bluuebunny/crossref_metadata_2025 huggingface dataset:
Identification of population substructure among Jews using STR markers and dependence on reference populations included
Authors: Listman Jennifer B , Hasin Deborah , Kranzler Henry R , Malison Robert T , Mutirangura Apiwat , Sughondhabirom Atapol , Aharonovich Efrat , Spivak Baruch , Gelernter Joel
Published: June 2010

Background

Detecting population substructure is a critical issue for association studies of health behaviors and other traits. Whether inherent in the population or an artifact of marker choice, determining aspects of a population's genetic history as potential sources of substructure can aid in design of future genetic studies. Jewish populations, among which association studies are often conducted, have a known history of migrations. As a necessary step in understanding population structure to conduct valid association studies of health behaviors among Israeli Jews, we investigated genetic signatures of this history and quantified substructure to facilitate future investigations of these phenotypes in this population.

Results

Using 32 autosomal STR markers and the program STRUCTURE, we differentiated between Ashkenazi (AJ, N = 135) and non-Ashkenazi (NAJ, N = 226) Jewish populations in the form of Northern and Southern geographic genetic components (AJ north 73%, south 23%, NAJ north 33%, south 60%). The ability to detect substructure within these closely related populations using a small STR panel was contingent on including additional samples representing major continental populations in the analyses.

Conclusions

Although clustering programs such as STRUCTURE are designed to assign proportions of ancestry to individuals without reference population information, when Jewish samples were analyzed in the absence of proxy parental populations, substructure within Jews was not detected. Generally, for samples with a given grandparental country of birth, STRUCTURE assignment values to Northern, Southern, African and Asian clusters agreed with mitochondrial DNA and Y-chromosomal data from previous studies as well as historical records of migration and intermarriage.
Expression profiling of Crambe abyssinicaunder arsenate stress identifies genes and gene networks involved in arsenic metabolism and detoxification
Authors: Paulose Bibin , Kandasamy Suganthi , Dhankher Om Parkash
Published: June 2010

Background

Arsenic contamination is widespread throughout the world and this toxic metalloid is known to cause cancers of organs such as liver, kidney, skin, and lung in human. In spite of a recent surge in arsenic related studies, we are still far from a comprehensive understanding of arsenic uptake, detoxification, and sequestration in plants. Crambe abyssinica, commonly known as 'abyssinian mustard', is a non-food, high biomass oil seed crop that is naturally tolerant to heavy metals. Moreover, it accumulates significantly higher levels of arsenic as compared to other species of the Brassicaceae family. Thus, C. abyssinica has great potential to be utilized as an ideal inedible crop for phytoremediation of heavy metals and metalloids. However, the mechanism of arsenic metabolism in higher plants, including C. abyssinica, remains elusive.

Results

To identify the differentially expressed transcripts and the pathways involved in arsenic metabolism and detoxification, C. abyssinica plants were subjected to arsenate stress and a PCR-Select Suppression Subtraction Hybridization (SSH) approach was employed. A total of 105 differentially expressed subtracted cDNAs were sequenced which were found to represent 38 genes. Those genes encode proteins functioning as antioxidants, metal transporters, reductases, enzymes involved in the protein degradation pathway, and several novel uncharacterized proteins. The transcripts corresponding to the subtracted cDNAs showed strong upregulation by arsenate stress as confirmed by the semi-quantitative RT-PCR.

Conclusions

Our study revealed novel insights into the plant defense mechanisms and the regulation of genes and gene networks in response to arsenate toxicity. The differential expression of transcripts encoding glutathione-S-transferases, antioxidants, sulfur metabolism, heat-shock proteins, metal transporters, and enzymes in the ubiquitination pathway of protein degradation as well as several unknown novel proteins serve as molecular evidence for the physiological responses to arsenate stress in plants. Additionally, many of these cDNA clones showing strong upregulation due to arsenate stress could be used as valuable markers. Further characterization of these differentially expressed genes would be useful to develop novel strategies for efficient phytoremediation as well as for engineering arsenic tolerant crops with reduced arsenic translocation to the edible parts of plants.
Is aging raw cattle urine efficient for sampling Anopheles arabiensisPatton?
Authors: Mahande Aneth M , Mwang'onde Beda J , Msangi Shandala , Kimaro Epiphania , Mnyone Ladslaus L , Mazigo Humphrey D , Mahande Michael J , Kweka Eliningaya J
Published: June 2010

Background

To ensure sustainable routine surveillance of mosquito vectors, simple, effective and ethically acceptable tools are required. As a part of that, we evaluated the efficiency of resting boxes baited with fresh and aging cattle urine for indoor and outdoor sampling of An. arabiensis in the lower Moshi rice irrigation schemes.

Methods

A cattle urine treatment and re-treatment schedule was used, including a box with a piece of cloth re-treated with urine daily, and once after 3 and 7 day. Resting box with piece of black cloth not treated with urine was used as a control. Each treatment was made in pair for indoor and outdoor sampling. A 4 by 4 Latin square design was used to achieve equal rotation of each of the four treatments across the experimental houses. Sampling was done over a period of 6 months, once per week.

Results

A total of 7871 mosquitoes were collected throughout the study period. 49.8% of the mosquitoes were collected from resting box treated with urine daily; 21.6% and 20.0% were from boxes treated 3 and 7 days respectively. Only 8.6% were from untreated resting box (control). The proportion collected indoors was ~2 folds greater than the outdoor. Of all mosquitoes, 12.3% were unfed, 4.1% full fed, 34.2% semi-gravid and 49.4% gravid.

