bluuebunny/crossref_metadata_2025 huggingface dataset:
Treatment of Sexual-Orientation Obsessions in Obsessive-Compulsive Disorder Using Exposure and Ritual Prevention
Authors: Williams Monnica T. , Crozier Marjorie , Powers Mark
Published: January 2011

Presented is a case report of exposure and ritual prevention (EX/RP) therapy administered to a 51-year-old, White, heterosexual male with sexual-orientation obsessions in obsessive-compulsive disorder (OCD). The patient had been previously treated with pharmacotherapy, resulting in inadequate symptom reduction and unwanted side effects. OCD symptoms included anxiety about the possibility of becoming gay, mental reassurance, and avoidance of other men, which resulted in depressive symptoms and marital distress. The patient received 17 EX/RP sessions, administered twice per week. The effect of treatment was evaluated using standardized rating instruments and self-monitoring by the patient. OCD symptoms on the Yale-Brown Obsessive Compulsive Scale (YBOCS) fell from 24 at intake to 3 at posttreatment and to 4 at a 6-week follow-up, indicating minimal symptoms. Improvement also occurred in mood, quality of life, and social adjustment. Issues concerning the assessment and treatment of homosexuality-themed obsessions in OCD are highlighted and discussed.
Functional Assessment and Behavioral Treatment of Skin Picking in a Teenage Girl With Prader-Willi Syndrome
Authors: Radstaake Maartje , Didden Robert , Bolio Marjolein , Lang Russell , Lancioni Giulio E. , Curfs Leopold M. G.
Published: January 2011

Skin picking is common in individuals with Prader-Willi Syndrome (PWS) but few treatment studies exist. This study reports the successful functional behavioral assessment (FBA) and treatment of skin picking in a 16-year-old female with PWS. A treatment package based on FBA results consisted of differential reinforcement for alternative and incompatible behavior, self-evaluation of progress, and reinforcement for weekly progress and participation in treatment. Pictures of wounds resulting from skin picking were taken during treatment. A total of 30 pictures were randomly selected and shown in a random order to 16 individuals unfamiliar with the study. The individuals then rated severity of the wounds displayed in the pictures. Pearson’s χ2 was used to assess changes in the ratings of severity during the course of treatment, and significant results indicate improvement over the course of intervention, χ 2(1) = 246.6, p < .001. This study adds to the very small literature on treatment of skin picking in people with PWS.
Smoking counseling practices of physicians in the United Arab Emirates
Authors: Awad Manal A. , El Kouatly Mona , Fakhry Randa
Published: January 2011

Background. Despite the cost effectiveness of physician smoking cessation counseling, many physicians do not adhere to current clinical practice guidelines. Methods. A cross-sectional mail survey was conducted in a sample of general practitioners in the United Arab Emirates (UAE), emirates of Sharjah, Dubai and Abu Dhabi, to document cessation-counseling practices and identify correlates of these activities. Results. Of 391 eligible GPs, 218 (56%) completed the questionnaire. Despite favorable beliefs/attitudes about cessation counseling, less than half of GPs (47%) indicated that they have the skills to help their patients quit smoking and only 24% knew of community resources to refer patients to. GPs who perceived physician barriers in offering smoking counseling as very important were significantly less likely to ascertain smoking status of most of their patients (OR: 0.28, 95% CI: 0.09,0.88). Moreover, high self-efficacy and favorable beliefs/attitudes were significantly associated with high level of counseling completeness (OR: 4.44, 95% CI: 1.21, 16.37; OR: 3.78, 95% CI: 1.25, 11.35; respectively). Conclusion. Support, training and intervention programs to overcome lack of awareness and knowledge, unfavorable beliefs/attitudes, and low self-efficacy could increase and enhance cessation-counseling practices among general practitioners in the UAE.
Why we need success stories in reporting the health of Australian Aboriginal and Torres Strait Islander peoples: a personal perspective
Authors: Ritchie Jan
Published: January 2011

A recent workshop reporting on success stories in addressing the appalling ill-health of Australian Aboriginal and Torres Strait peoples has resulted in a report which is now available to visitors of the IUHPE website. This commentary presents a personal perspective on the importance of highlighting success after decades of negative reporting.
Inhibition of immune activation by a novel nuclear factor-kappa B inhibitor in HTLV-I–associated neurologic disease
Authors: Oh Unsong , McCormick Matthew J. , Datta Dibyadeep , Turner Richard V. , Bobb Kathryn , Monie Dileep D. , Sliskovic D. Robert , Tanaka Yuetsu , Zhang Jie , Meshulam Jeffrey , Jacobson Steven
Published: January 2011

The human T-lymphotropic virus type I (HTLV-I) causes a chronic inflammatory disorder of the central nervous system termed HTLV-I–associated myelopathy/tropical spastic paraparesis (HAM/TSP). HTLV-I encodes a protein known to activate several host-signaling pathways involved in inflammation, such as the nuclear factor-κB (NF-κB). The contribution of the NF-κB pathway to the pathogenesis of HAM/TSP, however, has not been fully defined. We show evidence of canonical NF-κB activation in short-term cultures of peripheral blood mononuclear cells (PBMCs) from subjects with HAM/TSP. NF-κB activation was closely linked to HTLV-I viral protein expression. The NF-κB activation in HAM/TSP PBMCs was reversed by a novel small-molecule inhibitor that demonstrates potent and selective NF-κB antagonist activity. Inhibition of NF-κB activation led to a reduction in the expression of lymphocyte activation markers and resulted in reduced cytokine signaling in HAM/TSP PBMCs. Furthermore, NF-κB inhibition led to a reduction in spontaneous lymphoproliferation, a key ex vivo correlate of the immune activation associated with HAM/TSP. These results indicate that NF-κB activation plays a critical upstream role in the immune activation of HAM/TSP, and identify the NF-κB pathway as a potential target for immunomodulation in HAM/TSP.
Robust joint analysis allowing for model uncertainty in two-stage genetic association studies
Authors: Pan Dongdong , Li Qizhai , Jiang Ningning , Liu Aiyi , Yu Kai
Published: January 2011

