bluuebunny/crossref_metadata_2025 huggingface dataset:
Why are family carers of people with dementia dissatisfied with general hospital care? a qualitative study
Authors: Jurgens Fiona J , Clissett Philip , Gladman John RF , Harwood Rowan H
Published: September 2012

Background

Families and other carers report widespread dissatisfaction with general hospital care for confused older people.

Methods

We undertook a qualitative interviews study of 35 family carers of 34 confused older patients to ascertain their experiences of care on geriatric and general medical, and orthopaedic wards of a large English hospital. Transcripts were analysed using a grounded theory approach. Themes identified in interviews were categorised, and used to build a model explaining dissatisfaction with care.

Results

The experience of hospital care was often negative. Key themes were events (illness leading to admission, experiences in the hospital, adverse occurrences including deterioration in health, or perceived poor care); expectations (which were sometimes unrealistic, usually unexplored by staff, and largely unmet from the carers’ perspective); and relationships with staff (poor communication and conflict over care). Expectations were influenced by prior experience. A cycle of discontent is proposed. Events (or ‘crises’) are associated with expectations. When these are unmet, carers become uncertain or suspicious, which leads to a period of ‘hyper vigilant monitoring’ during which carers seek out evidence of poor care, culminating in challenge, conflict with staff, or withdrawal, itself a crisis. The cycle could be completed early during the admission pathway, and multiple cycles within a single admission were seen.

Conclusion

People with dementia who have family carers should be considered together as a unit. Family carers are often stressed and tired, and need engaging and reassuring. They need to give and receive information about the care of the person with dementia, and offered the opportunity to participate in care whilst in hospital. Understanding the perspective of the family carer, and recognising elements of the ‘cycle of discontent’, could help ward staff anticipate carer needs, enable relationship building, to pre-empt or avoid dissatisfaction or conflict.
Genetic association with overall survival of taxane-treated lung cancer patients - a genome-wide association study in human lymphoblastoid cell lines followed by a clinical association study
Authors: Niu Nifang , Schaid Daniel J , Abo Ryan P , Kalari Krishna , Fridley Brooke L , Feng Qiping , Jenkins Gregory , Batzler Anthony , Brisbin Abra G , Cunningham Julie M , Li Liang , Sun Zhifu , Yang Ping , Wang Liewei
Published: September 2012

Background

Taxane is one of the first line treatments of lung cancer. In order to identify novel single nucleotide polymorphisms (SNPs) that might contribute to taxane response, we performed a genome-wide association study (GWAS) for two taxanes, paclitaxel and docetaxel, using 276 lymphoblastoid cell lines (LCLs), followed by genotyping of top candidate SNPs in 874 lung cancer patient samples treated with paclitaxel.

Methods

GWAS was performed using 1.3 million SNPs and taxane cytotoxicity IC50 values for 276 LCLs. The association of selected SNPs with overall survival in 76 small or 798 non-small cell lung cancer (SCLC, NSCLC) patients were analyzed by Cox regression model, followed by integrated SNP-microRNA-expression association analysis in LCLs and siRNA screening of candidate genes in SCLC (H196) and NSCLC (A549) cell lines.

Results

147 and 180 SNPs were associated with paclitaxel or docetaxel IC50s with p-values <10-4 in the LCLs, respectively. Genotyping of 153 candidate SNPs in 874 lung cancer patient samples identified 8 SNPs (p-value < 0.05) associated with either SCLC or NSCLC patient overall survival. Knockdown of PIP4K2A, CCT5, CMBL, EXO1, KMO and OPN3, genes within 200 kb up-/downstream of the 3 SNPs that were associated with SCLC overall survival (rs1778335, rs2662411 and rs7519667), significantly desensitized H196 to paclitaxel. SNPs rs2662411 and rs1778335 were associated with mRNA expression of CMBL or PIP4K2A through microRNA (miRNA) hsa-miR-584 or hsa-miR-1468.

Conclusions

GWAS in an LCL model system, joined with clinical translational and functional studies, might help us identify genetic variations associated with overall survival of lung cancer patients treated paclitaxel.
Electronic monitoring of symptoms and syndromes associated with cancer: methods of a randomized controlled trial SAKK 95/06 E-MOSAIC
Authors: Blum David , Koeberle Dieter , Ribi Karin , Schmitz Shu-Fang Hsu , Utiger Urs , Klingbiel Dirk , Strasser Florian
Published: September 2012

Background

In patients with advanced, incurable cancer, anticancer treatment may be used to alleviate cancer-related symptoms, but monitoring of them in daily practice is rarely done. We aim to test the effectiveness of a real-time symptom and syndrome assessment using the E-MO
S
AIC software installed in handheld computer generating a longitudinal monitoring sheet (LoMoS) provided to the oncologists in a phase III setting.

