bluuebunny/crossref_metadata_2025 huggingface dataset:
Diagnosis of chronic obstructive pulmonary disease in lung cancer screening Computed Tomography scans: independent contribution of emphysema, air trapping and bronchial wall thickening
Authors: Mets Onno M , Schmidt Michael , Buckens Constantinus F , Gondrie Martijn J , Isgum Ivana , Oudkerk Matthijs , Vliegenthart Rozemarijn , de Koning Harry J , van der Aalst Carlijn M , Prokop Mathias , Lammers Jan-Willem J , Zanen Pieter , Hoesein Firdaus A Mohamed , Mali Willem PThM , van Ginneken Bram , van Rikxoort Eva M , de Jong Pim A
Published: May 2013

Background

Beyond lung cancer, screening CT contains additional information on other smoking related diseases (e.g. chronic obstructive pulmonary disease, COPD). Since pulmonary function testing is not regularly incorporated in lung cancer screening, imaging biomarkers for COPD are likely to provide important surrogate measures for disease evaluation. Therefore, this study aims to determine the independent diagnostic value of CT emphysema, CT air trapping and CT bronchial wall thickness for COPD in low-dose screening CT scans.

Methods

Prebronchodilator spirometry and volumetric inspiratory and expiratory chest CT were obtained on the same day in 1140 male lung cancer screening participants. Emphysema, air trapping and bronchial wall thickness were automatically quantified in the CT scans. Logistic regression analysis was performed to derivate a model to diagnose COPD. The model was internally validated using bootstrapping techniques.

Results

Each of the three CT biomarkers independently contributed diagnostic value for COPD, additional to age, body mass index, smoking history and smoking status. The diagnostic model that included all three CT biomarkers had a sensitivity and specificity of 73.2% and 88.%, respectively. The positive and negative predictive value were 80.2% and 84.2%, respectively. Of all participants, 82.8% was assigned the correct status. The C-statistic was 0.87, and the Net Reclassification Index compared to a model without any CT biomarkers was 44.4%. However, the added value of the expiratory CT data was limited, with an increase in Net Reclassification Index of 4.5% compared to a model with only inspiratory CT data.

Conclusion

Quantitatively assessed CT emphysema, air trapping and bronchial wall thickness each contain independent diagnostic information for COPD, and these imaging biomarkers might prove useful in the absence of lung function testing and may influence lung cancer screening strategy. Inspiratory CT biomarkers alone may be sufficient to identify patients with COPD in lung cancer screening setting.
Transcription analysis of the porcine alveolar macrophage response to porcine circovirus type 2
Authors: Li Wentao , Liu Shuqing , Wang Yang , Deng Feng , Yan Weidong , Yang Kun , Chen Huanchun , He Qigai , Charreyre Catherine , Audoneet Jean-Christophe
Published: May 2013

Background

Porcine circovirus type 2 (PCV2) is the causal agent of postweaning multisystemic wasting syndrome (PMWS), which has severely impacted the swine industry worldwide. PCV2 triggers a weak and atypical innate immune response, but the key genes and mechanisms by which the virus interferes with host innate immunity have not yet been elucidated. In this study, genes that control the response of primary porcine alveolar macrophages (PAMs), the main target of PCV2, were profiled in vitro.

Results

PAMs were successfully infected by PCV2-WH strain, as evidenced quantitative real-time polymerase chain reaction (qPCR) and immunofluorescence assay (IFA) results. Infection-related differential gene expression was investigated using pig microarrays from the US Pig Genome Coordination Program and validated by real-time PCR and enzyme-linked immunosorbent assay (ELISA). Microarray analysis at 24 and 48 hours post-infection (HPI) revealed 266 and 175 unique genes, respectively, that were differentially expressed (false discovery rate <0.05; fold-change >2). Only six genes were differentially expressed between 24 and 48 HPI. The up-regulated genes were principally related to immune response, cytokine activity, locomotion, regulation of cell proliferation, apoptosis, cell growth arrest, and antigen procession and presentation. The down-regulated genes were mainly involved in terpenoid biosynthesis, carbohydrate metabolism, translation, proteasome degradation, signal transducer activity, and ribosomal proteins, which were representative of the reduced vital activity of PCV2-infected cells.

Conclusions

PCV2 infection of PAMs causes up-regulation of genes related to inflammation, indicating that PCV2 may induce systematic inflammation. PCV2 persistently induced cytokines, mainly through the Toll-like receptor (TLR) 1 and TLR9 pathways, which may promote high levels of cytokine secretion. PCV2 may prevent apoptosis in PAMs by up-regulating SERPINB9 expression, possibly to lengthen the duration of PCV2 replication-permissive conditions. The observed gene expression profile may provide insights into the underlying immunological response and pathological changes that occur in pigs following PCV2 infection.
Tomato breeding in the genomics era: insights from a SNP array
Authors: Víquez-Zamora Marcela , Vosman Ben , van de Geest Henri , Bovy Arnaud , Visser Richard GF , Finkers Richard , van Heusden Adriaan W
Published: May 2013

Background

The major bottle neck in genetic and linkage studies in tomato has been the lack of a sufficient number of molecular markers. This has radically changed with the application of next generation sequencing and high throughput genotyping. A set of 6000 SNPs was identified and 5528 of them were used to evaluate tomato germplasm at the level of species, varieties and segregating populations.

Results

From the 5528 SNPs, 1980 originated from 454-sequencing, 3495 from Illumina Solexa sequencing and 53 were additional known markers. Genotyping different tomato samples allowed the evaluation of the level of heterozygosity and introgressions among commercial varieties. Cherry tomatoes were especially different from round/beefs in chromosomes 4, 5 and 12. We were able to identify a set of 750 unique markers distinguishing S. lycopersicum ‘Moneymaker’ from all its distantly related wild relatives. Clustering and neighbour joining analysis among varieties and species showed expected grouping patterns, with S. pimpinellifolium as the most closely related to commercial tomatoesearlier results.

