bluuebunny/crossref_metadata_2025 huggingface dataset:
Arterial elasticity in American Indian and Caucasian children, adolescents, and young adults
Authors: Gardner Andrew W , Parker Donald E
Published: August 2011

We compared arterial elasticity in American Indian and Caucasian children, adolescents, and young adults, and we assessed whether demographic, body composition, and ambulatory activity measures were predictive of arterial elasticity within each group. Fifty-one American Indians and 66 Caucasians between the ages of 8 and 30 years were assessed on large artery elasticity index, small artery elasticity index, body fat percentage, and daily ambulatory activity during 7 consecutive days. American Indians had a higher percentage of body fat than Caucasians ( p = 0.002), whereas daily ambulatory activity measures were similar ( p > 0.05). American Indians had a 16% lower large artery elasticity index ( p = 0.007) and a 19% lower small artery elasticity index ( p < 0.001) than Caucasians. The regression model for large artery elasticity index included average cadence ( p = 0.001), fat-free mass ( p < 0.001), age component (Caucasian only) ( p < 0.001), and sex ( p = 0.025). The regression model for small artery elasticity index included fat-free mass ( p < 0.001), maximum cadence for 30 continuous minutes ( p = 0.009), race ( p = 0.005), and average cadence ( p = 0.049). Between 8 and 30 years of age, elasticity means for the large and small arteries is lower in American Indians than in Caucasians. A smaller difference was observed in children, with a trend to a much larger difference in young adults. Furthermore, greater fat-free mass and higher daily ambulatory cadence are associated with higher arterial elasticity in both American Indians and Caucasians.
Go Fast! Reaction Time Differences between Adults and Adolescents in Evaluating Risky Traffic Situations
Authors: Feenstra Hans , Ruiter Robert A.C. , Kok Gerjo
Published: August 2011

This study investigated the hypothesis that adults are faster than adolescents in responding to risks. Twenty-six adolescents ( Mage = 15 years) and 26 adults ( Mage = 47 years) responded to risky situations (e.g. ‘Is it a good idea to drive a car while having drunk alcohol?’) and non-risky situations (e.g. ‘… wear a helmet while riding a moped?’) in a choice reaction time task. Adults responded 110ms faster to both risky and non-risky questions than adolescents. Both adolescents and adults responded on average 100ms faster to risky questions than to non-risky questions. The results of this study suggest a possible explanation for the increased accident involvement of adolescents in traffic.
Impact of aliskiren treatment on urinary aldosterone levels in patients with type 2 diabetes and nephropathy: an AVOID substudy
Authors: Persson Frederik , Lewis Julia B , Lewis Edmund J , Rossing Peter , Hollenberg Norman K , Hans-Henrik Parving
Published: August 2011

Introduction: Aldosterone blockade reduces albuminuria in diabetic patients with chronic kidney disease (CKD), and improves prognosis in chronic heart failure. This study assessed the effects of direct renin inhibition with aliskiren in combination with losartan and optimal antihypertensive therapy on urinary aldosterone, plasma renin activity (PRA) and plasma renin concentration (PRC).

Materials and methods: In the AVOID study, 599 patients with type 2 diabetes, hypertension and nephropathy received 6 months aliskiren (150 mg force titrated to 300 mg once daily after 3 months) or placebo added to losartan 100 mg and optimal antihypertensive therapy. Urinary aldosterone excretion, PRA and PRC were measured at baseline and after 24 weeks in a prespecified subset of 133 patients.

Results: Aliskiren added to losartan provided reductions from baseline in urinary aldosterone compared with adding placebo (−24% vs. −4%, p = 0.017) at week 24. There was no significant difference between the aliskiren and placebo groups in the proportion of patients with aldosterone breakthrough (aliskiren 35%, placebo 46%, p = 0.199). Aliskiren treatment reduced PRA by 90% at 24 weeks and increased PRC by 328%.

Conclusions: Adding aliskiren to recommended renoprotective treatment with losartan and optimal antihypertensive therapy provided significant reductions in urinary aldosterone excretion which may attenuate decline in kidney function.
Sound Pools: Cultural Polyphony in Sound and Music
Authors: Norment Camille
Published: August 2011

This article explores some of the ‘texts that have fled’ from cultivated sound and music through the conscious and unconscious strategic signifiers employed by musicians, shamans and artists. Written from the perspective of an artist with a music, performance and literary background, the author contemplates the workings of sound upon the mind and the body as explored in music, science, magic and art. These explorations are offered within a framework of sound spaces or ‘audiotopias’ – sound as physical, psychological and cultural places. Flowing centrally through the text is an argument that likens cultural polyphony in sound and music to genetic diversity in human evolution – the expansion of the gene pool. Recent theories in neuroscience claim that the creation and use of music by early humans is adaptive rather than a byproduct of language as was accepted by previous scientific arguments. The collection of all possible differences would constitute the sonic utopia, a task never to be exhausted and never complete. The author discusses how these notions manifest themselves in her own artistic production strategies as well as several other related socio-cultural examples.
Time-Lapse Phonography and the Visual Processing of Music
Authors: DuBois R. Luke
Published: August 2011