Methods

In this prospective multicentre cluster randomized phase-III trial patients with any incurable solid tumor and having defined cancer related symptoms, who receive new outpatient chemotherapy in palliative intention (expected tumor-size response rate ≤20%) are eligible. Immediately before the weekly visit to oncologists, all patients complete with nurse assistance the E-MO
S
AIC Assessment: Edmonton Symptom Assessment Scale, ≤3 additional symptoms, estimated nutritional intake, body weight, Karnofsky and medications for pain and cachexia. Experienced oncologists will be randomized to receive the LoMoS or not. To minimize contamination, LoMoS are removed from the medical charts after visits. Primary endpoint is the difference in global quality of life (items 29 & 30 of EORTC-QlQ-C30) between baseline and last study visit at week 6, with a 10 point between-arm difference considered to be clinically relevant. 20 clusters (=oncologists) per treatment arm with 4–8 patients each are aimed for to achieve a significance level of 5% and a power of 80% in a mixed model approach. Selected co- variables are included in the model for adjustment. Secondary endpoints include patient-perceived patient-physician communication symptom burden over time, and oncologists’ symptom management performance (predefined thresholds of symptoms compared to oncologists’ pharmacological, diagnostic or counselling actions [structured chart review]).

Discussion

This trial will contribute to the research question, whether structured, longitudinal monitoring of patients’ multidimensional symptoms, indicators for symptom management, and clinical benefit outcomes can influence patients’ quality of life and symptom distress, in a setting of routine oncology practice.

Trial registration

Current Controlled Trials NCT00477919
An efficient procedure for protein extraction from formalin-fixed, paraffin-embedded tissues for reverse phase protein arrays
Authors: Guo Huifang , Liu Wenbin , Ju Zhenlin , Tamboli Pheroze , Jonasch Eric , Mills Gordon B , Lu Yiling , Hennessy Bryan T , Tsavachidou Dimitra
Published: September 2012

Introduction

Protein extraction from formalin-fixed paraffin-embedded (FFPE) tissues is challenging due to extensive molecular crosslinking that occurs upon formalin fixation. Reverse-phase protein array (RPPA) is a high-throughput technology, which can detect changes in protein levels and protein functionality in numerous tissue and cell sources. It has been used to evaluate protein expression mainly in frozen preparations or FFPE-based studies of limited scope. Reproducibility and reliability of the technique in FFPE samples has not yet been demonstrated extensively. We developed and optimized an efficient and reproducible procedure for extraction of proteins from FFPE cells and xenografts, and then applied the method to FFPE patient tissues and evaluated its performance on RPPA.

Results

Fresh frozen and FFPE preparations from cell lines, xenografts and breast cancer and renal tissues were included in the study. Serial FFPE cell or xenograft sections were deparaffinized and extracted by six different protein extraction protocols. The yield and level of protein degradation were evaluated by SDS-PAGE and Western Blots. The most efficient protocol was used to prepare protein lysates from breast cancer and renal tissues, which were subsequently subjected to RPPA. Reproducibility was evaluated and Spearman correlation was calculated between matching fresh frozen and FFPE samples.

The most effective approach from six protein extraction protocols tested enabled efficient extraction of immunoreactive protein from cell line, breast cancer and renal tissue sample sets. 85% of the total of 169 markers tested on RPPA demonstrated significant correlation between FFPE and frozen preparations (p < 0.05) in at least one cell or tissue type, with only 23 markers common in all three sample sets. In addition, FFPE preparations yielded biologically meaningful observations related to pathway signaling status in cell lines, and classification of renal tissues.

Conclusions

With optimized protein extraction methods, FFPE tissues can be a valuable source in generating reproducible and biologically relevant proteomic profiles using RPPA, with specific marker performance varying according to tissue type.
Preparation and characterization of nanosized P(NIPAM-MBA) hydrogel particles and adsorption of bovine serum albumin on their surface
Authors: Zhu Xiaoli , Gu Xiangling , Zhang Lina , Kong Xiang-Zheng
Published: September 2012

Thermosensitive polymer hydrogel particles with size varying from 480 to 620 nm were prepared through precipitation copolymerization of N-isopropylacrylamide with N,N′-methylenebisacrylamide (MBA) in water with ammonium persulfate as the initiator. Only polymer hydrogels without any coagula were obtained when MBA concentration in the monomer mixture was kept between 2.5 and 10.0 wt%; with increased MBA concentration, the monomer conversion was enhanced, the size of the hydrogels was increased, and their shrinking was lessened when heated from 25°C to 40°C. Bovine serum albumin adsorption on the surface of the hydrogels of different MBA content was measured at different pH levels and under different temperatures. The results demonstrated that the adsorption of the protein on the hydrogels could be controlled by adjusting the pH, the temperature of adsorption, and the crosslinking in the hydrogels. The results were interpreted, and the mechanisms of the polymerization were proposed.
The Non-Synonymous SNP, R1150W, in SCN9A is Not Associated with Chronic Widespread Pain Susceptibility
Authors: Holliday Kate L , Thomson Wendy , Neogi Tuhina , Felson David T , Wang Ke , Wu Frederick C , Huhtaniemi Ilpo T , Bartfai Gyorgy , Casanueva Felipe , Forti Gianni , Kula Krzysztof , Punab Margus , Vanderschueren Dirk , Macfarlane Gary J , Horan Michael A , Ollier William , Payton Antony , Pendleton Neil , McBeth John
Published: September 2012

Background:

Mutations in SCN9A, encoding the alpha subunit of the voltage-gated sodium channel (Nav1.7), have caused severe pain disorders and congenital insensitivity to pain. The aim of this study was to validate the previously reported association between a common non-synonymous polymorphism (R1150W, rs6746030) in SCN9A and chronic widespread pain (CWP), in independent population-based cohorts.

