bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparative genomics of Shiga toxin encoding bacteriophages
Authors: Smith Darren L , Rooks David J , Fogg Paul CM , Darby Alistair C , Thomson Nick R , McCarthy Alan J , Allison Heather E
Published: July 2012

Background

Stx bacteriophages are responsible for driving the dissemination of Stx toxin genes (stx) across their bacterial host range. Lysogens carrying Stx phages can cause severe, life-threatening disease and Stx toxin is an integral virulence factor. The Stx-bacteriophage vB_EcoP-24B, commonly referred to as Ф24B, is capable of multiply infecting a single bacterial host cell at a high frequency, with secondary infection increasing the rate at which subsequent bacteriophage infections can occur. This is biologically unusual, therefore determining the genomic content and context of Ф24B compared to other lambdoid Stx phages is important to understanding the factors controlling this phenomenon and determining whether they occur in other Stx phages.

Results

The genome of the Stx2 encoding phage, Ф24B was sequenced and annotated. The genomic organisation and general features are similar to other sequenced Stx bacteriophages induced from Enterohaemorrhagic Escherichia coli (EHEC), however Ф24B possesses significant regions of heterogeneity, with implications for phage biology and behaviour. The Ф24B genome was compared to other sequenced Stx phages and the archetypal lambdoid phage, lambda, using the Circos genome comparison tool and a PCR-based multi-loci comparison system.

Conclusions

The data support the hypothesis that Stx phages are mosaic, and recombination events between the host, phages and their remnants within the same infected bacterial cell will continue to drive the evolution of Stx phage variants and the subsequent dissemination of shigatoxigenic potential.
Transposable elements in phytopathogenic Verticillium spp.: insights into genome evolution and inter- and intra-specific diversification
Authors: Amyotte Stefan G , Tan Xiaoping , Pennerman Kayla , del Mar Jimenez-Gasco Maria , Klosterman Steven J , Ma Li-Jun , Dobinson Katherine F , Veronese Paola
Published: July 2012

Background

Verticillium dahliae (Vd) and Verticillium albo-atrum (Va) are cosmopolitan soil fungi causing very disruptive vascular diseases on a wide range of crop plants. To date, no sexual stage has been identified in either microorganism suggesting that somatic mutation is a major force in generating genetic diversity. Whole genome comparative analysis of the recently sequenced strains VdLs.17 and VaMs.102 revealed that non-random insertions of transposable elements (TEs) have contributed to the generation of four lineage-specific (LS) regions in VdLs.17.

Results

We present here a detailed analysis of Class I retrotransposons and Class II “cut-and-paste” DNA elements detected in the sequenced Verticillium genomes. We report also of their distribution in other Vd and Va isolates from various geographic origins. In VdLs.17, we identified and characterized 56 complete retrotransposons of the Gypsy-, Copia- and LINE-like types, as well as 34 full-length elements of the “cut-and-paste” superfamilies Tc1/mariner, Activator and Mutator. While Copia and Tc1/mariner were present in multiple identical copies, Activator and Mutator sequences were highly divergent. Most elements comprised complete ORFs, had matching ESTs and showed active transcription in response to stress treatment. Noticeably, we found evidences of repeat-induced point mutation (RIP) only in some of the Gypsy retroelements. While Copia-, Gypsy- and Tc1/mariner-like transposons were prominent, a large variation in presence of the other types of mobile elements was detected in the other Verticillium spp. strains surveyed. In particular, neither complete nor defective “cut-and-paste” TEs were found in VaMs.102.

Conclusions

Copia-, Gypsy- and Tc1/mariner-like transposons are the most wide-spread TEs in the phytopathogens V. dahliae and V. albo-atrum. In VdLs.17, we identified several retroelements and “cut-and-paste” transposons still potentially active. Some of these elements have undergone diversification and subsequent selective amplification after introgression into the fungal genome. Others, such as the ripped Copias, have been potentially acquired by horizontal transfer. The observed biased TE insertion in gene-rich regions within an individual genome (VdLs.17) and the “patchy” distribution among different strains point to the mobile elements as major generators of Verticillium intra- and inter-specific genomic variation.
Deep ancestry of mammalian X chromosome revealed by comparison with the basal tetrapod Xenopus tropicalis
Authors: Mácha Jaroslav , Teichmanová Radka , Sater Amy K , Wells Dan E , Tlapáková Tereza , Zimmerman Lyle B , Krylov Vladimír
Published: July 2012

Background

The X and Y sex chromosomes are conspicuous features of placental mammal genomes. Mammalian sex chromosomes arose from an ordinary pair of autosomes after the proto-Y acquired a male-determining gene and degenerated due to suppression of X-Y recombination. Analysis of earlier steps in X chromosome evolution has been hampered by the long interval between the origins of teleost and amniote lineages as well as scarcity of X chromosome orthologs in incomplete avian genome assemblies.

Results

This study clarifies the genesis and remodelling of the Eutherian X chromosome by using a combination of sequence analysis, meiotic map information, and cytogenetic localization to compare amniote genome organization with that of the amphibian Xenopus tropicalis. Nearly all orthologs of human X genes localize to X. tropicalis chromosomes 2 and 8, consistent with an ancestral X-conserved region and a single X-added region precursor. This finding contradicts a previous hypothesis of three evolutionary strata in this region. Homologies between human, opossum, chicken and frog chromosomes suggest a single X-added region predecessor in therian mammals, corresponding to opossum chromosomes 4 and 7. A more ancient X-added ancestral region, currently extant as a major part of chicken chromosome 1, is likely to have been present in the progenitor of synapsids and sauropsids. Analysis of X chromosome gene content emphasizes conservation of single protein coding genes and the role of tandem arrays in formation of novel genes.