Background

The cost efficient two-stage design is often used in genome-wide association studies (GWASs) in searching for genetic loci underlying the susceptibility for complex diseases. Replication-based analysis, which considers data from each stage separately, often suffers from loss of efficiency. Joint test that combines data from both stages has been proposed and widely used to improve efficiency. However, existing joint analyses are based on test statistics derived under an assumed genetic model, and thus might not have robust performance when the assumed genetic model is not appropriate.

Results

In this paper, we propose joint analyses based on two robust tests, MERT and MAX3, for GWASs under a two-stage design. We developed computationally efficient procedures and formulas for significant level evaluation and power calculation. The performances of the proposed approaches are investigated through the extensive simulation studies and a real example. Numerical results show that the joint analysis based on the MAX3 test statistic has the best overall performance.

Conclusions

MAX3 joint analysis is the most robust procedure among the considered joint analyses, and we recommend using it in a two-stage genome-wide association study.
TEAD1-dependent expression of the FoxO3a gene in mouse skeletal muscle
Authors: Qiu Haifang , Wang Fengli , Liu Chuxin , Xu Xuewen , Liu Bang
Published: January 2011

Background

TEAD1 (TEA domain family member 1) is constitutively expressed in cardiac and skeletal muscles. It acts as a key molecule of muscle development, and trans-activates multiple target genes involved in cell proliferation and differentiation pathways. However, its target genes in skeletal muscles, regulatory mechanisms and networks are unknown.

Results

In this paper, we have identified 136 target genes regulated directly by TEAD1 in skeletal muscle using integrated analyses of ChIP-on-chip. Most of the targets take part in the cell process, physiology process, biological regulation metabolism and development process. The targets also play an important role in MAPK, mTOR, T cell receptor, JAK-STAT, calcineurin and insulin signaling pathways. TEAD1 regulates foxo3a transcription through binding to the M-CAT element in foxo3a promoter, demonstrated with independent ChIP-PCR, EMSA and luciferase reporter system assay. In addition, results of over-expression and inhibition experiments suggest that foxo3a is positively regulated by TEAD1.

Conclusions

Our present data suggests that TEAD1 plays an important role in the regulation of gene expression and different signaling pathways may co-operate with each other mediated by TEAD1. We have preliminarily concluded that TEAD1 may regulate FoxO3a expression through calcineurin/MEF2/NFAT and IGF-1/PI3K/AKT signaling pathways in skeletal muscles. These findings provide important clues for further analysis of the role of FoxO3a gene in the formation and transformation of skeletal muscle fiber types.
Targeting choroid plexus epithelia and ventricular ependyma for drug delivery to the central nervous system
Authors: Gonzalez Ana Maria , Leadbeater Wendy E , Burg Michael , Sims Karen , Terasaki Tetsuya , Johanson Conrad E , Stopa Edward G , Eliceiri Brian P , Baird Andrew
Published: January 2011

Background

Because the choroid plexus (CP) is uniquely suited to control the composition of cerebrospinal fluid (CSF), there may be therapeutic benefits to increasing the levels of biologically active proteins in CSF to modulate central nervous system (CNS) functions. To this end, we sought to identify peptides capable of ligand-mediated targeting to CP epithelial cells reasoning that they could be exploited to deliver drugs, biotherapeutics and genes to the CNS.

Methods

A peptide library displayed on M13 bacteriophage was screened for ligands capable of internalizing into CP epithelial cells by incubating phage with CP explants for 2 hours at 37C and recovering particles with targeting capacity.

Results

Three peptides, identified after four rounds of screening, were analyzed for specific and dose dependant binding and internalization. Binding was deemed specific because internalization was prevented by co-incubation with cognate synthetic peptides. Furthermore, after i.c.v. injection into rat brains, each peptide was found to target phage to epithelial cells in CP and to ependyma lining the ventricles.

Conclusion

These data demonstrate that ligand-mediated targeting can be used as a strategy for drug delivery to the central nervous system and opens the possibility of using the choroid plexus as a portal of entry into the brain.
Application of Weibull model for survival of patients with gastric cancer
Authors: Zhu Hui P , Xia Xin , Yu Chuan H , Adnan Ahmed , Liu Shun F , Du Yu K
Published: January 2011

Background

Researchers in the medical sciences prefer employing Cox model for survival analysis. In some cases, however, parametric methods can provide more accurate estimates. In this study, we used Weibull model to analyze the prognostic factors in patients with gastric cancer and compared with Cox.

Methods

We retrospectively studied 1715 patients with gastric cancer. Age at diagnosis, gender, family history, past medical history, tumor location, tumor size, eradicative degree of surgery, depth of tumor invasion, combined evisceration, pathologic stage, histologic grade and lymph node status were chosen as potential prognostic factors. Weibull and Cox model were performed with hazard rate and Akaike Information Criterion (AIC) to compare the efficiency of models.