Findings:

Genotype data for rs6746030 was available in four population-based cohorts (EPIFUND, the European Male Ageing Study (EMAS), the Framingham study and the Dyne Steel DNA Bank of Ageing and Cognition). Pain was assessed using body manikins and CWP was scored using American College of Rheumatology (ACR) criteria in all cohorts, except the Framingham study which assessed widespread pain (WP) using ACR criteria on a joint pain homunculus. Controls were subjects who reported no pain. Logistic regression (additive genetic model) was used to test for association between rs6746030 and CWP compared to controls, adjusting for study centre in EMAS. Generalised estimating equation regression was used to test for association between rs6746030 and WP, whilst accounting for relatedness between subjects in the Framingham study. Genotype data for rs6746030 was available for 1071 CWP cases and 3212 controls. There was no significant association between CWP and rs6476030 in individual cohorts or when combined in a fixed-effects meta-analysis (Odds Ratio = 0.96 (95% confidence interval 0.82, 1.11) p = 0.567).

Conclusions:

In contrast to a previous study, no association between a non-synonymous polymorphism in SCN9A and CWP was observed in multiple population-based cohorts.
Improving patient-centeredness of fertility care using a multifaceted approach: study protocol for a randomized controlled trial
Authors: Huppelschoten Aleida G , van Duijnhoven Noortje TL , Hermens Rosella PMG , Verhaak Chris , Kremer Jan AM , Nelen Willianne LDM
Published: September 2012

Background

Beside traditional outcomes of safety and (cost-)effectiveness, the Institute of Medicine states patient-centeredness as an independent outcome indicator to evaluate the quality of healthcare. Providing patient-centered care is important because patients want to be heard for their ideas and concerns. Healthcare areas associated with high emotions and intensive treatment periods could especially benefit from patient-centered care. How care can become optimally improved in patient-centeredness is unknown. Therefore, we will conduct a study in the context of Dutch fertility care to determine the effects of a multifaceted approach on patient-centeredness, patients’ quality of life (QoL) and levels of distress. Our aims are to investigate the effectiveness of a multifaceted approach and to identify determinants of a change in the level of patient-centeredness, patients’ QoL and distress levels. This paper presents the study protocol.

Methods/Design

In a cluster-randomized trial in 32 Dutch fertility clinics the effects of a multifaceted approach will be determined on the level of patient-centeredness (Patient-centredness Questionnaire – Infertility), patients’ QoL (FertiQoL) and levels of distress (SCREENIVF). The multifaceted approach includes audit and feedback, educational outreach visits and patient-mediated interventions. Potential determinants of a change in patient-centeredness, patients’ QoL and levels of distress will be collected by an addendum to the patients’ questionnaire and a professionals’ questionnaire. The latter includes the Organizational Culture Assessment Instrument about the clinic’s culture as a possible determinant of an increase in patient-centered care.

Discussion

The study is expected to yield important new evidence about the effects of a multifaceted approach on levels of patient-centeredness, patients’ QoL and distress in fertility care. Furthermore, determinants associated with a change in these outcome measures will be studied. With knowledge of these results, patient-centered care and thus the quality of healthcare can be improved. Moreover, the results of this study could be useful for similar initiatives to improve the quality of care delivery. The results of this project are expected at the end of 2013.

Trial registration

Clinicialtrials.gov NCT01481064
A role of ghrelin in canine mammary carcinoma cells proliferation, apoptosis and migration
Authors: Majchrzak Kinga , Pawłowski Karol M , Orzechowska Emilia J , Dolka Izabella , Mucha Joanna , Motyl Tomasz , Król Magdalena
Published: September 2012

Background

Ghrelin is a natural ligand of the growth hormone secretagogue receptor (GHS-R). They are often co-expressed in multiple human tumors and related cancer cell lines what can indicate that the ghrelin/GHS-R axis may have an important role in tumor growth and progression. However, a role of ghrelin in canine tumors remains unknown. Thus, the aim of our study was two-fold: (1) to assess expression of ghrelin and its receptor in canine mammary cancer and (2) to examine the effect of ghrelin on carcinoma cells proliferation, apoptosis, migration and invasion. The expression of ghrelin and its receptor in canine mammary cancer tissues and cell lines (isolated from primary tumors and their metastases) was examined using Real-time qPCR and immunohistochemistry. For apoptosis analysis the Annexin V and propidium iodide dual staining was applied whereas cell proliferation was evaluated by MTT assay and BrdU incorporation test. The influence of ghrelin on cancer cells migration and invasion was assessed using Boyden chamber assays and wound healing assay.

Results

The highest expression of ghrelin was observed in metastatic cancers whereas the lowest expression of ghrelin receptor was detected in tumors of the 3rd grade of malignancy. Higher expression of ghrelin and its receptor was detected in cancer cell lines isolated from metastases than in cell lines isolated from primary tumors. In vitro experiments demonstrated that exposure to low doses of ghrelin stimulates cellular proliferation, inhibits apoptosis and promotes motility and invasion of canine mammary cancer cells. Growth hormone secretagogue receptor inhibitor ([D-Lys3]-GHRP6) as well as RNA interference enhances early apoptosis.

