout the study. There were 14 mice in each of the 3 treatment groups. The level of EPA + DHA was 0.44 g/100 g in the krill oil diet and 0.47 g/100 g in the fish oil diet. Severity of arthritis was determined using a clinical scoring system. Arthritis joints were analysed by histopathology and graded. Serum samples were obtained at the end of the study and the levels of IL-1α, IL-1β, IL-7, IL-10, IL-12p70, IL-13, IL-15, IL-17 and TGF-β were determined by a Luminex™ assay system.

Results

Consumption of krill oil and supplemented diet significantly reduced the arthritis scores and hind paw swelling when compared to a control diet not supplemented with EPA and DHA. However, the arthritis score during the late phase of the study was only significantly reduced after krill oil administration. Furthermore, mice fed the krill oil diet demonstrated lower infiltration of inflammatory cells into the joint and synovial layer hyperplasia, when compared to control. Inclusion of fish oil and krill oil in the diets led to a significant reduction in hyperplasia and total histology score. Krill oil did not modulate the levels of serum cytokines whereas consumption of fish oil increased the levels of IL-1α and IL-13.

Conclusions

The study suggests that krill oil may be a useful intervention strategy against the clinical and histopathological signs of inflammatory arthritis.
New clinically relevant, orthotopic mouse models of human chondrosarcoma with spontaneous metastasis
Authors: Clark Jonathan CM , Akiyama Toru , Dass Crispin R , Choong Peter FM
Published: June 2010

Background

Chondrosarcoma responds poorly to adjuvant therapy and new, clinically relevant animal models are required to test targeted therapy.

Methods

Two human chondrosarcoma cell lines, JJ012 and FS090, were evaluated for proliferation, colony formation, invasion, angiogenesis and osteoclastogenesis. Cell lines were also investigated for VEGF, MMP-2, MMP-9, and RECK expression. JJ012 and FS090 were injected separately into the mouse tibia intramedullary canal or tibial periosteum. Animal limbs were measured, and x-rayed for evidence of tumour take and progression. Tibias and lungs were harvested to determine the presence of tumour and lung metastases.

Results

JJ012 demonstrated significantly higher proliferative capacity, invasion, and colony formation in collagen I gel. JJ012 conditioned medium stimulated endothelial tube formation and osteoclastogenesis with a greater potency than FS090 conditioned medium, perhaps related to the effects of VEGF and MMP-9. In vivo, tumours formed in intratibial and periosteal groups injected with JJ012, however no mice injected with FS090 developed tumours. JJ012 periosteal tumours grew to 3 times the non-injected limb size by 7 weeks, whereas intratibial injected limbs required 10 weeks to achieve a similar tumour size. Sectioned tumour tissue demonstrated features of grade III chondrosarcoma. All JJ012 periosteal tumours (5/5) resulted in lung micro-metastases, while only 2/4 JJ012 intratibial tumours demonstrated metastases.

Conclusions

The established JJ012 models replicate the site, morphology, and many behavioural characteristics of human chondrosarcoma. Local tumour invasion of bone and spontaneous lung metastasis offer valuable assessment tools to test the potential of novel agents for future chondrosarcoma therapy.
Exposure to benzene at work and the risk of leukemia: a systematic review and meta-analysis
Authors: Khalade Abdul , Jaakkola Maritta S , Pukkala Eero , Jaakkola Jouni JK
Published: June 2010

Background

A substantial number of epidemiologic studies have provided estimates of the relation between exposure to benzene at work and the risk of leukemia, but the results have been heterogeneous. To bridge this gap in knowledge, we synthesized the existing epidemiologic evidence on the relation between occupational exposure to benzene and the risk of leukemia, including all types combined and the four main subgroups acute myeloid leukemia (AML), acute lymphocytic leukemia (ALL), chronic lymphocytic leukemia (CLL), and chronic myeloid leukemia (CML).

Methods

A systematic literature review was carried out using two databases 'Medline' and 'Embase' from 1950 through to July 2009. We selected articles which provided information that can be used to estimate the relation between benzene exposure and cancer risk (effect size).