Results

The results from both Weibull and Cox indicated that patients with the past history of having gastric cancer had the risk of death increased significantly followed by poorly differentiated or moderately differentiated in histologic grade. Eradicative degree of surgery, pathologic stage, depth of tumor invasion and tumor location were also identified as independent prognostic factors found significant. Age was significant only in Weibull model.

Conclusion

From the results of multivariate analysis, the data strongly supported the Weibull can elicit more precise results as an alternative to Cox based on AIC.
Becoming and staying physically active in adolescents with cerebral palsy: protocol of a qualitative study of facilitators and barriers to physical activity
Authors: Claassen Aniek AOM , Gorter Jan Willem , Stewart Debra , Verschuren Olaf , Galuppi Barbara E , Shimmell Lorie J
Published: January 2011

Background

Adolescents with cerebral palsy (CP) show a reduced physical activity (PA). Currently there are no interventions for adolescents with CP in this critical life phase that optimise and maintain the individuals' physical activity in the long term. To develop such a program it is important to fully understand the factors that influence physical activity behaviours in adolescents with CP. The aim of this study is to explore what makes it easy or hard for adolescents with CP to be and to become physically active.

Methods/Design

A qualitative research method is chosen to allow adolescents to voice their own opinion. Because we will investigate the lived experiences this study has a phenomenological approach. Thirty ambulatory and non-ambulatory adolescents (aged 10-18 years) with CP, classified as level I to IV on the Gross Motor Function Classification System and 30 parents of adolescents with CP will be invited to participate in one of the 6 focus groups or an individual interview. Therapists from all Children's Treatment Centres in Ontario, Canada, will be asked to fill in a survey. Focus groups will be audio- and videotaped and will approximately take 1.5 hours. The focus groups will be conducted by a facilitator and an assistant. In preparation of the focus groups, participants will fill in a demographic form with additional questions on physical activity. The information gathered from these questions and recent research on barriers and facilitators to physical activity will be used as a starting point for the content of the focus groups. Recordings of the focus groups will be transcribed and a content analysis approach will be used to code the transcripts. A preliminary summary of the coded data will be shared with the participants before themes will be refined.

Discussion

This study will help us gain insight and understanding of the participants' experiences and perspectives in PA, which can be of great importance when planning programs aimed at helping them to stay or to become physically active.
Does directly observed therapy (DOT) reduce drug resistant tuberculosis?
Authors: Moonan Patrick K , Quitugua Teresa N , Pogoda Janice M , Woo Gary , Drewyer Gerry , Sahbazian Behzad , Dunbar Denise , Jost Kenneth C , Wallace Charles , Weis Stephen E
Published: January 2011

Background

Directly observed therapy (DOT) is a widely recommended and promoted strategy to manage tuberculosis (TB), however, there is still disagreement about the role of DOT in TB control and the impact it has on reducing the acquisition and transmission of drug resistant TB. This study compares the portion of drug resistant genotype clusters, representing recent transmission, within and between communities implementing programs differing only in their directly observed therapy (DOT) practices.

Methods

Genotype clusters were defined as 2 or more patient members with matching IS6110 restriction fragment length polymorphism (RFLP) and spoligotype patterns from all culture-positive tuberculosis cases diagnosed between January 1, 1995 and December 31, 2001. Logistic regression was used to compute maximum-likelihood estimates of odds ratios (ORs) and 95% confidence intervals (CIs) comparing cluster members with and without drug resistant isolates. In the universal DOT county, all patients received doses under direct observation of health department staff; whereas in selective DOT county, the majority of received patients doses under direct observation of health department staff, while some were able to self-administer doses.

Results

Isolates from 1,706 persons collected during 1,721 episodes of tuberculosis were genotyped. Cluster members from the selective DOT county were more than twice as likely than cluster members from the universal DOT county to have at least one isolate resistant to isoniazid, rifampin, and/or ethambutol (OR = 2.3, 95% CI: 1.7, 3.1). Selective DOT county isolates were nearly 5 times more likely than universal DOT county isolates to belong to clusters with at least 2 resistant isolates having identical resistance patterns (OR = 4.7, 95% CI: 2.9, 7.6).

Conclusions

Universal DOT for tuberculosis is associated with a decrease in the acquisition and transmission of resistant tuberculosis.
Characterization of the insulin sensitivity of ghrelin receptor KO mice using glycemic clamps
Authors: Qi Yong , Longo Kenneth A , Giuliana Derek J , Gagne Samantha , McDonagh Tom , Govek Elizabeth , Nolan Anna , Zou Chaoseng , Morgan Kristen , Hixon Jeffrey , Saunders Jeffrey O , DiStefano Peter S , Geddes Brad J
Published: January 2011

Background

We and others have demonstrated previously that ghrelin receptor (GhrR) knock out (KO) mice fed a high fat diet (HFD) have increased insulin sensitivity and metabolic flexibility relative to WT littermates. A striking feature of the HFD-fed GhrR KO mouse is the dramatic decrease in hepatic steatosis. To characterize further the underlying mechanisms of glucose homeostasis in GhrR KO mice, we conducted both hyperglycemic (HG) and hyperinsulinemic-euglycemic (HI-E) clamps. Additionally, we investigated tissue glucose uptake and specifically examined liver insulin sensitivity.