Conclusions

Chromosomal regions orthologous to Therian X chromosomes have been located in the genome of the frog X. tropicalis. These X chromosome ancestral components experienced a series of fusion and breakage events to give rise to avian autosomes and mammalian sex chromosomes. The early branching tetrapod X. tropicalis’ simple diploid genome and robust synteny to amniotes greatly enhances studies of vertebrate chromosome evolution.
Extensive remodeling of the Pseudomonas syringae pv. avellanae type III secretome associated with two independent host shifts onto hazelnut
Authors: O’Brien Heath E , Thakur Shalabh , Gong Yunchen , Fung Pauline , Zhang Jianfeng , Yuan Lijie , Wang Pauline W , Yong Choseung , Scortichini Marco , Guttman David S
Published: July 2012

Background

Hazelnut (Corylus avellana) decline disease in Greece and Italy is caused by the convergent evolution of two distantly related lineages ofPseudomonas syringaepv.avellanae(Pav). We sequenced the genomes of threePavisolates to determine if their convergent virulence phenotype had a common genetic basis due to either genetic exchange between lineages or parallel evolution.

Results

We found little evidence for horizontal transfer (recombination) of genes betweenPavlineages, but two large genomic islands (GIs) have been recently acquired by one of the lineages. Evolutionary analyses of the genes encoding type III secreted effectors (T3SEs) that are translocated into host cells and are important for both suppressing and eliciting defense responses show that the twoPavlineages have dramatically different T3SE profiles, with only two shared putatively functional T3SEs. OnePavlineage has undergone unprecedented secretome remodeling, including the acquisition of eleven new T3SEs and the loss or pseudogenization of 15, including five of the six core T3SE families that are present in the otherPavlineage. Molecular dating indicates that divergence within both of thePavlineages predates their observation in the field. This suggest that bothPavlineages have been cryptically infecting hazelnut trees or wild relatives for many years, and that the emergence of hazelnut decline in the 1970s may have been due to changes in agricultural practice.

Conclusions

These data show that divergent lineages ofP. syringaecan converge on identical disease etiology on the same host plant using different virulence mechanisms and that dramatic shifts in the arsenal of T3SEs can accompany disease emergence.
Relationship between serum uric acid and internal carotid resistive index in hypertensive women: a cross-sectional study
Authors: Cipolli José Alexandre Addeo , Ferreira-Sae Maria Carolina , Martins Rafael Prado , Pio-Magalhães José Alexandre , Bellinazzi Vera Regina , Matos-Souza José Roberto , Junior Wilson Nadruz
Published: July 2012

Background

The impact of serum uric acid (SUA) on arteries of hypertensive subjects remains to be fully established. This study investigated the relationship between SUA and carotid structural and hemodynamic parameters in hypertensive men and women.

Methods

Three hundred and thirty eight patients (207 women and 131 men) were cross-sectionally evaluated by clinical, laboratory, hemodynamic and carotid ultrasound analysis. Common carotid diameters, circumferential wall tensions, Young’s Elastic Modulus, Stiffness Index, Arterial Compliance and intima-media thickness (IMT) were determined. Internal carotid artery resistive index (ICRI), a hemodynamic measure that reflects local vascular impedance and microangiopathy, was also assessed.

Results

Univariate analysis showed no significant correlation of SUA with carotid diameters, elasticity/stiffness indexes, IMT and circumferential wall tensions in both genders. Conversely, SUA correlated with ICRI (r = 0.34; p < 0.001) in women, but not in men, and hyperuricemic women presented higher ICRI than normouricemic ones (0.684 ± 0.007 vs. 0.649 ± 0.004; p < 0.001). Stepwise and logistic regression analyses adjusted for potential confounding factors showed that ICRI was independently associated with SUA and hyperuricemia in women.

Conclusions

This study demonstrated that SUA was associated with ICRI in hypertensive women, suggesting that there might gender-related differences in the relationship between SUA and vascular damage in subjects with systemic hypertension.
Identification of 3 novel VHL germ-line mutations in Danish VHL patients
Authors: Dandanell Mette , Friis-Hansen Lennart , Sunde Lone , Nielsen Finn C , Hansen Thomas v O
Published: July 2012

Background

von Hippel-Lindau (VHL) disease is a hereditary cancer syndrome in which the patients develop retinal and central nervous system hemangioblastomas, pheochromocytomas and clear-cell renal tumors. The autosomal dominant disease is caused by mutations in the VHL gene.

Methods

VHL mutational analysis was carried out by sequencing of the coding sequence and by multiplex ligation-dependent probe amplification analysis. The functional consequence of the variants was investigated using in silico prediction tools.

Results

A total of 289 probands suspected of having VHL syndrome have been screened for mutations in the VHL gene. Twenty-six different VHL mutations were identified in 36 families including one in-frame duplication, two frame-shift mutations, four nonsense mutations, twelve missense mutations, three intronic mutations and four large genomic rearrangements. Three of these mutations (c.319 C > T, c.342_343dupGGT and c.520_521dupAA) were novel.