Conclusions

Our results show that a SNP search in only a few breeding lines already provides generally applicable markers in tomato and its wild relatives. It also shows that the Illumina bead array generated data are highly reproducible. Our SNPs can roughly be divided in two categories: SNPs of which both forms are present in the wild relatives and in domesticated tomatoes (originating from common ancestors) and SNPs unique for the domesticated tomato (originating from after the domestication event). The SNPs can be used for genotyping, identification of varieties, comparison of genetic and physical linkage maps and to confirm (phylogenetic) relations. In the SNPs used for the array there is hardly any overlap with the SolCAP array and it is strongly recommended to combine both SNP sets and to select a core collection of robust SNPs completely covering the entire tomato genome.
The mxd operon in Shewanella oneidensis MR-1 is induced in response to starvation and regulated by ArcS/ArcA and BarA/UvrY
Authors: Müller Jana , Shukla Soni , Jost Kathinka A , Spormann Alfred M
Published: May 2013

Background

S. oneidensis MR-1 is a dissimilatory metal-reducing bacterium. Under anoxic conditions S. oneidensis MR-1 attaches to and uses insoluble minerals such as Fe(III) and Mn(IV) oxides as electron acceptors. In the laboratory, S. oneidensis MR-1 forms biofilms under hydrodynamic flow conditions on a borosilicate glass surface; formation of biofilms was previously found to be dependent on the mxd gene cluster (mxdABCD).

Results

This study revealed environmental and genetic factors regulating expression of the mxd genes in S. oneidensis MR-1. Physiological experiments conducted with a S. oneidensis MR-1 strain carrying a transcriptional lacZ fusion to the mxd promoter identified electron donor starvation as a key factor inducing mxd gene expression. Tn5 mutagenesis identified the ArcS/ArcA two-component signaling system as a repressor of mxd expression in S. oneidensis MR-1 under planktonic conditions. Biofilms of ∆arcS and ∆arcA strains carrying a transcriptional gfp -reporter fused to the mxd promoter revealed a reduced mxd expression, suggesting that ArcS/ArcA are necessary for activation of mxd expression under biofilm conditions. Biofilms of ∆arcS and ∆arcA mutants were unable to form a compact three-dimensional structure consistent with a low level of mxd expression. In addition, BarA/UvrY was identified as a major regulator of mxd expression under planktonic conditions. Interestingly, biofilms of ∆barA and ∆uvrY mutants were able to form three-dimensional structures that were, however, less compact compared to wild type biofilms.

Conclusions

We have shown here that the mxd genes in S. oneidensis MR-1 are controlled transcriptionally in response to carbon starvation and by the ArcS/ArcA and the BarA/UvrY signaling system. BarA might function as a sensor to assess the metabolic state of the cell, including carbon starvation, leading to expression of the mxd operon and therefore control biofilm formation.
A multi-country study of intussusception in children under 2 years of age in Latin America: analysis of prospective surveillance data
Authors: Sáez-Llorens Xavier , Velázquez F Raúl , Lopez Pio , Espinoza Felix , Linhares Alexandre C , Abate Hector , Nuñez Ernesto , Venegas Guillermo , Vergara Rodrigo , Jimenez Ana L , Rivera Maribel , Aranza Carlos , Richardson Vesta , Macias-Parra Mercedes , Palacios Guillermo Ruiz , Rivera Luis , Ortega-Barria Eduardo , Cervantes Yolanda , Rüttimann Ricardo , Rubio Pilar , Acosta Camilo J , Newbern Claire , Verstraeten Thomas , Breuer Thomas
Published: May 2013

Background

Intussusception (IS) is a form of acute intestinal obstruction that occurs mainly in infants and is usually of unknown cause. An association between IS and the first licensed rotavirus vaccine, a reassortant-tetravalent, rhesus-based rotavirus vaccine (RRV-TV), led to the withdrawal of the vaccine. New rotavirus vaccines have now been developed and extensively studied for their potential association with IS. This study aimed to describe the epidemiology and to estimate the incidence of IS in Latin American infants prior to new vaccine introduction.

Methods

Children under 2 years of age representing potential IS cases were enrolled in 16 centers in 11 Latin American countries from January 2003 to May 2005. IS cases were classified as definite, probable, possible or suspected as stated on the Brighton Collaboration Working Group guidelines.

Results

From 517 potential cases identified, 476 (92%) cases were classified as definite, 21 probable, 10 possible and 10 suspected for intussusception. Among the 476 definite IS cases, the median age at presentation was 6.4 months with 89% of cases aged <1 year. The male to female ratio was 1.5:1. The incidence of definite IS per 100,000 subject-years ranged from 1.9 in Brazil to 62.4 in Argentina for children <2 years of age, and from 3.8 in Brazil to 105.3 in Argentina for children aged <1 year. Median hospital stay was 4 days with a high prevalence of surgery as the primary treatment (65%). Most cases (88%) made a complete recovery, but 13 (3%) died. No clear seasonal pattern of IS cases emerged.

Conclusions

This study describes the epidemiology and estimates the incidence of IS in Latin American infants prior to the introduction of new rotavirus vaccines. The incidence of IS was found to vary between different countries, as observed in previous studies.

