bluuebunny/crossref_metadata_2025 huggingface dataset:
Methylphenidate Transdermal System in Adults With Past Stimulant Misuse
Authors: McRae-Clark Aimee L. , Brady Kathleen T. , Hartwell Karen J. , White Kathleen , Carter Rickey E.
Published: June 2010

Objective: This 8-week, open-label trial assessed the efficacy of methylphenidate transdermal system (MTS) in 14 adult individuals diagnosed with ADHD and with a history of stimulant misuse, abuse, or dependence. Method: The primary efficacy endpoint was the Wender-Reimherr Adult ADHD Scale (WRAADS), and secondary efficacy endpoints included the Clinical Global Impression (CGI) ratings and substance abuse as quantified by urine drug screens and self-reported use. Results: Significant improvements from baseline were found on both the WRAADS and CGI measurements. No abuse of the study medication was observed. Conclusion: The findings suggested that MTS may improve ADHD symptoms in adults with a history of stimulant misuse; however, there were limitations. The study data showed the need for subsequent randomized studies that further explore findings made in this study.
Nocebo effects in multiple sclerosis trials: a meta-analysis
Authors: Papadopoulos D. , Mitsikostas DD
Published: June 2010

Objective: To estimate the incidence and severity of nocebo responses in trials of symptomatic treatments (STs) and disease-modifying treatments (DMTs) for multiple sclerosis (MS).

Methods: We conducted a systematic Medline search for all randomised, placebo-controlled MS trials published between 1989 and 2009. Meta-analysis of the incidence of nocebo responses was performed by pooling the percentage of placebo-treated patients that exhibited adverse events. Nocebo severity was calculated from the percentage of placebo-treated patients that dropped-out due to drug-related adverse events.

Results: Data were extracted from 56 DMT and 44 ST eligible trials. The pooled incidence of nocebo responses was 74.4% (95% CI: 69.92—88.30) in DMT trials and 25.3% (95% CI: 15.24—36.90) in ST trials and was significantly higher in the former ( p < 0.0001). The pooled nocebo severity was 2.1% (95% CI: 1.6—2.67) in DMT and 2.34% (95% CI: 1.54—3.29) in ST trials. Meta-regression analysis revealed a higher nocebo incidence in parallel design ST studies compared to crossover ones ( p = 0.013) and a higher nocebo severity in phase II ST studies compared to phase III ones ( p = 0.0001). Nocebo severity in DMT trials exhibited an association with the year of study publication ( p = 0.011) and the frequency of drug administration ( p = 0.0082).

Conclusions: Nocebo responses in MS trials are substantial and appear to have increased significantly in recent years with important implications for both trial design and clinical practice. Furthermore, nocebo responses exhibit an association with medication and trial-related factors.
Response to interferon in multiple sclerosis is related to lipid-specific oligoclonal IgM bands
Authors: Bosca I. , Villar LM , Coret F. , Magraner MJ , Simó-Castelló M. , Alvarez-Cermeño JC , Casanova B.
Published: June 2010

The objective of this study was to investigate whether the presence of lipid-specific oligoclonal IgM bands (LS-OCMB) in cerebrospinal fluid (CSF) influences the response to treatment with beta-interferon in relapsing—remitting multiple sclerosis (RRMS) patients. We performed a collaborative prospective study including RRMS patients with brain MRI and LS-OCMB studies performed before starting interferon treatment. The primary endpoint was the risk of having a relapse after treatment initiation. Secondary endpoints included relapse rate, relapse-rate reduction, proportion of relapse-free patients and proportion of patients with sustained disability increase during follow-up. One-hundred and two patients were included. After a mean follow-up of 37.4 months, the risk of suffering a relapse was two-fold higher in patients with LS-OCMB (hazard ratio 2.0, 95% confidence interval 1.1—3.8). LS-OCMB+ patients showed lower reduction in relapse rate (51.8% versus 80.8%; p < 0.0001), higher relapse rate in the first year (0.8 versus 0.2; p = 0.001), lower proportion of relapse-free patients (25% versus 61.3%; p = 0.003), and higher proportion of patients with sustained 1.0 increase in the Expanded Disability Status Score (45% versus 12.9%; p = 0.0003). In conclusion, LS-OCMB can have an influence on the response to interferon treatment in RRMS patients. They could be used as a biological marker to predict high inflammatory activity after treatment.
Training for Public Information Officers in Communication to Reduce Health Disparities: A Needs Assessment
Authors: Golding Lenette , Rubin Donald
Published: June 2010

Government public information officers and risk communicators bear the burden for reaching all Americans with public health and emergency messages. To assess needs specifically regarding communication to reduce health disparities, an Internet survey is made available to members of the National Public Health Information Coalition. Respondents are asked to rate their own needs at their level of organizational responsibility as well as the needs of staff whom they may be supervising on 25 communication and cultural competencies. Multicultural understanding, culturally appropriate message development, and ways to better collaborate with diverse populations are identified as communication competencies in which more training is especially needed.
Stent Grafting a Ruptured Para-Anastomotic Iliac Aneurysm
Authors: Menke Vivianda , Castenmiller Peter H. , Versteijlen Rob J. , Van der Laan Lijckle
Published: June 2010

