bluuebunny/crossref_metadata_2025 huggingface dataset:
Endotoxin levels in homes and classrooms of Dutch school children and respiratory health
Authors: Jacobs José H. , Krop Esmeralda J.M. , de Wind Siegfried , Spithoven Jack , Heederik Dick J.J.
Published: October 2012

Several studies describe indoor pollutant exposure in homes and to a lesser extent in schools. Population studies that include both environments are sparse. This study aims to assess endotoxin levels in primary schools and homes of children. Endotoxin was also studied in relation to asthma and sensitisation.

10 schools with (index) and without (reference) dampness were selected, based on reports and inspections. Cases and controls were selected from 169 homes based on the presence or absence of asthma-like symptoms of children. Classroom and bedroom airborne settled dust was sampled using electrostatic dust fall collectors.

Average endotoxin levels in schools ranged from 2178 to 6914 endotoxin units (EU)·m−2per week compared with 462–1285 EU·m−2per week in homes. After mutual adjustment for home and school endotoxin, school endotoxin was positively associated with nonatopic asthma (OR 1.11, 95% CI 0.97–1.27), while no associations with endotoxin were found at home.

The high endotoxin levels in schools compared with homes indicate that exposure at school can contribute considerably to environmental endotoxin exposure of children and teachers. Our results also suggest that endotoxin in schools may be associated with nonatopic asthmatic symptoms in pupils, although the results require reproduction because of the modest sample size.
Influence of perfusate temperature on nasal potential difference
Authors: Bronsveld Inez , Vermeulen François , Sands Dorotha , Leal Teresinha , Leonard Anissa , Melotti Paola , Yaakov Yasmin , de Nooijer Roel , De Boeck Kris , Sermet Isabelle , Wilschanski Michael , Middleton Peter G.
Published: October 2012

Nasal potential difference (NPD) quantifies abnormal ion transport in cystic fibrosis. It has gained acceptance as an outcome measure for the investigation of new therapies.

To quantify the effect of solution temperature on NPD, we first examined the effect of switching from room temperature (20–25°C) to warmed (32–37°C) solutions andvice versaduring each perfusion step. Secondly, standard protocols were repeated at both temperatures in the same subjects.

Changing solution temperature did not alter NPD during perfusion with Ringer’s solution (<1 mV) (p>0.1). During perfusion with zero chloride solution, changing from room temperature to warmed solutions tended to decrease absolute NPD (i.e.it became less negative) by 0.9 mV (p>0.1); changing from warmed to room temperature increased NPD by 2.1 mV (p<0.05). During isoprenaline perfusion, changing from room temperature to warmed solutions increased NPD by 1.5 mV (p<0.01) and from warmed to room temperature decreased NPD by 1.4 mV (p<0.05).

For full protocols at room temperature or warmed in the same subjects, mean values were similar (n = 24). During warmed perfusion, group results for total chloride response had a larger standard deviation. As this increased variability will probably decrease the power of trials, this study suggests that solutions at room temperature should be recommended for the measurement of NPD.
Assessing spatial heterogeneity of multidrug-resistant tuberculosis in a high-burden country
Authors: Jenkins Helen E. , Plesca Valeriu , Ciobanu Anisoara , Crudu Valeriu , Galusca Irina , Soltan Viorel , Serbulenco Aliona , Zignol Matteo , Dadu Andrei , Dara Masoud , Cohen Ted
Published: October 2012

Multidrug-resistant tuberculosis (MDR-TB) is a major concern in countries of the former Soviet Union. The reported risk of resistance among tuberculosis (TB) cases in the Republic of Moldova is among the highest in the world. We aimed to produce high-resolution spatial maps of MDR-TB risk and burden in this setting.

We analysed national TB surveillance data collected between 2007 and 2010 in Moldova. High drug susceptibility testing coverage and detailed location data permitted identification of subregional areas of higher MDR-TB risk. We investigated whether the distribution of cases with MDR-TB risk factors could explain this observed spatial variation in MDR-TB.