Trial registration

Clinical study identifier 999910/204 (SERO-EPI-IS-204)
Prognostic significance of maximum primary tumor diameter in nasopharyngeal carcinoma
Authors: Liang Shao-Bo , Deng Yan-Ming , Zhang Ning , Lu Rui-Liang , Zhao Hai , Chen Hai-Yang , Li Shao-En , Liu Dong-Sheng , Chen Yong
Published: May 2013

Background

To evaluate the prognostic value of maximum primary tumor diameter (MPTD) in nasopharyngeal carcinoma (NPC).

Methods

Three hundred and thirty-three consecutive, newly-diagnosed NPC patients were retrospectively reviewed. Kaplan-Meier analysis and the log-rank test were used to estimate overall survival (OS), failure-free survival (FFS), distant metastasis-free survival (DMFS) and local relapse-free survival (LRFS). Cox proportional hazards regression analysis was used to assess the prognostic value of MPTD.

Results

Median follow-up was 66 months (range, 2–82 months). Median MPTD in stage T1, T2, T3 and T4 was 27.9, 37.5, 45.0 and 61.3 mm, respectively. The proportion of T1 patients with a MPTD ≤ 30 mm was 62.3%; 72% and 62.9% of T2 and T3 patients had a MPTD > 30–50 mm, and 83.5% of T4 patients had a MPTD > 50 mm. For patients with a MPTD ≤ 30 mm, > 30–50 mm and > 50 mm, the 5-year OS, FFS, DMFS and LRFS rates were 85.2%, 74.2% and 56.3% (P < 0.001); 87%, 80.7% and 62.8% (P < 0.001); 88.7%, 86.4% and 72.5% (P = 0.003); and 98.2%, 93.2% and 86.3% (P = 0.012), respectively. In multivariate analysis, MPTD was a prognostic factor for OS, FFS and DMFS, and the only independent prognostic factor for LRFS. For T3-T4 patients with a MPTD ≤ 50 mm and > 50 mm, the 5-year OS, FFS and DMFS rates were 70.4% vs. 58.4% (P = 0.010), 77.5% vs. 65.2% (P = 0.013) and 83.6% vs. 73.6% (P = 0.047), respectively. In patients with a MPTD ≤ 30 mm, 5-year LRFS in T1, T2, T3 and T4 was 100%, 100%, 88.9% and 100% (P = 0.172).

Conclusions

Our data suggest that MPTD is an independent prognostic factor in NPC, and incorporation of MPTD might lead to a further refinement of T staging.
Histone modifications and traditional Chinese medicinals
Authors: Hsieh Hsin-Ying , Chiu Pei-Hsun , Wang Sun-Chong
Published: May 2013

Background

Chromatin, residing in the nuclei of eukaryotic cells, comprises DNA and histones to make up chromosomes. Chromatin condenses to compact the chromosomes and loosens to facilitate gene transcription and DNA replication/repair. Chemical modifications to the histones mediate changes in chromatin structure. Histone-modifying enzymes are potential drug targets. How herbs affect phenotypes through histone modifications is interesting.

Methods

Two public traditional Chinese medicine (TCM) databases were accessed to retrieve the chemical constituents and TCM natures of 3,294 TCM medicinals. NCBI taxonomy database was accessed to build the phylogenetic tree of the TCM medicinals. Statistical test was used to test if TCM natures of the medicinals cluster in the phylogenetic tree. A public chemical-protein interaction database was accessed to identify TCM medicinals whose constituent chemicals interact with human histone-modifying enzymes. For each histone modification, a correlation coefficient was calculated between the medicinals’ TCM natures and modification modulabilities. Information of the ingredient medicinals of 200 classical TCM formulas was accessed from a public database.

Results

It was found that 1,170 or 36% of the 3,294 TCM medicinals interact with human histone-modifying enzymes. Among the histone-modifying medicinals, 56% of them promote chromatin condensation. The cold-hot natures of TCM medicinals were found to be phylogenetically correlated. Furthermore, cold (hot) TCM medicinals were found to be associated with heterochromatinization (euchromatinization) through mainly H3K9 methylation and H3K4 demethylation. The associations were weak yet statistically significant. On the other hand, analysis of TCM formulas, the major form of TCM prescriptions in clinical practice, found that 99% of 200 government approved TCM formulas are histone-modifying. Furthermore, in formula formation, heterochromatic medicinals were found to team up with other heterochromatic medicinals to enhance the heterochromatinization of the formula. The synergy was mainly through concurrent DNMT and HDAC inhibition, co-inhibition of histone acetylation and H3S10 phosphorylation, or co-inhibition of H3K4 demethylation and H3K36 demethylation.

Conclusions

TCM prescriptions’ modulation of the human epigenome helps elucidation of phyto-pharmacology and discovery of epigenetic drugs. Furthermore, as TCM medicinals’ properties are closely tied to patient TCM syndromes, results of this materia-medica-wide, bioinformatic analysis of TCM medicinals may have implications for molecular differentiation of TCM syndromes.
Disruption of mediator complex subunit 19 (Med19) inhibits cell growth and migration in tongue cancer
Authors: Zhu Li-Jun , Yan Wang-Xiang , Chen Zhong-Wei , Chen Yu , Chen Dan , Zhang Tong-Han , Liao Gui-Qing
Published: May 2013

Background

Mediator complex subunit 19 (Med19) is a critical subunit of the mediator complex that forms a bridge between the transcription factors and RNA polymerase II. Although it has been reported that Med19 plays an important role in stabilizing the whole mediator complex, its biological importance in tongue cancer cell proliferation and migration has not been addressed.

Methods

By using MTT, BrdU incorporation, colony formation, flow cytometric, tumorigenesis and transwell assays, We tested the Med19 role on tongue cancer cell growth and migration.