In this case report, we present an 83-year-old man with a ruptured para-anastomotic aneurysm who underwent a stent graft in spite of his condition of acute shock. Our patient presented at the emergency room (ER) with acute abdominal pain. Shortly after arrival, he collapsed because of a ruptured para-anastomotic aneurysm after the previous aorto-bi-iliac aneurysm repair in 1984. He was charged with a cardiac history that made him unsuitable for surgery. We chose for resuscitation followed by inflation of an aortic balloon that made the patient hemodynamically stable. He then underwent iliac stent grafting and was discharged from the hospital at 22 days after the procedure. The mortality rate of patients with a ruptured para-anastomotic aortic aneurysm arriving at hospital ranges from 32% to 70%. Endovascular stent placement for ruptured iliac aneurysmal arteries can be a safe treatment in selected patients.
Cryo Perforator Surgery With a Diamond Dust-Coated Cryoprobe
Authors: Leonardus Klem Taco Marius Adrianus , van der Ham Arie , van Brussel Jerome , Wittens Cees
Published: June 2010

This study was conducted to determine the efficacy of cryoperforator surgery in the treatment of incompetent perforating veins with a diamond dust coated cryoprobe. Eleven patients with clinical severity class C2-C4 were enrolled in this study. Under local anesthesia, incompetent perforating veins were duplex guided treated with a diamond dust coated cryoprobe. Duplex scan was performed 4 weeks after treatment. Eleven patients with 15 incompetent perforating veins were treated with cryoperforator surgery. Distribution of incompetent perforating veins was as follows: thigh perforator, 6; leg perforators, 9. Median diameter was 4mm (range = 2.0—6.2 mm). Follow-up showed successful treatment of 3 incompetent perforating veins (20%). Distribution of perforating veins in successful treatment: thigh perforator, 1; leg perforator, 2. This study showed that cryoperforator surgery is not feasible for treatment of incompetent perforating veins. The procedure is difficult and painful with a disturbing success rate and it should be considered obsolete.
Medication Adherence and Its Connection With Depression and Lifestyle Medicine
Authors: Lenz Thomas L.
Published: June 2010

Depression is the leading cause of disability in the United States. Research has shown that exercise can improve the symptoms associated with depression, in part by influencing many of the same chemicals that antidepressants do, such as serotonin, dopamine, and norepinephrine. Medication adherence research shows that patients who are depressed are less likely than nondepressed patients to adhere to their drug therapy, even for medications that are not related to depression. It is presumable, then, that patients with depression may have difficulty adhering to their healthy lifestyle behaviors as well. The purpose of this article is to discuss medication adherence and its possible effects on the management of depression and lifestyle medicine activities as well as the role that pharmacists have in adherence to lifestyle medicine activities.
Bronchoscopic lung volume reduction with a dedicated coil: a clinical pilot study
Authors: Herth Felix JF. , Eberhard Ralf , Gompelmann Daniela , Slebos Dirk-Jan , Ernst Armin
Published: June 2010

Background: Lung volume reduction aims to improve symptoms by reducing hyperinflation. Endoscopic approaches so far have generally been hampered in their efficacy by collateral ventilation (CV). We sought to determine the safety and feasibility of a new endoscopic lung volume reduction approach independent of the effects of CV.

Methods: Patients with severe emphysema were eligible. Inclusion and exclusion criteria were modeled after the National Emphysema Treatment Trial (NETT) study. Homogenous and heterogeneous disease was allowed. Treatment consisted of the placement of coils into the parenchyma of the most diseased area with the intent of achieving parenchymal compression. Primary endpoints were safety and feasibility assessments. Secondary endpoints were efficacy outcomes.

Results: Eleven patients underwent 21 procedures. Procedures were performed under general anesthesia and lasted 45±15 minutes and per procedure 4.9±0.6 coils were placed. All procedures were well tolerated. The total follow-up time was 7-11 months and in that time 33 adverse events were reported, none of them severe. No pneumothorax occurred. Efficacy seemed better in heterogeneous rather than homogenous disease.

Conclusion: Endoscopic lung volume reduction with coils is safe and feasible. Further studies of the efficacy are indicated.
Bisphosphonates for the treatment of osteoporosis: insights for clinicians
Authors: Lewiecki E. Michael
Published: June 2010

Osteoporosis is a common skeletal disease characterized by a reduction in bone strength and increased risk of fractures. Osteoporotic fractures are associated with substantial morbidity, mortality, and high healthcare costs. Treatments for osteoporosis have been shown to increase bone strength and reduce fracture risk. The drugs most commonly used to treat osteoporosis are bisphosphonates: stable analogs of naturally occurring inorganic pyrophosphate. The bisphosphonates share a common chemical structure with side chain variations that convey differences in their pharmacological properties, such as affinity for bone mineral and inhibitory effect on osteoclastic bone resorption. The clinical profiles of bisphosphonates, such as time of onset and offset of effect, may differ according to these pharmacological properties. Bisphosphonates can be administered orally or intravenously with a wide range of doses and dosing intervals. Randomized placebo-controlled clinical trials have shown that bisphosphonates reduce fracture risk in postmenopausal women with osteoporosis and have a generally excellent safety record. Clinical challenges in using bisphosphonates to treat osteoporosis include appropriate selection of patients for initiating therapy, choosing which bisphosphonate to use, monitoring therapy to assure that medication is taken correctly and the desired effect is achieved, determining when drug discontinuation should be considered, and managing side effects, possible side effects, and fear of side effects. Strategies for treating patients with bisphosphonates should consider each of these issues.
Thymic stromal lymphopoietin from trophoblasts induces dendritic cell–mediated regulatory TH2 bias in the decidua during early gestation in humans
Authors: Guo Pei-Fen , Du Mei-Rong , Wu Hai-Xia , Lin Yi , Jin Li-Ping , Li Da-Jin
Published: June 2010