Conclusions

In this study we report the VHL germ-line mutations found in Danish families. We found three novel VHL mutations where two were classified as pathogenic and the latter was classified as a variant of unknown significance. Together, our findings contribute to the interpretation of the potential pathogenicity of VHL germ-line mutations.
Should we adjust erythropoiesis-stimulating agent dosage to postdialysis hemoglobin levels? A pilot study
Authors: Castillo Nieves , García-García Patricia , Rivero Antonio , Jiménez-Sosa Alejandro , Macía Manuel , Getino María Adela , Méndez María Luisa , García-Pérez Javier , Navarro-González Juan F
Published: July 2012

Background

Predialysis hemoglobin (Hb) may overestimate the true erithropoiesis-stimulating agents (ESA) requeriments. We tested whether predialysis Hb is a reliable predictor of the postdialysis level to better control ESA dosage, and evaluated the relation between ESA, Hb and cardiovascular events (CVE).

Methods

Cohort study including 67 stable hemodialysis patients. Pre- and post-dialysis Hb concentrations were measured, and ESA doses were calculated. A model to predict post-dialysis Hb is proposed. During 18 months follow-up, CVE, hospitalizations and mortality were collected.

Results

After dialysis, Hb cocentration rise by 6.1 ± 5.6%. Using postdialysis Hb, the weight-adjusted ESA dosage would be lower respect to the prescription using predialysis Hb: 104 ± 120 vs 128 ± 124 U/kg/week (P < 0.001). Using predialysis Hb, 40.2% of subjects had a Hb level above 12 g/dL, whereas this percent increased to 70.1% using postdialysis Hb. During the follow-up, 15 patients had a CVE, without differences in Hb levels respect to subjects without CVE. However, patients with CVE had received higher ESA doses: 186 ± 180 vs 111 ± 98 U/Kg/week (P = 0.001). The prediction model is: Postdialysis Hb (g/dL) = 1.636 + 0.871 x predialysis Hb* (g/dL) + 0.099 x UF rate** (mL/kg/h) - 0.39 for women***. [R2 = 0.74; *P < 0,001; **P = 0.001; ***P = 0.03).

Conclusions

Postdialysis Hb can be a better reflect of the real Hb level in hemodialysis patients. Using postdialysis Hb would avoid the use of inappropriately high ESA doses. The prediction of postdialysis Hb with an adjusted model would help us to identify those patients at risk for ESA overdosification.
Impact of Dry Eye Syndrome on Vision-Related Quality of Life in a Non-Clinic-Based General Population
Authors: Le Qihua , Zhou Xiaodong , Ge Ling , Wu Liangcheng , Hong Jiaxu , Xu Jianjiang
Published: July 2012

Background

Dry eye syndrome (DES) is a common ocular disorder occurring in general population. The purpose of this study is to evaluate the impact of DES on vision-related quality of life (QoL) in a non-clinic-based general population.

Methods

This population-based cross-sectional study enrolled subjects older than 40 years, who took part in an epidemiological study on dry eye in Sanle Community, Shanghai. Apart from the collection of sociodemographics, dry eye symptoms, and other clinical data, a Chinese version of the 25-item National Eye Institute Visual Functioning Questionnaire (NEI VFQ-25) was administered to all subjects. Comparisons of the NEI VFQ-25 subscale item scores and composite score were made among subgroups divided according to the presence of dry eye symptoms or signs. Multivariate regression analysis was performed to investigate the relationship between the clinical variables and the VFQ-25 composite score.

Results

A total of 229 participants were enrolled in the study, with an average age of (60.7 ±10.1) years old. Majority of these participants were female (59.8 %, 137/229). The total DES symptom scores (TDSS) in subjects either with definite DES or only with dry eye symptoms were significantly higher (F = 60.331, P < 0.001). The values of tear break-up time (TBUT) and Schirmer test were significantly lower in participants with DES and those with dry eye signs only (F = 55.158 and 40.778, P < 0.001). The composite score of the NEI VFQ-25 was significantly lower in subjects with DES (F = 4.901, P = 0.003). Moreover, the subscale scores of ocular pain and mental health were significantly lower in those with either DES or dry eye symptoms only (F = 10.962 and 7.362 respectively, both P < 0.001). The multiple regression analysis showed that the TDSS had a significant negative correlation with the VFQ-25 composite score as well as with the subscale score for ocular pain and mental health, even after the adjustment of all other factors (all P < 0.01).

Conclusions

The symptoms of dry eye are associated with an adverse impact on vision-related QoL in non-clinic-based general population, which is mainly represented as more ocular pain and discomfort, and impaired mental health as well. Apart from clinical examination, it is also important to refer to subjective symptoms and QoL scores when assessing the severity of DES.
Benefits of Iron supplementation for low birth weight infants: A systematic review
Authors: Long Hui , Yi Jing-Mei , Hu Pei-Li , Li Zhi-Bin , Qiu Wei-Ya , Wang Fang , Zhu Sing
Published: July 2012

Background

A number of studies have reported on the effects of iron supplementation in low birth weight infants; however, no systematic review of the available evidence has been conducted to date. Hence, we performed a systematic review of the literature to examine the effects of iron supplementation on hematologic iron status, growth, neurodevelopment, and adverse effects in low birth weight/premature infants.

