bluuebunny/crossref_metadata_2025 huggingface dataset:
SNP microarray analyses reveal copy number alterations and progressive genome reorganization during tumor development in SVT/t driven mice breast cancer
Authors: Standfuß Christoph , Pospisil Heike , Klein Andreas
Published: August 2012

Background

Tumor development is known to be a stepwise process involving dynamic changes that affect cellular integrity and cellular behavior. This complex interaction between genomic organization and gene, as well as protein expression is not yet fully understood. Tumor characterization by gene expression analyses is not sufficient, since expression levels are only available as a snapshot of the cell status. So far, research has mainly focused on gene expression profiling or alterations in oncogenes, even though DNA microarray platforms would allow for high-throughput analyses of copy number alterations (CNAs).

Methods

We analyzed DNA from mouse mammary gland epithelial cells using the Affymetrix Mouse Diversity Genotyping array (MOUSEDIVm520650) and calculated the CNAs. Segmental copy number alterations were computed based on the probeset CNAs using the circular binary segmentation algorithm. Motif search was performed in breakpoint regions (inter-segment regions) with the MEME suite to identify common motif sequences.

Results

Here we present a four stage mouse model addressing copy number alterations in tumorigenesis. No considerable changes in CNA were identified for non-transgenic mice, but a stepwise increase in CNA was found during tumor development. The segmental copy number alteration revealed informative chromosomal fragmentation patterns. In inter-segment regions (hypothetical breakpoint sides) unique motifs were found.

Conclusions

Our analyses suggest genome reorganization as a stepwise process that involves amplifications and deletions of chromosomal regions. We conclude from distinctive fragmentation patterns that conserved as well as individual breakpoints exist which promote tumorigenesis.
Eye movements during visual search in patients with glaucoma
Authors: Smith Nicholas D , Glen Fiona C , Crabb David P
Published: September 2012

Background

Glaucoma has been shown to lead to disability in many daily tasks including visual search. This study aims to determine whether the saccadic eye movements of people with glaucoma differ from those of people with normal vision, and to investigate the association between eye movements and impaired visual search.

Methods

Forty patients (mean age: 67 [SD: 9] years) with a range of glaucomatous visual field (VF) defects in both eyes (mean best eye mean deviation [MD]: –5.9 (SD: 5.4) dB) and 40 age-related people with normal vision (mean age: 66 [SD: 10] years) were timed as they searched for a series of target objects in computer displayed photographs of real world scenes. Eye movements were simultaneously recorded using an eye tracker. Average number of saccades per second, average saccade amplitude and average search duration across trials were recorded. These response variables were compared with measurements of VF and contrast sensitivity.

Results

The average rate of saccades made by the patient group was significantly smaller than the number made by controls during the visual search task (P = 0.02; mean reduction of 5.6% (95% CI: 0.1 to 10.4%). There was no difference in average saccade amplitude between the patients and the controls (P = 0.09). Average number of saccades was weakly correlated with aspects of visual function, with patients with worse contrast sensitivity (PR logCS; Spearman’s rho: 0.42; P = 0.006) and more severe VF defects (best eye MD; Spearman’s rho: 0.34; P = 0.037) tending to make less eye movements during the task. Average detection time in the search task was associated with the average rate of saccades in the patient group (Spearman’s rho = −0.65; P < 0.001) but this was not apparent in the controls.

Conclusions

The average rate of saccades made during visual search by this group of patients was fewer than those made by people with normal vision of a similar average age. There was wide variability in saccade rate in the patients but there was an association between an increase in this measure and better performance in the search task. Assessment of eye movements in individuals with glaucoma might provide insight into the functional deficits of the disease.
Improvdent: Improving dentures for patient benefit. A crossover randomised clinical trial comparing impression materials for complete dentures
Authors: Gray Janine C , Navarro-Coy Nuria , Pavitt Sue H , Hulme Claire , Godfrey Mary , Craddock Helen L , Brunton Paul A , Brown Sarah , Dillon Sean , Dukanovic Gillian , Fernandez Catherine , Wright Jonathan , Collier Howard , Swithenbank Shirley , Lee Carol , Hyde T Paul
Published: September 2012

Background

According to the UK Adult Dental Health Survey (2009) 15% of adults aged 65–74, 30% aged 75–84 and 47% aged >85 years are edentulous and require complete dentures. Patients’ quality of life and nutrition status are affected by poor dentures. The quality of the dental impression is the most important issue for improving the fit and comfort of new dentures. There is paucity of RCT evidence for which impression material is best for complete dentures construction. This study aims to compare two impression materials for effectiveness and cost effectiveness.

Methods/Design

IMPROVDENT is a double-blind crossover trial comparing the use of alginate and silicone, two commonly used denture impression materials, in terms of patient preference and cost-effectiveness. Eighty five edentulous patients will be recruited and provided with two sets of dentures, similar in all aspects except for the impression material used (alginate or silicone). Patients will try both sets of dentures for a two-week period, unadjusted, to become accustomed to the feel of the new dentures (habituation period). Patients will then wear each set of dentures for a period of 8 weeks (in random order) during which time the dentures will be adjusted for optimum comfort. Finally, patients will be given both sets of dentures for a further two weeks to wear whichever denture they prefer (confirmation period).