Conclusion

Fresh and decaying cattle urine odour baited resting boxes offer an alternative tool for sampling particularly semi-gravid and gravid An. arabiensis. Evaluation in low density seasons of An. arabiensis in different ecological settings remains necessary. This sampling method may be standardized for replacing human landing catch.
Lung cancer risk in never-smokers: a population-based case-control study of epidemiologic risk factors
Authors: Brenner Darren R , Hung Rayjean J , Tsao Ming-Sound , Shepherd Frances A , Johnston Michael R , Narod Steven , Rubenstein Warren , McLaughlin John R
Published: June 2010

Background

We conducted a case-control study in the greater Toronto area to evaluate potential lung cancer risk factors including environmental tobacco smoke (ETS) exposure, family history of cancer, indoor air pollution, workplace exposures and history of previous respiratory diseases with special consideration given to never smokers.

Methods

445 cases (35% of which were never smokers oversampled by design) between the ages of 20-84 were identified through four major tertiary care hospitals in metropolitan Toronto between 1997 and 2002 and were frequency matched on sex and ethnicity with 425 population controls and 523 hospital controls. Unconditional logistic regression models were used to estimate adjusted odds ratios (OR) and 95% confidence intervals (CI) for the associations between exposures and lung cancer risk.

Results

Any previous exposure to occupational exposures (OR total population 1.6, 95% CI 1.4-2.1, OR never smokers 2.1, 95% CI 1.3-3.3), a previous diagnosis of emphysema in the total population (OR 4.8, 95% CI 2.0-11.1) or a first degree family member with a previous cancer diagnosis before age 50 among never smokers (OR 1.8, 95% CI 1.0-3.2) were associated with increased lung cancer risk.

Conclusions

Occupational exposures and family history of cancer with young onset were important risk factors among never smokers.
Inferring predominant pathways in cellular models of breast cancer using limited sample proteomic profiling
Authors: Kulkarni Yogesh M , Suarez Vivian , Klinke David J
Published: June 2010

Background

Molecularly targeted drugs inhibit aberrant signaling within oncogenic pathways. Identifying the predominant pathways at work within a tumor is a key step towards tailoring therapies to the patient. Clinical samples pose significant challenges for proteomic profiling, an attractive approach for identifying predominant pathways. The objective of this study was to determine if information obtained from a limited sample (i.e., a single gel replicate) can provide insight into the predominant pathways in two well-characterized breast cancer models.

Methods

A comparative proteomic analysis of total cell lysates was obtained from two cellular models of breast cancer, BT474 (HER2+/ER+) and SKBR3 (HER2+/ER-), using two-dimensional electrophoresis and MALDI-TOF mass spectrometry. Protein interaction networks and canonical pathways were extracted from the Ingenuity Pathway Knowledgebase (IPK) based on association with the observed pattern of differentially expressed proteins.

Results

Of the 304 spots that were picked, 167 protein spots were identified. A threshold of 1.5-fold was used to select 62 proteins used in the analysis. IPK analysis suggested that metabolic pathways were highly associated with protein expression in SKBR3 cells while cell motility pathways were highly associated with BT474 cells. Inferred protein networks were confirmed by observing an up-regulation of IGF-1R and profilin in BT474 and up-regulation of Ras and enolase in SKBR3 using western blot.

Conclusion

When interpreted in the context of prior information, our results suggest that the overall patterns of differential protein expression obtained from limited samples can still aid in clinical decision making by providing an estimate of the predominant pathways that underpin cellular phenotype.
"Cough officer screening" improves detection of pulmonary tuberculosis in hospital in-patients
Authors: Lin Ching-Hsiung , Tsai Cheng-Hung , Liu Chun-Eng , Huang Mei-Li , Chang Shu-Chen , Wen Jen-Ho , Chai Woei-Horng
Published: June 2010

Background

Current tuberculosis (TB) reporting protocols are insufficient to achieve the goals established by the Stop TB partnership. Some countries have recommended implementation of active case finding program. We assessed the effect of Cough Officer Screening (an active screening system) on the rate of TB detection and health care system delays over the course of four years.

Methods

Patients who were hospitalized at the Changhua Christian Hospital (Changhua, Taiwan) were enrolled from September 2004 to July 2006 (Stage I) and August 2006 to August 2008 (Stage II). Stage II was implemented after a Plan-Do-Check-Act (PDCA) cycle analysis indicated that we should exclude ICU and paediatric patients.

Results

In Stage I, our COS system alerted physicians to 19,836 patients, and 7,998 were examined. 184 of these 7,998 patients (2.3%) had TB. Among these 184 patients, 142 (77.2%) were examined for TB before COS alarming and 42 were diagnosed after COS alarming. In Stage II, a total of 11,323 patients were alerted by the COS system. Among them, 6,221 patients were examined by physicians, and 125 of these patients (2.0%) had TB. Among these 125 patients, 113 (90.4%) were examined for TB before COS alarming and 12 were diagnosed after COS alarming. The median time from COS alarm to clinical action was significantly less (p = 0.041) for Stage I (1 day; range: 0-16 days) than for Stage II (2 days; range: 0-10 days).