Results

In total 15 studies were identified in the search, providing 16 effect estimates for the main analysis. The summary effect size for any leukemia from the fixed-effects model was 1.40 (95% CI, 1.23-1.57), but the study-specific estimates were strongly heterogeneous (I2 = 56.5%, Q stat = 34.47, p = 0.003). The random-effects model yielded a summary- effect size estimate of 1.72 (95% CI, 1.37-2.17). Effect estimates from 9 studies were based on cumulative exposures. In these studies the risk of leukemia increased with a dose-response pattern with a summary-effect estimate of 1.64 (95% CI, 1.13-2.39) for low (< 40 ppm-years), 1.90 (95% CI, 1.26-2.89) for medium (40-99.9 ppm-years), and 2.62 (95% CI, 1.57-4.39) for high exposure category (> 100 ppm-years). In a meta-regression, the trend was statistically significant (P = 0.015). Use of cumulative exposure eliminated heterogeneity. The risk of AML also increased from low (1.94, 95% CI, 0.95-3.95), medium (2.32, 95% CI, 0.91-5.94) to high exposure category (3.20, 95% CI, 1.09-9.45), but the trend was not statistically significant.

Conclusions

Our study provides consistent evidence that exposure to benzene at work increases the risk of leukemia with a dose-response pattern. There was some evidence of an increased risk of AML and CLL. The meta-analysis indicated a lack of association between benzene exposure and the risk of CML.
Primary breast lymphomas: a multicentric experience
Authors: Avenia Nicola , Sanguinetti Alessandro , Cirocchi Roberto , Bistoni Giovanni , Trastulli Stefano , D'Ajello Fabio , Barberini Francesco , Cavallaro Giuseppe , Rulli Antonio , Sidoni Angelo , Noya Giuseppe , De Toma Giorgio , Sciannameo Francesco
Published: June 2010

Background

The Primary Breast Lymphomas (PBL) represent 0,38-0,70% of all non-Hodgkin lymphomas (NHL), 1,7-2,2% of all extranodal NHL and only 0,04-0,5% of all breast cancer. Most frequent PBLs are the diffuse large B cell lymphomas; in any case-reports MALT lymphomas lack or are a rare occurrence. Their incidence is growing. From 1880 (first breast resection for "lymphadenoid sarcoma" carried out by Gross) to the recent past the gold standard treatment for such diseases was surgery. At present such role has lost some of its importance, and it is matter of debate.

Methods

Twenty-three women affected by PBL underwent surgery. Average age was 63 years (range: 39-83). Seven suffered of hypothyroidism secondary to autoimmune thyroiditis. Fourteen patients underwent mastectomy, nine patients received quadrantectomy (average neoplasm diameter: 1,85 cm, range: 1,1-2,6 cm). In 10 cases axillary dissection was carried out. Pathologic examination revealed 16 diffuse large B cell lymphomas and 7 MALT lymphomas.

Results

Seven patients in the mastectomy group had a recurrence (50%), and all of them with diffuse large B cell lymphomas at stage II. Two of these had not received chemotherapy. No patient undergoing quadrantectomy had recurrence. In the mastectomy group disease free survival (DFS) at 5 and 10 years was 57 and 50%. Overall survival (OS) at 5 and 10 years was 71.4% and 57.1% respectively. All recurrences were systemic. DFS and OS at 5 and 10 years was 100% in the quadrantectomy group. In the patients with recurrence mortality was 85.7%. For stage IE DFS and OS at 5 and 10 years were 100%. For stage II DFS at 10 years was 62.5% and 56.2% respectively; OS at 5 and 10 years was 75% and 62.5% respectively. For MALT lymphomas DFS and OS at 5 and 10 years were 100%. For diffuse large B cell lymphomas DFS at 5 and 10 years was 62.5% and 56.2% respectively; OS at 5 and 10 years was 75% and 62,5% respectively.

Conclusions

The role of surgery in this disease should be limited to get a definitive diagnosis while for the staging and the treatment CT scan and chemio/radioterapy are repectively mandatory. MALT PBLs have a definitely better prognosis compared to large B cell lymphomas. The surgical treatment must always be oncologically radical (R0); mastectomy must not be carried out as a rule, but only when tissue sparing procedures are not feasible. Axillary dissection must always be performed for staging purposes, so avoiding the risk of under-staging II o IE, due to the possibility of clinically silent axillary node involvement.
Dietary n-3:n-6 fatty acid ratios differentially influence hormonal signature in a rodent model of metabolic syndrome relative to healthy controls
Authors: Burghardt Paul R , Kemmerer Elyse S , Buck Bradley J , Osetek Andrew J , Yan Charles , Koch Lauren G , Britton Steven L , Evans Simon J
Published: June 2010