Synaesthesia, as a rich metaphor for artistic discussion and collaboration, has been with us for quite some time, as visual and musical artists (with or without actual synaesthesia) have mined each other’s forms for inspiration in their own. The capability of computers to seamlessly ‘transcode’ digital media, whether they are sound, image, video, or any other information, from one sense-domain to another, has provided an interesting opportunity to reintroduce ideas of synaesthetic art into new media practice through the malleability of digital representation. This article looks at some of the author’s own work in composing music through visual idioms (and visual art through musical techniques) by using transcoding strategies. These techniques for audio-visual art provide an interesting lens through which cultural understanding of media can be critiqued and interrogated.
Challenges of Older Patients’ Knowledge About Warfarin Therapy
Authors: Nasser Sayeed , Mullan Judy , Bajorek Beata
Published: August 2011

Objective: To review the challenges of warfarin education for older patients (aged 65 years or older) in terms of knowledge, access to warfarin education, and education resources. Methods: A quasi-systematic review of the literature was performed via electronic database searches (eg, Medline, Embase, Cumulative Index to Nursing and Allied Health Literature, International Pharmaceutical Abstracts, Meditext, and Google Scholar) from 1990 to May 2011. Results: The 62 articles reviewed found that improved patient knowledge results in better anticoagulation control. The review also found that between 50% and 80% of older patients have inadequate knowledge about the basic aspects of warfarin therapy (eg, action, benefits and risks, interactions with other drugs or foods, international normalized ratio management). Demographic factors, such as advancing age, lower family income, and limited health literacy, were found to inversely affect patients’ warfarin knowledge, and access to warfarin education and information resources were often suboptimal in different practice settings. Finally, a number of educational strategies and resources that could be readily incorporated to improve the effectiveness of current warfarin education programs were extracted from the review. Conclusion: This comprehensive review highlights that education about warfarin in older patients is currently suboptimal and may in part contribute to poor therapeutic outcomes. This review article also acknowledges the need to identify, target, and develop educational strategies and resources to further improve older patients’ knowledge about their warfarin therapy.
BKM-react, an integrated biochemical reaction database
Authors: Lang Maren , Stelzer Michael , Schomburg Dietmar
Published: August 2011

Background

The systematic, complete and correct reconstruction of genome-scale metabolic networks or metabolic pathways is one of the most challenging tasks in systems biology research. An essential requirement is the access to the complete biochemical knowledge - especially on the biochemical reactions. This knowledge is extracted from the scientific literature and collected in biological databases. Since the available databases differ in the number of biochemical reactions and the annotation of the reactions, an integrated knowledge resource would be of great value.

Results

We developed a comprehensive non-redundant reaction database containing known enzyme-catalyzed and spontaneous reactions. Currently, it comprises 18,172 unique biochemical reactions. As source databases the biochemical databases BRENDA, KEGG, and MetaCyc were used. Reactions of these databases were matched and integrated by aligning substrates and products. For the latter a two-step comparison using their structures (via InChIs) and names was performed. Each biochemical reaction given as a reaction equation occurring in at least one of the databases was included.

Conclusions

An integrated non-redundant reaction database has been developed and is made available to users. The database can significantly facilitate and accelerate the construction of accurate biochemical models.
Genome-wide prediction of splice-modifying SNPs in human genes using a new analysis pipeline called AASsites
Authors: Faber Kirsten , Glatting Karl-Heinz , Mueller Phillip J , Risch Angela , Hotz-Wagenblatt Agnes
Published: August 2011

Background

Some single nucleotide polymorphisms (SNPs) are known to modify the risk of developing certain diseases or the reaction to drugs. Due to next generation sequencing methods the number of known human SNPs has grown. Not all SNPs lead to a modified protein, which may be the origin of a disease. Therefore, the recognition of functional SNPs is needed. Because most SNP annotation tools look for SNPs which lead to an amino acid exchange or a premature stop, we designed a new tool called AASsites which searches for SNPs which modify splicing.

Results

AASsites uses several gene prediction programs and open reading frame prediction to compare the wild type (wt) and the variant gene sequence. The results of the comparison are combined by a handmade rule system to classify a change in splicing as “likely, probable, unlikely”. Having received good results from tests with SNPs known for changing the splicing pattern we checked 80,000 SNPs from the human genome which are located near splice sites for their ability to change the splicing pattern of the gene and hereby result in a different protein. We identified 301 “likely” and 985 “probable” classified SNPs with such characteristics. Within this set 33 SNPs are described in the ssSNP Target database to cause modified splicing.

Conclusions

With AASsites single SNPs can be checked for those causing splice modifications. Screening 80,000 known human SNPs we detected about 1,200 SNPs which probably modify splicing. AASsites is available at http://genius.embnet.dkfz-heidelberg.de/menu/biounit/open-husar using any web browser.
A robust approach to optimizing multi-source information for enhancing genomics retrieval performance
Authors: Hu Qinmin , Huang Jimmy Xiangji , Miao Jun
Published: August 2011

Background

The users desire to be provided short, specific answers to questions and put them in context by linking original sources from the biomedical literature. Through the use of information retrieval technologies, information systems retrieve information to index data based on all kinds of pre-defined searching techniques/functions such that various ranking strategies are designed depending on different sources. In this paper, we propose a robust approach to optimizing multi-source information for improving genomics retrieval performance.