Conclusion

Our COS system improves detection of TB by reducing the delay from infection to diagnosis. Modifications of scope may be needed to improve cost-effectiveness.
Knowledge and risk behaviors related to HIV/AIDS, and their association with information resource among men who have sex with men in Heilongjiang province, China
Authors: Liu Shengyuan , Wang Kaili , Yao Songpo , Guo Xiaotong , Liu Yancheng , Wang Binyou
Published: June 2010

Backgroud

In Heilongjiang province, the HIV prevalence in men who have sex with men (MSM) is generally lower than other part of China. However, the official perception for their risk of HIV/AIDS infection has been increasing in the province over the years. Moreover, little information on HIV/AIDS was provided to the communities so that we have disadvantage of controlling HIV/AIDS epidemic in the region. The purpose of this study is to investigate the prevalence of HIV among MSM in Heilongjiang province, to assess their knowledge levels and risk behaviors related to HIV/AIDS, and to explore their associations with information resources.

Methods

A cross-sectional study using a standardized questionnaire and blood test was administered in 2008 by local interviewers to a sample (1353) of MSM in four cities in Heilongjiang province.

Results

Among 1353 MSM, 2.3% were identified with HIV infection. About 48.7% of the subjects had multiple male sexual partners and only 37.3% of the subjects had consistent condom use (use every time) in the past 6 months. Most had a fair level of knowledge on HIV/AIDS, with the highest mean knowledge score among the MSM from Jiamusi, those with income 2000-3000 RMB/month, those searching sexual partners via internet and those performed HIV testing over 1 year ago). However, some myths regarding viral transmission (e.g., via mosquito bites or sharing kitchen utensils) also existed. Resources of information from which knowledge and risk behaviors related to HIV/AIDS was most available were television (58.6%) among MSM, followed by sexual partner (51.6%), publicity material (51.0%) and internet (48.7%). Significantly statistical differences of mean knowledge score were revealed in favor of book (P = 0.0002), medical staff (P = 0.0007), publicity material (P = 0.005) and sexual partner (P = 0.02). Press (P = 0.04) and book (P = 0.0003) were contributory to the most frequent condom use (condom use every time), while medical staff (P = 0.005) and publicity material (P = 0.04) is associated with moderate rate of condom use (condom use often).

Conclusions

Although the prevalence of HIV infection is low among MSM in Heilongjiang province, the situation that the risk behaviors were frequent in the population is alarming. The study suggests that some strategies like condom use and education intervention are practical approaches and need to be strengthened.
Oncology patients' and professional nurses' perceptions of important nurse caring behaviors
Authors: Zamanzadeh Vahid , Azimzadeh Roghaieh , Rahmani Azad , Valizadeh Leila
Published: June 2010

Background

Caring is the essence of nursing. Caring to be meaningful needs to be based on mutual agreement between nurses and patients as to what constitutes nurse caring behaviors. As a result, healthcare professional can enhance patients' satisfaction of care by providing appropriate caring behavior. However, previous research that combined multiple types of patients, nurses and institutions demonstrated disagreement in prioritizing important behaviors. This paper reports a study that aimed at determining the caring behaviors which oncology patients and oncology nurses perceive to be the most important.

Methods

This study is a comparative descriptive design that was conducted in an Iranian oncology centre. Convenience sampling was used to recruit 200 patients and 40 nurses to take part in the study. Data were collected over a period of 4 months in 2009 using the Caring Assessment Questionnaire, developed by Larson. Caring behaviors (n = 57) were ranked on a 5-point Likert-type scale and ordered in six subscales: "Being accessible", "Explains and facilitates", "Comforts", "Anticipates", "Trusting relationship", "Monitors and follows through". The data were analyzed using SPSS software version 13.0. The overall mean was calculated for each subscale to determine the rank distribution of the subscales. The nonparametric Mann-Whitney U test analysis of variables was used to compare patients' and nurses' scores on subscales.

Results

The results demonstrate that both groups considered the same order of importance of caring, the high ranking of "Monitors and Follows through and "Being Accessible" and the low ranking of "Comforts" and "Trusting Relationships". Also, Patients only ranked "Being accessible" (p = 0.04) and "Explains and facilitates" (p = 0.03) higher than nurses.

Conclusions

The oncology patients and nurses perceived highly physical aspects of caring and the results provide for nurses to be aware of the need, during their interactions with patients, to validate the effect their intended caring has upon patients. By so doing and with further refinement of the concept of caring for nursing in studies such as this, the practical aim of making patients feel cared for can be achieved.
MARINE-EXPRESS: taking advantage of high throughput cloning and expression strategies for the post-genomic analysis of marine organisms
Authors: Groisillier Agnès , Hervé Cécile , Jeudy Alexandra , Rebuffet Etienne , Pluchon Pierre F , Chevolot Yann , Flament Didier , Geslin Claire , Morgado Isabel M , Power Déborah , Branno Margherita , Moreau Hervé , Michel Gurvan , Boyen Catherine , Czjzek Mirjam
Published: June 2010

Background

The production of stable and soluble proteins is one of the most important steps prior to structural and functional studies of biological importance. We investigated the parallel production in a medium throughput strategy of genes coding for proteins from various marine organisms, using protocols that involved recombinatorial cloning, protein expression screening and batch purification. This strategy was applied in order to respond to the need for post-genomic validation of the recent success of a large number of marine genomic projects. Indeed, the upcoming challenge is to go beyond the bioinformatic data, since the bias introduced through the genomes of the so called model organisms leads to numerous proteins of unknown function in the still unexplored world of the oceanic organisms.