3447 MDR-TB cases were notified during this period; 24% of new and 62% of previously treated patients had MDR-TB. Nationally, the estimated annual MDR-TB incidence was 54 cases per 100 000 persons and >1000 cases per 100 000 persons within penitentiaries. We identified substantial geographical variation in MDR-TB burden and hotspots of MDR-TB. Locations with a higher percentage of previously incarcerated TB cases were at greater risk of being MDR-TB hotspots.

Spatial analyses revealed striking geographical heterogeneity of MDR-TB. Methods to identify locations of high MDR-TB risk and burden should allow for better resource allocation and more appropriate targeting of studies to understand local mechanisms driving resistance.
Lung clearance index in adult cystic fibrosis patients: the role of convection-dependent lung units
Authors: Verbanck Sylvia , Paiva Manuel , Paeps Erika , Schuermans Daniel , Malfroot Anne , Vincken Walter , Vanderhelst Eef
Published: October 2012

We investigated the extent of convective ventilation heterogeneity contributing to the observed lung clearance index values in adult cystic fibrosis patients, as the result of two simulated scenarios, either 1) a fixed part of the lungs becoming increasingly less compliant, or 2) an increasingly greater part of the lung being less compliant.

In 25 cystic fibrosis patients and 25 matched controls, we computed the lung clearance index and also quantified curvilinearity of the washout concentration curve, where curvilinearity is equal to 0 (linear in semilog plot) reflects homogeneous ventilation and curvilinearity equal to 1 corresponds to the presence of an infinitesimally slowly emptying lung unit.

In the cystic fibrosis group (forced expiratory volume in 1 s 27–100% predicted), lung clearance index and curvilinearity average±sdvalues were 10.3±2.3 and 0.57±0.13, respectively, and were significantly different from control values (6.2±0.4 and 0.18±0.07; both p<0.001); lung clearance index and curvilinearity were also correlated (R = 0.67; p<0.001). The average curvilinearity value in the cystic fibrosis group was found to be compatible with a cumulative volume of underventilated lung of 40–50%, depending on the simulation scenario considered.

The degree of washout curvilinearity observed here indicates that a major determinant of the abnormal lung clearance index values observed in adult cystic fibrosis patients is ventilation heterogeneity generated between convection-dependent lung units, while the remainder of lung clearance index abnormality with respect to normal controls potentially represents the small airways within these lung zones.
Resistance to fluoroquinolones and second-line injectable drugs: impact on multidrug-resistant TB outcomes
Authors: Falzon Dennis , Gandhi Neel , Migliori Giovanni B. , Sotgiu Giovanni , Cox Helen S. , Holtz Timothy H. , Hollm-Delgado Maria-Graciela , Keshavjee Salmaan , DeRiemer Kathryn , Centis Rosella , D'Ambrosio Lia , Lange Christoph G. , Bauer Melissa , Menzies Dick
Published: October 2012

A meta-analysis for response to treatment was undertaken using individual data of multidrug-resistant tuberculosis (MDR-TB) (resistance to isoniazid and rifampicin) patients from 26 centres. The analysis assessed the impact of additional resistance to fluoroquinolones and/or second-line injectable drugs on treatment outcome.

Compared with treatment failure, relapse and death, treatment success was higher in MDR-TB patients infected with strains without additional resistance (n=4763; 64%, 95% CI 57–72%) or with resistance to second-line injectable drugs only (n=1130; 56%, 95% CI 45–66%), than in those having resistance to fluoroquinolones alone (n=426; 48%, 95% CI 36–60%) or to fluoroquinolones plus second-line injectable drugs (extensively drug resistant (XDR)-TB) (n=405; 40%, 95% CI 27–53%). In XDR-TB patients, treatment success was highest if at least six drugs were used in the intensive phase (adjusted OR 4.9, 95% CI 1.4–16.6; reference fewer than three drugs) and four in the continuation phase (OR 6.1, 95% CI 1.4–26.3). The odds of success in XDR-TB patients was maximised when the intensive phase reached 6.6–9.0 months duration and the total duration of treatment 20.1–25.0 months.