Results

Consistent with glucose tolerance-test data, in HG clamp experiments, GhrR KO mice showed a reduction in glucose-stimulated insulin release relative to WT littermates. Nevertheless, a robust 1st phase insulin secretion was still achieved, indicating that a healthy β-cell response is maintained. Additionally, GhrR KO mice demonstrated both a significantly increased glucose infusion rate and significantly reduced insulin requirement for maintenance of the HG clamp, consistent with their relative insulin sensitivity. In HI-E clamps, both LFD-fed and HFD-fed GhrR KO mice showed higher peripheral insulin sensitivity relative to WT littermates as indicated by a significant increase in insulin-stimulated glucose disposal (Rd), and decreased hepatic glucose production (HGP). HFD-fed GhrR KO mice showed a marked increase in peripheral tissue glucose uptake in a variety of tissues, including skeletal muscle, brown adipose tissue and white adipose tissue. GhrR KO mice fed a HFD also showed a modest, but significant decrease in conversion of pyruvate to glucose, as would be anticipated if these mice displayed increased liver insulin sensitivity. Additionally, the levels of UCP2 and UCP1 were reduced in the liver and BAT, respectively, in GhrR KO mice relative to WT mice.

Conclusions

These results indicate that improved glucose homeostasis of GhrR KO mice is characterized by robust improvements of glucose disposal in both normal and metabolically challenged states, relative to WT controls. GhrR KO mice have an intact 1st phase insulin response but require significantly less insulin for glucose disposal. Our experiments reveal that the insulin sensitivity of GhrR KO mice is due to both BW independent and dependent factors. We also provide several lines of evidence that a key feature of the GhrR KO mouse is maintenance of hepatic insulin sensitivity during metabolic challenge.
Effects of dietary cold-pressed turnip rapeseed oil and butter on serum lipids, oxidized LDL and arterial elasticity in men with metabolic syndrome
Authors: Palomäki Ari , Pohjantähti-Maaroos Hanna , Wallenius Marja , Kankkunen Päivi , Aro Heikki , Husgafvel Sari , Pihlava Juha-Matti , Oksanen Kalevi
Published: January 2011

Background

Rapeseed oil is the principal dietary source of monounsaturated and n-3 polyunsaturated fatty acids in the Northern Europe. However, the effect of rapeseed oil on the markers of subclinical atherosclerosis is not known. The purpose of this study was to compare the effects of dietary intake of cold-pressed turnip rapeseed oil (CPTRO) and butter on serum lipids, oxidized LDL and arterial elasticity in men with metabolic syndrome.

Methods

Thirty-seven men with metabolic syndrome completed an open and balanced crossover study. Treatment periods lasted for 6 to 8 weeks and they were separated from each other with an eight-week washout period. Subjects maintained their normal dietary habits and physical activity without major variations. The daily fat adjunct consisted either of 37.5 grams of butter or 35 mL of VirginoR CPTRO. Participants were asked to spread butter on bread on the butter period and to drink CPTRO on the oil period. The fat adjunct was used as such without heating or frying.

Results

Compared to butter, administration of CPTRO was followed by a reduction of total cholesterol by 8% (p < 0.001) and LDL cholesterol by 11% (p < 0.001). The level of oxidized LDL was 16% lower after oil period (p = 0.024). Minimal differences in arterial elasticity were not statistically significant.

Conclusion

Cold-pressed turnip rapeseed oil had favourable effects on circulating LDL cholesterol and oxidized LDL, which may be important in the management of patients at high cardiovascular risk.

Trial registration

ClinicalTrial.gov NCT01119690
A label-free differential quantitative mass spectrometry method for the characterization and identification of protein changes during citrus fruit development
Authors: Katz Ehud , Fon Mario , Eigenheer Richard A , Phinney Brett S , Fass Joseph N , Lin Dawei , Sadka Avi , Blumwald Eduardo
Published: January 2011

Background

Citrus is one of the most important and widely grown commodity fruit crops. In this study a label-free LC-MS/MS based shot-gun proteomics approach was taken to explore three main stages of citrus fruit development. These approaches were used to identify and evaluate changes occurring in juice sac cells in various metabolic pathways affecting citrus fruit development and quality.

Results

Protein changes in citrus juice sac cells were identified and quantified using label-free shotgun methodologies. Two alternative methods, differential mass-spectrometry (dMS) and spectral counting (SC) were used to analyze protein changes occurring during earlier and late stages of fruit development. Both methods were compared in order to develop a proteomics workflow that could be used in a non-model plant lacking a sequenced genome. In order to resolve the bioinformatics limitations of EST databases from species that lack a full sequenced genome, we established iCitrus. iCitrus is a comprehensive sequence database created by merging three major sources of sequences (HarvEST:citrus, NCBI/citrus/unigenes, NCBI/citrus/proteins) and improving the annotation of existing unigenes. iCitrus provided a useful bioinformatics tool for the high-throughput identification of citrus proteins. We have identified approximately 1500 citrus proteins expressed in fruit juice sac cells and quantified the changes of their expression during fruit development. Our results showed that both dMS and SC provided significant information on protein changes, with dMS providing a higher accuracy.