Results

We present here the results of expression tests for 192 targets using a 96-well plate format. Genes were PCR amplified and cloned in parallel into expression vectors pFO4 and pGEX-4T-1, in order to express proteins N-terminally fused to a six-histidine-tag and to a GST-tag, respectively. Small-scale expression and purification permitted isolation of 84 soluble proteins and 34 insoluble proteins, which could also be used in refolding assays. Selected examples of proteins expressed and purified to a larger scale are presented.

Conclusions

The objective of this program was to get around the bottlenecks of soluble, active protein expression and crystallization for post-genomic validation of a number of proteins that come from various marine organisms. Multiplying the constructions, vectors and targets treated in parallel is important for the success of a medium throughput strategy and considerably increases the chances to get rapid access to pure and soluble protein samples, needed for the subsequent biochemical characterizations. Our set up of a medium throughput strategy applied to genes from marine organisms had a mean success rate of 44% soluble protein expression from marine bacteria, archaea as well as eukaryotic organisms. This success rate compares favorably with other protein screening projects, particularly for eukaryotic proteins. Several purified targets have already formed the base for experiments aimed at post-genomic validation.
A rolling-gliding wear simulator for the investigation of tribological material pairings for application in total knee arthroplasty
Authors: Richter Berna I , Ostermeier Sven , Turger Anke , Denkena Berend , Hurschler Christof
Published: June 2010

Background

Material wear testing is an important technique in the development and evaluation of materials for use in implant for total knee arthroplasty. Since a knee joint induces a complex rolling-gliding movement, standardised material wear testing devices such as Pin-on-Disc or Ring-on-Disc testers are suitable to only a limited extent because they generate pure gliding motion only.

Methods

A rolling-gliding wear simulator was thus designed, constructed and implemented, which simulates and reproduces the rolling-gliding movement and loading of the knee joint on specimens of simplified geometry. The technical concept was to run a base-plate, representing the tibia plateau, against a pivoted cylindrical counter-body, representing one femur condyle under an axial load. A rolling movement occurs as a result of the friction and pure gliding is induced by limiting the rotation of the cylindrical counter-body. The set up also enables simplified specimens handling and removal for gravimetrical wear measurements. Long-term wear tests and gravimetrical wear measurements were carried out on the well known material pairings: cobalt chrome-polyethylene, ceramic-polyethylene and ceramic-ceramic, over three million motion cycles to allow material comparisons to be made.

Results

The observed differences in wear rates between cobalt-chrome on polyethylene and ceramic on polyethylene pairings were similar to the differences of published data for existing material-pairings. Test results on ceramic-ceramic pairings of different frontal-plane geometry and surface roughness displayed low wear rates and no fracture failures.

Conclusions

The presented set up is able to simulate the rolling-gliding movement of the knee joint, is easy to use, and requires a minimum of user intervention or monitoring. It is suitable for long-term testing, and therefore a useful tool for the investigation of new and promising materials which are of interest for application in knee joint replacement implants.
Membrane plasmalogen composition and cellular cholesterol regulation: a structure activity study
Authors: Mankidy Rishikesh , Ahiahonu Pearson WK , Ma Hong , Jayasinghe Dushmanthi , Ritchie Shawn A , Khan Mohamed A , Su-Myat Khine K , Wood Paul L , Goodenowe Dayan B
Published: June 2010

Background

Disrupted cholesterol regulation leading to increased circulating and membrane cholesterol levels is implicated in many age-related chronic diseases such as cardiovascular disease (CVD), Alzheimer's disease (AD), and cancer. In vitro and ex vivo cellular plasmalogen deficiency models have been shown to exhibit impaired intra- and extra-cellular processing of cholesterol. Furthermore, depleted brain plasmalogens have been implicated in AD and serum plasmalogen deficiencies have been linked to AD, CVD, and cancer.

Results

Using plasmalogen deficient (NRel-4) and plasmalogen sufficient (HEK293) cells we investigated the effect of species-dependent plasmalogen restoration/augmentation on membrane cholesterol processing. The results of these studies indicate that the esterification of cholesterol is dependent upon the amount of polyunsaturated fatty acid (PUFA)-containing ethanolamine plasmalogen (PlsEtn) present in the membrane. We further elucidate that the concentration-dependent increase in esterified cholesterol observed with PUFA-PlsEtn was due to a concentration-dependent increase in sterol-O-acyltransferase-1 (SOAT1) levels, an observation not reproduced by 3-hydroxy-3-methyl-glutaryl-CoA (HMG-CoA) reductase inhibition.

Conclusion

The present study describes a novel mechanism of cholesterol regulation that is consistent with clinical and epidemiological studies of cholesterol, aging and disease. Specifically, the present study describes how selective membrane PUFA-PlsEtn enhancement can be achieved using 1-alkyl-2-PUFA glycerols and through this action reduce levels of total and free cholesterol in cells.
Quantitative proteomic analysis by iTRAQ® for the identification of candidate biomarkers in ovarian cancer serum
Authors: Boylan Kristin LM , Andersen John D , Anderson Lorraine B , Higgins LeeAnn , Skubitz Amy PN
Published: June 2010

Background

Ovarian cancer is the most lethal gynecologic malignancy, with the majority of cases diagnosed at an advanced stage when treatments are less successful. Novel serum protein markers are needed to detect ovarian cancer in its earliest stage; when detected early, survival rates are over 90%. The identification of new serum biomarkers is hindered by the presence of a small number of highly abundant proteins that comprise approximately 95% of serum total protein. In this study, we used pooled serum depleted of the most highly abundant proteins to reduce the dynamic range of proteins, and thereby enhance the identification of serum biomarkers using the quantitative proteomic method iTRAQ®.