In XDR-TB patients, regimens containing more drugs than those recommended in MDR-TB but given for a similar duration were associated with the highest odds of success.

All data were from observational studies and methodologies varied between centres, therefore, the bias may be substantial. Better quality evidence is needed to optimise regimens.
The successful experimental induction of necrotic enteritis in chickens by Clostridium perfringens: a critical review
Authors: Shojadoost Bahram , Vince Andrew R , Prescott John F
Published: October 2012

Necrotic enteritis (NE) is one of the most important enteric diseases in poultry and is a high cost to the industry worldwide. It is caused by avian-specific, Necrotic Enteritis Beta toxin (NetB)-producing, strains of Clostridium perfringens that also possess in common other virulence-associated genes. In Europe the disease incidence has increased since the ban on in-feed “growth promoting” antibiotics. Because of this, many recent studies of NE have focused on finding different ways to control the disease, and on understanding its pathogenesis. Frustratingly, reproduction of the disease has proven impossible for some researchers. This review describes and discusses factors known to be important in reproducing the disease experimentally, as well as other considerations in reproducing the disease. The critical bacterial factor is the use of virulent, netB-positive, strains; virulence can be enhanced by using tpeL- positive strains and by the use of young rather than old broth cultures to increase toxin expression. Intestinal damaging factors, notably the use of concurrent or preceding coccidial infection, or administration of coccidial vaccines, combined with netB-positive C. perfringens administration, can also be used to induce NE. Nutritional factors, particularly feeding high percentage of cereals containing non-starch polysaccharides (NSP) (wheat, rye, and barley) enhance disease by increasing digesta viscosity, mucus production and bacterial growth. Animal proteins, especially fish meal, enhance C. perfringens proliferation and toxin production. Other factors are discussed that may affect outcome but for which evidence of their importance is lacking. The review compares the different challenge approaches; depending on the aim of particular studies, the different critical factors can be adjusted to affect the severity of the lesions induced. A standardized scoring system is proposed for international adoption based on gross rather than histopathological lesions; if universally adopted this will allow better comparison between studies done by different researchers. Also a scoring system is provided to assist decisions on humane euthanasia of sick birds.
Euchromatin islands in large heterochromatin domains are enriched for CTCF binding and differentially DNA-methylated regions
Authors: Wen Bo , Wu Hao , Loh Yuin-Han , Briem Eirikur , Daley George Q , Feinberg Andrew P
Published: October 2012

Background

The organization of higher order chromatin is an emerging epigenetic mechanism for understanding development and disease. We and others have previously observed dynamic changes during differentiation and oncogenesis in large heterochromatin domains such as Large Organized Chromatin K (lysine) modifications (LOCKs), of histone H3 lysine-9 dimethylation (H3K9me2) or other repressive histone posttranslational modifications. The microstructure of these regions has not previously been explored.

Results

We analyzed the genome-wide distribution of H3K9me2 in two human pluripotent stem cell lines and three differentiated cells lines. We identified > 2,500 small regions with very low H3K9me2 signals in the body of LOCKs, which were termed as euchromatin islands (EIs). EIs are 6.5-fold enriched for DNase I Hypersensitive Sites and 8-fold enriched for the binding of CTCF, the major organizer of higher-order chromatin. Furthermore, EIs are 2–6 fold enriched for differentially DNA-methylated regions associated with tissue types (T-DMRs), reprogramming (R-DMRs) and cancer (C-DMRs). Gene ontology (GO) analysis suggests that EI-associated genes are functionally related to organ system development, cell adhesion and cell differentiation.