Results

We demonstrated that lentivirus-mediated Med19 knockdown could arrest tongue cancer cells at G1 phase, inhibit tongue cancer cell proliferation and migration in vitro. The tumorigenicity of Med19 short hairpin RNA (shRNA)-expressing lentivirus infected tongue cancer cells were decreased after inoculating into nude mice.

Conclusions

These results indicate that Med19 plays an important role in tongue cancer proliferation and migration, and suggest possible applications for tongue cancer therapy.
Prognostic predictive values of gemcitabine sensitivity-related gene products for unresectable or recurrent biliary tract cancer treated with gemcitabine alone
Authors: Murata Akihiro , Amano Ryosuke , Yamada Nobuya , Kimura Kenjiro , Yashiro Masakazu , Nakata Bunzo , Hirakawa Kosei
Published: May 2013

Background

Gemcitabine is a pyrimidine nucleoside analog that is a commonly used chemotherapeutic agent for unresectable or recurrent biliary tract cancer (BTC). Several molecules involved in gemcitabine metabolism, including human equilibrative nucleoside transporter (hENT1), deoxycytidine kinase (dCK), and ribonucleotide reductase subunit M1 (RRM1), have been investigated as predictive biomarkers of gemcitabine efficacy, mostly in pancreatic cancer. The aim of this study is to clarify which biomarker is the most reliable among hENT1, dCK, and RRM1 to predict survival in patients with advanced BTC treated with gemcitabine alone.

Methods

The analysis was performed on samples from 28 patients with unresectable or recurrent BTC who were treated with gemcitabine alone as first-line therapy. The starting date of overall survival (OS) and progression-free survival (PFS) was defined as the date of first treatment with gemcitabine. Intratumoral hENT1, dCK, and RRM1 expressions were examined by immunohistochemistry.

Results

The expressions of hENT1, dCK, and RRM1 had no significant relationships with age, gender, primary tumor site, recurrence/unresectable, or histological type. Among the three molecules, only hENT1 expression was a significant factor affecting OS and PFS in univariate analysis; OS was 11.4 months for high hENT1 expression versus 5.7 months for low, P = 0.0057; PFS was 7.7 months for high versus 2.5 months for low, P = 0.0065. Multivariate analyses also identified hENT1 expression as an independent predictive factor for OS.

Conclusions

hENT1 is the most reliable predictive marker of survival in patients with advanced BTC treated with gemcitabine.
Isothermal loop-mediated amplification (lamp) for diagnosis of contagious bovine pleuro-pneumonia
Authors: Mair Georg , Vilei Edy M , Wade Abel , Frey Joachim , Unger Hermann
Published: May 2013

Background

Contagious Bovine Pleuropneumonia (CBPP) is the most important chronic pulmonary disease of cattle on the African continent causing severe economic losses. The disease, caused by infection with Mycoplasma mycoides subsp. mycoides is transmitted by animal contact and develops slowly into a chronic form preventing an early clinical diagnosis. Because available vaccines confer a low protection rate and short-lived immunity, the rapid diagnosis of infected animals combined with traditional curbing measures is seen as the best way to control the disease. While traditional labour-intensive bacteriological methods for the detection of M. mycoides subsp. mycoides have been replaced by molecular genetic techniques in the last two decades, these latter approaches require well-equipped laboratories and specialized personnel for the diagnosis. This is a handicap in areas where CBPP is endemic and early diagnosis is essential.

Results

We present a rapid, sensitive and specific diagnostic tool for M. mycoides subsp. mycoides detection based on isothermal loop-mediated amplification (LAMP) that is applicable to field conditions. The primer set developed is highly specific and sensitive enough to diagnose clinical cases without prior cultivation of the organism. The LAMP assay detects M. mycoides subsp. mycoides DNA directly from crude samples of pulmonary/pleural fluids and serum/plasma within an hour using a simple dilution protocol. A photometric detection of LAMP products allows the real-time visualisation of the amplification curve and the application of a melting curve/re-association analysis presents a means of quality assurance based on the predetermined strand-inherent temperature profile supporting the diagnosis.

Conclusion

The CBPP LAMP developed in a robust kit format can be run on a battery-driven mobile device to rapidly detect M. mycoides subsp. mycoides infections from clinical or post mortem samples. The stringent innate quality control allows a conclusive on-site diagnosis of CBPP such as during farm or slaughter house inspections.
Development of a non-invasive fibrosis test for chronic hepatitis B patients and comparison with other unpatented scores
Authors: Hsu Chao-Wei , Liang Kung-Hao , Huang Shiu-Feng , Tsao Kuo-Chien , Yeh Chau-Ting
Published: May 2013

Background

Despite the availability of patented non-invasive methods, evaluation of the degrees of liver fibrosis remains difficult when conducting a retrospective study. Such inadequacy is largely caused by requirement of biochemical parameters rarely performed in routine clinical tests. We developed a novel fibrosis HB-F score using commonly performed tests for HBV infected patients.

Methods

424 patients with chronic HBV infection were included. Using clinical and virological data, HB-F score was developed from a training cohort (n = 213) and validated in a separate cohort (n = 211). The performance was compared with five other unpatented scores using ROC curves.

Results

Univariate and multivariate analysis revealed that age, AST/ALT ratio, platelet count and prothrombin time prolongation were significantly associated with the ISHAK fibrosis score, and were used to calculate the HB-F score. When HB-F was used to assess prominent fibrosis and cirrhosis, the AUC was 0.81 and 0.80 respectively in the training cohort, and 0.80 and 0.76 respectively in the validation cohort. HB-F had the highest AUC compared with other scores. Furthermore, in assessing paired liver biopsies with increase or decrease of ISHAK scores, HB-F showed significant change in the same direction.