Results

In the proposed approach, we first consider a common scenario for a metasearch system that has access to multiple baselines with retrieving and ranking documents/passages by their own models. Then, given selected baselines from multiple sources, we investigate three modified fusion methods in the proposed approach, reciprocal, CombMNZ and CombSUM, to re-rank the candidates as the outputs for evaluation. Our empirical study on both 2007 and 2006 genomics data sets demonstrates the viability of the proposed approach for obtaining better performance. Furthermore, the experimental results show that the reciprocal method provides notable improvements on the individual baseline, especially on the passage2-level MAP and the aspect-level MAP.

Conclusions

From the extensive experiments on two TREC genomics data sets, we draw the following conclusions. For the three fusion methods proposed in the robust approach, the reciprocal method outperforms the CombMNZ and CombSUM methods obviously, and CombSUM works well on the passage2-level when compared with CombMNZ. Based on the multiple sources of DFR, BM25 and language model, we can observe that the alliance of giants achieves the best result. Meanwhile, under the same combination, the better the baseline performance is, the more contribution the baseline provides. These conclusions are very useful to direct the fusion work in the field of biomedical information retrieval.
Strong differences in the clonal variation of two Daphnia species from mountain lakes affected by overwintering strategy
Authors: Hamrová Eva , Mergeay Joachim , Petrusek Adam
Published: August 2011

Background

The population structure of cyclical parthenogens such as water fleas is strongly influenced by the frequency of alternations between sexual and asexual (parthenogenetic) reproduction, which may differ among populations and species. We studied genetic variation within six populations of two closely related species of water fleas of the genusDaphnia(Crustacea, Cladocera).D. galeataandD. longispinaboth occur in lakes in the Tatra Mountains (Central Europe), but their populations show distinct life history strategies in that region. In three studied lakes inhabited byD. galeata, daphnids overwinter under the ice as adult females. In contrast, in lakes inhabited byD. longispina, populations apparently disappear from the water column and overwinter as dormant eggs in lake sediments. We investigated to what extent these different strategies lead to differences in the clonal composition of late summer populations.

Results

Analysis of genetic variation at nine microsatellite loci revealed that clonal richness (expressed as the proportion of different multilocus genotypes, MLGs, in the whole analysed sample) consistently differed between the two studied species. In the threeD. longispinapopulations, very high clonal richness was found (MLG/N ranging from 0.97 to 1.00), whereas inD. galeatait was much lower (0.05 to 0.50). The dominant MLGs in allD. galeatapopulations were heterozygous at five or more loci, suggesting that such individuals all represented the same clonal lineages rather than insufficiently resolved groups of different clones.

Conclusions

The low clonal diversities and significant deviations from Hardy-Weinberg equilibrium inD. galeatapopulations were likely a consequence of strong clonal erosion over extended periods of time (several years or even decades) and the limited influence of sexual reproduction. Our data reveal that populations of closely relatedDaphniaspecies living in relatively similar habitats (permanent, oligotrophic mountain lakes) within the same region may show strikingly different genetic structures, which most likely depend on their reproductive strategy during unfavourable periods. We assume that similar impacts of life history on population structures are also relevant for other cyclical parthenogen groups. In extreme cases, prolonged clonal erosion may result in the dominance of a single clone within a population, which might limit its microevolutionary potential if selection pressures suddenly change.
Molecular evolution of a chordate specific family of G protein-coupled receptors
Authors: Kurtenbach Stefan , Mayer Christoph , Pelz Thomas , Hatt Hanns , Leese Florian , Neuhaus Eva M
Published: August 2011

Background

Chordate evolution is a history of innovations that is marked by physical and behavioral specializations, which led to the development of a variety of forms from a single ancestral group. Among other important characteristics, vertebrates obtained a well developed brain, anterior sensory structures, a closed circulatory system and gills or lungs as blood oxygenation systems. The duplication of pre-existing genes had profound evolutionary implications for the developmental complexity in vertebrates, since mutations modifying the function of a duplicated protein can lead to novel functions, improving the evolutionary success.

Results

We analyzed here the evolution of the GPRC5 family of G protein-coupled receptors by comprehensive similarity searches and found that the receptors are only present in chordates and that the size of the receptor family expanded, likely due to genome duplication events in the early history of vertebrate evolution. We propose that a single GPRC5 receptor coding gene originated in a stem chordate ancestor and gave rise by duplication events to a gene family comprising three receptor types (GPRC5A-C) in vertebrates, and a fourth homologue present only in mammals (GPRC5D). Additional duplications of GPRC5B and GPRC5C sequences occurred in teleost fishes. The finding that the expression patterns of the receptors are evolutionarily conserved indicates an important biological function of these receptors. Moreover, we found that expression of GPRC5B is regulated by vitamin A in vivo, confirming previous findings that linked receptor expression to retinoic acid levels in tumor cell lines and strengthening the link between the receptor expression and the development of a complex nervous system in chordates, known to be dependent on retinoic acid signaling.