Patients will be asked about quality of life and to rate dentures on function and comfort at the end of each trial period and asked which set they prefer at the end of the habituation period (unadjusted denture preference) and confirmation period (adjusted denture preference). A health economic evaluation will estimate incremental cost-effectiveness ratios of producing dentures from the two materials. A qualitative study will investigate the impact of dentures on behaviour and quality of life.

Funding: IMPROVDENT is funded by NIHR RfPB (PB-PG-0408-16300).

Discussion

This trial aims to provide evidence on the costs and quality of dentures cast from two different commonly used impression materials; the intention is to significantly impact on the quality of denture production within NHS dentistry.

Trial Registration

ISRCTN Register: ISRCTN01528038

UKCRN Portfolio ID: 8305
4,8-Sphingadienine and 4-hydroxy-8-sphingenine activate ceramide production in the skin
Authors: Shirakura Yoshiyuki , Kikuchi Kanako , Matsumura Kenji , Mukai Katsuyuki , Mitsutake Susumu , Igarashi Yasuyuki
Published: September 2012

Background

Ingestion of glucosylceramide improves transepidermal water loss (TEWL) from the skin, but the underlying mechanism by which a small amount of dietary glucosylceramide can vastly improve skin conditions remains unclear. In a previous report, glucosylceramides were shown to be digested to sphingoids, which were shown to be absorbed through the intestinal epithelium. Based on these observations, we hypothesized that sphingoids are the key molecules facilitating endogenous ceramide production. In this study, we assessed the effect of 4,8-sphingadienine (d18:2) and 4-hydroxy-8-sphingenine (t18:1), derived from konjac glucosylceramide, on stimulating ceramide production.

Methods

Konjac glucosylceramide acidolysis was performed using hydrochloric acid; the resulting d18:2 and t18:1 were fractionated by column chromatography. Real-time quantitative RT-PCR was performed to assess the effect of d18:2 and t18:1 on gene expression in normal human epidermal keratinocytes, while their effect on the nuclear receptor, peroxisome proliferator-activated receptor (PPAR)γ, was measured using a receptor-cofactor assay system. The effect of d18:2 and t18:1 on stimulating ceramide production was evaluated using HPTLC analysis in a 3-dimensional human skin model.

Results

We noted the upregulation of genes related to de novo ceramide synthesis as well as of those encoding the elongases of very long-chain fatty acids by d18:2 and t18:1, but not by glucosylceramide and 4-sphingenine. Both these sphingoids also facilitated the expression of PPARβ/δ and PPARγ; moreover, they also demonstrated ligand activity for PPARγ. These results indicated that d18:2 and t18:1 promote the differentiation of keratinocytes. Analysis of the lipids within the 3-dimensional human skin model indicated that treatment with d18:2 and t18:1 not only upregulated gene expression but also increased ceramide production.

Conclusions

The sphingoids d18:2 and t18:1 activated genes related to de novo ceramide synthesis and increased ceramide production, whereas glucosylceramide and 4-sphingenine could not. These results suggest that the effect of dietary glucosylceramides on the skin is mediated by d18:2 and t18:1.
Measuring infertility in populations: constructing a standard definition for use with demographic and reproductive health surveys
Authors: Mascarenhas Maya N , Cheung Hoiwan , Mathers Colin D , Stevens Gretchen A
Published: September 2012

Background

Infertility is a significant disability, yet there are no reliable estimates of its global prevalence. Studies on infertility prevalence define the condition inconsistently, rendering the comparison of studies or quantitative summaries of the literature difficult. This study analyzed key components of infertility to develop a definition that can be consistently applied to globally available household survey data.

Methods

We proposed a standard definition of infertility and used it to generate prevalence estimates using 53 Demographic and Health Surveys (DHS). The analysis was restricted to the subset of DHS that contained detailed fertility information collected through the reproductive health calendar. We performed sensitivity analyses for key components of the definition and used these to inform our recommendations for each element of the definition.

Results

Exposure type (couple status, contraceptive use, and intent), exposure time, and outcomes were key elements of the definition that we proposed. Our definition produced estimates that ranged from 0.6% to 3.4% for primary infertility and 8.7% to 32.6% for secondary infertility. Our sensitivity analyses showed that using an exposure measure of five years is less likely to misclassify fertile unions as infertile. Additionally, using a current, rather than continuous, measure of contraceptive use over five years resulted in a median relative error in secondary infertility of 20.7% (interquartile range of relative error [IQR]: 12.6%-26.9%), while not incorporating intent produced a corresponding error in secondary infertility of 58.2% (IQR: 44.3%-67.9%).

Conclusions

In order to estimate the global burden of infertility, prevalence estimates using a consistent definition need to be generated. Our analysis provided a recommended definition that could be applied to widely available global household data. We also summarized potential biases that should be considered when making estimates of infertility prevalence using household survey data.
Targeting wild-type Erythrocyte receptors for Plasmodium falciparum and vivax Merozoites by Zinc Finger Nucleases In- silico: Towards a Genetic Vaccine against Malaria
Authors: Kajumbula Henry , Byarugaba Wilson , Wayengera Misaki
Published: September 2012

Background

Malaria causes immense human morbidity and mortality globally. The plasmodium species vivax and falciparum cause over 75 % clinical malaria cases. Until now, gene-based strategies against malaria have only been applied to plasmodium species and their mosquito-vector. Merozoites of these two respective plasmodium species target and invade red blood cells (RBCs) by using the duffy antigen receptor for chemokines (DARC), and Sialic Acid (SLC4A1) residues of the O-linked glycans of Glycophorin A. RBCs of naturally selected duffy-negative blacks are resistant to P.vivax tropism. We hypothesized that artificial aberration of the host-pathway by target mutagenesis of either RBC –receptors, may abolish or reduce susceptibility of the host to malaria. As a first step towards the experimental actualization of these concepts, we aimed to identify zinc finger arrays (ZFAs) for constructing ZFNs that target genes of either wild-type host-RBC- receptors.