Thymic stromal lymphopoietins (TSLPs) play critical roles in dendritic cell–mediated immune responses. In this study, we found that human trophoblasts and decidual epithelial cells in maternal-fetal interface of early placentas express TSLP mRNA and protein, but only trophoblast cells secret soluble TSLP. Human decidual CD1c+ DCs (dDCs) highly express the functional TSLP receptor complex TSLP receptor and interleukin-7 receptor-α. Recombinant human TSLP activates CD1C+ decidual DCs and peripheral monocyte-derived DCs with increased costimulatory molecules, major histocompatibility complex class II, and OX-40L. Human TSLP or supernatants from human trophoblasts specifically stimulate dDCs to highly produce interleukin-10 and TH2-attracting chemokine CCL-17. The TSLP-activated dDCs prime decidual CD4+ T cells for TH2 cell differentiation, involved in maternal-fetal immunotolerance. Interestingly, the protein expression of TSLP in normal pregnancy with significant TH2 bias is much higher than that of miscarriage showing TH1 bias at the maternal-fetal interface. Therefore, human trophoblasts may contribute to maternal-fetal tolerance by instructing dDCs to induce regulatory TH2 bias in human early pregnancy via TSLP.
Platelet transcriptional profile and protein expression in patients with systemic lupus erythematosus: up-regulation of the type I interferon system is strongly associated with vascular disease
Authors: Lood Christian , Amisten Stefan , Gullstrand Birgitta , Jönsen Andreas , Allhorn Maria , Truedsson Lennart , Sturfelt Gunnar , Erlinge David , Bengtsson Anders A.
Published: June 2010

Patients with systemic lupus erythematosus (SLE) have a markedly increased risk to develop cardiovascular disease, and traditional cardiovascular risk factors fail to account for this increased risk. We used microarray to probe the platelet transcriptome in patients with SLE and healthy controls, and the gene and protein expression of a subset of differentially expressed genes was further investigated and correlated to platelet activation status. Real-time PCR was used to confirm a type I interferon (IFN) gene signature in patients with SLE, and the IFN-regulated proteins PRKRA, IFITM1 and CD69 (P < .0001) were found to be up-regulated in platelets from SLE patients compared with healthy volunteers. Notably, patients with a history of vascular disease had increased expression of type I IFN-regulated proteins as well as more activated platelets compared with patients without vascular disease. We suggest that interferogenic immune complexes stimulate production of IFNα that up-regulates the megakaryocytic type I IFN-regulated genes and proteins. This could affect platelet activation and contribute to development of vascular disease in SLE. In addition, platelets with type I IFN signature could be a novel marker for vascular disease in SLE.
A revised model for the secretion of tPA and cytokines from cultured endothelial cells
Authors: Knipe Laura , Meli Athinoula , Hewlett Lindsay , Bierings Ruben , Dempster John , Skehel Paul , Hannah Matthew J. , Carter Tom
Published: June 2010

Endothelial cells are reported to contain several distinct populations of regulated secretory organelles, including Weibel-Palade bodies (WPBs), the tissue plasminogen activator (tPA) organelle, and the type-2 chemokine-containing organelle. We show that the tPA and type-2 organelles in human endothelial cells represent a single compartment primarily responsible for unstimulated secretion of tPA or, in cells exposed to interleukin-1β (IL-1β), the cytokines IL-8, IL-6, monocyte chemoattractant protein-1 (MCP-1), and growth-regulated oncogene-α (GRO-α). This compartment was distinct from WPBs in that it lacked detectable von Willebrand factor, P-selectin, Rab27a, or CD63 immunoreactivity, displayed no time-dependent decrease in intragranule pH, underwent detectable unstimulated exocytosis, and was very poorly responsive to Ca2+-elevating secretagogues. WPBs could also contain tPA, and in IL-1β–treated cells, IL-8, IL-6, MCP-1, and GRO-α, and were the primary source for histamine or ionomycin-stimulated secretion of these molecules. However, analysis of the storage efficiency of cytokines and tPA revealed that all were very poorly stored compared with von Willebrand factor. The nonmammalian, nonsecretory protein EGFP, when expressed in the secretory pathway, also entered WPBs and had a storage efficiency similar to tPA and the cytokines tested. Based on these data, we proposed a revised model for storage and secretion of cytokines and tPA.
Comparable survival after HLA-well-matched unrelated or matched sibling donor transplantation for acute myeloid leukemia in first remission with unfavorable cytogenetics at diagnosis
Authors: Gupta Vikas , Tallman Martin S. , He Wensheng , Logan Brent R. , Copelan Edward , Gale Robert Peter , Khoury Hanna J. , Klumpp Thomas , Koreth John , Lazarus Hillard M. , Marks David I. , Martino Rodrigo , Rizzieri David A. , Rowe Jacob M. , Sabloff Mitchell , Waller Edmund K. , DiPersio John F. , Bunjes Donald W. , Weisdorf Daniel J.
Published: June 2010