Results

Medium and low abundance proteins from 6 serum pools of 10 patients each from women with serous ovarian carcinoma, and 6 non-cancer control pools were labeled with isobaric tags using iTRAQ®to determine the relative abundance of serum proteins identified by MS. A total of 220 unique proteins were identified and fourteen proteins were elevated in ovarian cancer compared to control serum pools, including several novel candidate ovarian cancer biomarkers: extracellular matrix protein-1, leucine-rich alpha-2 glycoprotein-1, lipopolysaccharide binding protein-1, and proteoglycan-4. Western immunoblotting validated the relative increases in serum protein levels for several of the proteins identified.

Conclusions

This study provides the first analysis of immunodepleted serum in combination with iTRAQ®to measure relative protein expression in ovarian cancer patients for the pursuit of serum biomarkers. Several candidate biomarkers were identified which warrant further development.
Molecular epidemiology of Japanese encephalitis virus circulating in South Korea, 1983-2005
Authors: Yun Seok-Min , Cho Jung Eun , Ju Young-Ran , Kim Su Yeon , Ryou Jungsang , Han Myung Guk , Choi Woo-Young , Jeong Young Eui
Published: June 2010

We sequenced the envelope (E) gene of 17 strains of the Japanese encephalitis virus (JEV) isolated in South Korea in 1983-2005 and compared the sequences with those from previously reported strains. Our results show the remarkable genetic stability of the E gene sequence in Korean JEV strains. Five pairs of E gene sequences from 10 Korean strains were identical, despite geographical differences and a maximum five-year time span. Sequence comparisons with other Asian strains revealed that the Korean strains are closely related to those from China, Japan, and Vietnam. Genotype 3 strains were predominant in Korea before 1993, when genotype 1 strain K93A07 was first isolated. The two genotypes were detected simultaneously in 1994 but since then, only genotype 1 has been isolated in South Korea. Thus, the genotype change occurred according to the year of isolation rather than the geographical origin.
Solving a 50 year mystery of a missing OPA1 mutation: more insights from the first family diagnosed with autosomal dominant optic atrophy
Authors: Fuhrmann Nico , Schimpf Simone , Kamenisch York , Leo-Kottler Beate , Alexander Christiane , Auburger Georg , Zrenner Eberhart , Wissinger Bernd , Alavi Marcel V
Published: June 2010

Background

Up to the 1950s, there was an ongoing debate about the diversity of hereditary optic neuropathies, in particular as to whether all inherited optic atrophies can be ascribed to Leber's hereditary optic neuropathy (LHON) or represent different disease entities. In 1954 W. Jaeger published a detailed clinical and genealogical investigation of a large family with explicit autosomal dominant segregation of optic atrophy thus proving the existence of a discrete disease different from LHON, which is nowadays known as autosomal dominant optic atrophy (ADOA). Since the year 2000 ADOA is associated with genomic mutations in the OPA1 gene, which codes for a protein that is imported into mitochondria where it is required for mitochondrial fusion. Interestingly enough, the underlying mutation in this family has not been identified since then.

Results

We have reinvestigated this family with the aim to identify the mutation and to further clarify the underlying pathomechanism. Patients showed a classical non-syndromic ADOA. The long term deterioration in vision in the two teenagers examined 50 years later is of particular note 5/20 to 6/120. Multiplex ligation probe amplification revealed a duplication of the OPA1 exons 7-9 which was confirmed by long distance PCR and cDNA analysis, resulting in an in-frame duplication of 102 amino acids. Segregation was verified in 53 available members of the updated pedigree and a penetrance of 88% was calculated. Fibroblast cultures from skin biopsies were established to assess the mitochondrial network integrity and to qualitatively and quantitatively study the consequences of the mutation on transcript and protein level. Fibroblast cultures demonstrated a fragmented mitochondrial network. Processing of the OPA1 protein was altered. There was no correlation of the OPA1 transcript levels and the OPA1 protein levels in the fibroblasts. Intriguingly an overall decrease of mitochondrial proteins was observed in patients' fibroblasts, while the OPA1 transcript levels were elevated.

Conclusions

The thorough study of this family provides a detailed clinical picture accompanied by a molecular investigation of patients' fibroblasts. Our data show a classic OPA1-associated non-syndromic ADOA segregating in this family. Cell biological findings suggest that OPA1 is regulated by post-translational mechanisms and we would like to hypothesize that loss of OPA1 function might lead to impaired mitochondrial quality control. With the clinical, genetic and cell biological characterisation of a family described already more than 50 years ago, we span more than half a century of research in optic neuropathies.
Holmium-166 radioembolization for the treatment of patients with liver metastases: design of the phase I HEPAR trial
Authors: Smits Maarten LJ , Nijsen Johannes FW , van den Bosch Maurice AAJ , Lam Marnix GEH , Vente Maarten AD , Huijbregts Julia E , van het Schip Alfred D , Elschot Mattijs , Bult Wouter , de Jong Hugo WAM , Meulenhoff Pieter CW , Zonnenberg Bernard A
Published: June 2010