Methods

In-Silico Gene & Genome Informatics

Results

Using the genomic contextual nucleotide-sequences of homo-sapiens darc and glycophorin-a, and the ZFN-consortia software- CoDA-ZiFiT-ZFA and CoDA-ZiFiT-ZFN: we identified 163 and over 1,000 single zinc finger arrays (sZFAs) that bind sequences within the genes for the two respective RBC-receptors. Second, 2 and 18 paired zinc finger arrays (pZFAs) that are precursors for zinc finger nucleases (ZFNs) capable of cleaving the genes for darc and glycophorin-a were respectively assembled. Third, a mega-BLAST evaluation of the genome-wide cleavage specificity of this set of ZFNs was done, revealing alternate homologous nucleotide targets in the human genome other than darc or glycophorin A.

Conclusions

ZFNs engineered with these ZFA-precursors--with further optimization to enhance their specificity to only darc and glycophorin-a, could be used in constructing an experimental gene-based-malaria vaccine. Alternatively, meganucleases and transcription activator-like (TAL) nucleases that target conserved stretches of darc and glycophorin-a DNA may serve the purpose of abrogating invasion of RBCs by falciparam and vivax plasmodia species.
Hematopoietic stem cell transplantation induces immunologic tolerance in renal transplant patients via modulation of inflammatory and repair processes
Authors: Wu Duojiao , Qi Guisheng , Wang Xuanchuan , Xu Ming , Rong Ruiming , Wang Xiangdong , Zhu Tongyu
Published: August 2012

Background

Inducing donor-specific tolerance in renal transplant patients could potentially prevent allograft rejection and calcineurin inhibitor nephrotoxicity. Combined kidney and hematopoietic stem cell transplant from an HLA-matched donor is an exploratory and promising therapy to induce immune tolerance. Investigtion of molecular mechanisms involved in the disease is needed to understand the potential process of cell therapy and develop strategies to prevent this immunologic rejection.

Methods

We enrolled nine patients in a clinical study in which cryopreserved donor hematopoietic stem cells were infused on days 2, 4, and 6 after kidney transplantation. One month post-transplant, 4 plasma samples were collected from combined transplants (C + Tx), and 8 plasma samples from patients with kidney transplantation alone (Tx). High abundance proteins in plasma were depleted and the two-dimensional liquid chromatography-tandem mass spectrometry coupled with iTRAQ labeling was utilized to identify the protein profiling between the two groups. Clusters of up- and down-regulated protein profiles were submitted to MetaCore for the construction of transcriptional factors and regulation networks.

Results and Discussion

Among the 179 identified proteins, 65 proteins were found in C + Tx with at least a 2-fold change as compared with Tx. A subset of proteins related to the complement and coagulation cascade, including complement C3a,complement C5a, precrusors to fibrinogen alpha and beta chains,was significantly downregulated in C + Tx. Meanwhile, Apolipoprotein-A1(ApoA1), ApoC1, ApoA2, ApoE, and ApoB were significantly lower in Tx compared to C + Tx. Gene ontology analysis showed that the dominant processes of differentially expressed proteins were associated with the inflammatory response and positive regulation of plasma lipoprotein particle remodeling.

Conclusions

Thus, our study provides new insight into the molecular events in the hematopoietic stem cell-induced immunologic tolerance.
Genetic mechanisms and age-related macular degeneration: common variants, rare variants, copy number variations, epigenetics, and mitochondrial genetics
Authors: Liu Melissa M , Chan Chi-Chao , Tuo Jingsheng
Published: September 2012

Age-related macular degeneration (AMD) is a complex and multifaceted disease involving contributions from both genetic and environmental influences. Previous work exploring the genetic contributions of AMD has implicated numerous genomic regions and a variety of candidate genes as modulators of AMD susceptibility. Nevertheless, much of this work has revolved around single-nucleotide polymorphisms (SNPs), and it is apparent that a significant portion of the heritability of AMD cannot be explained through these mechanisms. In this review, we consider the role of common variants, rare variants, copy number variations, epigenetics, microRNAs, and mitochondrial genetics in AMD. Copy number variations in regulators of complement activation genes (CFHR1 and CFHR3) and glutathione S transferase genes (GSTM1 and GSTT1) have been associated with AMD, and several additional loci have been identified as regions of potential interest but require further evaluation. MicroRNA dysregulation has been linked to the retinal pigment epithelium degeneration in geographic atrophy, ocular neovascularization, and oxidative stress, all of which are hallmarks in the pathogenesis of AMD. Certain mitochondrial DNA haplogroups and SNPs in mitochondrially encoded NADH dehydrogenase genes have also been associated with AMD. The role of these additional mechanisms remains only partly understood, but the importance of their further investigation is clear to elucidate more completely the genetic basis of AMD.
Toll-like receptor 4 signaling promotes epithelial-mesenchymal transition in human hepatocellular carcinoma induced by lipopolysaccharide
Authors: Jing Ying-Ying , Han Zhi-Peng , Sun Kai , Zhang Shan-Shan , Hou Jing , Liu Yan , Li Rong , Gao Lu , Zhao Xue , Zhao Qiu-Dong , Wu Meng-Chao , Wei Li-Xin
Published: September 2012