Methods

We searched the Cochrane Library, Medline, and PubMed for articles reporting on the effects of iron supplementation in low weight infants. The following search terms were used: “preterm born infant(s)/children”; “preterm infants”; “prematurely born children” “weight less than 1500 g at birth”; “born prematurely”; “low birth weight infant(s)”; “infants born preterm”; “prematurity”; “small-for-gestational age”; “very small gestational age infants”; “iron supplementation”; “iron intake”; “iron supplements”; “ferric and/or ferrous compounds”; and “ferrous sulphate/fumarate/sulfate”.

Results

A total of 15 studies were identified and included in the systematic review. Supplemental iron was given orally or as an iron-fortified formula in 14/15 studies. The duration of treatment ranged from 1 week to 18 months. Iron supplementation significantly increased hematologic measures of iron status (including hemoglobin, hematocrit, serum ferritin) relative to placebo or over time in most studies. All controlled studies that examined iron-deficiency anemia (IDA)/ID reported a decreased prevalence of IDA/ID with iron supplementation. Dose dependent decreases in the prevalence of IDA/ID were reported in several studies. Of the 5 studies reporting on growth, none found any significant effect on growth-related parameters (length, height, weight, and head circumference). Only 2 studies reported on neurodevelopment; no marked effects were reported. There were no consistently reported adverse effects, including oxidative stress, inhibited nutrient absorption, morbidity, or the requirement for blood transfusion.

Conclusion

The available data suggest that iron supplementation increases the levels of hematologic indicators of iron status and reduces the prevalence of IDA/ID in low birth weight/premature infants. There is insufficient evidence to make a definitive statement regarding the effects of iron supplementation on growth, neurodevelopment, or the occurrence of adverse effects in low birth weight/premature infants.
Evaluation of dietary intake of lactating women in China and its potential impact on the health of mothers and infants
Authors: Chen Haijiao , Wang Ping , Han Yaofeng , Ma Jing , Troy Frederic A , Wang Bing
Published: July 2012

Background

Optimal nutrition for lactating mothers is importance for mother and infants’ health and well-being. We determined the nutrient intake and dietary changes during the first 3-month of lactation, and its potential effect on health and disease risk.

Method

Personal interviews were conducted to collect a 24h diet recall questionnaire from 199 healthy lactating women in the postpartum days 2, 7, 30, 90 and healthy 58 non-pregnant women served as the controls.

Results

We found in lactating women (1) the mean daily energy and carbohydrate intake was lower than that of the Chinese Recommended Nutrient Intake (RNI, 2600 Kcal, 357.5 ~ 422.5g) by 11% ~ 17% and 33% ~ 49%, respectively; (2) the fat intake increased from 3% to 13%, which was 9 ~ 77% higher than the RNI (57 ~ 86.7g); (3) the protein intake exceeded the RNI of 85g by 32 ~ 53%; (4) the total calories consumed from carbohydrate (39%-44%), fat (34% ~ 42%) and protein (20%-23%) failed to meet Chinese RNI (5) the intake of vitamin C, B1, folate, zinc, dietary fiber, and calcium was 5% ~ 73% lower than the RNI while vitamin B2, B3, E, iron and selenium intake was 20% to 3 times higher than the RNI. Nutrient intake in the control group was lower for all nutrients than the recommended RNI.

Conclusion

Lactating women on a self-selected diet did not meet the Chinese RNI for many important micronutrients, which may influence the nutritional composition of breast milk and thus impact the potential health of mothers and infants. RNI should consider the regional dietary habits and culture. A single national RNI is not applicable for all of China. Nutritional education into the community is needed.
A six-month crossover chemoprevention clinical trial of tea in smokers and non-smokers: methodological issues in a feasibility study
Authors: Dash Chiranjeev , Chung Fung-Lung , Rohan Joy Ann Phillips , Greenspan Emily , Christopher Patrick D , Makambi Kepher , Hara Yukihiko , Newkirk Kenneth , Davidson Bruce , Adams-Campbell Lucile L
Published: July 2012

Background

Chemoprevention crossover trials of tea can be more efficient than parallel designs but the attrition and compliance rates with such trials are unknown.

Methods

Attrition (dropouts) and compliance with treatment were assessed in a 25-week randomized, placebo controlled, crossover, feasibility clinical trial of four tea treatments to investigate the effect of tea on oral cancer biomarkers. Each treatment lasted 4 weeks with 2 weeks of washout in between. Participants were 32 smokers and 33 non-smokers without any evidence of premalignant oral lesions. The interventions consisted of packets of green tea, black tea, caffeinated water, or placebo. Participants were assigned to each treatment for four weeks, and were instructed to drink five packets per day while on the treatment. Dropout from the trial and compliance (consumption of ≥ 85% of the prescribed treatment packets) are the main outcome measures reported.

Results

There was a high rate of dropout (51%) from the study, and the rates were significantly higher among smokers (64%) than non-smokers (36%). Among participants who completed the study the rate of compliance was 72%. The highest rates of dropouts occurred between the first and second treatment visits in both smokers (38% dropout) and non-smokers (18% dropout). Throughout the study smokers were more likely to dropout than non-smokers. Black tea treatment was associated with the highest rates of dropout among smokers (37%), but was associated with the lowest rate of dropout among non-smokers (4%).

Conclusions

In a study conducted to test the feasibility of a four-treatment crossover tea trial, a high rate of dropout among smokers and non-smokers was observed. Multi-arm crossover tea trials might pose a higher burden on participants and research is needed to improve adherence and treatment compliance in such trials.