We compared the outcomes of unrelated donor (URD, n = 358) with human leukocyte antigen (HLA)–matched sibling donor (MSD, n = 226) transplantations in patients with acute myeloid leukemia (AML) in first complete remission (CR1) having unfavorable cytogenetics at diagnosis. Unfavorable cytogenetic abnormalities were: complex (≥ 3 abnormalities), 32%; and noncomplex involving chromosome 7, 25%; chromosome 5, 9%; 11q or MLL rearrangements, 18%; t(6;9), 5%; and other noncomplex, 10%. URDs were HLA-well-matched (n = 254; 71%) or partially-matched (n = 104; 29%). Three-year leukemia-free survival (LFS) for MSD was 42% (95% confidence interval [CI], 35%-48%) compared with 34% (95% CI, 28%-41%) for HLA-well-matched URD and 29% (95% CI, 20%-39%) for partially-matched URD (P = .08). In multivariate analysis, HLA-well-matched URD and MSD yielded similar LFS (relative risk [RR] = 1.1, 95% CI, 0.86-1.40, P = .44) and overall survival (OS; RR = 1.06, 95% CI, 0.83-1.37, P = .63). LFS and OS were significantly inferior for HLA-partially-matched URD recipients, those with prior myelodysplastic syndrome, and those older than 50 years. All cytogenetic cohorts had similar outcomes. Patients with chronic graft-versus-host disease had a significantly lower risk of relapse (RR = 0.68, 95% CI, 0.47-0.99, P = .05). Hematopoietic cell transplantation (HCT) using HLA-well-matched URD and MSD resulted in similar LFS and OS in AML patients in CR1 with unfavorable cytogenetics. Outcomes of HCT from HLA-partially- matched URD were inferior.
Revised diagnostic criteria and classification for the autoimmune lymphoproliferative syndrome (ALPS): report from the 2009 NIH International Workshop
Authors: Oliveira Joao B. , Bleesing Jack J. , Dianzani Umberto , Fleisher Thomas A. , Jaffe Elaine S. , Lenardo Michael J. , Rieux-Laucat Frederic , Siegel Richard M. , Su Helen C. , Teachey David T. , Rao V. Koneti
Published: June 2010

Lymphadenopathy in children for which no infectious or malignant cause can be ascertained constitutes a challenging diagnostic dilemma. Autoimmune lymphoproliferative syndrome (ALPS) is a human genetic disorder of lymphocyte apoptosis resulting in an accumulation of lymphocytes and childhood onset chronic lymphadenopathy, splenomegaly, multilineage cytopenias, and an increased risk of B-cell lymphoma. In 1999, investigators at the National Institutes of Health (NIH) suggested criteria to establish the diagnosis of ALPS. Since then, with approximately 500 patients with ALPS studied worldwide, significant advances in our understanding of the disease have prompted the need for revisions to the existing diagnostic criteria and classification scheme. The rationale and recommendations outlined here stem from an international workshop held at NIH on September 21 and 22, 2009, attended by investigators from the United States, Europe, and Australia engaged in clinical and basic science research on ALPS and related disorders. It is hoped that harmonizing the diagnosis and classification of ALPS will foster collaborative research and better understanding of the pathogenesis of autoimmune cytopenias and B-cell lymphomas.
Molecular genetic analysis of a cattle population to reconstitute the extinct Algarvia breed
Authors: Ginja Catarina , Penedo Maria CT , Sobral Maria F , Matos José , Borges Carla , Neves Dina , Rangel-Figueiredo Teresa , Cravador Alfredo
Published: June 2010

Background

Decisions to initiate conservation programmes need to account for extant variability, diversity loss and cultural and economic aspects. Molecular markers were used to investigate if putative Algarvia animals could be identified for use as progenitors in a breeding programme to recover this nearly extinct breed.

Methods

46 individuals phenotypically representative of Algarvia cattle were genotyped for 27 microsatellite loci and compared with 11 Portuguese autochthonous and three imported breeds. Genetic distances and factorial correspondence analyses (FCA) were performed to investigate the relationship among Algarvia and related breeds. Assignment tests were done to identify representative individuals of the breed. Y chromosome and mtDNA analyses were used to further characterize Algarvia animals. Gene- and allelic-based conservation analyses were used to determine breed contributions to overall genetic diversity.

Results

Genetic distance and FCA results confirmed the close relationship between Algarvia and southern Portuguese breeds. Assignment tests without breed information classified 17 Algarvia animals in this cluster with a high probability (q > 0.95). With breed information, 30 cows and three bulls were identified (q > 0.95) that could be used to reconstitute the Algarvia breed. Molecular and morphological results were concordant. These animals showed intermediate levels of genetic diversity (MNA = 6.0 ± 1.6, Rt = 5.7 ± 1.4, Ho = 0.63 ± 0.19 and He = 0.69 ± 0.10) relative to other Portuguese breeds. Evidence of inbreeding was also detected (Fis = 0.083, P < 0.001). The four Algarvia bulls had Y-haplotypes H6Y2 and H11Y2, common in Portuguese cattle. The mtDNA composition showed prevalence of T3 matrilines and presence of the African-derived T1a haplogroup. This analysis confirmed the genetic proximity of Algarvia and Garvonesa breeds (Fst = 0.028, P > 0.05). Algarvia cattle provide an intermediate contribution (CB = 6.18, CW = -0.06 and D1 = 0.50) to the overall gene diversity of Portuguese cattle. Algarvia and seven other autochthonous breeds made no contribution to the overall allelic diversity.

Conclusions

Molecular analyses complemented previous morphological findings to identify 33 animals that can be considered remnants of the Algarvia breed. Results of genetic diversity and conservation analyses provide objective information to establish a management program to reconstitute the Algarvia breed.
Comparative mitogenomics of Braconidae (Insecta: Hymenoptera) and the phylogenetic utility of mitochondrial genomes with special reference to Holometabolous insects
Authors: Wei Shu-jun , Shi Min , Sharkey Michael J , van Achterberg Cornelis , Chen Xue-xin
Published: June 2010

Background

Animal mitochondrial genomes are potential models for molecular evolution and markers for phylogenetic and population studies. Previous research has shown interesting features in hymenopteran mitochondrial genomes. Here, we conducted a comparative study of mitochondrial genomes of the family Braconidae, one of the largest families of Hymenoptera, and assessed the utility of mitochondrial genomic data for phylogenetic inference at three different hierarchical levels, i.e., Braconidae, Hymenoptera, and Holometabola.