Conclusions

A new non-invasive score was developed, which could be used to assess severity of liver fibrosis in retrospective longitudinal studies in HBV patients.
Correlations of non-exercise activity thermogenesis to metabolic parameters in Japanese patients with type 2 diabetes
Authors: Hamasaki Hidetaka , Yanai Hidekatsu , Mishima Shuichi , Mineyama Tomoka , Yamamoto-Honda Ritsuko , Kakei Masafumi , Ezaki Osamu , Noda Mitsuhiko
Published: May 2013

Background

Non-exercise activity thermogenesis (NEAT) is the energy expenditure due to physical activities besides active sports-like exercise and resistance training in daily life.

Methods

We studied 45 subjects (22 women and 23 men) with type 2 diabetes who did not take any hypoglycemic, anti-hypertensive, or cholesterol-lowering agents and asked them about physical activity concerned with NEAT using an original questionnaire modified from a compendium of physical activities. We studied the association of the NEAT score to body weight, waist circumference, blood pressure, glucose and lipid metabolism, and arterial stiffness.

Results

The NEAT score was negatively correlated with serum insulin levels (r = -0.42, P < 0.05) in all subjects. The NEAT score was also negatively correlated with waist circumference (r = -0.509, P < 0.05) and positively correlated with high-density lipoprotein-cholesterol levels (r = 0.494, P < 0.05) in women, and negatively associated with serum insulin levels (r = -0.732, p < 0.005), systolic (r = -0.482, P < 0.05) and diastolic blood pressure (r = -0.538, P < 0.05) in patients with abdominal obesity. Furthermore, the NEAT score was negatively associated with pulse wave velocity (r = -0.719, P < 0.005) in smokers.

Conclusion

The study demonstrated that NEAT is associated with amelioration in insulin sensitivity, waist circumference, high-density lipoprotein-cholesterol, blood pressure and the marker for atherosclerosis in patients with type 2 diabetes.
Resistance training decreases 24-hour blood pressure in women with metabolic syndrome
Authors: Tibana Ramires Alsamir , Pereira Guilherme Borges , de Souza Jéssica Cardoso , Tajra Vitor , Vieira Denis Cesar Leite , Campbell Carmen Silvia Grubert , Cavaglieri Claudia Regina , Prestes Jonato
Published: May 2013

Background

The purpose of this study was to verify the effects of eight weeks of resistance training (RT) on 24 hour blood pressure (BP) in patients with and without metabolic syndrome (MetS).

Methods

Seventeen women volunteered to participate in this study, 9 with MetS (37.0 ± 8.7 yrs; body mass 77.3 ± 9.7 kg; body mass index 30.3 ± 4.2 kg · m-2) and 8 without MetS (35.1 ± 7.2 yrs; body mass 61.3 ± 8.1 kg; body mass index 24.2 ± 2.5 kg · m-2). Individuals were subjected to eight weeks (3 times/week) of whole body RT comprised of one exercise for each main muscle group with three sets of 8–12 repetitions of each subject’s maximal load . A rest interval of one minute was allowed between sets and exercises. Twenty-four hour BP was measured by ambulatory blood pressure monitoring.

Results

Mean and diastolic night-time BP decreased (−3.9 mmHg, p = 0.04; -5.5 mmHg, p = 0.03, respectively) after eight weeks of training in MetS patients. This decrease was observed at 11:00 pm, 02:00 am (only diastolic), 07:00 am, and 6:00 pm. There was no training effect on BP in women without MetS.

Conclusions

Considering the elevation of BP as a contributor to the pathogenesis of MetS, and also to the increase of cardiovascular risk, this study supports RT as a non-pharmacological therapy in the management of BP control for MetS.
Catabolic and anabolic periarticular bone changes in patients with rheumatoid arthritis: a computed tomography study on the role of age, disease duration and bone markers
Authors: Aschenberg Sophie , Finzel Stephanie , Schmidt Sarah , Kraus Sebastian , Engelke Klaus , Englbrecht Matthias , Rech Jürgen , Schett Georg
Published: May 2013

Introduction

The aim of this study was to determine the factors, including markers of bone resorption and bone formation, which determine catabolic and anabolic periarticular bone changes in patients with rheumatoid arthritis (RA).

Methods

Forty RA patients received high-resolution peripheral quantitative computed tomography (HR-pQCT) analysis of the metacarpophalangeal joints II and III of the dominantly affected hand at two sequential time points (baseline, one year follow-up). Erosion counts and scores as well as osteophyte counts and scores were recorded. Simultaneously, serum markers of bone resorption (C-terminal telopeptide of type I collagen (CTX I), tartrate-resistant acid phosphatase 5b (TRAP5b)), bone formation (bone alkaline phosphatase (BAP), osteocalcin (OC)) and calcium homeostasis (parathyroid hormone (PTH), 25-hydroxyvitamin D3 (Vit D)) were assessed. Bone biomarkers were correlated to imaging data by partial correlation adjusting for various demographic and disease-specific parameters. Additionally, imaging data were analyzed by mixed linear model regression.

Results

Partial correlation analysis showed that TRAP5b levels correlate significantly with bone erosions, whereas BAP levels correlate with osteophytes at both time points. In the mixed linear model with erosions as the dependent variable, disease duration (P <0.001) was the key determinant for these catabolic bone changes. In contrast, BAP (P = 0.001) as well as age (P = 0.018), but not disease duration (P = 0.762), were the main determinants for the anabolic changes (osteophytes) of the periarticular bone in patients with RA.