Trial registration number

ISRCTN70410203
Physiological heterogeneities in microbial populations and implications for physical stress tolerance
Authors: Carlquist Magnus , Fernandes Rita Lencastre , Helmark Søren , Heins Anna-Lena , Lundin Luisa , Sørensen Søren J , Gernaey Krist V , Lantz Anna Eliasson
Published: July 2012

Background

Traditionally average values of the whole population are considered when analysing microbial cell cultivations. However, a typical microbial population in a bioreactor is heterogeneous in most phenotypes measurable at a single-cell level. There are indications that such heterogeneity may be unfavourable on the one hand (reduces yields and productivities), but also beneficial on the other hand (facilitates quick adaptation to new conditions - i.e. increases the robustness of the fermentation process). Understanding and control of microbial population heterogeneity is thus of major importance for improving microbial cell factory processes.

Results

In this work, a dual reporter system was developed and applied to map growth and cell fitness heterogeneities within budding yeast populations during aerobic cultivation in well-mixed bioreactors. The reporter strain, which was based on the expression of green fluorescent protein (GFP) under the control of the ribosomal protein RPL22a promoter, made it possible to distinguish cell growth phases by the level of fluorescence intensity. Furthermore, by exploiting the strong correlation of intracellular GFP level and cell membrane integrity it was possible to distinguish subpopulations with high and low cell membrane robustness and hence ability to withstand freeze-thaw stress. A strong inverse correlation between growth and cell membrane robustness was observed, which further supports the hypothesis that cellular resources are limited and need to be distributed as a trade-off between two functions: growth and robustness. In addition, the trade-off was shown to vary within the population, and the occurrence of two distinct subpopulations shifting between these two antagonistic modes of cell operation could be distinguished.

Conclusions

The reporter strain enabled mapping of population heterogeneities in growth and cell membrane robustness towards freeze-thaw stress at different phases of cell cultivation. The described reporter system is a valuable tool for understanding the effect of environmental conditions on population heterogeneity of microbial cells and thereby to understand cell responses during industrial process-like conditions. It may be applied to identify more robust subpopulations, and for developing novel strategies for strain improvement and process design for more effective bioprocessing.
Distinct placental malaria pathology caused by different Plasmodium berghei lines that fail to induce cerebral malaria in the C57BL/6 mouse
Authors: Rodrigues-Duarte Lurdes , de Moraes Luciana Vieira , Barboza Renato , Marinho Claudio RF , Franke-Fayard Blandine , Janse Chris J , Penha-Gonçalves Carlos
Published: July 2012

Background

Placental malaria (PM) is one major feature of malaria during pregnancy. A murine model of experimental PM using BALB/c mice infected with Plasmodium berghei ANKA was recently established, but there is need for additional PM models with different parasite/host combinations that allow to interrogate the involvement of specific host genetic factors in the placental inflammatory response to Plasmodium infection.

Methods

A mid-term infection protocol was used to test PM induction by three P. berghei parasite lines, derived from the K173, NK65 and ANKA strains of P. berghei that fail to induce experimental cerebral malaria (ECM) in the susceptible C57BL/6 mice. Parasitaemia course, pregnancy outcome and placenta pathology induced by the three parasite lines were compared.

Results

The three P. berghei lines were able to evoke severe PM pathology and poor pregnancy outcome features. The results indicate that parasite components required to induce PM are distinct from ECM. Nevertheless, infection with parasites of the ANKAΔpm4 line, which lack expression of plasmepsin 4, displayed milder disease phenotypes associated with a strong innate immune response as compared to infections with NK65 and K173 parasites.

Conclusions

Infection of pregnant C57BL/6 females with K173, NK65 and ANKAΔpm4 P. berghei parasites provide experimental systems to identify host molecular components involved in PM pathogenesis mechanisms.
Three years of insecticide resistance monitoring in Anopheles gambiae in Burkina Faso: resistance on the rise?
Authors: Badolo Athanase , Traore Alphonse , Jones Christopher M , Sanou Antoine , Flood Lori , Guelbeogo Wamdaogo M , Ranson Hilary , Sagnon N’Fale
Published: July 2012

Background and methods

A longitudinal Anopheles gambiae s.l. insecticide-resistance monitoring programme was established in four sentinel sites in Burkina Faso. For three years, between 2008 and 2010, WHO diagnostic dose assays were used to measure the prevalence of resistance to all the major classes of insecticides at the beginning and end of the malaria transmission season. Species identification and genotyping for target site mutations was also performed and the sporozoite rate in adults determined.

Results

At the onset of the study, resistance to DDT and pyrethroids was already prevalent in An. gambiae s.l. from the south-west of the country but mosquitoes from the two sites in central Burkina Faso were largely susceptible. Within three years, DDT and permethrin resistance was established in all four sites. Carbamate and organophosphate resistance remains relatively rare and largely confined to the south-western areas although a small number of bendiocarb survivors were found in all sites by the final round of monitoring. The ace-1

R
target site resistance allele was present in all localities and its frequency exceeded 20% in 2010 in two of the sites. The frequency of the 1014F kdr mutation increased throughout the three years and by 2010, the frequency of 1014F in all sites combined was 0.02 in Anopheles arabiensis, 0.56 in An. gambiae M form and 0.96 in An. gambiae S form. This frequency did not differ significantly between the sites. The 1014S kdr allele was only found in An. arabiensis but its frequency increased significantly throughout the study (P = 0.0003) and in 2010 the 1014S allele frequency was 0.08 in An. arabiensis. Maximum sporozoite rates (12%) were observed in Soumousso in 2009 and the difference between sites is significant for each year.