Background

The endotoxin level in the portal and peripheral veins of hepatocellular carcinoma (HCC) patients is higher and lipopolysaccharide (LPS), a cell wall constituent of gram-negative bacteria, has been reported to inhibit tumor growth. However, in this study, we found that LPS-induced toll-like receptor 4 (TLR4) signaling was involved in tumor invasion and survival, and the molecular mechanism was investigated,

Methods

Four HCC cell lines and a splenic vein metastasis of the nude mouse model were used to study the invasion ability of LPS-induced HCC cells and the epithelia-mesenchymal transition (EMT) in vitro and in vivo. A total of 106 clinical samples from HCC patients were used to evaluate TLR4 expression and analyze its association with clinicopathological characteristics

Results

The in
vitro and in vivo experiments demonstrated that LPS could significantly enhance the invasive potential and induce EMT in HCC cells with TLR4 dependent. Further studies showed that LPS could directly activate nuclear factor kappa B (NF-κB) signaling through TLR4 in HCC cells. Interestingly, blocking NF-κB signaling significantly inhibited transcription factor Snail expression and thereby inhibited EMT occurrence. High expression of TLR4 in HCC tissues was strongly associated with both poor cancer-free survival and overall survival in patients.

Conclusions

Our results indicate that TLR4 signaling is required for LPS-induced EMT, tumor cell invasion and metastasis, which provide molecular insights for LPS-related pathogenesis and a basis for developing new strategies against metastasis in HCC.
Two types of nanoparticle-based bio-barcode amplification assays to detect HIV-1 p24 antigen
Authors: Dong Huahuang , Liu Jianli , Zhu Hong , Ou Chin-Yih , Xing Wenge , Qiu Maofeng , Zhang Guiyun , Xiao Yao , Yao Jun , Pan Pinliang , Jiang Yan
Published: August 2012

Background

HIV-1 p24 antigen is a major viral component of human immunodeficiency virus type 1 (HIV-1) which can be used to identify persons in the early stage of infection and transmission of HIV-1 from infected mothers to infants. The detection of p24 is usually accomplished by using an enzyme-linked immunosorbent assay (ELISA) with low detection sensitivity. Here we report the use of two bio-barcode amplification (BCA) assays combined with polymerase chain reaction (PCR) and gel electrophoresis to quantify HIV-1 p24 antigen.

Method

A pair of anti-p24 monoclonal antibodies (mAbs) were used in BCA assays to capture HIV-1 p24 antigen in a sandwich format and allowed for the quantitative measurement of captured p24 using PCR and gel electrophoresis. The first 1 G12 mAb was coated on microplate wells or magnetic microparticles (MMPs) to capture free p24 antigens. Captured p24 in turn captured 1D4 mAb coated gold nanoparticle probes (GNPs) containing double-stranded DNA oligonucleotides. One strand of the oligonucleotides was covalently immobilized whereas the unbound complimentary bio-barcode DNA strand could be released upon heating. The released bio-barcode DNA was amplified by PCR, electrophoresed in agarose gel and quantified.

Results

The in-house ELISA assay was found to quantify p24 antigen with a limit of detection (LOD) of 1,000 pg/ml and a linear range between 3,000 and 100,000 pg/ml. In contrast, the BCA-based microplate method yielded an LOD of 1 pg/ml and a linear detection range from 1 to 10,000 pg/ml. The BCA-based MMP method yielded an LOD of 0.1 pg/ml and a linear detection range from 0.1 to 1,000 pg/ml.

Conclusions

When combined with PCR and simple gel electrophoresis, BCA-based microplate and MMPs assays can be used to quantify HIV-1 p24 antigen. These methods are 3–4 orders of magnitude more sensitive than our in-house ELISA-based assay and may provide a useful approach to detect p24 in patients newly infected with HIV.
Malignant transformation of Madelung’s disease in a patient with a coincidental diagnosis of breast cancer: a case report
Authors: Borriello Maddalena , Lucidi Alessandro , Carbone Arnaldo , Iannone Vito , Ferrandina Gabriella
Published: September 2012

Madelung’s disease or multiple symmetric lipomatosis (MSL) is a rare disorder of unknown etiology which typically presents symmetrically subcutaneous accumulation of non-encapsulated adipose tissue which slowly grows around the neck, upper part of the arms, pelvis, back and thigh. This disease is also frequently associated with hepatopathy, glucose intolerance, hyperuricemia, and malignant tumors of the upper airways. Nevertheless, only one description of malignant transformation of Madelung’s disease has been presented in literature. Here, we report a case of liposarcomatous transformation of Madelung’s disease in a 59-year-old Italian woman with a coincidental diagnosis of breast cancer.

Virtual slide

The virtual slide for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/3480884087499351
Image-Guided Robotic Stereotactic Radiation Therapy with Fiducial-Free Tumor Tracking for Lung Cancer
Authors: Bibault Jean-Emmanuel , Prevost Bernard , Dansin Eric , Mirabel Xavier , Lacornerie Thomas , Lartigau Eric
Published: September 2012

Purpose

Stereotactic body radiation therapy (SBRT) for early-stage lung cancer can be achieved with several methods: respiratory gating, body frame, or real-time target and motion tracking. Two target tracking methods are currently available with the CyberKnife® System: the first one, fiducial tracking, requires the use of radio-opaque markers implanted near or inside the tumor, while the other, Xsight® Lung Tracking System, (XLTS) is fiducial-free. With XLTS, targeting is synchronized directly with target motion, which occurs due to respiration. While the former method (fiducial tracking) is well documented, the clinical relevance of the latter (tracking without fiducials) has never been well described to this date.