Conclusions

This study shows that structural bone changes assessed with HR-pQCT are accompanied by alterations in systemic markers of bone resorption and bone formation. Besides, it can be shown that bone erosions in RA patients depend on disease duration, whereas osteophytes are associated with age as well as serum level of BAP. Therefore, these data not only suggest that different variables are involved in formation of bone erosions and osteophytes in RA patients, but also that periarticular bone changes correlate with alterations in systemic markers of bone metabolism, pointing out BAP as an important parameter.
Circulating serum xenoestrogens and mammographic breast density
Authors: Sprague Brian L , Trentham-Dietz Amy , Hedman Curtis J , Wang Jue , Hemming Jocelyn DC , Hampton John M , Buist Diana SM , Aiello Bowles Erin J , Sisney Gale S , Burnside Elizabeth S
Published: May 2013

Introduction

Humans are widely exposed to estrogenically active phthalates, parabens, and phenols, raising concerns about potential effects on breast tissue and breast cancer risk. We sought to determine the association of circulating serum levels of these chemicals (reflecting recent exposure) with mammographic breast density (a marker of breast cancer risk).

Methods

We recruited postmenopausal women aged 55 to 70 years from mammography clinics in Madison, Wisconsin (N = 264). Subjects completed a questionnaire and provided a blood sample that was analyzed for mono-ethyl phthalate, mono-butyl phthalate, mono-benzyl phthalate, butyl paraben, propyl paraben, octylphenol, nonylphenol, and bisphenol A (BPA). Percentage breast density was measured from mammograms by using a computer-assisted thresholding method.

Results

Serum BPA was positively associated with mammographic breast density after adjusting for age, body mass index, and other potentially confounding factors. Mean percentage density was 12.6% (95% confidence interval (CI), 11.4 to 14.0) among the 193 women with nondetectable BPA levels, 13.7% (95% CI, 10.7 to 17.1) among the 35 women with detectable levels below the median (<0.55 ng/ml), and 17.6% (95% CI, 14.1 to 21.5) among the 34 women with detectable levels above the median (>0.55 ng/ml; Ptrend = 0.01). Percentage breast density was also elevated (18.2%; 95% CI, 13.4 to 23.7) among the 18 women with serum mono-ethyl phthalate above the median detected level (>3.77 ng/ml) compared with women with nondetectable BPA levels (13.1%; 95% CI, 11.9 to 14.3; Ptrend = 0.07). No other chemicals demonstrated associations with percentage breast density.

Conclusions

Postmenopausal women with high serum levels of BPA and mono-ethyl phthalate had elevated breast density. Further investigation of the impact of BPA and mono-ethyl phthalate on breast cancer risk by using repeated serum measurements or other markers of xenoestrogen exposure are needed.
Is early ventricular dysfunction or dilatation associated with lower mortality rate in adult severe sepsis and septic shock? A meta-analysis
Authors: Huang Stephen J , Nalos Marek , McLean Anthony S
Published: May 2013

Introduction

Reversible myocardial depression occurs early in severe sepsis and septic shock. The question of whether or not early ventricular depression or dilatation is associated with lower mortality in these patients remains controversial. Most studies on this topic were small in size and hence lacked statistical power to answer the question. This meta-analysis attempted to answer the question by increasing the sample size via pooling relevant studies together.

Methods

PubMed, Embase (and Medline) databases and conference abstracts were searched to July 2012 for primary studies using well-defined criteria. Two authors independently screened and selected studies. Eligible studies were appraised using defined criteria. Additional information was sought the corresponding authors if necessary. Study results were pooled using random effects models. Standardized mean differences (SMD) between survivor and non-survivor groups were used as the main effect measures.

Results

A total of 62 citations were found. Fourteen studies were included in the analysis. The most apparent differences between the studies were sample sizes and exclusion criteria. All studies, except four pre-1992 studies, adopted the Consensus definition of sepsis. Altogether, there were >700 patients available for analysis of the left ventricle and >400 for the right ventricle. There were no significant differences in left ventricular ejection fractions, right ventricular ejection fractions, and right ventricular dimensions between the survivor and non-survivor groups. When indexed against body surface area or body height, the survivors and non-survivors had similar left ventricular dimensions. However, the survivors had larger non-indexed left ventricular dimensions.

Conclusion

This meta-analysis failed to find any evidence to support the view that the survivors from severe sepsis or septic shock had lower ejection fractions. However, non-indexed left ventricular dimensions were mildly increased in the survivor group but the indexed dimensions were similar between the groups. Both survivors and non-survivors had similar right ventricular dimensions.
Anti-vascular endothelial growth factor antibody attenuates inflammation and decreases mortality in an experimental model of severe sepsis
Authors: Jeong Su Jin , Han Sang Hoon , Kim Chang Oh , Choi Jun Yong , Kim June Myung
Published: May 2013

Introduction

Severe sepsis is associated with an unacceptably high rate of mortality. Recent studies revealed elevated levels of vascular endothelial growth factor (VEGF), a potent angiogenic and vascular permeability factor, in patients with sepsis. There was also an association between VEGF levels and sepsis severity. Here we investigate the effects of an anti-VEGF antibody (Bevacizumab, Bev) in an experimental model of sepsis.

Methods

Human umbilical vein endothelial cells (HUVECs), murine cecal ligation and puncture (CLP), and endotoxemia models of sepsis were used. HUVECs were treated with lipopolysaccharide (LPS) and/or Bev, harvested and cytokine mRNA levels determined using a semi-quantitative reverse transcription-polymerase chain reaction assay. The levels of inflammatory cytokine were also determined in HUVECs supernatants. In addition, the effects of Bev on mortality in the CLP and endotoxemia models of sepsis were evaluated.