Conclusion

Pyrethroid and DDT resistance is now established in An. gambiae s.l. throughout Burkina Faso. Results from diagnostic dose assays are highly variable within and between rounds of testing, and hence it is important that resistance monitoring is carried out on more than one occasion before decisions on insecticide procurement for vector control are made. The presence of 1014S in An. gambiae s.l., in addition to 1014F, is not unexpected given the recent report of 1014S in Benin but highlights the importance of monitoring for both mutations throughout the continent. Future research must now focus on the impact that this resistance is having on malaria control in Burkina Faso.
Clinical significance of clusterin expression in pancreatic adenocarcinoma
Authors: Jin Junshuo , Kim Joon-Mee , Hur Yoon-Seok , Cho Won Pyo , Lee Keon-Young , Ahn Seung-Ik , Hong Kee Chun , Park In-Sun
Published: July 2012

Background

Clusterin is known to be expressed in many human neoplasms, and is believed to participate in the regeneration, migration, and anti-apoptosis of tumor cells. However, few reports have addressed the relationship between the manifestation of clusterin and clinicopathologic parameters in pancreas cancer patients. In the present study, the authors investigated the expression of clusterin and its clinical significance in pancreatic adenocarcinoma.

Methods

Immunohistochemical staining was performed for clusterin in tumor tissues obtained from patients who received pancreatic resection with radical intent, and the associations of clusterin expression with various clinicopathologic parameters were analyzed in addition to the relation between its expression and survival.

Results

Immunoreactivity for clusterin was observed in 17 of the 52 (33%) pancreatic adenocarcinomas examined. In addition, clusterin positivity was found to be associated with preoperative serum carcinoembryonic antigen level, perineural invasion, and, most strongly, lymph node metastasis. The survival analysis identified tumor differentiation and lymph node metastasis as the only significant prognostic factors.

Conclusion

Although not an independent prognostic factor, clusterin immunoreactivity can be used in conjunction with lymph node metastasis to predict survival in cases of pancreatic adenocarcinoma.
Feasibility of purely laparoscopic resection of locally advanced rectal cancer in obese patients
Authors: Oyasiji Tolutope , Baldwin Keith , Katz Steven C , Espat N Joseph , Somasundar Ponnandai
Published: July 2012

Background

Totally laparoscopic (without hand-assist) resection for rectal cancer continues to evolve, and both obesity and locally advanced disease are perceived to add to the complexity of these procedures. There is a paucity of data on the impact of obesity on perioperative and oncologic outcomes for totally-laparoscopic rectal cancer resection (TLRR) for locally advanced disease.

Methods

In order to identify potential limitations of TLRR, a single-institution database was queried and identified 26 patients that underwent TLRR for locally advanced rectal cancers (T3/T4) over a three-year period. Patients were classified as normal-weight (NW, body mass index (BMI)=18.5 to 24.9kg/m2), overweight (OW, BMI=25 to 29.9kg/m2) and obese (OB, BMI >/= 30kg/m2). Perioperative outcomes, lymph node harvest and margin status were assessed.

Results

Seven patients were classified as NW (26.9%), 12 as OW (46.2%) and 7 as OB (26.9%). Age, tumor stage, gender and American Society of Anesthesiologists (ASA) scores were similar. OB had more co-morbidities (median 3.0, range 0.0 to 5.0 vs. 2.0, range 0.0 to 3.0 for NW and 1.0, range 0.0 to 3.0 for OW). Five patients had tumors <5cm from anal verge (NW=2; OW=1; OB=2). A median of 19.0, range 9.0 to 32.0; 20.0, range 9.0 to 46.0 and 19.0, range 15.0 to 31.0 lymph nodes were retrieved in the NW, OW and OB, respectively (Not Significant (NS)). Median node ratios for NW, OW and OB were 0.32, 0.13 and 0.00, respectively. All groups had negative proximal and distal margins. Radial margins were negative for 100% of NW, 83.3% of OW and 85.7% of OB (NS). Conversion rates were 14.3% for NW, 16.7% for OW & 0% for OB (NS). NW, OW and OB had complication rates of 28.3%, 33.3% and 14.3%, respectively. Median operative time, median estimated blood loss and median length of hospital stay were similar for all groups.