Conclusions

We identify the existence of EIs as a finer layer of epigenomic architecture within large heterochromatin domains. Their enrichment for CTCF sites and DNAse hypersensitive sites, as well as association with DMRs, suggest that EIs play an important role in normal epigenomic architecture and its disruption in disease.
Quantitative GPCR and ion channel transcriptomics in primary alveolar macrophages and macrophage surrogates
Authors: Groot-Kormelink Paul J , Fawcett Lindsay , Wright Paul D , Gosling Martin , Kent Toby C
Published: October 2012

Background

Alveolar macrophages are one of the first lines of defence against invading pathogens and play a central role in modulating both the innate and acquired immune systems. By responding to endogenous stimuli within the lung, alveolar macrophages contribute towards the regulation of the local inflammatory microenvironment, the initiation of wound healing and the pathogenesis of viral and bacterial infections. Despite the availability of protocols for isolating primary alveolar macrophages from the lung these cells remain recalcitrant to expansionin-vitroand therefore surrogate cell types, such as monocyte derived macrophages and phorbol ester-differentiated cell lines (e.g. U937, THP-1, HL60) are frequently used to model macrophage function.

Methods

The availability of high throughput gene expression technologies for accurate quantification of transcript levels enables the re-evaluation of these surrogate cell types for use as cellular models of the alveolar macrophage. Utilising high-throughput TaqMan arrays and focussing on dynamically regulated families of integral membrane proteins, we explore the similarities and differences in G-protein coupled receptor (GPCR) and ion channel expression in alveolar macrophages and their widely used surrogates.

Results

The complete non-sensory GPCR and ion channel transcriptome is described for primary alveolar macrophages and macrophage surrogates. The expression of numerous GPCRs and ion channels whose expression were hitherto not described in human alveolar macrophages are compared across primary macrophages and commonly used macrophage cell models. Several membrane proteins known to have critical roles in regulating macrophage function, including CXCR6, CCR8 and TRPV4, were found to be highly expressed in macrophages but not expressed in PMA-differentiated surrogates.

Conclusions

The data described in this report provides insight into the appropriate choice of cell models for investigating macrophage biology and highlights the importance of confirming experimental data in primary alveolar macrophages.
The value of high-frequency and color Doppler ultrasonography in diagnosing congenital muscular torticollis
Authors: Wang Lei , Zhang Lingyan , Tang Yuanjiao , Qiu Li
Published: October 2012

Background

Congenital muscular torticollis (CMT) is a relatively common neck deformity in infancy. The aim of our research was to determine the value of high-frequency and color Doppler ultrasonography in diagnosing CMT.

Methods

Patients with a clinical suspicion of CMT underwent an ultrasound examination before diagnosis, and the sonographic characteristics were analyzed and compared with the clinical findings.

Results

The sensitivity and specificity of an ultrasound diagnosis for CMT was 95.83% and 83.33%, respectively. The patients were divided into 2 groups based on the stage of the disease: the early-stage group (age <1 year) and the late-stage group(age ≥1 year). Differences existed between the two groups with respect to sonographic findings and clinical characteristics. The sonographic characteristics of the early-stage group included local thickening of the sternocleidomastoid muscle (SCM), weak or uneven echoes, and blood flow signals around or inside most of the lesions. The sonographic characteristics of the late-stage group included diffusely hyperechoic, or cord-like hyperechoic signals inside the muscle layer without significant blood flow signals.

Conclusions

Different stage of CMT patients had different sonographic characteristics. High-frequency and color Doppler ultrasonography can serve as adjunct confirmation tool for the diagnosis of CMT.
Fluorescent bioassays for toxic metals in milk and yoghurt
Authors: Siddiki Mohammad Shohel Rana , Ueda Shunsaku , Maeda Isamu
Published: October 2012

Background

From a human health viewpoint, contaminated milk and its products could be a source of long-term exposure to toxic metals. Simple, inexpensive, and on-site assays would enable constant monitoring of their contents. Bioassays that can measure toxic metals in milk or yoghurt might reduce the risk. For this purpose, the green fluorescent protein (GFP)-tagged trans factors, ArsR-GFP and CadC-GFP, together with their cis elements were used to develop such bioassays.