Results

Treatment with Bev and LPS significantly decreased the expression and the level of inflammatory cytokines in HUVECs relative to LPS alone. In CLP and endotoxemia models, survival benefits were evident in mice given 0.1 mg/kg of Bev relative to the CLP or LPS alone (P <0.001 and P = 0.028, respectively), and in 6 h post-treated mice relative to the CLP alone for the effect of different time of Bev (P = 0.033). In addition, Bev treatment inhibited LPS-induced vascular leak in the lung, spleen and kidney in the murine endotoxemia model (P <0.05).

Conclusions

Anti-VEGF antibody may be a promising therapeutic agent due to its beneficial effects on the survival of sepsis by decreasing inflammatory responses and endothelial permeability.
Invasive mechanical ventilation as a risk factor for acute kidney injury in the critically ill: a systematic review and meta-analysis
Authors: van den Akker Johannes PC , Egal Mahamud , Groeneveld AB Johan
Published: May 2013

Introduction

Mechanical ventilation (MV) is commonly regarded as a risk factor for acute kidney injury (AKI) in the critically ill. We investigated the strength of this association and whether settings of tidal volume (Vt) and positive end-expiratory pressure (PEEP) affect the risk for AKI.

Methods

We performed a systematic review and meta-analysis using studies found by searching MEDLINE, EMBASE, and references in relevant reviews and articles. We included studies reporting on a relation between the use of invasive MV and subsequent onset of AKI, or comparing higher with lower Vt or PEEP and subsequent onset of AKI. All studies clearly stating that MV was initiated after onset of AKI were excluded. We extracted the proportion with and without MV and AKI. We included 31 studies on invasive MV.

Results

The pooled odds ratio (OR) for the overall effect of MV on AKI was 3.16 (95% CI 2.32 to 4.28, P <0.001). Nearly all subgroups showed that MV increases the risk for AKI. The pooled OR for studies with a multivariate analysis including MV as a risk factor for AKI was 3.58 (95% CI 1.85 to 6.92; P <0.001). Different settings of Vt and PEEP showed no effect.

Conclusions

Invasive MV is associated with a threefold increase in the odds of developing AKI and various Vt or PEEP settings do not modify this risk. The latter argues in favour of a haemodynamic origin of AKI during MV.
Susceptibility to ventilator induced lung injury is increased in senescent rats
Authors: Setzer Florian , Oschatz Karsten , Hueter Lars , Schmidt Barbara , Schwarzkopf Konrad , Schreiber Torsten
Published: May 2013

Introduction

The principal mechanisms of ventilator induced lung injury (VILI) have been investigated in numerous animal studies. However, prospective data on the effect of old age on VILI are limited. Under the hypothesis that susceptibility to VILI is increased in old age, we investigated the pulmonary and extrapulmonary effects of mechanical ventilation with high tidal volume (VT) in old compared to young adult animals.

Interventions

Old (19.1 ± 3.0 months) and young adult (4.4 ± 1.3 months) male Wistar rats were anesthetized and mechanically ventilated (positive end-expiratory pressure 5 cmH2O, fraction of inspired oxygen 0.4, respiratory rate 40/minute) with a tidal volume (VT) of either 8, 16 or 24 ml/kg for four hours.

Respiratory and hemodynamic variables, including cardiac output, and markers of systemic inflammation were recorded throughout the ventilation period. Lung histology and wet-to-dry weight ratio, injury markers in lung lavage and respiratory system pressure-volume curves were assessed post mortem. Basic pulmonary characteristics were assessed in non-ventilated animals.

Results

Compared to young adult animals, high VT (24 ml/kg body weight) caused more lung injury in old animals as indicated by decreased oxygenation (arterial oxygen tension (PaO2): 208 ± 3 vs. 131 ± 20 mmHg; P <0.05), increased lung wet-to-dry-weight ratio (5.61 ± 0.29 vs. 7.52 ± 0.27; P <0.05), lung lavage protein (206 ± 52 mg/l vs. 1,432 ± 101; P <0.05) and cytokine (IL-6: 856 ± 448 vs. 3,283 ± 943 pg/ml; P <0.05) concentration. In addition, old animals ventilated with high VT had more systemic inflammation than young animals (IL-1β: 149 ± 44 vs. 272 ± 36 pg/ml; P <0.05 - young vs. old, respectively).

Conclusions

Ventilation with unphysiologically large tidal volumes is associated with more lung injury in old compared to young rats. Aggravated pulmonary and systemic inflammation is a key finding in old animals developing VILI.
Photoinduced Charge Separation of 10-Phenyl-10H-phenothiazine–2-Phenylanthraquinone Dyad Bridged by Bicyclo[2.2.2]octane
Authors: Karimata Ayumu , Kawauchi Hidetoshi , Suzuki Shuichi , Kozaki Masatoshi , Ikeda Noriaki , Keyaki Kazutoshi , Nozaki Koichi , Akiyama Kimio , Okada Keiji
Published: May 2013

Photoinduced charge separation of a phenothiazine–anthraquinone dyad 1 with a rigid bicyclo[2.2.2]octane spacer was investigated by means of picosecond and nanosecond transient absorption and time-resolved ESR spectroscopies. Irradiation of the anthraquinone chromophore in 1 produced the charge-separated (CS) state in THF. Time constants of the formation and the decay of the CS state were determined to be 1.3 ns and 1.0 µs, respectively. Time-resolved ESR showed spin-polarized all-emission signals due to the formation of the CS state via the triplet mechanism.
Development of Positive Photoresist for Controlling Cell Culture Shape on Organic Substrates
Authors: Kumashiro Yoshikazu , Itoga Kazuyoshi , Kinoshita Yohei , Yamato Masayuki , Okano Teruo
Published: May 2013