Results

Seven mitochondrial genomes from seven subfamilies of Braconidae were sequenced. Three of the four sequenced A+T-rich regions are shown to be inverted. Furthermore, all species showed reversal of strand asymmetry, suggesting that inversion of the A+T-rich region might be a synapomorphy of the Braconidae. Gene rearrangement events occurred in all braconid species, but gene rearrangement rates were not taxonomically correlated. Most rearranged genes were tRNAs, except those ofCotesia vestalis, in which 13 protein-coding genes and 14 tRNA genes changed positions or/and directions through three kinds of gene rearrangement events. Remote inversion is posited to be the result of two independent recombination events. Evolutionary rates were lower in species of the cyclostome group than those of noncyclostomes. Phylogenetic analyses based on complete mitochondrial genomes and secondary structure ofrrnSsupported a sister-group relationship between Aphidiinae and cyclostomes. Many well accepted relationships within Hymenoptera, such as paraphyly of Symphyta and Evaniomorpha, a sister-group relationship between Orussoidea and Apocrita, and monophyly of Proctotrupomorpha, Ichneumonoidea and Aculeata were robustly confirmed. New hypotheses, such as a sister-group relationship between Evanioidea and Aculeata, were generated. Among holometabolous insects, Hymenoptera was shown to be the sister to all other orders. Mecoptera was recovered as the sister-group of Diptera. Neuropterida (Neuroptera + Megaloptera), and a sister-group relationship with (Diptera + Mecoptera) were supported across all analyses.

Conclusions

Our comparative studies indicate that mitochondrial genomes are a useful phylogenetic tool at the ordinal level within Holometabola, at the superfamily within Hymenoptera and at the subfamily level within Braconidae. Variation at all of these hierarchical levels suggests that the utility of mitochondrial genomes is likely to be a valuable tool for systematics in other groups of arthropods.
In planta gene expression analysis of Xanthomonas oryzae pathovar oryzae, African strain MAI1
Authors: Soto-Suárez Mauricio , Bernal Diana , González Carolina , Szurek Boris , Guyot Romain , Tohme Joe , Verdier Valérie
Published: June 2010

Background

Bacterial leaf blight causes significant yield losses in rice crops throughout Asia and Africa. Although both the Asian and African strains of the pathogen, Xanthomonas oryzae pv. oryzae (Xoo), induce similar symptoms, they are nevertheless genetically different, with the African strains being more closely related to the Asian X. oryzae pv. oryzicola (Xoc).

Results

Changes in gene expression of the African Xoo strain MAI1 in the susceptible rice cultivar Nipponbare were profiled, using an SSH Xoo DNA microarray. Microarray hybridization was performed comparing bacteria recovered from plant tissues at 1, 3, and 6 days after inoculation (dai) with bacteria grown in vitro. A total of 710 bacterial genes were found to be differentially expressed, with 407 up-regulated and 303 down-regulated. Expression profiling indicated that less than 20% of the 710 bacterial transcripts were induced in the first 24 h after inoculation, whereas 63% were differentially expressed at 6 dai. The 710 differentially expressed genes were one-end sequenced. 535 sequences were obtained from which 147 non-redundant sequences were identified. Differentially expressed genes were related to metabolism, secretion and transport, pathogen adherence to plant tissues, plant cell-wall degradation, IS elements, and virulence. In addition, various other genes encoding proteins with unknown function or showing no similarity to other proteins were also induced. The Xoo MAI1 non-redundant set of sequences was compared against several X. oryzae genomes, revealing a specific group of genes that was present only in MAI1. Numerous IS elements were also found to be differentially expressed. Quantitative real-time PCR confirmed 86% of the identified profile on a set of 14 genes selected according to the microarray analysis.

Conclusions

This is the first report to compare the expression of Xoo genes in planta across different time points during infection. This work shows that as-yet-unidentified and potentially new virulence factors are appearing in an emerging African pathogen. It also confirms that African Xoo strains do differ from their Asian counterparts, even at the transcriptional level.
Intricate environment-modulated genetic networks control isoflavone accumulation in soybean seeds
Authors: Gutierrez-Gonzalez Juan J , Wu Xiaolei , Gillman Jason D , Lee Jeong-Dong , Zhong Rui , Yu Oliver , Shannon Grover , Ellersieck Mark , Nguyen Henry T , Sleper David A
Published: June 2010

Background

Soybean (Glycine max [L] Merr.) seed isoflavones have long been considered a desirable trait to target in selection programs for their contribution to human health and plant defense systems. However, attempts to modify seed isoflavone contents have not always produced the expected results because their genetic basis is polygenic and complex. Undoubtedly, the extreme variability that seed isoflavones display over environments has obscured our understanding of the genetics involved.

Results

In this study, a mapping population of RILs with three replicates was analyzed in four different environments (two locations over two years). We found a total of thirty-five main-effect genomic regions and many epistatic interactions controlling genistein, daidzein, glycitein and total isoflavone accumulation in seeds. The use of distinct environments permitted detection of a great number of environment-modulated and minor-effect QTL. Our findings suggest that isoflavone seed concentration is controlled by a complex network of multiple minor-effect loci interconnected by a dense epistatic map of interactions. The magnitude and significance of the effects of many of the nodes and connections in the network varied depending on the environmental conditions. In an attempt to unravel the genetic architecture underlying the traits studied, we searched on a genome-wide scale for genomic regions homologous to the most important identified isoflavone biosynthetic genes. We identified putative candidate genes for several of the main-effect and epistatic QTL and for QTL reported by other groups.