Conclusion

The presence of ghrelin and GHS-R in all of the examined canine mammary tumors may indicate their biological role in cancer growth and development. Our experiments conducted in vitro confirmed that ghrelin promotes cancer development and metastasis.
A survey of Mycoplasma agalactiaein dairy sheep farms in Spain
Authors: Ariza-Miguel Jaime , Rodríguez-Lázaro David , Hernández Marta
Published: September 2012

Background

Contagious Agalactia (CA) is one of the major animal health problems in small ruminants because of its economic significance. Currently, four Mycoplasma spp. have been associated with this syndrome: M. agalactiae, M. mycoides subsp. capri, M. capricolum subsp. capricolum and M. putrefaciens. Their presence has been evaluated in several studies conducted in CA-endemic countries. However, previous Spanish studies have been focused on caprine CA, and there is a knowledge gap regarding which Mycoplasma species are present in sheep flocks from Spain, which has the second highest number of sheep amongst the 27 European Union member states. Consequently, we investigated the presence and geographic distribution of the four CA-causing mycoplasmas in Spanish dairy sheep farms. This is the first time such an investigation has been performed.

Results

Three hundred thirty nine out of 922 sheep flocks were positive for M. agalactiae by real time PCR (36.8%) and 85 by microbiological identification (9.2%). Interestingly, all 597 milk samples assessed for the presence of M. mycoides subsp. capri, M. capricolum subsp. capricolum and M. putrefaciens tested negative. To evaluate the intermittent excretion of the pathogen in milk, we sampled 391 additional farms from 2 to 5 times, resulting that in 26.3% of the cases a previously positive farm tested negative in a later sampling.

Conclusions

M. agalactiae was the only Mycoplasma species detected in the study area showing a high frequency of presence and wide distribution. Therefore, the establishment of a permanent surveillance network is advantageous, as well as the implementation of control and prevention measures to hinder the dissemination of M. agalactiae and to prevent the entrance of other Mycoplasma species.
Influence of ischemia before vein grafting on early hyperplasia of the graft and the dynamic changes of the intima after grafting
Authors: Zou RongJiang , Sun MingJuan , Lu ZhiQian , Guo QingKui
Published: September 2012

Background

To investigate both the influence of ischemia before grafting on early hyperplasia of the vein grafts, and the dynamic changes of the intima after grafting in a rabbit model of vein graft disease.

Methods

We performed paired vein graft experiments under different ischemic conditions (15 vs. 60 min; 15 vs. 90 min) in the neck of the rabbits and compared the differences between the grafts. Clopidogrel, an anti-platelet agent, was administered before and after surgery. Twenty-eight days after the grafting procedure, the veins were evaluated microscopically. The dynamic changes of the intima after grafting were evaluated by scanning electron microscopy over time.

Results

The vein grafts subjected to 60- or 90-min ischemia exhibited no differences compared to those subjected to 15-min ischemia in terms of the mean thickness of the intimal, medial, and adventitial layers of the graft. Similarly, there was no difference in the Ki-67 labeling index (proliferation marker) between the vein grafts. Vein grafts with 15-min ischemia lost endothelial cells (ECs) but healed by 3 days post graft, whereas vein grafts with 90-min ischemia suffered serious EC loss, which was restored with new ECs during days 2 to 14 post graft.

Conclusions

Ninety-minute ischemia before vein grafting can cause serious EC loss, but does not increase early intimal hyperplasia when clopidogrel is administered. Protecting the vein from ischemia and reperfusion injury preserves ECs.
Reduced elastogenesis: a clue to the arteriosclerosis and emphysematous changes in Schimke immuno-osseous dysplasia?
Authors: Morimoto Marie , Yu Zhongxin , Stenzel Peter , Clewing J Marietta , Najafian Behzad , Mayfield Christy , Hendson Glenda , Weinkauf Justin G , Gormley Andrew K , Parham David M , Ponniah Umakumaran , André Jean-Luc , Asakura Yumi , Basiratnia Mitra , Bogdanović Radovan , Bokenkamp Arend , Bonneau Dominique , Buck Anna , Charrow Joel , Cochat Pierre , Cordeiro Isabel , Deschenes Georges , Fenkçi M Semin , Frange Pierre , Fründ Stefan , Fryssira Helen , Guillen-Navarro Encarna , Keller Kory , Kirmani Salman , Kobelka Christine , Lamfers Petra , Levtchenko Elena , Lewis David B , Massella Laura , McLeod D Ross , Milford David V , Nobili François , Saraiva Jorge M , Semerci C Nur , Shoemaker Lawrence , Stajić Nataša , Stein Anja , Taha Doris , Wand Dorothea , Zonana Jonathan , Lücke Thomas , Boerkoel Cornelius F
Published: September 2012

Background

Arteriosclerosis and emphysema develop in individuals with Schimke immuno-osseous dysplasia (SIOD), a multisystem disorder caused by biallelic mutations in SMARCAL1 (SWI/SNF-related, matrix-associated, actin-dependent regulator of chromatin, subfamily a-like 1). However, the mechanism by which the vascular and pulmonary disease arises in SIOD remains unknown.

Methods

We reviewed the records of 65 patients with SMARCAL1 mutations. Molecular and immunohistochemical analyses were conducted on autopsy tissue from 4 SIOD patients.