Conclusions

GPRC5 receptors, a class of G protein-coupled receptors with unique sequence characteristics, may represent a molecular novelty that helped non-chordates to become chordates.
The mosaicism of plasmids revealed by atypical genes detection and analysis
Authors: Bosi Emanuele , Fani Renato , Fondi Marco
Published: August 2011

Background

From an evolutionary viewpoint, prokaryotic genomes are extremely plastic and dynamic, since large amounts of genetic material are continuously added and/or lost through promiscuous gene exchange. In this picture, plasmids play a key role, since they can be transferred between different cells and, through genetic rearrangement(s), undergo gene(s) load, leading, in turn, to the appearance of important metabolic innovations that might be relevant for cell life. Despite their central position in bacterial evolution, a massive analysis of newly acquired functional blocks [likely the result of horizontal gene transfer (HGT) events] residing on plasmids is still missing.

Results

We have developed a computational, composition-based, pipeline to scan almost 2000 plasmids for genes that differ significantly from their hosting molecule. Plasmids atypical genes (PAGs) were about 6% of the total plasmids ORFs and, on average, each plasmid possessed 4.4 atypical genes. Nevertheless, conjugative plasmids were shown to possess an amount of atypical genes than that found in not mobilizable plasmids, providing strong support for the central role suggested for conjugative plasmids in the context of HGT. Part of the retrieved PAGs are organized into (mainly short) clusters and are involved in important biological processes (detoxification, antibiotic resistance, virulence), revealing the importance of HGT in the spreading of metabolic pathways within the whole microbial community. Lastly, our analysis revealed that PAGs mainly derive from other plasmid (rather than coming from phages and/or chromosomes), suggesting that plasmid-plasmid DNA exchange might be the primary source of metabolic innovations in this class of mobile genetic elements.

Conclusions

In this work we have performed the first large scale analysis of atypical genes that reside on plasmid molecules to date. Our findings on PAGs function, organization, distribution and spreading reveal the importance of plasmids-mediated HGT within the complex bacterial evolutionary network and in the dissemination of important biological traits.
In silico predicted epitopes from the COOH-terminal extension of cysteine proteinase B inducing distinct immune responses during Leishmania (Leishmania) amazonensis experimental murine infection
Authors: Pereira Bernardo AS , Silva Franklin S , Rebello Karina M , Marín-Villa Marcel , Traub-Cseko Yara M , Andrade Thereza CB , Bertho Álvaro L , Caffarena Ernesto R , Alves Carlos R
Published: August 2011

Background

Leishmaniaparasites have been reported to interfere and even subvert their host immune responses to enhance their chances of survival and proliferation. ExperimentalLeishmaniainfection in mice has been widely used in the identification of specific parasite virulence factors involved in the interaction with the host immune system. Cysteine-proteinase B (CPB) is an important virulence factor in parasites from theLeishmania (Leishmania) mexicanacomplex: it inhibits lymphocytes Th1 and/or promotes Th2 responses either through proteolytic activity or through epitopes derived from its COOH-terminal extension. In the present study we analyzed the effects ofLeishmania (Leishmania) amazonensisCPB COOH-terminal extension-derived peptides on cell cultures from murine strains with distinct levels of susceptibility to infection: BALB/c, highly susceptible, and CBA, mildly resistant.

Results

Predicted epitopes, obtained byin silicomapping, displayed the ability to induce cell proliferation and expression of cytokines related to Th1 and Th2 responses. Furthermore, we appliedin silicosimulations to investigate how the MHC/epitopes interactions could be related to the immunomodulatory effects on cytokines, finding evidence that specific interaction patterns can be related toin vitroactivities.

Conclusions

Based on our results, we consider that some peptides from the CPB COOH-terminal extension may influence host immune responses in the murine infection, thus helpingLeishmaniasurvival.
Cardiac arrest associated with sildenafil ingestion in a patient with an abnormal origin of the left coronary artery: case report
Authors: Huber Bruno C , von Ziegler Franz , Bamberg Fabian , Franz Wolfgang-Michael , Becker Alexander
Published: August 2011

Background

Left coronary artery arising from the right sinus of Valsalva is an uncommon congenital coro-nary anomaly that seems to be associated with sudden death in young patients.

Case presentation

We report a case of cardiac arrest in a 59-year-old patient after sexual intercourse and Silde-nafil ingestion. A coronary arteriography and an angiographic computed tomography scan subsequently revealed a LCA origin from the right aortic sinus along with an intramural course of the left main stem. In addition a distal stenosis of the right coronary artery was detected. After successful resuscitation without neurological deficits coronary artery bypass surgery was performed.