Patients and Methods

A study was performed at our department for each patient treated for lung cancer with CyberKnife using XLTS. Selection criteria were: primary or recurring T1 or T2 stage non-small-cell lung cancer (NSCLC) with 15–60 mm tumor size. Initial staging included CT-Scan and FDG-PET.

Results

Fifty-one patients not amenable to surgery were treated with XLTS. Median follow-up was 15 months (range, 5–30 months). Median tumor size was 24 mm (range, 15–60 mm). Median total dose was 60 Gy (36–60 Gy) in three fractions. Actuarial overall survival was 85.5% (95% CI = 74.5–96%) at 1 year and 79.4% (95% CI = 64–94.8%) at 2 years. Actuarial local control rate was 92% (95% CI = 84–99%) at one1 year and 86% (95% CI = 75–97%) at 2 years.

Conclusion

Local control and overall survival rates were similar to previous reports that used fiducials for tumor tracking. Toxicity was lower than most studies since tumor tracking did not require fiducial implantion. This fiducial-free method for respiratory motion tracking is a valid option for the most fragile patients.
Stochastic errors vs. modeling errors in distance based phylogenetic reconstructions
Authors: Doerr Daniel , Gronau Ilan , Moran Shlomo , Yavneh Irad
Published: September 2012

Background

Distance-based phylogenetic reconstruction methods use evolutionary distances between species in order to reconstruct the phylogenetic tree spanning them. There are many different methods for estimating distances from sequence data. These methods assume different substitution models and have different statistical properties. Since the true substitution model is typically unknown, it is important to consider the effect of model misspecification on the performance of a distance estimation method.

Results

This paper continues the line of research which attempts to adjust to each given set of input sequences a distance function which maximizes the expected topological accuracy of the reconstructed tree. We focus here on the effect of systematic error caused by assuming an inadequate model, but consider also the stochastic error caused by using short sequences. We introduce a theoretical framework for analyzing both sources of error based on the notion ofdeviation from additivity, which quantifies the contribution of model misspecification to the estimation error. We demonstrate this framework by studying the behavior of the Jukes-Cantor distance function when applied to data generated according to Kimura’s two-parameter model with a transition-transversion bias. We provide both a theoretical derivation for this case, and a detailed simulation study on quartet trees.

Conclusions

We demonstrate both analytically and experimentally that by deliberately assuming an oversimplified evolutionary model, it is possible to increase the topological accuracy of reconstruction. Our theoretical framework provides new insights into the mechanisms that enables statistically inconsistent reconstruction methods to outperform consistent methods.
Paraneoplastic leukocytoclastic vasculitis as an initial presentation of malignant pleural mesothelioma: a case report
Authors: Wong Shu Fen , Newland Lisa , John Thomas , White Shane C
Published: September 2012

Introduction

Vasculitis has been associated with malignancies, more commonly hematological rather than solid malignancies. Due to the rarity of these conditions and the lack of a temporal association, the relationship between vasculitis and malignancy remains unclear. Paraneoplastic vasculitis as a phenomenon of lung cancer has been described in the literature. To the best of our knowledge, this is the first case report of leukocytoclastic vasculitis being an initial presentation of malignant pleural mesothelioma.

Case presentation

We report the case of an 84-year old Greek man who presented to our facility with an erythematous, pruritic and purpuric rash affecting his limbs. This was biopsy-proven to be leukocytoclastic vasculitis and treated conservatively with topical corticosteroids as well as oral prednisolone, with good results. Six months later, he was diagnosed as having malignant pleural mesothelioma. As he remained asymptomatic from his malignancy, no systemic chemotherapy was instituted. He had a recurrence of biopsy-proven leukocytoclastic vasculitis two months after he was diagnosed as having mesothelioma, which again settled with conservative measures.

Conclusions

It is important to remain vigilant with regard to the association between leukocytoclastic vasculitis and malignancies. A diagnosis of vasculitis requires a search for malignancies as well as other possible etiologies. This is particularly of relevance when the vasculitis becomes chronic, recurrent or treatment is no longer effective. Should our patient have experienced refractory vasculitis, we would have instituted systemic chemotherapy to treat the underlying malignancy.
Systemic dissemination of chronic necrotizing pulmonary aspergillosis in an elderly woman without comorbidity: a case report
Authors: Tokui Kotaro , Kawagishi Yukio , Inomata Minehiko , Taka Chihiro , Okazawa Seisuke , Yamada Toru , Miwa Toshiro , Hayashi Ryuji , Matsui Shoko , Takano Yasuo , Tobe Kazuyuki
Published: September 2012

Introduction

Chronic necrotizing pulmonary aspergillosis usually occurs in mildly immune-compromised hosts or those with underlying pulmonary disease. The radiographic pattern of chronic necrotizing pulmonary aspergillosis is typically a progressive upper lobe cavitary infiltrate with pleural thickening. We report here an atypical case of chronic necrotizing pulmonary aspergillosis mimicking lung cancer, which developed into a disseminated fatal disease in an older woman with no comorbidity.