Results

Thirty-two of 63 patients had signs of arteriosclerosis and 3 of 51 had signs of emphysema. The arteriosclerosis was characterized by intimal and medial hyperplasia, smooth muscle cell hyperplasia and fragmented and disorganized elastin fibers, and the pulmonary disease was characterized by panlobular enlargement of air spaces. Consistent with a cell autonomous disorder, SMARCAL1 was expressed in arterial and lung tissue, and both the aorta and lung of SIOD patients had reduced expression of elastin and alterations in the expression of regulators of elastin gene expression.

Conclusions

This first comprehensive study of the vascular and pulmonary complications of SIOD shows that these commonly cause morbidity and mortality and might arise from impaired elastogenesis. Additionally, the effect of SMARCAL1 deficiency on elastin expression provides a model for understanding other features of SIOD.
PathNet: a tool for pathway analysis using topological information
Authors: Dutta Bhaskar , Wallqvist Anders , Reifman Jaques
Published: September 2012

Background

Identification of canonical pathways through enrichment of differentially expressed genes in a given pathway is a widely used method for interpreting gene lists generated from high-throughput experimental studies. However, most algorithms treat pathways as sets of genes, disregarding any inter- and intra-pathway connectivity information, and do not provide insights beyond identifying lists of pathways.

Results

We developed an algorithm (PathNet) that utilizes the connectivity information in canonical pathway descriptions to help identify study-relevant pathways and characterize non-obvious dependencies and connections among pathways using gene expression data. PathNet considers both the differential expression of genes and their pathway neighbors to strengthen the evidence that a pathway is implicated in the biological conditions characterizing the experiment. As an adjunct to this analysis, PathNet uses the connectivity of the differentially expressed genes among all pathways to score pathway contextual associations and statistically identify biological relations among pathways. In this study, we used PathNet to identify biologically relevant results in two Alzheimer’s disease microarray datasets, and compared its performance with existing methods. Importantly, PathNet identified de-regulation of the ubiquitin-mediated proteolysis pathway as an important component in Alzheimer’s disease progression, despite the absence of this pathway in the standard enrichment analyses.

Conclusions

PathNet is a novel method for identifying enrichment and association between canonical pathways in the context of gene expression data. It takes into account topological information present in pathways to reveal biological information. PathNet is available as an R workspace image fromhttp://www.bhsai.org/downloads/pathnet/.
Gastric lipoma presenting as a giant bulging mass in an oligosymptomatic patient: a case report
Authors: Neto Francisco Américo Fernandes , Ferreira Maria Cristina Furian , Bertoncello Luiz Carlos Nascimento , Neto André Amate , de Aveiro Wilson Chubassi , Bento Caroline Agnelli , Cecchino Gustavo Nardini , Rocha Marco Antonio Mendes
Published: September 2012

Introduction

Lipomas of the gastrointestinal tract are a rare condition. Only 5% are of gastric origin, and this corresponds to 2% to 3% of all benign tumors of the stomach and less than 1% of all gastric neoplasms. It is our purpose to report an unusual presentation of a giant gastric lipoma in an oligosymptomatic patient and highlight the importance of discussing differential diagnosis in this situation. A review of the literature has shown that this is one of the largest gastric lipomas described.

Case presentation

We describe a rare case of a benign gastric tumor with uncommon features in a 63-year-old Caucasian woman. She was admitted with abdominal discomfort, nausea, and upper abdominal fullness after eating. The lesion was suspicious of malignancy because of its dimension and central contrast enhancement on computed tomography. Conventional upper digestive endoscopy revealed a large bulging mass in the gastric posterior wall and three ulcerated areas. In this procedure, a technical limitation due to the location of the mass in the submucosa prevented an adequate biopsy from being obtained. The fragments obtained from the ulcers revealed nothing but necrotic mucosa. Our patient underwent a subtotal gastrectomy and D1 lymphadenectomy with a Roux-en-Y reconstruction. Macroscopic findings revealed a 12 × 8 × 6cm mass with a volume of 576cm3, and the histological pattern demonstrated well-differentiated mature adipose tissue surrounded by a fibrous capsule, confirming the diagnosis of gastric submucosal lipoma.

Conclusions

Gastric lipoma is a rare benign disease that eventually simulates a malignant tumor.
Transcriptomic analysis of the oleaginous microalga Neochloris oleoabundans reveals metabolic insights into triacylglyceride accumulation
Authors: Rismani-Yazdi Hamid , Haznedaroglu Berat Z , Hsin Carol , Peccia Jordan
Published: September 2012

Background

The lack of sequenced genomes for oleaginous microalgae limits our understanding of the mechanisms these organisms utilize to become enriched in triglycerides. Here we report thede novotranscriptome assembly and quantitative gene expression analysis of the oleaginous microalgaNeochloris oleoabundans, with a focus on the complex interaction of pathways associated with the production of the triacylglycerol (TAG) biofuel precursor.

Results

After growth under nitrogen replete and nitrogen limiting conditions, we quantified the cellular content of major biomolecules including total lipids, triacylglycerides, starch, protein, and chlorophyll. Transcribed genes were sequenced, the transcriptome was assembledde novo, and the expression of major functional categories, relevant pathways, and important genes was quantified through the mapping of reads to the transcriptome. Over 87 million, 77 base pair high quality reads were produced on the Illumina HiSeq sequencing platform. Metabolite measurements supported by genes and pathway expression results indicated that under the nitrogen-limiting condition, carbon is partitioned toward triglyceride production, which increased fivefold over the nitrogen-replete control. In addition to the observed overexpression of the fatty acid synthesis pathway, TAG production during nitrogen limitation was bolstered by repression of the β-oxidation pathway, up-regulation of genes encoding for the pyruvate dehydrogenase complex which funnels acetyl-CoA to lipid biosynthesis, activation of the pentose phosphate pathway to supply reducing equivalents to inorganic nitrogen assimilation and fatty acid biosynthesis, and the up-regulation of lipases—presumably to reconstruct cell membranes in order to supply additional fatty acids for TAG biosynthesis.