Conclusion

To our knowledge, this is the first report demonstrating sudden cardiac arrest associated with Sildenafil ingestion in a patient with this type of coronary anomaly. The question arises, whether a cardiac screening is necessary before a Sildenafil therapy is initiated.
Metabolic alteration of urinary steroids in pre- and post-menopausal women, and men with papillary thyroid carcinoma
Authors: Choi Man Ho , Moon Ju-Yeon , Cho Sung-Hee , Chung Bong Chul , Lee Eun Jig
Published: August 2011

Background

To evaluate the metabolic changes in urinary steroids in pre- and post-menopausal women and men with papillary thyroid carcinoma (PTC).

Methods

Quantitative steroid profiling combined with gas chromatography-mass spectrometry was used to measure the urinary concentrations of 84 steroids in both pre- (n = 21, age: 36.95 ± 7.19 yr) and post-menopausal female (n = 19, age: 52.79 ± 7.66 yr), and male (n = 16, age: 41.88 ± 8.48 yr) patients with PTC. After comparing the quantitative data of the patients with their corresponding controls (pre-menopause women: n = 24, age: 33.21 ± 10.48 yr, post-menopause women: n = 16, age: 49.67 ± 8.94 yr, male: n = 20, age: 42.75 ± 4.22 yr), the levels of steroids in the patients were normalized to the mean concentration of the controls to exclude gender and menopausal variations.

Results

Many urinary steroids were up-regulated in all PTC patients compared to the controls. Among them, the levels of three active androgens, androstenedione, androstenediol and 16α-hydroxy DHEA, were significantly higher in the pre-menopausal women and men with PTC. The corticoid levels were increased slightly in the PTC men, while progestins were not altered in the post-menopausal PTC women. Estrogens were up-regulated in all PTC patients but 2-hydroxyestrone and 2-hydroxy-17β-estradiol were remarkably changed in both pre-menopausal women and men with PTC. For both menopausal and gender differences, the 2-hydroxylation, 4-hydroxylation, 2-methoxylation, and 4-methoxylation of estrogens and 16α-hydroxylation of DHEA were differentiated between pre- and post-menopausal PTC women (P < 0.001). In particular, the metabolic ratio of 2-hydroxyestrone to 2-hydroxy-17β-estradiol, which could reveal the enzyme activity of 17β-hydroxysteroid dehydrogenase, showed gender differences in PTC patients (P < 1 × 10-7).

Conclusions

These results are expected be helpful for better understanding the pathogenic differences in PTC according to gender and menopausal conditions.
Adeno-associated virus type 2 infection activates caspase dependent and independent apoptosis in multiple breast cancer lines but not in normal mammary epithelial cells
Authors: Alam Samina , Bowser Brian S , Conway Michael J , Israr Mohd , Tandon Apurva , Meyers Craig
Published: August 2011

Background

In normal cells proliferation and apoptosis are tightly regulated, whereas in tumor cells the balance is shifted in favor of increased proliferation and reduced apoptosis. Anticancer agents mediate tumor cell death via targeting multiple pathways of programmed cell death. We have reported that the non-pathogenic, tumor suppressive Adeno-Associated Virus Type 2 (AAV2) induces apoptosis in Human Papillomavirus (HPV) positive cervical cancer cells, but not in normal keratinocytes. In the current study, we examined the potential of AAV2 to inhibit proliferation of MCF-7 and MDA-MB-468 (both weakly invasive), as well as MDA-MB-231 (highly invasive) human breast cancer derived cell lines. As controls, we used normal human mammary epithelial cells (nHMECs) isolated from tissue biopsies of patients undergoing breast reduction surgery.

Results

AAV2 infected MCF-7 line underwent caspase-independent, and MDA-MB-468 and MDA-MB-231 cell lines underwent caspase-dependent apoptosis. Death of MDA-MB-468 cells was marked by caspase-9 activation, whereas death of MDA-MB-231 cells was marked by activation of both caspase-8 and caspase-9, and resembled a mixture of apoptotic and necrotic cell death. Cellular demise was correlated with the ability of AAV2 to productively infect and differentially express AAV2 non-structural proteins: Rep78, Rep68 and Rep40, dependent on the cell line. Cell death in the MCF-7 and MDA-MB-231 lines coincided with increased S phase entry, whereas the MDA-MB-468 cells increasingly entered into G2. AAV2 infection led to decreased cell viability which correlated with increased expression of proliferation markers c-Myc and Ki-67. In contrast, nHMECs that were infected with AAV2 failed to establish productive infection or undergo apoptosis.

Conclusion

AAV2 regulated enrichment of cell cycle check-point functions in G1/S, S and G2 phases could create a favorable environment for Rep protein expression. Inherent Rep associated endonuclease activity and AAV2 genomic hair-pin ends have the potential to induce a cellular DNA damage response, which could act in tandem with c-Myc regulated/sensitized apoptosis induction. In contrast, failure of AAV2 to productively infect nHMECs could be clinically advantageous. Identifying the molecular mechanisms of AAV2 targeted cell cycle regulation of death inducing signals could be harnessed for developing novel therapeutics for weakly invasive as well as aggressive breast cancer types.
Lamivudine plus adefovir combination therapy versus entecavir monotherapy for lamivudine-resistant chronic hepatitis B: a systematic review and meta-analysis
Authors: Sheng Yun-Jian , Liu Jun-Ying , Tong Shi-Wen , Hu Huai-Dong , Zhang Da-Zhi , Hu Peng , Ren Hong
Published: August 2011

Background

Chronic hepatitis B virus (HBV) infection represents a serious global health problem and resistance to lamivudine (LAM) has become a serious clinical challenge. Previous rescue therapy for the treatment of chronic LAM-resistant hepatitis B infected patients included switching to entecavir (ETV) and adding adefovir (ADV) or tenofovir (TFV). At present, switching to ETV is not recommended for rescue therapy for LAM-resistant chronic hepatitis B (CHB). The aim of this report was to determine whether add-on ADV was a superior rescue strategy in the treatment of CHB patients with LAM resistance.