Conclusions

To better understand the underlying genetics of isoflavone accumulation, we performed a large scale analysis to identify genomic regions associated with isoflavone concentrations. We not only identified a number of such regions, but also found that they can interact with one another and with the environment to form a complex adaptable network controlling seed isoflavone levels. We also found putative candidate genes in several regions and overall we advanced the knowledge of the genetics underlying isoflavone synthesis.
Incidence of chemotherapy-induced amenorrhea associated with epirubicin, docetaxel and navelbine in younger breast cancer patients
Authors: Zhou Wen-Bin , Yin Hong , Liu Xiao-An , Zha Xiao-Ming , Chen Lin , Dai Jun-Cheng , Tao Ai-di , Chen Ling , Ma Jing-Jing , Ling Li-Jun , Wang Shui
Published: June 2010

Background

The rates of chemotherapy-induced amenorrhea (CIA) associated with docetaxel-based regimens reported by previous studies are discordant. For navelbine-based chemotherapies, rates of CIA have seldom been reported.

Methods

Of 170 premenopausal patients recruited between January 2003 and September 2008, 78 were treated with fluorouracil plus epirubicin and cyclophosphamide (FEC), 66 were treated with docetaxel plus epirubicin (TE), and 26 were treated with navelbine plus epirubicin (NE). Patient follow-up was carried up every 3-4 months during the first year, then every 9-12 months during subsequent years.

Results

In univariate analysis, the rates of CIA were 44.87% for the FEC regimen, 30.30% for the TE regimen and 23.08% for the NE regimen (P = 0.068). Significant differences in the rates of CIA were not found between the FEC and TE treatment groups (P > 0.05), but were found between the FEC and NE treatment groups (P < 0.05). Furthermore, no significant differences were found between the TE and NE regimens (P > 0.05). Tamoxifen use was a significant predictor for CIA (P = 0.001), and age was also a significant predictor (P < 0.001). In multivariate analysis, age (P < 0.001), the type of chemotherapy regimens (P = 0.009) and tamoxifen use (P = 0.003) were all significant predictors.

Conclusions

Age and administration of tamoxifen were found to be significant predictive factors of CIA, whereas docetaxel and navelbine based regimens were not associated with higher rates of CIA than epirubicin-based regimen.
Identification of three single nucleotide polymorphisms in Anopheles gambiae immune signaling genes that are associated with natural Plasmodium falciparum infection
Authors: Horton Ashley A , Lee Yoosook , Coulibaly Cheick A , Rashbrook Vanessa K , Cornel Anthony J , Lanzaro Gregory C , Luckhart Shirley
Published: June 2010

Background

Laboratory studies have demonstrated that a variety of immune signaling pathways regulate malaria parasite infection inAnopheles gambiae, the primary vector species in Africa.

Methods

To begin to understand the importance of these associations under natural conditions, an association mapping approach was adopted to determine whether single nucleotide polymorphisms (SNPs) in selected immune signaling genes inA. gambiaecollected in Mali were associated with the phenotype ofPlasmodium falciparuminfection.

Results

Three SNPs were identified in field-collected mosquitoes that were associated with parasite infection in molecular form-dependent patterns: two were detected in theToll5Bgene and one was detected in the gene encoding insulin-like peptide 3 precursor. In addition, one infection-associatedToll5BSNP was in linkage disequilibrium with a SNP in sequence encoding a mitogen-activated protein kinase that has been associated with Toll signaling in mammalian cells. BothToll5BSNPs showed divergence from Hardy-Weinberg equilibrium, suggesting that selection pressure(s) are acting on these loci.

Conclusions

Seven of these eight infection-associated and linked SNPs alter codon frequency or introduce non-synonymous changes that would be predicted to alter protein structure and, hence, function, suggesting that these SNPs could alter immune signaling and responsiveness to parasite infection.
Integrative analysis of DNA copy number and gene expression in metastatic oral squamous cell carcinoma identifies genes associated with poor survival
Authors: Xu Chang , Liu Yan , Wang Pei , Fan Wenhong , Rue Tessa C , Upton Melissa P , Houck John R , Lohavanichbutr Pawadee , Doody David R , Futran Neal D , Zhao Lue Ping , Schwartz Stephen M , Chen Chu , Méndez Eduardo
Published: June 2010

Background

Lymphotropism in oral squamous cell carcinoma (OSCC) is one of the most important prognostic factors of 5-year survival. In an effort to identify genes that may be responsible for the initiation of OSCC lymphotropism, we examined DNA copy number gains and losses and corresponding gene expression changes from tumor cells in metastatic lymph nodes of patients with OSCC.

Results

We performed integrative analysis of DNA copy number alterations (CNA) and corresponding mRNA expression from OSCC cells isolated from metastatic lymph nodes of 20 patients using Affymetrix 250 K Nsp I SNP and U133 Plus 2.0 arrays, respectively. Overall, genome CNA accounted for expression changes in 31% of the transcripts studied. Genome region 11q13.2-11q13.3 shows the highest correlation between DNA CNA and expression. With a false discovery rate < 1%, 530 transcripts (461 genes) demonstrated a correlation between CNA and expression. Among these, we found two subsets that were significantly associated with OSCC (n = 122) when compared to controls, and with survival (n = 27), as tested using an independent dataset with genome-wide expression profiles for 148 primary OSCC and 45 normal oral mucosa. We fit Cox models to calculate a principal component analysis-derived risk-score for these two gene sets ('122-' or '27-transcript PC'). The models combining the 122- or 27-transcript PC with stage outperformed the model using stage alone in terms of the Area Under the Curve (AUC = 0.82 or 0.86 vs. 0.72, with p = 0.044 or 0.011, respectively).