Conclusions

Our quantitative transcriptome study reveals a broad overview of how nitrogen stress results in excess TAG production inN. oleoabundans, and provides a variety of genetic engineering targets and strategies for focused efforts to improve the production rate and cellular content of biofuel precursors in oleaginous microalgae.
LibKiSAO: a Java library for Querying KiSAO
Authors: Zhukova Anna , Adams Richard , Laibe Camille , Le Novère Nicolas
Published: September 2012

Background

The Kinetic Simulation Algorithm Ontology (KiSAO) supplies information about existing algorithms available for the simulation of Systems Biology models, their characteristics, parameters and inter-relationships. KiSAO enables the unambiguous identification of algorithms from simulation descriptions. Information about analogous methods having similar characteristics and about algorithm parameters incorporated into KiSAO is desirable for simulation tools. To retrieve this information programmatically an application programming interface (API) for KiSAO is needed.

Findings

We developed libKiSAO, a Java library to enable querying of the KiSA Ontology. It implements methods to retrieve information about simulation algorithms stored in KiSAO, their characteristics and parameters, and methods to query the algorithm hierarchy and search for similar algorithms providing comparable results for the same simulation set-up. Using libKiSAO, simulation tools can make logical inferences based on this knowledge and choose the most appropriate algorithm to perform a simulation. LibKiSAO also enables simulation tools to handle a wider range of simulation descriptions by determining which of the available methods are similar and can be used instead of the one indicated in the simulation description if that one is not implemented.

Conclusions

LibKiSAO enables Java applications to easily access information about simulation algorithms, their characteristics and parameters stored in the OWL-encoded Kinetic Simulation Algorithm Ontology. LibKiSAO can be used by simulation description editors and simulation tools to improve reproducibility of computational simulation tasks and facilitate model re-use.
Technical and clinical analysis of microEEG: a miniature wireless EEG device designed to record high-quality EEG in the emergency department
Authors: Omurtag Ahmet , Baki Samah G Abdel , Chari Geetha , Cracco Roger Q , Zehtabchi Shahriar , Fenton André A , Grant Arthur C
Published: September 2012

Background

We describe and characterize the performance of microEEG compared to that of a commercially available and widely used clinical EEG machine. microEEG is a portable, battery-operated, wireless EEG device, developed by Bio-Signal Group to overcome the obstacles to routine use of EEG in emergency departments (EDs).

Methods

The microEEG was used to obtain EEGs from healthy volunteers in the EEG laboratory and ED. The standard system was used to obtain EEGs from healthy volunteers in the EEG laboratory, and studies recorded from patients in the ED or ICU were also used for comparison. In one experiment, a signal splitter was used to record simultaneous microEEG and standard EEG from the same electrodes.

Results

EEG signal analysis techniques indicated good agreement between microEEG and the standard system in 66 EEGs recorded in the EEG laboratory and the ED. In the simultaneous recording the microEEG and standard system signals differed only in a smaller amount of 60 Hz noise in the microEEG signal. In a blinded review by a board-certified clinical neurophysiologist, differences in technical quality or interpretability were insignificant between standard recordings in the EEG laboratory and microEEG recordings from standard or electrode cap electrodes in the ED or EEG laboratory. The microEEG data recording characteristics such as analog-to-digital conversion resolution (16 bits), input impedance (>100MΩ), and common-mode rejection ratio (85 dB) are similar to those of commercially available systems, although the microEEG is many times smaller (88 g and 9.4 × 4.4 × 3.8 cm).

Conclusions

Our results suggest that the technical qualities of microEEG are non-inferior to a standard commercially available EEG recording device. EEG in the ED is an unmet medical need due to space and time constraints, high levels of ambient electrical noise, and the cost of 24/7 EEG technologist availability. This study suggests that using microEEG with an electrode cap that can be applied easily and quickly can surmount these obstacles without compromising technical quality.
OGRO: The Overview of functionally characterized Genes in Rice online database
Authors: Yamamoto Eiji , Yonemaru Jun-ichi , Yamamoto Toshio , Yano Masahiro
Published: September 2012

Background

The high-quality sequence information and rich bioinformatics tools available for rice have contributed to remarkable advances in functional genomics. To facilitate the application of gene function information to the study of natural variation in rice, we comprehensively searched for articles related to rice functional genomics and extracted information on functionally characterized genes.

Results

As of 31 March 2012, 702 functionally characterized genes were annotated. This number represents about 1.6% of the predicted loci in the Rice Annotation Project Database. The compiled gene information is organized to facilitate direct comparisons with quantitative trait locus (QTL) information in the Q-TARO database. Comparison of genomic locations between functionally characterized genes and the QTLs revealed that QTL clusters were often co-localized with high-density gene regions, and that the genes associated with the QTLs in these clusters were different genes, suggesting that these QTL clusters are likely to be explained by tightly linked but distinct genes. Information on the functionally characterized genes compiled during this study is now available in the O verview of Functionally Characterized G enes in R ice O nline database (OGRO) on the Q-TARO website (http://qtaro.abr.affrc.go.jp/ogro). The database has two interfaces: a table containing gene information, and a genome viewer that allows users to compare the locations of QTLs and functionally characterized genes.