Methods

We searched Medline/PubMed, EMBASE, Web of Knowledge, and the Cochrane Library. Relative risks (RRs) of virologic response, virologic breakthrough, normalization of serum alanine aminotransferase (ALT) levels and HBeAg seroconversion rates were studied. Factors predicting virologic response, standardized mean differences (SMD) in HBV DNA levels and safety were reviewed.

Results

Six eligible trials (451 patients in total) were included in the analysis. The rate of virologic breakthrough in the ETV group was higher than that in the LAM plus ADV group. There were no statistical differences in virologic response, ALT normalization and HBeAg seroconversion in either group 48 weeks post treatment. LAM plus ADV combination therapy produced faster and greater HBV DNA reduction rates 24 weeks post therapy compared to ETV monotherapy. HBV DNA baseline levels and the initial virologic response (IVR) were predictive of the virologic response. Additionally, combination therapy or monotherapy were both well tolerated.

Conclusions

LAM plus ADV combination therapy was more effective and produced longer-lasting effects than switching to ETV monotherapy in treating CHB patients with LAM resistance. However, considering the practical benefits and limitations of ADV, individualized therapy will be needed in patients with prior history of LAM resistant infections.
Infective endocarditis with Lactococcus garvieae in Japan: a case report
Authors: Watanabe Yukiko , Naito Toshio , Kikuchi Ken , Amari Yu , Uehara Yuki , Isonuma Hiroshi , Hisaoka Teruhiko , Yoshida Terutoyo , Yaginuma Kenji , Takaya Norihide , Daida Hiroyuki , Hiramatsu Keiichi
Published: August 2011

Introduction

Lactococcus garvieae is a well-recognized fish pathogen, and it is considered a rare pathogen with low virulence in human infection. We describe the 11th case of L. garvieae infective endocarditis reported in the literature, and the first reported case in Japan.

Case presentation

We report a case of a 55-year-old Japanese woman who had native valve endocarditis with L. garvieae. The case was complicated by renal infarction, cerebral infarction, and mycotic aneurysms. After anti-microbial treatment, she was discharged from the hospital and is now well while being monitored in the out-patient clinic.

Conclusion

We encountered a case of L. garvieae endocarditis that occurred in a native valve of a healthy woman. The 16S ribosomal RNA gene sequencing was useful for the identification of this pathogen. Although infective endocarditis with L. garvieae is uncommon, it is possible to treat high virulence clinically.
Malaria control in the African Region: perceptions and viewspoints on proceedings of the Africa Leaders Malaria Alliance (ALMA)
Authors: Sambo Luis Gomes , Ki-Zerbo Georges , Kirigia Joses Muthuri
Published: August 2011

Background

In 2009 a total of 153,408 malaria deaths were reported in Africa. Eleven countries showed a reduction of more than 50% in either confirmed malaria cases or malaria admissions and deaths in recent years. However, many African countries are not on track to achieve the malaria component of the Millennium Development Goal (MDG) 6. The African Leaders Malaria Alliance (ALMA) working session at the 15th African Union Summit discussed the bottlenecks to achieving MDG 6 (specifically halting and beginning to reverse the incidence of malaria by 2015), success factors, and what countries needed to do to accelerate achievement of the MDG. The purpose of this article is to reflect on the proceedings of the ALMA working session.

Methods

Working methods of the session included speeches and statements by invited speakers and high-level panel discussions.

Discussion

The main bottlenecks identified related to the capacity of the health systems to deliver quality care and accessibility issues; need for strong, decentralized malaria-control programmes with linkages with other health and development sectors, the civil society and private sector entities; benefits of co-implementation of malaria control programmes with child survival or other public health interventions; systematic application of integrated promotive, preventive, diagnostic and case management interventions with full community participation; adapting approaches to local political, socio-cultural and administrative environments.

The following prerequisites for success were identified: a clear vision and effective leadership of national malaria control programmes; high level political commitment to ensure adequate capacity in expertise, skill mix and number of managers, technicians and service providers; national ownership, intersectoral collaboration and accountability, as well as strong civil society and private sector involvement; functional epidemiological surveillance systems; and levering of African Union and regional economic communities to address the cross-border dimension of malaria control.

It was agreed that countries needed to secure adequate domestic and external funding for sustained commitment to malaria elimination; strengthen national malaria control programmes in the context of broader health system strengthening; ensure free access to long-lasting insecticide treated nets and malaria diagnosis and treatment for vulnerable groups; strengthen human resource capacity at central, district and community levels; and establish strong logistics, information and surveillance systems.