Micropatterns on organic materials were fabricated using various positive photoresist solutions for clearly patterning the culture of cells on organic materials. The surface erosion of organic materials with positive photoresist solvents was quantitatively characterized, and a suitable solute/solvent combination was found. Clear cell patterns were observed on a surface when using the newly developed photoresist, mainly because the developed photoresist hardly eroded on the surface of organic materials.
Unexpected Occurrence of Face-centered-cubic Nickel Phase in Air-atmosphere Sol–Gel Process
Authors: Li Pingyun , Jiang Wei , Li Fengsheng
Published: May 2013

The air-atmosphere sol–gel process is often used to prepare metallic oxides powders. This letter addresses for the first time that face-centered-cubic (FCC) metallic Ni phase also can be obtained by using sol–gel process in air atmosphere. The as-prepared nanoparticles have grain sizes in the range of 20 to 90 nm. Our results provide new insight into the sol–gel process.
Thermal Enhancement of Gene Transfection in Tumor Cells Mediated by the Photothermal Effect of Gold Nanorods
Authors: Sakamura Yuki , Yoshiura Moemi , Tang Hengmin , Mori Takeshi , Katayama Yoshiki , Niidome Takuro
Published: May 2013

A plasmid DNA and gold nanorods were directly injected to tumor in mice, and the tumor was heated to 39–42 °C through the photothermal effect of the gold nanorods. The heat treatment enhanced transgene expression from the plasmid DNA in the tumor and induced heat shock protein HSP70, related to several immune responses. This transfection technique combined with heat treatment will be applicable to DNA vaccination and gene therapy for immunological diseases.
Synthesis of Spirooxindoles from Carbamoyl Chlorides via Cyclopropyl Methine C(sp3)–H Activation Using Palladium Catalyst
Authors: Tsukano Chihiro , Okuno Masataka , Takemoto Yoshiji
Published: May 2013

The synthesis of spirooxindoles fused with cyclopropanes from carbamoyl chlorides, via methine C(sp3)–H activation, is reported. The regioselectivity of C–H activation in the presence of competitive C–H bonds at the appropriate position was investigated under the optimized conditions.
Near-infrared-responsive Liquid Marbles Stabilized with Carbon Nanotubes
Authors: Nakai Keita , Nakagawa Hinari , Kuroda Keita , Fujii Syuji , Nakamura Yoshinobu , Yusa Shin-ichi
Published: May 2013

Near-infrared (NIR)-responsive liquid marbles were prepared using carbon nanotube (CNT) and fullerene (C60) powders. The liquid marbles were transferred to the surface of bulk water. The liquid marbles immediately disintegrated upon NIR irradiation due to conversion of NIR energy to heat. The NIR-responsive liquid marbles can be used to induce chemical reactions, if a liquid marble containing one reactant was floated on bulk water containing another reactant. Upon NIR irradiation, the liquid marble burst and the two reactants came in contact, triggering the reaction.
Oxidative Conversion of Tetraaryldihydrodibenzothiepins into Elemental Sulfur and Stable Cationic Dyes Accompanied by Dual UV–vis and CD Spectral Changes
Authors: Suzuki Takanori , Kuroda Takuma , Tamaoki Hitomi , Higasa Sho , Katoono Ryo , Fujiwara Kenshu , Fukushima Takanori , Yamada Hidetoshi
Published: May 2013

Upon oxidation of the title heterocycles with dimethylamino groups, elemental sulfur is extruded to form dicationic dyes, which regenerate the heterocycles by the reaction with Na2S. The electrolysis of the heterocycles induces a drastic change in UV–vis spectrum exhibiting several isosbestic points. The bay-region substituents enhance configurational stability, so the optically pure heterocycle can be obtained in terms of helicity of one-handedness, and its chromism is accompanied by a large chiroptical response as detected by CD spectroscopy.
Towards a model of Strategic Roster Planning and Control: an empirical study of nurse rostering practices in the UK National Health Service
Authors: Silvestro Rhian , Silvestro Claudio
Published: May 2013

Despite the criticality of nurse rostering practices, there is a surprising lack of attention paid to this managerial activity both in practice and in the health-service management literature. This paper reports the results of an inductive, empirical study of rostering practices in the UK National Health Service with a view to developing a shared understanding of roster planning processes and of what constitutes rostering effectiveness. A survey of rostering practices in 50 wards, followed by five in-depth, longitudinal case studies, revealed the complexity of rostering activities, and identified the main design parameters, which were used to specify rostering systems and to prepare periodic rosters. Rostering activities were perceived to directly impact upon service delivery, resource utilization and nurse retention. A number of poor rostering practices were identified, which could lead to dysfunctional behaviour. This analysis points to a clear managerial imperative to improve local competencies in roster planning and control, recognizing their strategic significance in contributing to hospital effectiveness. A ‘Strategic Roster Planning and Control (SRPC)’ model is proposed, which may provide a framework for evaluating rostering effectiveness, and a platform for the sharing of best practice, in order to stimulate organizational learning and achieve nationwide improvements in hospital performance.
The effects of the global budget system on cost containment and the quality of care: experience in Taiwan
Authors: Chang Li , Hung Jung-Hua
Published: May 2013

This study is an attempt to determine whether the implementation of the Global Budget (GB) as a method of health reform has improved cost containment and quality of care in Taiwan. Panel-data analysis is used to investigate cost containment and quality of care in Taipei municipal hospitals before and after the introduction of the GB. The results suggest that there is a trade-off effect. The post-GB data indicate that cost containment comes at the expense of health-care quality. It may, therefore, be the case that policy-makers can more effectively balance cost containment and quality by refining the GB so that reimbursements would be linked to standards of quality. Another way to enhance the reforms would be a more effective monitoring and review system.