Case presentation

An 80-year-old Japanese woman was referred to our hospital for a chest roentgenogram abnormality. Repeated fiber-optic bronchoscopy could not confirm any definite diagnosis, and she refused further examinations. Considering the roentgenogram findings and her age, she was followed-up as a suspected case of lung cancer without any treatment. Then, 10 months later, she complained of visual disturbance and was admitted to our department of ophthalmology. She was diagnosed as having endophthalmitis. After treatment with corticosteroids for 20 days, she developed acute encephalitis and died four weeks later. Autopsy revealed dissemination of Aspergillus hyphae throughout her body, including her brain.

Conclusions

In older patients, even if they do not have any comorbidity, chronic necrotizing pulmonary aspergillosis should be added to the differential diagnosis of solitary pulmonary lesions in a chest roentgenogram.
Validation of a computer case definition for sudden cardiac death in opioid users
Authors: Kawai Vivian K , Murray Katherine T , Stein C Michael , Cooper William O , Graham David J , Hall Kathi , Ray Wayne A
Published: September 2012

Background

To facilitate the use of automated databases for studies of sudden cardiac death, we previously developed a computerized case definition that had a positive predictive value between 86% and 88%. However, the definition has not been specifically validated for prescription opioid users, for whom out-of-hospital overdose deaths may be difficult to distinguish from sudden cardiac death.

Findings

We assembled a cohort of persons 30-74 years of age prescribed propoxyphene or hydrocodone who had no life-threatening non-cardiovascular illness, diagnosed drug abuse, residence in a nursing home in the past year, or hospital stay within the past 30 days. Medical records were sought for a sample of 140 cohort deaths within 30 days of a prescription fill meeting the computer case definition. Of the 140 sampled deaths, 81 were adjudicated; 73 (90%) were sudden cardiac deaths. Two deaths had possible opioid overdose; after removing these two the positive predictive value was 88%.

Conclusions

These findings are consistent with our previous validation studies and suggest the computer case definition of sudden cardiac death is a useful tool for pharmacoepidemiologic studies of opioid analgesics.
High risk human papillomavirus and Epstein Barr virus in human breast milk
Authors: Glenn Wendy K , Whitaker Noel J , Lawson James S
Published: September 2012

Background

Multiple viruses, including human immunodeficiency virus, Epstein Barr virus (EBV) and mouse mammary tumour virus have been identified in human milk. High risk human papillomavirus (HPV) sequences have been identified in breast cancer. The aim of this study is to determine if viral sequences are present in human milk from normal lactating women.

Findings

Standard (liquid) and in situ polymerase chain reaction (PCR) techniques were used to identify HPV and EBV in human milk samples from normal lactating Australian women who had no history of breast cancer.

High risk human papillomavirus was identified in milk samples of 6 of 40 (15%) from normal lactating women - sequencing on four samples showed three were HPV 16 and one was HPV 18. Epstein Barr virus was identified in fourteen samples (33%).

Conclusion

The presence of high risk HPV and EBV in human milk suggests the possibility of milk transmission of these viruses. However, given the rarity of viral associated malignancies in young people, it is possible but unlikely, that such transmission is associated with breast or other cancers.
The relationship between ventricular dilatation, neuropathological and neurobehavioural changes in hydrocephalic rats
Authors: Olopade Funmilayo Eniola , Shokunbi Matthew Temitayo , Sirén Anna-Leena
Published: September 2012

Background

The motor and cognitive deficits observed in hydrocephalus are thought to be due to axonal damage within the periventricular white matter. This study was carried out to investigate the relationship between ventricular size, cellular changes in brain, and neurobehavioural deficits in rats with experimental hydrocephalus.

Methods

Hydrocephalus was induced in three-week old rats by intracisternal injection of kaolin. Behavioural and motor function were tested four weeks after hydrocephalus induction and correlated to ventricular enlargement which was classified into mild, moderate or severe. Gross brain morphology, routine histology and immunohistochemistry for oligodendrocytes (CNPase), microglia (Iba-1) and astrocytes (GFAP) were performed to assess the cellular changes.

Results

Decreases in open field activity and forelimb grip strength in hydrocephalus correlated with the degree of ventriculomegaly. Learning in Morris water maze was significantly impaired in hydrocephalic rats. Gradual stretching of the ependymal layer, thinning of the corpus callosum, extracellular oedema and reduced cortical thickness were observed as the degree of ventriculomegaly increased. A gradual loss of oligodendrocytes in the corpus callosum and cerebral cortex was most marked in the severely-hydrocephalic brains, whereas the widespread astrogliosis especially in the subependymal layer was most marked in the brains with mild hydrocephalus. Retraction of microglial processes and increase in Iba-1 immunoreactivity in the white matter was associated ventriculomegaly.

Conclusions

In hydrocephalic rats, oligodendrocyte loss, microglia activation, astrogliosis in cortical areas and thinning of the corpus callosum were associated with ventriculomegaly. The degree of ventriculomegaly correlated with motor and cognitive deficits.
Abundance, species composition of microzooplankton from the coastal waters of Port Blair, South Andaman Island
Authors: Sai Elangovan S , Arun Kumar M , Karthik R , Siva Sankar R , Jayabarathi R , Padmavati G
Published: September 2012

Background

Microzooplankton consisting of protists and metazoa <200 μm. It displays unique feeding mechanisms and behaviours that allow them to graze cells up to five times their own volume. They can grow at rates which equal or exceed prey growth and can serve as a viable food source for metazoans. Moreover, they are individually inconspicuous, their recognition as significant consumers of oceanic primary production. The microzooplankton can be the dominant consumers of phytoplankton production in both oligo- and eutrophic regions of the ocean and are capable of consuming >100% of primary production.