Conclusions

Genes exhibiting CNA-correlated expression may have biological impact on carcinogenesis and cancer progression in OSCC. Determination of copy number-associated transcripts associated with clinical outcomes in tumor cells with an aggressive phenotype (i.e., cells metastasized to the lymph nodes) can help prioritize candidate transcripts from high-throughput data for further studies.
Modulation of mu rhythm desynchronization during motor imagery by transcranial direct current stimulation
Authors: Matsumoto Jun , Fujiwara Toshiyuki , Takahashi Osamu , Liu Meigen , Kimura Akio , Ushiba Junichi
Published: June 2010

Background

The mu event-related desynchronization (ERD) is supposed to reflect motor preparation and appear during motor imagery. The aim of this study is to examine the modulation of ERD with transcranial direct current stimulation (tDCS).

Methods

Six healthy subjects were asked to imagine their right hand grasping something after receiving a visual cue. Electroencephalograms (EEGs) were recorded near the left M1. ERD of the mu rhythm (mu ERD) by right hand motor imagery was measured. tDCS (10 min, 1 mA) was used to modulate the cortical excitability of M1. Anodal, cathodal, and sham tDCS were tested in each subject with a randomized sequence on different days. Each condition was separated from the preceding one by more than 1 week in the same subject. Before and after tDCS, mu ERD was assessed. The motor thresholds (MT) of the left M1 were also measured with transcranial magnetic stimulation.

Results

Mu ERD significantly increased after anodal stimulation, whereas it significantly decreased after cathodal stimulation. There was a significant correlation between mu ERD and MT.

Conclusions

Opposing effects on mu ERD based on the orientation of the stimulation suggest that mu ERD is affected by cortical excitability.
Analysis of the vp2 gene sequence of a new mutated mink enteritis parvovirus strain in PR China
Authors: Zuo Jing , Rao Jiahui , Xu Huihui , Ma Liming , Li Bo , Wang Yuping , Cai Xuehui , Han Wenyu , Lei Liancheng , Liu Bin
Published: June 2010

Background

Mink enteritis virus (MEV) causes a highly contagious viral disease of mink with a worldwide distribution. MEV has a linear, single-stranded, negative-sense DNA with a genome length of approximately 5,000 bp. The VP2 protein is the major structural protein of the parvovirus encoded by thevp2 gene. VP2 is highly antigenic and plays important roles in determining viral host ranges and tissue tropisms. This study describes the bionomics andvp2 gene analysis of a mutated strain, MEV-DL, which was isolated recently in China and outlines its homologous relationships with other selected strains registered in Genbank.

Results

The MEV-DL strain can infect F81 cells with cytopathic effects. Pig erythrocytes were agglutinated by the MEV-DL strain. The generation of MEV-DL in F81 cells could infect mink within three months and cause a disease that was similar to that caused by wild-type MEV. A comparative analysis of thevp2 gene nucleotide (nt) sequence of MEV-DL showed that this was more than 99% homologous with other mink enteritis parvoviruses in Genbank. However, the nucleotide residues at positions 1,065 and 1,238 in the MEV-DL strain of thevp2 gene differed from those of all the other MEV strains described previously. It is noteworthy that the mutation at the nucleotide residues position 1,238 led to Asp/Gly replacement. This may lead to structural changes. A phylogenetic tree and sequence distance table were obtained, which showed that the MEV-DL and ZYL-1 strains had the closest inheritance distance.

Conclusions

A new variation of thevp2 gene exists in the MEV-DL strain, which may lead to structural changes of the VP2 protein. Phylogenetic analysis showed that MEV-DL may originate from the ZYL-1 strain in DaLian.
Effect of prolonged exposure to diesel engine exhaust on proinflammatory markers in different regions of the rat brain
Authors: Gerlofs-Nijland Miriam E , van Berlo Damien , Cassee Flemming R , Schins Roel PF , Wang Kate , Campbell Arezoo
Published: June 2010

Background

The etiology and progression of neurodegenerative disorders depends on the interactions between a variety of factors including: aging, environmental exposures, and genetic susceptibility factors. Enhancement of proinflammatory events appears to be a common link in different neurological impairments, including Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and multiple sclerosis. Studies have shown a link between exposure to particulate matter (PM), present in air pollution, and enhancement of central nervous system proinflammatory markers. In the present study, the association between exposure to air pollution (AP), derived from a specific source (diesel engine), and neuroinflammation was investigated. To elucidate whether specific regions of the brain are more susceptible to exposure to diesel-derived AP, various loci of the brain were separately analyzed. Rats were exposed for 6 hrs a day, 5 days a week, for 4 weeks to diesel engine exhaust (DEE) using a nose-only exposure chamber. The day after the final exposure, the brain was dissected into the following regions: cerebellum, frontal cortex, hippocampus, olfactory bulb and tubercles, and the striatum.

Results

Baseline levels of the pro-inflammatory cytokines tumor necrosis factor alpha (TNF-α) and interleukin-1 alpha (IL-1α) were dependent on the region analyzed and increased in the striatum after exposure to DEE. In addition, baseline level of activation of the transcription factors (NF-κB) and (AP-1) was also region dependent but the levels were not significantly altered after exposure to DEE. A similar, though not significant, trend was seen with the mRNA expression levels of TNF-α and TNF Receptor-subtype I (TNF-RI).