Background

Intra-arterial radioembolization with yttrium-90 microspheres ( 90Y-RE) is an increasingly used therapy for patients with unresectable liver malignancies. Over the last decade, radioactive holmium-166 poly(L-lactic acid) microspheres ( 166Ho-PLLA-MS) have been developed as a possible alternative to 90Y-RE. Next to high-energy beta-radiation, 166Ho also emits gamma-radiation, which allows for imaging by gamma scintigraphy. In addition, Ho is a highly paramagnetic element and can therefore be visualized by MRI. These imaging modalities are useful for assessment of the biodistribution, and allow dosimetry through quantitative analysis of the scintigraphic and MR images. Previous studies have demonstrated the safety of 166Ho-PLLA-MS radioembolization ( 166Ho-RE) in animals. The aim of this phase I trial is to assess the safety and toxicity profile of 166Ho-RE in patients with liver metastases.

Methods

The HEPAR study (Holmium Embolization Particles for Arterial Radiotherapy) is a non-randomized, open label, safety study. We aim to include 15 to 24 patients with liver metastases of any origin, who have chemotherapy-refractory disease and who are not amenable to surgical resection. Prior to treatment, in addition to the standard technetium-99m labelled macroaggregated albumin ( 99mTc-MAA) dose, a low radioactive safety dose of 60-mg 166Ho-PLLA-MS will be administered. Patients are treated in 4 cohorts of 3-6 patients, according to a standard dose escalation protocol (20 Gy, 40 Gy, 60 Gy, and 80 Gy, respectively). The primary objective will be to establish the maximum tolerated radiation dose of 166Ho-PLLA-MS. Secondary objectives are to assess tumour response, biodistribution, performance status, quality of life, and to compare the 166Ho-PLLA-MS safety dose and the 99mTc-MAA dose distributions with respect to the ability to accurately predict microsphere distribution.

Discussion

This will be the first clinical study on 166Ho-RE. Based on preclinical studies, it is expected that 166Ho-RE has a safety and toxicity profile comparable to that of 90Y-RE. The biochemical and radionuclide characteristics of 166Ho-PLLA-MS that enable accurate dosimetry calculations and biodistribution assessment may however improve the overall safety of the procedure.

Trial registration

ClinicalTrials.gov NCT01031784
How the relationships between general practitioners and intensivists can be improved: the general practitioners' point of view
Authors: Etesse Bérengère , Jaber Samir , Mura Thibault , Leone Marc , Constantin Jean-Michel , Michelet Pierre , Zoric Lana , Capdevila Xavier , Malavielle François , Allaouchiche Bernard , Orban Jean-Christophe , Fabbro-Peray Pascale , Lefrant Jean-Yves ,   the AzuRéa Group
Published: June 2010

Introduction

The present study assessed the opinion of general practitioners (GPs) concerning their relationships with intensivists.

Methods

An anonymous questionnaire was mailed to 7,239 GPs. GPs were asked about their professional activities, postgraduate intensive care unit (ICU) training, the rate of patient admittance to ICUs, and their relationships with intensivists. Relationship assessment was performed by using a graduated visual analogue scale (VAS) ranging from 0 (dissatisfaction) to 100 (satisfaction). A multivariate analysis with stepwise logistic regression was performed to isolate factors explaining dissatisfaction (VAS score, < 25th percentile).

Results

Twenty-two percent of the GPs (1,561) responded. The median satisfaction score was 57 of 100 (interquartile (IQ), 35 to 77]. Five independent factors of dissatisfaction were identified: no information provided to GPs at patient admission (odds ratio (OR) = 2.55 (1.71 to 3.80)); poor quality of family reception in the ICU (OR = 2.06 (1.40 to 3.02)); the ICU's family contact person's identity or function or both is unclear (OR = 1.48 (1.03 to 2.12)), lack of family information (OR = 2.02 (2.48 to 2.75)), and lack of discharge report (OR = 3.39 (1.70 to 6.76)). Three independent factors prevent dissatisfaction: age of GPs ≤45 years (OR = 0.69 (0.51 to 0.94)); the GP is called at patient ICU admission (OR = 0.44 (0.31 to 0.63)); and GP involvement in treatment decisions (OR = 0.17 (0.07 to 0.40)).

Conclusions

Considerable improvement in GP/intensivist relationships can be achieved through increased communication measures.
Kinetics of plasmatic cytokines and cystatin C during and after hemodialysis in septic shock-related acute renal failure
Authors: Mayeur Nicolas , Rostaing Lionel , Nogier Marie B , Jaafar Acil , Cointault Olivier , Kamar Nassim , Conil Jean M , Fourcade Olivier , Lavayssiere Laurence
Published: June 2010

Introduction

Cystatin C could be a relevant residual glomerular filtration rate marker during hemodialysis (HD), and a high cytokine plasma (p) rate is associated with an increase in mortality during sepsis. To the best of our knowledge, cytokines and cystatin C kinetics during and after HD during sepsis have never been studied. In this study, we described p cytokines and cystatin C variations during and after hemodialysis in septic-shock patients with acute kidney injury (AKI).

Methods

Ten patients, from two tertiary ICUs, with septic shock-related AKI, according to RIFLE class F, were studied. In this prospective observational study, blood samples were collected at the start, after 1 hour, 2 hours, and at the end of HD with a polymethymethacrylate (PMMA) hemodialyzer (D0, D1, D2, and endD), and 30, 60, 90, 120, and 180 min after HD (postD0.5, postD1, postD1.5, postD2, and postD3). We measured p interleukins (IL)-6, IL-8, IL-10, cystatin C, and albumin. Results are expressed as variations from D0 (mean ± SD).