Conclusion

The perceived limitation that obesity would have on TLRR was not demonstrated by the analyzed data. Although our findings are limited by the modest sized cohort, the results suggest that it is reasonable to offer TLRR to obese patients with rectal cancer.
Effect of etching time on morphological, optical, and electronic properties of silicon nanowires
Authors: Nafie Nesma , Lachiheb Manel Abouda , Bouaicha Mongi
Published: July 2012

Owing to their interesting electronic, mechanical, optical, and transport properties, silicon nanowires (SiNWs) have attracted much attention, giving opportunities to several potential applications in nanoscale electronic, optoelectronic devices, and silicon solar cells. For photovoltaic application, a superficial film of SiNWs could be used as an efficient antireflection coating. In this work we investigate the morphological, optical, and electronic properties of SiNWs fabricated at different etching times. Characterizations of the formed SiNWs films were performed using a scanning electron microscope, ultraviolet–visible-near-infrared spectroscopy, and light-beam-induced-current technique. The latter technique was used to determine the effective diffusion length in SiNWs films. From these investigations, we deduce that the homogeneity of the SiNWs film plays a key role on the electronic properties.
Metal electrode integration on macroporous silicon: pore distribution and morphology
Authors: Scheen Gilles , Bassu Margherita , Francis Laurent A
Published: July 2012

In this work, a new approach for the one-step integration of interdigitated electrodes on macroporous silicon substrates is presented. Titanium/gold interdigitated electrodes are used to pattern p-type silicon substrates prior the anodization in an organic electrolyte. The electrolyte characteristics, conductivity, and pH have been found to affect the adherence of the metal layer on the silicon surface during the electrochemical etching. The impact of the metal pattern on size distribution and morphology of the resulting macroporous silicon layer is analyzed. A formation mechanism supported by finite element simulation is proposed.
CD137 ligand activated microglia induces oligodendrocyte apoptosis via reactive oxygen species
Authors: Yeo Yee Andy , Martínez Gómez Julia M , Croxford J Ludovic , Gasser Stephan , Ling Eng-Ang , Schwarz Herbert
Published: July 2012

CD137 (4-1BB, TNFRSF9), a member of the tumor necrosis factor (TNF) receptor family, is a potent T cell co-stimulatory molecule. CD137 ligand (CD137L) is expressed by antigen presenting cells (APC) as a transmembrane protein and transmits activating signals into APC. In this study we investigated the effects of CD137L signaling in microglia, the resident APC in the central nervous system.In vitro, the murine microglia cell lines BV-2 and N9, as well as primary murine microglia responded with activation as evidenced by adherence and secretion of proinflammatory cytokines, MMP-9, and soluble intercellular adhesion molecule (ICAM). CD137L signaling is also important for microglia activationin vivo, since CD137L-deficient mice exhibited profoundly less microglia activation during experimental autoimmune encephalomyelitis (EAE) which is a well-established murine model for neuroinflammation and human multiple sclerosis (MS). Also CD137 is expressed in the CNS of mice during EAE. Activated microglia has been reported to mediate the destruction of axonal myelin sheaths and cause the death of oligodendrocytes, the main pathogenic mechanisms in EAE and MS. Corresponding to the lower microglia activation there were also fewer apoptotic oligodendrocytes in the CNS of CD137L-deficient mice.In vitroco-culture confirmed that CD137L-activated microglia induces apoptosis in oligodendrocytes, and identified reactive oxygen species as the mechanism of apoptosis induction. These data demonstrate activating effects of CD137L signaling to microglia, and show for the first time that the CD137 receptor/ligand system may be a mediator of neuroinflammatory and neurodegenerative disease, by activating microglia which in turn kill oligodendrocytes.
The effects of Global Fund financing on health governance in Brazil
Authors: Gómez Eduardo J , Atun Rifat
Published: July 2012

Objectives

The impact of donors, such as national government (bi-lateral), private sector, and individual financial (philanthropic) contributions, on domestic health policies of developing nations has been the subject of scholarly discourse. Little is known, however, about the impact of global financial initiatives, such as the Global Fund to Fight AIDS, Tuberculosis, and Malaria, on policies and health governance of countries receiving funding from such initiatives.

Methods

This study employs a qualitative methodological design based on a single case study: Brazil. Analysis at national, inter-governmental and community levels is based on in-depth interviews with the Global Fund and the Brazilian Ministry of Health and civil societal activists. Primary research is complemented with information from printed media, reports, journal articles, and books, which were used to deepen our analysis while providing supporting evidence.

Results

Our analysis suggests that in Brazil, Global Fund financing has helped to positively transform health governance at three tiers of analysis: the national-level, inter-governmental-level, and community-level. At the national-level, Global Fund financing has helped to increased political attention and commitment to relatively neglected diseases, such as tuberculosis, while harmonizing intra-bureaucratic relationships; at the inter-governmental-level, Global Fund financing has motivated the National Tuberculosis Programme to strengthen its ties with state and municipal health departments, and non-governmental organisations (NGOs); while at the community-level, the Global Fund’s financing of civil societal institutions has encouraged the emergence of new civic movements, participation, and the creation of new municipal participatory institutions designed to monitor the disbursement of funds for Global Fund grants.

Conclusions

Global Fund financing can help deepen health governance at multiple levels. Future work will need to explore how the financing of civil society by the Global Fund and other donors influence policy agenda-setting and institutional innovations for increased civic participation in health governance and accountability to citizens.
Effect of traditional Chinese medicine on outcomes in patients with mild/moderate chronic obstructive pulmonary disease: study protocol for a randomized placebo-controlled trial
Authors: Minghang Wang , Jiansheng Li , Suyun Li , Haifeng Wang , Xueqing Yu , Hailong Zhang
Published: July 2012

Background

Chronic obstructive pulmonary disease (COPD) has become a major public health problem worldwide because of its high and increasing prevalence, morbidity, and mortality. Little attention has been paid to earlier stages of COPD or before it has developed. Reportedly, TCM may have some advantages in relieving symptoms and reducing the incidence of COPD exacerbations. We postulate that patients with COPD will benefit from therapy with TCM treatment according to syndrome differentiation.