Conclusions

OGRO on Q-TARO will facilitate a candidate-gene approach to identifying the genes responsible for QTLs. Because the QTL descriptions in Q-TARO contain information on agronomic traits, such comparisons will also facilitate the annotation of functionally characterized genes in terms of their effects on traits important for rice breeding. The increasing amount of information on rice gene function being generated from mutant panels and other types of studies will make the OGRO database even more valuable in the future.
The effect of Camellia Sinensis (green tea) mouthwash on plaque-induced gingivitis: a single-blinded randomized controlled clinical trial
Authors: Jenabian Niloofar , Moghadamnia Ali Akbar , Karami Elaheh , Mir A Poorsattar Bejeh
Published: September 2012

Background and the purpose of the Study

Complementary medicine received high attention during last decades. We aimed to assess the efficacy of Green tea mouthwash on plaque-induced gingivitis as the most common form of periodontal disease.

Methods and materials

We designed a single blinded placebo controlled clinical trial. High school female students with chronic generalized plaque-induced gingivitis were distributed to receive either 5 ml of Green tea 5% two times/day or normal saline with the same dosage. Gingival index (Sillness & Loe), plaque index (Sillness & Loe) and bleeding index (Barnett) were recorded at baseline and five consecutive weeks. Comparisons were made by a general linear model, repeated measure ANOVA and a Bonferroni test applied for multiple comparisons.

Results

Twenty five students were recruited in each arm of the study. A significant improvement was observed in all periodontal indices during the study (P < 0.001). Two groups were contrasted by changing patterns of alteration of indices (P < 0.05). Although total amount of improvement was higher in mouthwash group, the differences did not reach a statistically significant level (P > 0.05, observed power for GI: 0.09, PI: 0.11 and BI: 0.07).

Conclusion

Green tea mouthwash may be a safe and feasible adjunct treatment for inflammatory periodontal diseases. A future larger scale study is warranted for better evaluating the effect of green tea.
Longitudinal neuroimaging and neuropsychological profiles of frontotemporal dementia with C9ORF72 expansions
Authors: Mahoney Colin J , Downey Laura E , Ridgway Gerard R , Beck Jon , Clegg Shona , Blair Melanie , Finnegan Sarah , Leung Kelvin K , Yeatman Tom , Golden Hannah , Mead Simon , Rohrer Jonathan D , Fox Nick C , Warren Jason D
Published: September 2012

Introduction

Frontotemporal dementia (FTD) is a common cause of early-onset dementia with a significant genetic component, as underlined by the recent identification of repeat expansions in the gene C9ORF72 as a major cause of FTD and motor neuron disease. Understanding the neurobiology and clinical phenomenology of this novel mutation is currently a major research focus. However, few data are available concerning the longitudinal evolution of this genetic disease. Here we present longitudinal neuropsychological and neuroimaging data on a cohort of patients with pathological repeat expansions in C9ORF72.

Methods

Following a review of the University College London FTD DNA database, 20 cases were retrospectively identified with a C9ORF72 expansion. Twelve cases had longitudinal neuropsychology data available and six of these cases also had longitudinal volumetric brain magnetic resonance imaging. Cortical and subcortical volumes were extracted using FreeSurfer. Rates of whole brain, hemispheric, cerebellar and ventricular change were calculated for each subject. Nonlinear fluid registration of follow-up to baseline scan was performed to visualise longitudinal intra-subject patterns of brain atrophy and ventricular expansion.

Results

Patients had low average verbal and performance IQ at baseline that became impaired (< 5th percentile) at follow-up. In particular, visual memory, naming and dominant parietal skills all showed deterioration. Mean rates of whole brain atrophy (1.4%/year) and ventricular expansion (3.2 ml/year) were substantially greater in patients with the C9ORF72 mutation than in healthy controls; atrophy was symmetrical between the cerebral hemispheres within the C9ORF72 mutation group. The thalamus and cerebellum showed significant atrophy whereas no cortical areas were preferentially affected. Longitudinal fluid imaging in individual patients demonstrated heterogeneous patterns of progressive volume loss; however, ventricular expansion and cerebellar volume loss were consistent findings.

Conclusion

Disease evolution in C9ORF72-associated FTD is linked neuropsychologically with increasing involvement of parietal and amnestic functions, and neuroanatomically with rather diffuse and variable cortical and central atrophy but more consistent involvement of the cerebellum and thalamus. These longitudinal profiles are consistent with disease spread within a distributed subcortical network and demonstrate the feasibility of longitudinal biomarkers for tracking the evolution of the C9ORF72 mutation phenotype.
Expression of IL-20 in synovium and lesional skin of patients with psoriatic arthritis: differential response to alefacept treatment
Authors: Lebre Maria C , Jonckheere Christina L , Kraan Maarten C , van Kuijk Arno WR , Bos Jan D , de Rie Menno , Gerlag Danielle M , Tak Paul P
Published: September 2012

Introduction

Psoriatic arthritis (PsA) is an inflammatory joint disease associated with psoriasis. Alefacept (a lymphocyte function-associated antigen (LFA)-3 Ig fusion protein that binds to CD2 and functions as an antagonist to T-cell activation) has been shown to result in improvement in psoriasis but has limited effectiveness in PsA. Interleukin-20 (IL-20) is a key proinflammatory cytokine involved in the pathogenesis of psoriasis. The effects of alefacept treatment on IL-20 expression in the synovium of patients with psoriasis and PsA are currently unknown.