Results

During HD, p[IL-6] did not vary significantly, whereas p[IL-8] and p[IL-10] reductions by D1 were 31.8 ± 21.2% and 36.3 ± 26%, respectively (P < 0.05 as compared with D0). At postD3, p[IL-8] and p[IL-10] returned to their initial values. p[Cystatin C] was significantly reduced from D1 to postD1, with a maximal reduction of 30 ± 6.7% on D2 (P < 0.05). Norepinephrine infusion rate decreased from D0 to postD3 (0.65 ± 0.39 to 0.49 ± 0.37 μg/kg/min; P < 0.05).

Conclusions

HD allows a transient and selective decrease in p cytokines, which are known as being correlated with mortality during septic shock. Because of a significant decrease in p cystatin C during HD, this should not be considered as an accurate marker for residual glomerular filtration rate during septic acute renal failure when receiving HD with a PMMA hemodialyzer.
High-throughput sequencing identifies STAT3 as the DNA-associated factor for p53-NF-κB-complex-dependent gene expression in human heart failure
Authors: Choy Mun-Kit , Movassagh Mehregan , Siggens Lee , Vujic Ana , Goddard Martin , Sánchez Ana , Perkins Neil , Figg Nichola , Bennett Martin , Carroll Jason , Foo Roger
Published: June 2010

Background

Genome-wide maps of DNA regulatory elements and their interaction with transcription factors may form a framework for understanding regulatory circuits and gene expression control in human disease, but how these networks, comprising transcription factors and DNA-binding proteins, form complexes, interact with DNA and modulate gene expression remains largely unknown.

Methods

Using microRNA-21 (mir-21), which is an example of genes that are regulated in heart failure, we performed chromatin immunoprecipitation (ChIP) assays to determine the occupancy of transcription factors at this genetic locus. Tissue ChIP was further performed using human hearts and genome-wide occupancies of these transcription factors were analyzed by high-throughput sequencing.

Results

We show that the transcription factor p53 piggy-backs onto NF-κB/RELA and utilizes the κB-motif at a cis-regulatory region to control mir-21 expression. p53 behaves as a co-factor in this complex because despite a mutation in its DNA binding domain, mutant p53 was still capable of binding RELA and the cis-element, and inducing mir-21 expression. In dilated human hearts where mir-21 upregulation was previously demonstrated, the p53-RELA complex was also associated with this cis-element. Using high-throughput sequencing, we analyzed genome-wide binding sites for the p53-RELA complex in diseased and control human hearts and found a significant overrepresentation of the STAT3 motif. We further determined that STAT3 was necessary for the p53-RELA complex to associate with this cis-element and for mir-21 expression.

Conclusions

Our results uncover a mechanism by which transcription factors cooperate in a multi-molecular complex at a cis-regulatory element to control gene expression.
Synthesis and Crystal Structures of 1,4,8,11-Tetraalkyl-6,13-diphenylpentacenes
Authors: Kitamura Chitoshi , Naito Takao , Yoneda Akio , Kawase Takeshi , Komatsu Toshiki
Published: June 2010

Two 1,4,8,11-tetraalkyl-6,13-diphenylpentacenes were prepared. X-ray analysis revealed that the methyl derivative had a herringbone arrangement with π-overlap, while the propyl derivative had a slipped-parallel structure without π-overlap. The solid-state order reflected UV–vis absorption spectra in the solid state.
Risk Management and Optimal Pricing in Online Storage Grids
Authors: Das Sanjukta , Du Anna Ye , Gopal Ram , Ramesh R.
Published: June 2010

Online storage service providers grant a way for companies to avoid spending resources on maintaining their own in-house storage infrastructure and thereby allowing them to focus on their core business activities. These providers, however, follow a fixed, posted pricing strategy that charges the same price in each time period and thus bear all the risk arising out of demand uncertainties faced by their client companies. We examine the effects of providing a spot market with dynamic prices and forward contracts to hedge against future revenue uncertainty. We derive revenue-maximizing spot and forward prices for a single seller facing a known set of buyers. We perform a simulation study using publicly available traffic data regarding Amazon S3 clients from Alexa.com to validate our analytical results. Our field study supports our analysis and indicates that spot markets alone can enhance revenues to Amazon, but this comes at the cost of increased risks due to the increased market share in the spot markets. Furthermore, adding a forward contract feature to the spot markets can reduce risks while still providing the benefits of enhanced revenues. Although the buyers incur an increase in costs in the spot market, adding a forward contract does not cause any additional cost increase while transferring the risk to the buyers. Thus, storage grid providers can greatly benefit by applying a forward contract alongside the spot market.
Protecting Privacy Against Record Linkage Disclosure: A Bounded Swapping Approach for Numeric Data
Authors: Li Xiao-Bai , Sarkar Sumit
Published: June 2010