Conclusion

Our data supports the notion of the complementary use of dMS and SC for label-free comparative proteomics, broadening the identification spectrum and strengthening the identification of trends in protein expression changes during the particular processes being compared.
Reconstructive challenge of dermatofibrosarcoma protuberans in the female breast
Authors: Park Tae Hwan , Seo Sang Won , Kim June Kyu , Chang Choong Hyun
Published: January 2011

Dermatofibrosarcoma protuberans is an uncommon locally aggressive malignant neoplasm that most frequently appears in the trunk, followed by the extremities, head, and neck. But occurrence in the breast is extremely rare. We present a case of a 28-year-old woman, who had a history of trauma 5 years previously and excision 1 year before presentation at our clinic. We performed wide excision, together with microscopic and immunohistochemical analysis. No postoperative oncologic treatment was used and she remains disease-free 1 year after the surgery without any tumor recurrence. Here, we report a case of dermatofibrosarcoma protuberans in the female breast and present a detailed discussion of the diagnosis and treatment with reference to available literatures.
Comparative genomic analysis of bacteriophages specific to the channel catfish pathogen Edwardsiella ictaluri
Authors: Carrias Abel , Welch Timothy J , Waldbieser Geoffrey C , Mead David A , Terhune Jeffery S , Liles Mark R
Published: January 2011

Background

The bacterial pathogenEdwardsiella ictaluriis a primary cause of mortality in channel catfish raised commercially in aquaculture farms. Additional treatment and diagnostic regimes are needed for this enteric pathogen, motivating the discovery and characterization of bacteriophages specific toE. ictaluri.

Results

The genomes of threeEdwardsiella ictaluri-specific bacteriophages isolated from geographically distant aquaculture ponds, at different times, were sequenced and analyzed. The genomes for phages eiAU, eiDWF, and eiMSLS are 42.80 kbp, 42.12 kbp, and 42.69 kbp, respectively, and are greater than 95% identical to each other at the nucleotide level. Nucleotide differences were mostly observed in non-coding regions and in structural proteins, with significant variability in the sequences of putative tail fiber proteins. The genome organization of these phages exhibit a pattern shared by otherSiphoviridae.

Conclusions

TheseE. ictaluri-specific phage genomes reveal considerable conservation of genomic architecture and sequence identity, even with considerable temporal and spatial divergence in their isolation. Their genomic homogeneity is similarly observed amongE. ictaluribacterial isolates. The genomic analysis of these phages supports the conclusion that these are virulent phages, lacking the capacity for lysogeny or expression of virulence genes. This study contributes to our knowledge of phage genomic diversity and facilitates studies on the diagnostic and therapeutic applications of these phages.
A Local Anesthetic, Ropivacaine, Suppresses Activated Microglia via a Nerve Growth Factor-Dependent Mechanism and Astrocytes via a Nerve Growth Factor-Independent Mechanism in Neuropathic Pain
Authors: Toda Shigeru , Sakai Atsushi , Ikeda Yumiko , Sakamoto Atsuhiro , Suzuki Hidenori
Published: January 2011

Background:

Local anesthetics alleviate neuropathic pain in some cases in clinical practice, and exhibit longer durations of action than those predicted on the basis of the pharmacokinetics of their blocking effects on voltage-dependent sodium channels. Therefore, local anesthetics may contribute to additional mechanisms for reversal of the sensitization of nociceptive pathways that occurs in the neuropathic pain state. In recent years, spinal glial cells, microglia and astrocytes, have been shown to play critical roles in neuropathic pain, but their participation in the analgesic effects of local anesthetics remains largely unknown.

Results:

Repetitive epidural administration of ropivacaine reduced the hyperalgesia induced by chronic constrictive injury of the sciatic nerve. Concomitantly with this analgesia, ropivacaine suppressed the increases in the immunoreactivities of CD11b and glial fibrillary acidic protein in the dorsal spinal cord, as markers of activated microglia and astrocytes, respectively. In addition, epidural administration of a TrkA-IgG fusion protein that blocks the action of nerve growth factor (NGF), which was upregulated by ropivacaine in the dorsal root ganglion, prevented the inhibitory effect of ropivacaine on microglia, but not astrocytes. The blockade of NGF action also abolished the analgesic effect of ropivacaine on neuropathic pain.

Conclusions:

Ropivacaine provides prolonged analgesia possibly by suppressing microglial activation in an NGF-dependent manner and astrocyte activation in an NGF-independent manner in the dorsal spinal cord. Local anesthetics, including ropivacaine, may represent a new approach for glial cell inhibition and, therefore, therapeutic strategies for neuropathic pain.
A forward genetic screen with a thalamocortical axon reporter mouse yields novel neurodevelopment mutants and a distinct emx2 mutant phenotype
Authors: Dwyer Noelle D , Manning Danielle K , Moran Jennifer L , Mudbhary Raksha , Fleming Michael S , Favero Carlita B , Vock Vita M , O'Leary Dennis DM , Walsh Christopher A , Beier David R
Published: January 2011

Background

The dorsal thalamus acts as a gateway and modulator for information going to and from the cerebral cortex. This activity requires the formation of reciprocal topographic axon connections between thalamus and cortex. The axons grow along a complex multistep pathway, making sharp turns, crossing expression boundaries, and encountering intermediate targets. However, the cellular and molecular components mediating these steps remain poorly understood.

Results

To further elucidate the development of the thalamocortical system, we first created a thalamocortical axon reporter line to use as a genetic tool for sensitive analysis of mutant mouse phenotypes. The TCA-tau-lacZ reporter mouse shows specific, robust, and reproducible labeling of thalamocortical axons (TCAs), but not the overlapping corticothalamic axons, during development. Moreover, it readily reveals TCA pathfinding abnormalities in known cortical mutants such as reeler. Next, we performed an unbiased screen for genes involved in thalamocortical development using random mutagenesis with the TCA reporter. Six independent mutant lines show aberrant TCA phenotypes at different steps of the pathway. These include ventral misrouting, overfasciculation, stalling at the corticostriatal boundary, and invasion of ectopic cortical cell clusters. An outcross breeding strategy coupled with a genomic panel of single nucleotide polymorphisms facilitated genetic mapping with small numbers of mutant mice. We mapped a ventral misrouting mutant to the Emx2 gene, and discovered that some TCAs extend to the olfactory bulbs in this mutant. Mapping data suggest that other lines carry mutations in genes not previously known for roles in thalamocortical development.