Methods

Eleven patients with active PsA and chronic plaque psoriasis were treated with alefacept (7.5 mg per week for 12 weeks) in an open-label study. Skin biopsies were taken before and after 1 and 6 weeks, whereas synovial biopsies were obtained before and 4 and 12 weeks after treatment. Synovial biopsies from patients with rheumatoid arthritis (RA) (n = 10) were used as disease controls. Immunohistochemical analysis was performed to detect IL-20 expression, and stained synovial tissue sections were evaluated with digital image analysis. Double staining was performed with IL-20 and CD68 (macrophages), and conversely with CD55 (fibroblast-like synoviocytes, FLSs) to determine the phenotype of IL-20-positive cells in PsA synovium. IL-20 expression in skin sections (n = 6) was analyzed semiquantitatively.

Results

IL-20 was abundantly expressed in both PsA and RA synovial tissues. In inflamed PsA synovium, CD68+ macrophages and CD55+ FLSs coexpressed IL-20, and its expression correlated with the numbers of FLSs. IL-20 expression in lesional skin of PsA patients decreased significantly (P = 0.04) 6 weeks after treatment and correlated positively with the Psoriasis Area and Severity Index (PASI). IL-20 expression in PsA synovium was not affected by alefacept.

Conclusions

Conceivably, the relatively limited effectiveness of alefacept in PsA patients (compared with anti-tumor necrosis factor (TNF) therapy) might be explained in part by persistent FLS-derived IL-20 expression.
Estimating source location using normalized magnetic source strength calculated from magnetic gradient tensor data
Authors: Beiki Majid , Clark David A. , Austin James R. , Foss Clive A.
Published: September 2012

For a number of widely used models, normalized source strength (NSS) can be derived from eigenvalues of the magnetic gradient tensor. The NSS is proportional to a constant [Formula: see text] normalized by the [Formula: see text]th power of the distance between observation and integration points where [Formula: see text] is a shape factor depending upon geometry of the model and [Formula: see text] is the structural index. The NSS is independent of magnetization direction, and its amplitude is only affected by the magnitude of magnetization. The NSS is also a homogenous function and satisfies Euler’s homogeneity equation. Therefore, Euler deconvolution of the NSS can be used to estimate source location. In our algorithm, we use data points enclosed by a square window centered at maxima of the NSS for simultaneously estimating the source location and structural index. The window size is increased until it exceeds a predefined limit. Then the most reliable solution is chosen based on some statistical analysis (minimum uncertainty). One of the advantages of the presented method is that it allows automatic identification of the structural index as the constant background field is eliminated. Another advantage is reduction of interference effects from neighboring sources by differentiation of the NSS. We have compared our method with the analytic signal amplitude and when the magnetic source contains remanent magnetization with a different direction to the inducing field, the NSS provides more reliable information about source geometry. Application of the method has been demonstrated on an aeromagnetic data set from the Tuckers Igneous Complex, Queensland, Australia. The NSS has improved interpretation of magnetic anomalies for this igneous complex, for which available geologic information shows relatively strong remanent magnetization.
Quantitative seismic analysis of a thin layer of CO2 in the Sleipner injection plume
Authors: Williams Gareth , Chadwick Andrew
Published: September 2012

Time-lapse seismic reflection data have proved to be the key monitoring tool at the Sleipner [Formula: see text] injection project. Thin layers of [Formula: see text] in the Sleipner injection plume show striking reflectivity on the time-lapse data, but the derivation of accurate layer properties, such as thickness and velocity, remains very challenging. This is because the rock physics properties are not well-constrained nor are [Formula: see text] distributions on a small scale. However, because the reflectivity is dominantly composed of interference wavelets from thin-layer tuning, the amplitude and frequency content of the wavelets can be diagnostic of their temporal thickness. A spectral decomposition algorithm based on the smoothed pseudo Wigner-Ville distribution has been developed. This enables single frequency slices to be extracted with sufficient frequency and temporal resolution to provide diagnostic spectral information on individual [Formula: see text] layers. The topmost layer of [Formula: see text] in the plume is particularly suitable for this type of analysis because it is not affected by attenuation from overlying [Formula: see text] layers and because there are areas in which it is temporally isolated from deeper layers. Initial application of the algorithm to the topmost layer shows strong evidence of thin-layer tuning effects. Analysis of tuning frequencies on high-resolution 2D data suggests that layer two-way temporal thicknesses in the range 6 to 11 ms can be derived with an accuracy of c. 2 ms. Direct measurements of reflectivity from the top and the base of the layer permit calculation of layer velocity, with values of around [Formula: see text], in reasonable agreement with existing rock physics estimates. The frequency analysis can, therefore, provide diagnostic information on layer thicknesses in the range of 4 to 8 ms. The method is currently being extended to the full 3D time-lapse data sets at Sleipner.