Dietary ratios of omega-3 (n-3) to omega-6 (n-6) polyunsaturated fatty acids (PUFAs) have been implicated in controlling markers of the metabolic syndrome, including insulin sensitivity, inflammation, lipid profiles and adiposity. However, the role of dietary PUFAs in regulating energy systems in healthy relative to metabolic diseased backgrounds has not been systematically addressed. We used dietary manipulation of n-3 to n-6 PUFA ratios in an animal model of metabolic syndrome and a related healthy line to assay feeding behavior and endocrine markers of feeding drive and energy regulation. Two related lines of rodents with a healthy and a metabolic syndrome phenotype were fed one of two isocaloric diets, comprised of either a 1:1 or a 1:30 n-3 to n-6 ratio, for 30 days. Food intake and weight gain were monitored; and leptin, ghrelin, adiponectin and a suite of hypothalamic neuropeptides involved in energy regulation were assayed following the dietary manipulation period. There was no difference in caloric intake or weight gain between diet groups, however there was a significant interaction between diet and phenotypic line on central and peripheral markers of energy homeostasis. Thus serum levels of leptin, acylated-ghrelin and adiponectin, and mRNA levels of the anorexigenic hypothalamic neuropeptide, cocaine-amphetamine related transcript (CART), showed differential, dietary responses with HCR rats showing an increase in anorexigenic signals in response to unbalanced n-3:6 ratios, while LCR did not. These data are the first to demonstrate that a rodent line with a metabolic syndrome-like phenotype responds differentially to dietary manipulation of n-3 and n-6 fatty acids relative to a related healthy line with regard to endocrine markers of energy homeostasis. The dietary n-3:n-6 ratios used in this experiment represent extreme points of natural human diets, however the data suggest that optimal recommendations regarding omega-3 and omega-6 intake may have differing effects in healthy subjects relative to metabolic syndrome patients. Further research is necessary to establish these responses in human populations.
Primary follicular lymphoma of the fallopian tube found incidentally in a patient treated for endometrial carcinoma: a case report
Authors: Alduaij Ahmad , Hansen Katrine , Zhang Cunxian
Published: June 2010

We report a rare case of primary lymphoma of fallopian tube in a 68-year-old woman who underwent total hysterectomy and bilateral salpingo-oophorectomy for endometrial carcinoma. The specimen showed a well-differentiated endometrioid adenocarcinoma with superficial myometrial invasion. The left fallopian tube revealed a 1 cm nodule that histologically showed diffuse lymphoid follicles consisting of small cleaved lymphocytes and occasional larger cells. The cells were immunopositive for CD20, BCL-2, and BCL-6 but negative for CD3 and CD43. Polymerase chain reaction confirmed a monoclonal B-cell population. Fluorescence in-situ hybridization revealed at (14, 18) translocation. The patient had absent lymphadenopathy and negative CT scan of chest, abdomen, and pelvis. The findings were consistent with a primary low grade follicular lymphoma of fallopian tube. She did not receive chemotherapy and remained disease free for 13 months after surgery. Our case suggests that primary lymphoma of fallopian tube may be associated with a favorable prognosis.
Helical tomotherapy with concurrent capecitabine for the treatment of inoperable pancreatic cancer
Authors: Ji Jeong-Seon , Han Chi-Wha , Jang Jeong-Won , Lee Bo-In , Kim Byung-Wook , Choi Hwang , Kim Ji-Yoon , Kang Young-Nam , Kay Chul-Seung , Choi Ihl-Bohng
Published: June 2010

Background

Helical tomotherapy, an advanced intensity-modulated radiation therapy with integrated CT imaging, permits highly conformal irradiation with sparing of normal tissue. Capecitabine, a pro-drug of 5-FU that induces thymidine phosphorylase can achieve higher levels of intracellular 5-FU when administered concurrently with radiation. We evaluated the feasibility as well as the clinical outcome of concurrent administration of capecitabine with tomotherapy in patients with advanced pancreatic cancer.

Methods

Nineteen patients with advanced pancreatic cancer including primarily unresectable disease and recurrence after curative surgery were included in the study. Two planning target volumes (PTV) were entered: PTV1 is gross tumor volume; and PTV2, the volume of the draining lymph nodes. The total doses to target 1 and target 2 were 55 and 50 Gy, respectively. Capecitabine at 1600 mg/m2/day was administered on each day of irradiation.

Results

Twenty six measurable lesions were evaluated. Overall in-field response rate was 42.3%; partial responses were achieved in 53.3% of the pancreatic masses, 28.6% of distant metastatic lesions and 25.0% of regional lymph nodes. The median duration of follow-up after tomotherapy was 6.5 months. None of the lesions showed in-field progression. Treatment was well tolerated with only minor toxicities such as grade 1 nausea (one patient), grade 1 hand-foot syndrome (one patient) and grade 1/2 fatigue (three patients).

Conclusions

Helical tomotherapy with concurrent capecitabine is a feasible option without significant toxicities in patients with advanced pancreatic cancer. We achieved excellent conformal distribution of radiation doses and minimal treatment-related toxicities with promising target volume responses.