Conclusions

These data demonstrate the feasibility of a forward genetic approach to understanding mammalian brain morphogenesis and wiring. A robust axonal reporter enabled sensitive analysis of a specific axon tract inside the mouse brain, identifying mutant phenotypes at multiple steps of the pathway, and revealing a new aspect of the Emx2 mutant. The phenotypes highlight vulnerable choice points and latent tendencies of TCAs, and will lead to a refined understanding of the elements and interactions required to form the thalamocortical system.

See Commentary: http://www.biomedcentral.com/1741-7007/9/1
Hemelipoglycoprotein from the ornate sheep tick, Dermacentor marginatus: structural and functional characterization
Authors: Dupejova Jarmila , Sterba Jan , Vancova Marie , Grubhoffer Libor
Published: January 2011

Background

Tick carrier proteins are able to bind, transport, and store host-blood heme, and thus they function also as antioxidants. Nevertheless, the role of carrier proteins in ticks is not fully understood. Some of them are found also in tick males which do not feed on hosts to such an extent such as females (there are differences in male feeding in different tick species) and thus they are not dealing with such an excess of heme; some of the carrier proteins were found in salivary glands where the processing of blood and thus release of heme does not occur. Besides, the carrier proteins bind relatively low amounts of heme (in one case only two molecules of heme per protein) compared to their sizes (above 200 kDa).

The main aim of this study is the biochemical characterization of a carrier protein from the ornate sheep tick Dermacentor marginatus, hemelipoglycoprotein, with emphasis on its size in native conditions, its glycosylation and identification of its modifying glycans, and examining its carbohydrate-binding specificity.

Results

Hemelipoglycoprotein from D. marginatus plasma was purified in native state by immunoprecipitation and denatured using electroelution from SDS-PAGE separated plasma. The protein (290 kDa) contains two subunits with molecular weights 100 and 95 kDa. It is glycosylated by high-mannose and complex N-glycans HexNAc2Hex9, HexNAc2Hex10, HexNAc4Hex7, and HexNAc4Hex8. The purified protein is able to agglutinate red blood cells and has galactose- and mannose-binding specificity. The protein is recognized by antibodies directed against plasma proteins with hemagglutination activity and against fibrinogen-related lectin Dorin M from the tick Ornithodoros moubata.

It forms high-molecular weight complexes with putative fibrinogen-related proteins and other unknown proteins under native conditions in tick plasma. Feeding does not increase its amounts in male plasma. The hemelipoglycoprotein was detected also in hemocytes, salivary glands, and gut. In salivary glands, the protein was present in both glycosylated and nonglycosylated forms.

Conclusion

A 290 kDa hemelipoglycoprotein from the tick Dermacentor marginatus, was characterized. The protein has two subunits with 95 and 100 kDa, and bears high-mannose and complex N-linked glycans. In hemolymph, it is present in complexes with putative fibrinogen-related proteins. This, together with its carbohydrate-binding activity, suggests its possible involvement in tick innate immunity. In fed female salivary glands, it was found also in a form corresponding to the deglycosylated protein.
Presynaptic protein synthesis required for NT-3-induced long-term synaptic modulation
Authors: Je H Shawn , Ji Yuanyuan , Wang Ying , Yang Feng , Wu Wei , Lu Bai
Published: January 2011

Background

Neurotrophins elicit both acute and long-term modulation of synaptic transmission and plasticity. Previously, we demonstrated that the long-term synaptic modulation requires the endocytosis of neurotrophin-receptor complex, the activation of PI3K and Akt, and mTOR mediated protein synthesis. However, it is unclear whether the long-term synaptic modulation by neurotrophins depends on protein synthesis in pre- or post-synaptic cells.

Results

Here we have developed an inducible protein translation blocker, in which the kinase domain of protein kinase R (PKR) is fused with bacterial gyrase B domain (GyrB-PKR), which could be dimerized upon treatment with a cell permeable drug, coumermycin. By genetically targeting GyrB-PKR to specific cell types, we show that NT-3 induced long-term synaptic modulation requires presynaptic, but not postsynaptic protein synthesis.

Conclusions

Our results provide mechanistic insights into the cell-specific requirement for protein synthesis in the long-term synaptic modulation by neurotrophins. The GyrB-PKR system may be useful tool to study protein synthesis in a cell-specific manner.
Comparison of hyperthermia and adrenaline to enhance the intratumoral accumulation of cisplatin in a murin model of peritoneal carcinomatosis
Authors: Facy Olivier , Radais François , Ladoire Sylvain , Delroeux Delphine , Tixier Hervé , Ghiringhelli François , Rat Patrick , Chauffert Bruno , Ortega-Deballon Pablo
Published: January 2011

Background

The best method to deliver intraperitoneal chemotherapy (IPC) for peritoneal carcinomatosis from ovarian cancer is not well defined. The aim of this study was to assess the ability of hyperthermia and adrenaline to enhance the intratumoral accumulation of cisplatin in a rat model of peritoneal carcinomatosis.