Conclusions

Our results indicate that different brain regions may be uniquely responsive to changes induced by exposure to DEE. This study once more underscores the role of neuroinflammation in response to ambient air pollution, however, it is valuable to assess if and to what extent the observed changes may impact the normal function and cellular integrity of unique brain regions.
Combined evaluation of bone marrow aspirate and biopsy is superior in the prognosis of multiple myeloma
Authors: Štifter Sanja , Babarović Emina , Valković Toni , Seili-Bekafigo Irena , Štemberger Christophe , Načinović Antica , Lučin Ksenija , Jonjić Nives
Published: June 2010

Background

Estimation of plasma cell infiltrates in bone marrow aspirates (BMA) and bone marrow biopsy (BMB) is a standard method in the diagnosis and monitoring of multiple myeloma (MM). Plasma cell fraction in the bone marrow is therefore critical for the classification and optimal clinical management of patients with plasma cell dyscrasias. The aim of the study was to compare the percentage of plasma cells obtained by both methods with the patient clinical parameters and survival.

Methods

This retrospective study included BMA and BMB of 59 MM patients. The conventional differential count was determined in BMA to estimate the percentage and cytologic grade of plasma cells. The pattern of neoplastic infiltration and percentage of plasma cells were estimated on CD138 immunostained BMB slides microscopically and by computer-assisted image analysis (CIA).

Results

Significantly higher values of plasma cell infiltrates were observed in pathologist (47.7 ± 24.8) and CIA (44.1 ± 30.6) reports in comparison with cytologist analysis (30.6 ± 17.1; P < 0.001 and P < 0.0048, respectively). BMB assessment by pathologist counting and using CIA showed strongest correlation (r = 0.8; P < 0.0001). Correlation was also observed between the pathologist and cytologist counts (r = 0.321; P = 0.015) as well as comparing the percentage of plasma cells in BMA and CIA (r = 0.27; P = 0.05). Patients with clinical stage I/II had a significantly lower CIA plasma cell count than those with clinical stage III (P = 0.008). Overall survival was shorter in patients with more than 25% of atypical plasma cell morphology estimated in BMA (P = 0.05) and a higher percentage of tumor cell infiltrates estimated by the pathologist and CIA (P = 0.0341 and P = 0.013, respectively).

Conclusion

Study results suggested the combined analyses to be useful as a routine procedure to achieve more accurate and informative diagnostic data.
Rab-mediated vesicular transport is required for neuronal positioning in the developing Drosophila visual system
Authors: Houalla Tarek , Shi Lei , van Meyel Donald J , Rao Yong
Published: June 2010

Background

The establishment of tissue architecture in the nervous system requires the proper migration and positioning of newly born neurons during embryonic development. Defects in nuclear translocation, a key process in neuronal positioning, are associated with brain diseases such as lissencephaly in humans. Accumulated evidence suggests that the molecular mechanisms controlling neuronal movement are conserved throughout evolution. While the initial events of neuronal migration have been extensively studied, less is known about the molecular details underlying the establishment of neuronal architecture after initial migration.

Results

In a search for novel players in the control of photoreceptor (R cell) positioning in the developing fly visual system, we found that misexpression of the RabGAP RN-Tre disrupted the apical localization of R-cell nuclei. RN-Tre interacts with Rab5 and Rab11 in the fly eye. Genetic analysis shows that Rab5, Shi and Rab11 are required for maintaining apical localization of R-cell nuclei.

Conclusions

We propose that Rab5, Shi and Rab11 function together in a vesicular transport pathway for regulating R-cell positioning in the developing eye.
Immune disease expressed in liver and platelets in an adolescent: a case report
Authors: Antunes Henedina , Rocha Ruben , Silva Nicole , Pontes Teresa , Antunes Ana , Martins Sofia
Published: June 2010

We report a case of a 15-year-old boy with autoimmune hepatitis lacking common serologic markers and normal gammaglobulinemia associated with immune thrombocytopenia and family history of psoriasis. He presented to our department with a 4-year history of a cervical posterior lymphadenopathy and recent petechiae. Previous laboratory results 6 months before already showed hepatocellular injury. After exclusion of other causes, the diagnosis of autoimmune hepatitis was made based on clinical grounds, associated immune disorder and histological features of liver biopsy.

The authors alert for this atypical presentation of autoimmune hepatitis and associated immune thrombocytopenia.
CD4+ lymphocyte adenosine triphosphate determination in sepsis: a cohort study
Authors: Lawrence Kevin L , White Patrick H , Morris Gerald P , Jennemann Jody , Phelan Donna L , Hotchkiss Richard S , Kollef Marin H
Published: June 2010

Introduction

Patients suffering from sepsis are currently classified on a clinical basis (i.e., sepsis, severe sepsis, septic shock); however, this clinical classification may not accurately reflect the overall immune status of an individual patient. Our objective was to describe a cohort of patients with sepsis in terms of their measured immune status.

Methods

Fifty-two patients with sepsis (n = 13), severe sepsis (n = 21), or septic shock (n = 18) were studied. The immune status was determined by measuring the CD4+ lymphocyte adenosine triphosphate (ATP) content after mitogen stimulation in whole blood.

Results

The measured CD4+ lymphocyte ATP content at the time of ICU admission did not differ among the various groups defined by the sepsis classification system (sepsis = 454 ± 79 ng/ml; severe sepsis = 359 ± 54 ng/ml; septic shock = 371 ± 53 ng/ml; P = 0.44). Furthermore, survivors of sepsis had a significantly higher CD4+ lymphocyte ATP content at the time of ICU admission than did nonsurvivors of sepsis (431 ± 41 ng/mL vs. 266 ± 53 ng/mL, respectively; P = 0.04).

Conclusions

The sepsis classification system that is currently used is not representative of the individual immune status as determined by measuring the CD4+ lymphocyte ATP content. Moreover, a lower CD4+ ATP content at the time of ICU admission is associated with a worse clinical outcome in those suffering from sepsis.