Results

The microzooplankton of the South Andaman Sea were investigated during September 2011 to January 2012. A total of 44 species belong to 19 genera were recorded in this study. Tintinnids made larger contribution to the total abundance (34%) followed in order by dinoflagellates (24%), ciliates (20%) and copepod nauplii (18%). Foraminifera were numerically less (4%). Tintinnids were represented by 20 species belong to 13 genera, Heterotrophic dinoflagellates were represented by 17 species belong to 3 genera and Ciliates comprised 5 species belong to 3 genera. Eutintinus tineus, Tintinnopsis cylindrical, T. incertum, Protoperidinium divergens, Lomaniella oviformes, Strombidium minimum were the most prevalent microzooplankton. Standing stock of tintinnids ranged from 30–80 cells.L-1 and showed a reverse distribution with the distribution of chlorophyll a relatively higher species diversity and equitability was found in polluted harbour areas.

Conclusions

The change of environmental variability affects the species composition and abundance of microzooplankton varied spatially and temporarily. The observations clearly demonstrated that the harbor area differed considerably from other area in terms of species present and phytoplankton biomass. Further, the phytoplankton abundance is showed to be strongly influenced by tintinnid with respect to the relationship of prey–predator. Consequently, further investigation on microzooplankton grazing would shed light on food web dynamics.
Urinary proteomic shotgun approach for identification of potential acute rejection biomarkers in renal transplant recipients
Authors: Loftheim Håvard , Midtvedt Karsten , Hartmann Anders , Reisæter Anna V , Falck Pål , Holdaas Hallvard , Jenssen Trond , Reubsaet Leon , Åsberg Anders
Published: August 2012

Background

Acute rejection (AR) episodes in renal transplant recipients are suspected when plasma creatinine is elevated and other potential causes out ruled. Graft biopsies are however needed for definite diagnosis. Non-invasive AR-biomarkers is an unmet clinical need. The urinary proteome is an interesting source in the search for such a biomarker in this population.

Methods

In this proof of principle study, serial urine samples in the early post transplant phase from 6 patients with biopsy verified acute rejections and 6 age-matched controls without clinical signs of rejection were analyzed by shotgun proteomics.

Results

Eleven proteins fulfilled predefined criteria for regulation in association with AR. They presented detectable regulation already several days before clinical suspicion of AR (increased plasma creatinine). The regulated proteins could be grouped by their biological function; proteins related to growth and proteins related to immune response. Growth-related proteins (IGFBP7, Vasorin, EGF and Galectin-3-binding protein) were significantly up-regulated in association with AR (P = 0.03) while proteins related to immune response (MASP2, C3, CD59, Ceruloplasmin, PiGR and CD74) tended to be up-regulated (P = 0.13).

Conclusion

The use of shotgun proteomics provides a robust and sensitive method for identification of potentially predictive urinary biomarkers of AR. Further validation of the current findings is needed to establish their potential clinical role with regards to clinical AR diagnosis.

Trial registration

ClinicalTrials.gov number NCT00139009
Impact of distance education via mobile phone text messaging on knowledge, attitude, practice and self efficacy of patients with type 2 diabetes mellitus in Iran
Authors: Goodarzi Mandana , Ebrahimzadeh Issa , Rabi Alireza , Saedipoor Bahman , Jafarabadi Mohammad Asghari
Published: September 2012

Objective

To evaluate the impacts of using SMS on improving laboratory test levels and Knowledge, Attitude, Practice (KAP) and Self Efficacy (SE) of patients with type 2 diabetes mellitus (DM) in Iran.

Materials and methods

In this randomized controlled trial study, a total of 81 type 2 diabetes patients were randomly assigned into two groups exp. group (n = 43) and cont. group (n = 38). Only exp. group received 4 messages weekly consisted of diet, exercise, medication taking and. The researchers provided the intervention for 12 weeks. Data were collected with results of laboratory tests and KAP, SE reliable and valid questionnaires and demographic characteristics list. Data gathering at the baseline of the study and after 3 months intervention and was analyzed by SPSS11.5 software using descriptive and inferential statistics methods.

Results

The results of this study showed that exp. group compared with cont. group improved significantly in HbA1C (p = 0.024), LDL (p = 0.019), cholesterol (p = 0.002), BUN (p ≤ 0.001), micro albumin (p ≤ 0.001), knowledge (p ≤ 0.001), practice (p ≤ 0.001) and self efficacy (p ≤ 0.001).