Methods

Four groups of 5 BDIX rats with ovarian peritoneal carcinomatosis underwent IPC with 30 mg/l of cisplatin according to the following conditions: normothermia at 37° for 1 or 2 hours, hyperthermia at 42°C for 1 hour or normothermia at 37°C for 2 hours with 2 mg/l adrenaline. Tissue platinum content was measured by atomic absorption spectroscopy. The effect of hyperthermia, adrenaline and the duration of exposure to the drug was measured in vivo (tissue concentration of platinum in tumor, abdominal and extra abdominal tissues) and in vitro (cytotoxicity on human ovarian cancer cells).

Results

In vitro, hyperthermia and longer exposure enhanced the accumulation and the cytotoxic effect of cisplatin on cancer cells. In vivo, only the 2 hours treatment with adrenaline resulted in increased platinum concentrations. The rats treated with adrenaline showed significantly lower concentrations of cisplatin in extra peritoneal tissues than those treated with hyperthermia.

Conclusion

Adrenaline is more effective than hyperthermia in order to enhance the intratumoral concentration of cisplatin in rats with peritoneal carcinomatosis from ovarian origin. It may also decrease the systemic absorption of the drug.
Polymorphisms in the SULF1 gene are associated with early age of onset and survival of ovarian cancer
Authors: Han Chan H , Huang Yu-Jing , Lu Karen H , Liu Zhensheng , Mills Gordon B , Wei Qingyi , Wang Li-E
Published: January 2011

Background

SULF1 (sulfatase 1) selectively removes the 6-O-sulphate group from heparan sulfate, changing the binding sites for extracellular growth factors. SULF1 expression has been reported to be decreased in various cancers, including ovarian cancer. We hypothesized that single nucleotide polymorphisms (SNPs) of SULF1 would impact clinicopathologic characteristics.

Methods

We genotyped five common (minor allele frequency>0.05) regulatory SNPs with predicted functionalities (rs2623047 G>A, rs13264163 A>G, rs6990375 G>A, rs3802278 G>A, and rs3087714 C>T) in 168 patients with primary epithelial ovarian cancer, using the polymerase chain reaction-restriction fragment length polymorphism method.

Results

We found that rs2623047 G>A was significantly associated with an early age of onset of ovarian cancer in the G allele dose-response manner (P = 0.027; P

trend
= 0.007) and that rs2623047 GG/GA genotypes were associated with longer progression-free survival; rs6990375 G>A was also associated with the early age of onset in the A allele dose-response manner (P = 0.013; P

trend
= 0.009). The significant differences in age of disease onset persisted among carriers of haplotypes of rs2623047 and rs6990375 (P = 0.014; P

trend
= 0.004). In luciferase reporter gene assays, rs2623047 G allele showed a slightly higher promoter activity than the A allele in the SKOV3 tumorigenic cell line.

Conclusions

These findings suggest that genetic variations in SULF1 may play a role in ovarian cancer onset and prognosis. Further studies with large sample sizes and of the mechanistic relevance of SULF1 SNPs are warranted.
Post-hypothermic cardiac left ventricular systolic dysfunction after rewarming in an intact pig model
Authors: Filseth Ole Magnus , How Ole-Jakob , Kondratiev Timofei , Gamst Tor Magne , Tveita Torkjel
Published: January 2011

Introduction

We developed a minimally invasive, closed chest pig model with the main aim to describe hemodynamic function during surface cooling, steady state severe hypothermia (one hour at 25°C) and surface rewarming.

Methods

Twelve anesthetized juvenile pigs were acutely catheterized for measurement of left ventricular (LV) pressure-volume loops (conductance catheter), cardiac output (Swan-Ganz), and for vena cava inferior occlusion. Eight animals were surface cooled to 25°C, while four animals were kept as normothermic time-matched controls.

Results

During progressive cooling and steady state severe hypothermia (25°C) cardiac output (CO), stroke volume (SV), mean arterial pressure (MAP), maximal deceleration of pressure in the cardiac cycle (dP/dtmin), indexes of LV contractility (preload recruitable stroke work, PRSW, and maximal acceleration of pressure in the cardiac cycle, dP/dtmax) and LV end diastolic and systolic volumes (EDV and ESV) were significantly reduced. Systemic vascular resistance (SVR), isovolumetric relaxation time (Tau), and oxygen content in arterial and mixed venous blood increased significantly. LV end diastolic pressure (EDP) remained constant. After rewarming all the above mentioned hemodynamic variables that were depressed during 25°C remained reduced, except for CO that returned to pre-hypothermic values due to an increase in heart rate. Likewise, SVR and EDP were significantly reduced after rewarming, while Tau, EDV, ESV and blood oxygen content normalized. Serum levels of cardiac troponin T (TnT) and tumor necrosis factor-alpha (TNF-α) were significantly increased.

Conclusions

Progressive cooling to 25°C followed by rewarming resulted in a reduced systolic, but not diastolic left ventricular function. The post-hypothermic increase in heart rate and the reduced systemic vascular resistance are interpreted as adaptive measures by the organism to compensate for a hypothermia-induced mild left ventricular cardiac failure. A post-hypothermic increase in TnT indicates that hypothermia/rewarming may cause degradation of cardiac tissue. There were no signs of inadequate global oxygenation throughout the experiments.
A new technique for bedside placement of enteral feeding tubes: a prospective cohort study
Authors: Zick Günther , Frerichs Alexander , Ahrens Markus , Schniewind Bodo , Elke Gunnar , Schädler Dirk , Frerichs Inéz , Steinfath Markus , Weiler Norbert
Published: January 2011

Introduction

To accomplish early enteral feeding in the critically ill patient a new transnasal endoscopic approach to the placement of postpyloric feeding tubes by intensive care physicians was evaluated.