Conclusion

It is critically important for countries to have a clear vision and strategy for malaria elimination; effective leadership of national malaria control programmes; draw lessons from other African countries that have succeeded to dramatically reduce the burden of malaria; and sustain funding and ongoing interventions.
Description of evandromyia spelunca, a new phlebotomine species of the cortelezzii complex, from a cave in Minas Gerais State, Brazil (Diptera: Psychodidae: Phlebotominae)
Authors: Carvalho Gustavo ML , Brazil Reginaldo P , Sanguinette Cristiani C , Andrade Filho José D
Published: August 2011

Background

The cave fauna of the Brazil is poorly documented, and among the insects those live or frequent caves and their adjacent environments phlebotomine sand flies call for special attention because several species are vectors of pathogens among vertebrates hosts. A new species of sand fly from Minas Gerais is described based in females and males collected in a cave of the municipality of Lassance.

Results

The morphological characters of the new species permit to include in the Evandromyia genus, cortelezzii complex. This complex consists of three species: Evandromyia corumbaensis (Galati, Nunes, Oshiro & Rego, 1989), Evandromyia cortelezzii (Brethes, 1923) and Evandromyia sallesi (Galvao & Coutinho, 1940).

Conclusions

The new species can be separate from the others of the cortelezzii complex through morphological characters of the male terminalia and female spermathecae.
Primary and secondary thyroid hormone transporters
Authors: Kinne Anita , Schülein Ralf , Krause Gerd
Published: August 2011

Thyroid hormones (TH) are essential for the development of the human brain, growth and cellular metabolism. Investigation of TH transporters became one of the emerging fields in thyroid research after the discovery of inactivating mutations in the Monocarboxylate transporter 8 (MCT8), which was found to be highly specific for TH transport. However, additional transmembrane transporters are also very important for TH uptake and efflux in different cell types. They transport TH as secondary substrates and include the aromatic amino acid transporting MCT10, the organic anion transporting polypeptides (e.g. OATP1C1, OATP1A2, OPTP1A4) and the large neutral amino acid transporters (LAT1 and LAT2). These TH transporters characteristically possess 12 transmembrane spanners but due to the strong differing sequences between the three transporter families we assume an identical conformation is not very likely. In contrast to the others, the LAT family members form a heterodimer with the escort protein 4F2hc/CD98. A comparison of sequence proportions, locations and types of functional sensitive features for TH transport discovered by mutations, revealed that transport sensitive charged residues occur as conserved amino acids only within each family of the transporter types but not in all putative TH transporters. Based on the lack of highly conserved sensitive charged residues throughout the three transporter families as a common counterpart for the amino acid moiety of the substrates, we conclude that the molecular transport mechanism is likely organized either a) by different molecular determinants in the divergent transporter types or b) the counterparts for the substrates` amino acid moiety at the transporter are not any charged side chains but other proton acceptors or donators. However, positions of transport sensitive residues coincide at transmembrane helix 8 in the TH transporter MCT8, OATP1C1 and another amino acid transporter, the L-cystine and L-glutamate exchanger xCT, which is highly homologous to LAT1 and LAT2. Here we review the data available and compare similarities and differences between these primary and secondary TH transporters regarding sequences, topology, potential structures, trafficking to the plasma membrane, molecular features and locations of transport sensitive functionalities. Thereby, we focus on TH transporters occurring in the blood-brain barrier.
MiR-106b promotes cell proliferation via targeting RB in laryngeal carcinoma
Authors: Cai Kemin , Wang Yu , Bao Xueli
Published: August 2011

MiR-106b is frequently up-regulated in various types of human cancer including laryngeal carcinoma. However the underlying mechanism of miR-106b involved in laryngeal carcinoma remains elusive. Here we showed that reduction of miR-106b induced cell cycle G0/G1 arrest by targeting tumor suppressor RB in human laryngeal carcinoma cells. Further, Introducing RB cDNA without 3'UTR abrogated miR-106b-induced cell proliferation. Finally, there was an inverse relationship between RB and miR-106b expression in laryngeal carcinoma tissues. To our knowledge, these data indicate for the first time that miR-106b directly regulate cell cycle by targeting RB in laryngeal carcinoma and that miR-106b could be potential therapeutic approaches for laryngeal carcinoma.
A retrospective analysis of clinicopathological and prognostic characteristics of ovarian tumors in the State of Espírito Santo, Brazil
Authors: Paes Marcela F , Daltoé Renata D , Madeira Klesia P , Rezende Lucas CD , Sirtoli Gabriela M , Herlinger Alice L , Souza Leticia S , Coitinho Luciana B , Silva Débora , Cerri Murilo F , Chiaradia Ana Cristina N , Carvalho Alex A , Silva Ian V , Rangel Leticia BA
Published: August 2011

Background

Ovarian cancer is sixth most common cancer among women and the leading cause of death in women with gynecological malignancies. Despite the great impact ovarian cancer has on women's health and its great impact in public economy, Brazil still lacks valuable information concerning epidemiological aspects of this disease

Methods

We've compiled clinical data of all ovarian tumors registered at the two public hospitals of reference (1997 - 2007), such as: patients' age at diagnosis, tumor histological type, tumor stage, chemotherapy regimens, chemotherapy responsiveness, disease-free survival, and overall survival.