Methods and design

A prospective, multi-center, double-blinded and randomized controlled method will be used to test the therapeutic effects of TCM treatment according to syndrome differentiation. A total of 504 patients will be enrolled into this study with 252 in each treatment group. Patients will receive medication according to their assigned group. TCM for COPD will be administered twice daily over 52 weeks, and all patients will follow the treatment program for 52 weeks. The FEV1 and exacerbations will be used as the primary outcome measures. The quality of life and the Modified Medical Research Council (MMRC) Dyspnea Scale, and the 6-min walk test (6MWD) will be used as the secondary outcome measures.

Discussion

We postulate that patients with COPD will benefit from therapy with TCM treatment according to syndrome differentiation.

Trial registration

This study is registered at ClinicalTrials.gov, NCT01486186
The drug cocktail network
Authors: Xu Ke-Jia , Song Jiangning , Zhao Xing-Ming
Published: July 2012

Background

Combination of different agents is widely used in clinic to combat complex diseases with improved therapy and reduced side effects. However, the identification of effective drug combinations remains a challenging task due to the huge number of possible combinations among candidate drugs that makes it impractical to screen putative combinations.

Results

In this work, we construct a 'drug cocktail network' using all the known effective drug combinations extracted from the Drug Combination Database (DCDB), and propose a network-based approach to investigate drug combinations. Our results show that the agents in an effective combination tend to have more similar therapeutic effects and share more interaction partners. Based on our observations, we further develop a statistical approach termed as DCPred (D rug C ombination Pred ictor) to predict possible drug combinations by exploiting the topological features of the drug cocktail network. Validating on the known drug combinations, DCPred achieves the overall AUC (Area Under the receiver operating characteristic Curve) score of 0.92, indicating the predictive power of our proposed approach.

Conclusions

The drug cocktail network constructed in this work provides useful insights into the underlying rules of effective drug combinations and offer important clues to accelerate the future discovery of new drug combinations.
Investigating the role of X chromosome breakpoints in premature ovarian failure
Authors: Baronchelli Simona , Villa Nicoletta , Redaelli Serena , Lissoni Sara , Saccheri Fabiana , Panzeri Elena , Conconi Donatella , Bentivegna Angela , Crosti Francesca , Sala Elena , Bertola Francesca , Marozzi Anna , Pedicini Antonio , Ventruto Marialuisa , Police Maria Adalgisa , Dalprà Leda
Published: July 2012

The importance of the genetic factor in the aetiology of premature ovarian failure (POF) is emphasized by the high percentage of familial cases and X chromosome abnormalities account for 10% of chromosomal aberrations. In this study, we report the detailed analysis of 4 chromosomal abnormalities involving the X chromosome and associated with POF that were detected during a screening of 269 affected women. Conventional and molecular cytogenetics were valuable tools for locating the breakpoint regions and thus the following karyotypes were defined: 46,X,der(X)t(X;19)(p21.1;q13.42)mat, 46,X,t(X;2)(q21.33;q14.3)dn, 46,X,der(X)t(X;Y)(q26.2;q11.223)mat and 46,X,t(X;13)(q13.3;q31)dn. A bioinformatic analysis of the breakpoint regions identified putative candidate genes for ovarian failure near the breakpoint regions on the X chromosome or on autosomes that were involved in the translocation event. HS6ST1, HS6ST2 and MATER genes were identified and their functions and a literature review revealed an interesting connection to the POF phenotype. Moreover, the 19q13.32 locus is associated with the age of onset of the natural menopause. These results support the position effect of the breakpoint on flanking genes, and cytogenetic techniques, in combination with bioinformatic analysis, may help to improve what is known about this puzzling disorder and its diagnostic potential.
Array-based comparative genomic hybridization is more informative than conventional karyotyping and fluorescence in situ hybridization in the analysis of first-trimester spontaneous abortion
Authors: Gao Jinsong , Liu Congcong , Yao Fengxia , Hao Na , Zhou Jing , Zhou Qian , Zhang Liang , Liu Xinyan , Bian Xuming , Liu Juntao
Published: July 2012

Background

Array-based comparative genomic hybridization (aCGH) is a new technique for detecting submicroscopic deletions and duplications, and can overcome many of the limitations associated with classic cytogenetic analysis. However, its clinical use in spontaneous abortion needs comprehensive evaluation. We used aCGH to investigate chromosomal imbalances in 100 spontaneous abortions and compared the results with G-banding karyotyping and fluorescence in situ hybridization (FISH). Inconsistent results were verified by quantitative fluorescence PCR.

Results

Abnormalities were detected in 61 cases. aCGH achieved the highest detection rate (93.4%, 57/61) compared with traditional karyotyping (77%, 47/61) and FISH analysis (68.9%, 42/61). aCGH identified all chromosome abnormalities reported by traditional karyotyping and interphase FISH analysis, with the exception of four triploids. It also detected three additional aneuploidy cases in 37 specimens with ‘normal’ karyotypes, one mosaicism and 10 abnormalities in 14 specimens that failed to grow in vitro.

Conclusions

aCGH analysis circumvents many limitations in traditional karyotyping or FISH. The accuracy and efficiency of aCGH in spontaneous abortions highlights its clinical usefulness for the future. As aborted tissues have the potential to be contaminated with maternal cells, the threshold value of detection in aCGH should be lowered to avoid false negatives.