Methods

This was a prospective cohort study in 27 critically ill patients subjected to transnasal endoscopy and intubation of the pylorus. Attending intensive care physicians were trained in the handling of the new endoscope for transnasal gastroenteroscopy for two days. A jejunal feeding tube was advanced via the instrument channel and the correct position assessed by contrast radiography. The primary outcome measure was successful postpyloric placement of the tube. Secondary outcome measures were time needed for the placement, complications such as bleeding and formation of loops, and the score of the placement difficulty graded from 1 (easy) to 4 (difficult). Data are given as mean values and standard deviation.

Results

Out of 34 attempted jejunal tube placements, 28 tubes (82%) were placed correctly in the jejunum. The duration of the procedure was 28 ± 12 minutes. The difficulty of the tube placement was judged as follows: grade 1: 17 patients, grade 2: 8 patients, grade 3: 7 patients, grade 4: 2 patients. In three cases, the tube position was incorrect, and in another three cases, the procedure had to be aborted. In one patient bleeding occurred that required no further treatment.

Conclusions

Fast and reliable transnasal insertion of postpyloric feeding tubes can be accomplished by trained intensive care physicians at the bedside using the presented procedure. This new technique may facilitate early initiation of enteral feeding in intensive care patients.
Interferometric correlogram-space analysis
Authors: Poliannikov Oleg V. , Willis Mark E.
Published: January 2011

Controlled-source seismic interferometry is a method of obtaining a virtual shot gather from a collection of physical shot gathers. The set of traces corresponding to two common receiver gathers from many physical shots is used to synthesize a virtual shot located at one of the receivers and a receiver at the other. An estimate of the Green’s function between these two receivers is obtained by first crosscorrelating corresponding pairs of traces from each of the shots and then stacking the resulting crosscorrelograms. We studied the structure of crosscorrelograms obtained from a VSP acquisition geometry using surface sources and downhole receivers. The model is purely acoustic and contains flat or dipping layers and/or point inclusions that act as diffractors. We propose a semblance analysis based on moveout curves for both point diffractors and flat or dipping layers, which can be used to improve the quality of redatumed traces either by rejecting certain events prior to stacking or by enhancing them.
Fumonisin: A template for methodology development and drug discovery
Authors: McDonald Frank E. , Pereira Claney L. , Chen Yi-Hung
Published: January 2011

The chemistry and biology of the fumonisin family of natural products has inspired an integrated research program featuring methods development for stereoselective synthesis of homoallylic alcohols, accompanied by applications of these methods to the first synthesis of fumonisin B1, and to preparing a family of stereoisomeric 2-amino-3,5-diol analogs of 1-deoxysphingolipids, as a possible approach to discovering new drugs for cancer chemotherapy.
A cocycle on the group of symplectic diffeomorphisms
Authors: Gal Światosław R. , Kędra Jarek
Published: January 2011

We define a cocycle on the group of Hamiltonian diffeomorphisms of a symplectically aspherical manifold and investigate its properties. The main application is an alternative proof of the Polterovich theorem about the distortion of cyclic subgroups in finitely generated groups of Hamiltonian diffeomorphisms.
Quaternionic Hermitian spinor systems and compatibility conditions
Authors: Damiano Alberto , Eelbode David , Sabadini Irene
Published: January 2011

In this paper we show that the systems introduced in [Eelbode, Adv. Appl. Clifford Algebr. 17: 635–649, 2007] and [Peña-Peña, Sabadini, Sommen, Complex Anal. Oper. Theory 1: 97–113, 2007] are equivalent, both giving the notion of quaternionic Hermitian monogenic functions. This makes it possible to prove that the free resolution associated to the system is linear in any dimension, and that the first cohomology module is nontrivial, thus generalizing the results in [Peña-Peña, Sabadini, Sommen, Complex Anal. Oper. Theory 1: 97–113, 2007]. Furthermore, exploiting the decomposition of the spinor space into 𝔰𝔭(m)-irreducibles, we find a certain number of “algebraic” compatibility conditions for the system, suggesting that the usual spinor reduction is not applicable.
Sixteen-dimensional locally compact translation planes with collineation groups of dimension at least 38
Authors: Hähl Hermann
Published: January 2011

This article completes the classification of all the planes mentioned in the title.
Long-term performance of fused borate rods for limiting internal decay in Douglas-fir utility poles
Authors: Freitag Camille , Morrell Jeffrey J. , Love Connie S.
Published: January 2011

The ability of boron to diffuse from fused boron rods into surrounding wood was investigated on pentachlorophenol-treated Douglas-fir poles. Boron readily diffused into the wood surrounding the treatment holes and was present at protective levels in most poles within 1 year after application. The protected zone was generally confined to the treatment zone. Effective levels of boron were still present in this zone 15 years after treatment. Attempts to correlate the presence of decay fungi with residual boron levels indicated that these fungi were sometimes present in zones with boron at the lower threshold level of 0.5 kg m-3 boric acid equivalent (BAE), but most of the isolations could be explained by localized variations in distribution. Boron rods provided excellent long term protection against internal decay in Douglas-fir poles.