Record linkage techniques have been widely used in areas such as antiterrorism, crime analysis, epidemiologic research, and database marketing. On the other hand, such techniques are also being increasingly used for identity matching that leads to the disclosure of private information. These techniques can be used to effectively reidentify records even in deidentified data. Consequently, the use of such techniques can lead to individual privacy being severely eroded. Our study addresses this important issue and provides a solution to resolve the conflict between privacy protection and data utility. We propose a data-masking method for protecting private information against record linkage disclosure that preserves the statistical properties of the data for legitimate analysis. Our method recursively partitions a data set into smaller subsets such that data records within each subset are more homogeneous after each partition. The partition is made orthogonal to the maximum variance dimension represented by the first principal component in each partitioned set. The attribute values of a record in a subset are then masked using a double-bounded swapping method. The proposed method, which we call multivariate swapping trees, is nonparametric in nature and does not require any assumptions about statistical distributions of the original data. Experiments conducted on real-world data sets demonstrate that the proposed approach significantly outperforms existing methods in terms of both preventing identity disclosure and preserving data quality.
Polymerase Chain Reaction Detection of HPV in Squamous Carcinoma of the Oropharynx
Authors: Agoston Elin S. , Robinson Stephen J. , Mehra Karishma K. , Birch Chandler , Semmel Dana , Mirkovic Jelena , Haddad Robert I. , Posner Marshall R. , Kindelberger David , Krane Jeffrey F. , Brodsky Joshua , Crum Christopher P.
Published: June 2010

Human papillomavirus (HPV) testing is routinely performed on oropharyngeal carcinomas. We compared the Access Genetics (Minneapolis, MN) polymerase chain reaction (PCR) assay (AGPCR), DNA-DNA in situ hybridization (ISH; Ventana, Tucson, AZ), and HPV-16 E7 PCR amplification in consecutively accessioned oropharyngeal cancers. We tested 126 cases by both PCR methods; 102 were positive by either for a maximum positive rate (MPR) of 81.0%. Relative to the MPR, the sensitivities of AGPCR and E7 PCR were 90.2% and 72.5%, respectively. Of 17 AGPCR+ cases tested by ISH, 14/14 unequivocally positive/negative were concordant. All cases (97/97) positive by either PCR assay were positive for p16. There was no relationship between level of histologic differentiation and HPV status. ISH and AGPCR have comparable performance for the detection of HPV in oropharyngeal carcinomas. PCR is a suitable and economical assay that is comparable to ISH in sensitivity and may provide logistical advantages relative to ISH for assessing HPV status in oropharyngeal malignancies. However, it is imperative that appropriate sensitivity controls be in place for such assays.
To Count and How to Count, That Is the Question
Authors: Parkash Vinita , Bifulco Carlo , Feinn Richard , Concato John , Jain Dhanpat
Published: June 2010

Optimal cancer staging requires retrieval of a minimal number of nodes. However, variability among pathologists in counting on a slide has not been studied. To study the differences in node counting among pathologists, 10 pathologists counted nodes on 15 slides on 2 occasions. They also opined on whether selected “structures” represented countable nodes. There was no slide on which all pathologists agreed on all occasions. The greatest variability was on slides on which the number of nodes exceeded 8. There was disagreement on the size of the smallest countable node, on how to count 2 closely related structures, and when the gross disagreed with the microscopic finding. With a mean count of 5.7 nodes per slide, the 95% confidence interval was ± 2.6, which could be clinically significant when the count approaches the set minimum. Uniform criteria are necessary to allow for meaningful comparisons between studies on minimal nodal counts for cancer lymphadenectomies.
Reviews
Authors: Atkinson David , Capdevila Arantxa , Rabaseda Joaquim
Published: June 2010

El Malestar en la Cultura Catalana, Josep-Anton Fernndez (2008) Barcelona: Biblioteca Universal Empries. 410 pp., ISBN 978-84-9787-341-3, Paperback. 20

La Construccin Meditica de las Crisis Polticas, Andreu Casero (2009) Madrid: Editorial Fragua, 342 pp.,
ISBN 978-84-7074-275-0, paperback, 35

Dodat De Sverac. Musical Identity in Fin de Sicle France, Robert F. Waters (2008) Hampshire: Ashgate, 288 pp., ISBN 978-0-7546-4105-6, 54
Seasonality of caulerpenyne content in native Caulerpa prolifera and invasive C. taxifolia and C. racemosa var. cylindracea in the western Mediterranean Sea
Authors: Box Antonio , Sureda Antoni , Tauler Pere , Terrados Jorge , Marbà Nuria , Pons Antoni , Deudero Salud
Published: June 2010

Fronds had higher mean caulerpenyne concentration than stolons in Caulerpa prolifera, C. taxifolia and C. racemosa. C. prolifera had higher mean caulerpenyne content [7.29±0.64% caulerpenyne/frond dry weight (DW)] than C. taxifolia (5.47±0.32% caulerpenyne/frond DW) and C. racemosa (0.43±0.07% caulerpenyne/frond DW). C. prolifera had reduced content from May to October in fronds, with no clear seasonal pattern in stolons. C. taxifolia reached a maximum caulerpenyne value in fronds in May, with a slight decrease until the onset of winter; there was no clear seasonal trend in stolons. Caulerpenyne content remained relatively constant through the year in fronds of C. racemosa; stolons showed a clear seasonal pattern of increasing caulerpenyne content in spring, reaching maximum values at the end of summer, and decreasing during winter. C. prolifera caulerpenyne contents were positively correlated with densities of the Caulerpa-feeding gastropod Ascobulla fragilis (ρ=0.84, p<0.05). The main finding of the present work is that C. prolifera has higher caulerpenyne concentrations than invasive Caulerpa species under similar climate conditions.