Conclusion

The finding of this study demonstrate the effectiveness of intervention using SMS via mobile phone in the management of type 2 diabetes mellitus (DM). Thus, further studies are recommended for wide usage of distance education with mobile phone utilization.
Lhx1 in the proximal region of the optic vesicle permits neural retina development in the chicken
Authors: Kawaue Takumi , Okamoto Mayumi , Matsuyo Akane , Inoue Junji , Ueda Yuhki , Tomonari Sayuri , Noji Sumihare , Ohuchi Hideyo
Published: September 2012

How the eye forms has been one of the fundamental issues in developmental biology. The retinal anlage first appears as the optic vesicle (OV) evaginating from the forebrain. Subsequently, its distal portion invaginates to form the two-walled optic cup, which develops into the outer pigmented and inner neurosensory layers of the retina. Recent work has shown that this optic-cup morphogenesis proceeds as a self-organizing activity without any extrinsic molecules. However, intrinsic factors that regulate this process have not been elucidated. Here we show that a LIM-homeobox gene, Lhx1, normally expressed in the proximal region of the nascent OV, induces a second neurosensory retina formation from the outer pigmented retina when overexpressed in the chicken OV. Lhx2, another LIM-homeobox gene supposed to be involved in early OV formation, could not substitute this function of Lhx1, while Lhx5, closely related to Lhx1, could replace it. Conversely, knockdown of Lhx1 expression by RNA interference resulted in the formation of a small or pigmented vesicle. These results suggest that the proximal region demarcated by Lhx1 expression permits OV development, eventually dividing the two retinal domains.
Adhesive and mechanical regulation of mesenchymal stem cell differentiation in human bone marrow and periosteum-derived progenitor cells
Authors: Eyckmans Jeroen , Lin Grace L. , Chen Christopher S.
Published: September 2012

It has previously been demonstrated that cell shape can influence commitment of human bone marrow-derived mesenchymal stem cells (hBMCs) to adipogenic, osteogenic, chondrogenic, and other lineages. Human periosteum-derived cells (hPDCs) exhibit multipotency similar to hBMCs, but hPDCs may offer enhanced potential for osteogenesis and chondrogenesis given their apparent endogenous role in bone and cartilage repair in vivo. Here, we examined whether hPDC differentiation is regulated by adhesive and mechanical cues comparable to that reported for hBMC differentiation. When cultured in the appropriate induction media, hPDCs at high cell seeding density demonstrated enhanced levels of adipogenic or chondrogenic markers as compared with hPDCs at low cell seeding density. Cell seeding density correlated inversely with projected area of cell spreading, and directly limiting cell spreading with micropatterned substrates promoted adipogenesis or chondrogenesis while substrates promoting cell spreading supported osteogenesis. Interestingly, cell seeding density influenced differentiation through both changes in cell shape and non-shape-mediated effects: density-dependent adipogenesis and chondrogenesis were regulated primarily by cell shape whereas non-shape effects strongly influenced osteogenic potential. Inhibition of cytoskeletal contractility by adding the Rho kinase inhibitor Y27632 further enhanced adipogenic differentiation and discouraged osteogenic differentiation of hPDCs. Together, our results suggest that multipotent lineage decisions of hPDCs are impacted by cell adhesive and mechanical cues, though to different extents than hBMCs. Thus, future studies of hPDCs and other primary stem cell populations with clinical potential should consider varying biophysical metrics for more thorough optimization of stem cell differentiation.
Carbon-based Cathode Materials Doped with a New Borazine Compound for Electrochemical Oxygen Reduction
Authors: Chang Cha Wen , Nabae Yuta , Kuroki Shigeki , Hayakawa Teruaki , Kakimoto Masa-aki , Miyata Seizo
Published: September 2012

A new compound, B,B′,B′′-tris(4-hydroxyphenyl)-N,N′,N′′-triphenylborazine (BZ) was prepared as a precursor for carbon-based oxygen reduction catalysts. The mixtures of BZ and phenolic resin were pyrolyzed under N2 at 1000 °C for 5 h and resulted in a carbonaceous material with high oxygen and boron contents. The oxygen reduction catalytic activity was much improved by the addition of this precursor. The improved catalytic activity is probably due to the oxygen-containing functionalities that are enriched in the presence of boron species.
Highly Selective and Low-swelling Phosphate-binding Polymer for Hyperphosphatemia Therapy
Authors: Inoue Atsushi , Minakami Satoshi , Kanno Takami , Suyama Kazuharu
Published: September 2012

A crosslinked poly(allylamine) was prepared by copolymerization of allylammonium dihydrogen phosphate with N,N′-diallyl-1,3-diaminopropane bis(dihydrogen phosphate). This polymer has both a high phosphate adsorption capacity and a low degree of swelling. Thus, the polymer should be useful as a therapeutic agent for hyperphosphatemia, and compared with sevelamer hydrochloride, should have fewer side effects such as constipation.
Facile Synthesis of Quinone Dimer Derivatives Substituted with Sulfanyl Groups and Their Properties
Authors: Kamimura Akio , Nokubi Tomomi , Nasu Kotaro , Takechi Yasuko , Ishihara Yuriko , Kato Kazunari , Noguchi Saori , Watanabe Masanori , Shirai Masashi , Sumimoto Michinori , Uno Hidemitsu
Published: September 2012

Quinone dimers are readily prepared quantitatively from 2-sulfanyl-1,4-dimethoxybenzene by oxidative treatment. The oxidative coupling progressed in a highly regioselective manner. Removal of O-protection and subsequent oxidation gave 5,5′-bis(sulfanylquinone) dimer in good yields. Physical properties of the dimer derivatives are also investigated.
Breath Figure of Water and Ethanol on Contaminated Solid Surfaces
Authors: Nonomura Yoshimune , Tanaka Tomoya
Published: September 2012

We observed the condensation of water and ethanol on a hydrophobic polymer film coated with fluorinated silicone particles and identified five states: the circular droplet, ellipsoidal droplet, network, huge droplet, and film states. The shape of the condensed droplets changed with the particle density and the wettability of the particles by the liquid.