Results

Women's mean age at diagnosis was 54.67 ± 13.84 for ovarian cancer, 46.15 ± 11.15 for borderline tumors, and 42.01 ± 15.06 for adenomas. Among epithelial ovarian cancer cases, 30.1% were of serous, 13.7% were of mucinous, and 13.7% were of endometrioid type; exceptionally serous carcinoma was diagnosed in women younger than 30 years old. Endometrioid cancer had lower disease-free survival than others (p < 0.05). Cases were predominantly diagnosed as poor prognosis disease (FIGO III and IV, 56.2%). Regarding responsiveness to platinum-based therapy, 17.1% of patients were resistant, whereas 24.6%, susceptible. From these, we found equally responsiveness to platinum alone or its association with paclitaxel or cyclophosphamide.

Discussion

Our data agreed with other studies regarding mean patients' age at diagnosis, histological type frequency, FIGO stages distribution, and chemotherapy regimens. However, the histological type distribution, with equal contribution of mucinous and endometrioid types seems to be a unique characteristic of the studied highly miscegenated population.

Conclusion

We have enlighten the profile of the studied ovarian cancer population, which might enable the development of more efficient political strategies to control this malignancy that is the fifth leading cause of cancer-related deaths among women.
Treatment as prevention: preparing the way
Authors: Williams Brian , Wood Robin , Dukay Victor , Delva Wim , Ginsburg David , Hargrove John , Stander Martinus , Sheneberger Robert , Montaner Julio , Welte Alex
Published: August 2011

Potent antiretroviral therapy (ART) reduces mortality and morbidity in people living with HIV by reducing viral load and allowing their immune systems to recover. The reduction in viral load soon after starting ART has led to the hypothesis that early and widespread ART could prevent onward transmission and therefore eliminate the HIV epidemic in the long term. While several authors have argued that it is feasible to use HIV treatment as prevention (TasP), provided treatment is started sufficiently early, others have reasonably drawn attention to the many operational difficulties that will need to be overcome if the strategy is to succeed in reducing HIV transmission. Furthermore, international public health policy must be based on more than theoretical studies, no matter how appealing. Community randomized controlled trials provide the gold standard for testing the extent to which early treatment reduces incidence, but much still needs to be understood and the immediate need is for operational studies to explore the practical feasibility of this approach. Here, we examine some of the issues to be addressed, the obstacles to be overcome, and strategies that may be necessary if TasP is to be effective. Studies of this kind will provide valuable information for the design of large‐scale trials, as well as essential information that will be needed if early treatment is to be incorporated into public health policy.
Effect of simulated gastro‐duodenal digestion on the allergenic reactivity of beta‐lactoglobulin
Authors: Bossios Apostolos , Theodoropoulou Maria , Mondoulet Lucie , Rigby Neil M , Papadopoulos Nikolaos G , Bernard Hervé , Adel‐Patient Karine , Wal Jean‐Michel , Mills Clare EN , Papageorgiou Photini
Published: August 2011

Background

Cow's milk (CM) allergy affects about 2% of infants. The allergenicity of dietary proteins, including those from CM, has been related to their digestibility although the generality of the link and its causality remains to be demonstrated. In this study we use an in vitro digestion system, to investigate the digestibility of β‐lactoglobulin (blg) during gastrointestinal transit and to assess the impact of this process on blg allergenic reactivity in CM allergic children.

Methods

Blg digesta were prepared using an in vitro digestion protocol simulating either gastric digestion alone or followed by duodenal digestion with or without phosphatidylcholine (PC). Biochemical analysis of blg digesta was performed by SDS‐PAGE and their concentration was measured by a sandwich ELISA. Assessment of their allergenic reactivity was done in vitro by EAST inhibition, specific basophil activation (basotest) and lymphocyte proliferation (PCNA‐flow cytometry) assays using sera and cells from patients allergic to blg and in vivo by skin prick testing (SPT) of these patients.

Results

Blg was only broken down to smaller peptides after gastro‐duodenal digestion although a sizeable amount of intact protein still remained. Digestion did not modify the IgE binding capacity of blg except for gastro‐duodenal digestion performed in the absence of PC. These results are consistent with the quantity of intact blg remaining in the digesta. Overall both gastric and gastroduodenal digestion enhanced activation of sensitized basophils and proliferation of sensitized lymphocytes by blg. However, there was a tendency towards reduction in mean diameter of SPT following digestion, the PC alone during phase 1 digestion causing a significant increase in mean diameter.

Conclusions

Digestion did not reduce the allergenic reactivity of blg to a clinically insignificant extent, PC inhibiting digestion and thereby protecting blg allergenic reactivity. SPT reactivity was reduced compared to blg immunoreactivity in in vitro tests.