Results

ArsR-GFP or CadC-GFP, which binds either toxic metal or DNA fragment including cis element, was directly mixed with cow’s milk or yoghurt within a neutral pH range. The fluorescence of GFP, which is reflected by the association/dissociation ratio between cis element and trans factor, significantly changed with increasing externally added As (III) or Cd (II) whereas smaller responses to externally added Pb (II) and Zn (II) were found. Preparation and dilution of whey fraction at low pH were essential to intrinsic zinc quantification using CadC-GFP. Using the extraction procedure and bioassay, intrinsic Zn (II) concentrations ranging from 1.4 to 4.8 mg/l for milk brands and from 1.2 to 2.9 mg/kg for yoghurt brands were determined, which correlated to those determined using inductively coupled plasma atomic emission spectroscopy.

Conclusions

GFP-tagged bacterial trans factors and cis elements can work in the neutralized whole composition and diluted whey fraction of milk and yoghurt. The feature of regulatory elements is advantageous for establishment of simple and rapid assays of toxic metals in dairy products.
Roles of prostaglandin F2alpha and hydrogen peroxide in the regulation of Copper/Zinc superoxide dismutase in bovine corpus luteum and luteal endothelial cells
Authors: Vu Hai V , Acosta Tomas J , Yoshioka Shin , Abe Hironori , Okuda Kiyoshi
Published: October 2012

Background

Prostaglandin F2alpha (PGF) induces luteolysis in cow by inducing a rapid reduction in progesterone production (functional luteolysis) followed by tissue degeneration (structural luteolysis). However the mechanisms of action of PGF remain unclear. Reactive oxygen species (ROS) play important roles in regulating the luteolytic action of PGF. The local concentration of ROS is controlled by superoxide dismutase (SOD), the main enzyme involved in the control of intraluteal ROS. Thus SOD seems to be involved in luteolysis process induced by PGF in cow.

Methods

To determine the dynamic relationship between PGF and ROS in bovine corpus luteum (CL) during luteolysis, we determined the time-dependent change of Copper/Zinc SOD (SOD1) in CL tissues after PGF treatment in vivo.We also investigated whether PGF and hydrogen peroxide (H2O2) modulates SOD1 expression and SOD activity in cultured bovine luteal endothelial cells (LECs) in vitro.

Results

Following administration of a luteolytic dose of PGF analogue (0 h) to cows at the mid-luteal stage, the expression ofSOD1mRNA and protein, and total SOD activity in CL tissues increased between 0.5 and 2 h, but fell below the initial (0 h) level at 24 h post-treatment. In cultured LECs, the expression ofSOD1mRNA was stimulated by PGF (1–10 microM) and H2O2 (10–100 microM) at 2 h (P<0.05). PGF and H2O2 increased SOD1 protein expression and total SOD activity at 2 h (P<0.05), whereas PGF and H2O2 inhibited SOD1 protein expressions and total SOD activity at 24 h (P<0.05). In addition, H2O2 stimulated PGF biosynthesis at 2 and 24 h in bovine LECs. Overall results indicate that, SOD is regulated by PGF and ROS in bovine LECs. SOD may play a role in controlling intraluteal PGF and ROS action during functional and structural luteolysis in cows.
Whole genome sequencing of phage resistant Bacillus anthracismutants reveals an essential role for cell surface anchoring protein CsaB in phage AP50c adsorption
Authors: Bishop-Lilly Kimberly A , Plaut Roger D , Chen Peter E , Akmal Arya , Willner Kristin M , Butani Amy , Dorsey Shakia , Mokashi Vishwesh , Mateczun Alfred J , Chapman Carol , George Matroner , Luu Truong , Read Timothy D , Calendar Richard , Stibitz Scott , Sozhamannan Shanmuga
Published: October 2012

Background

Spontaneous Bacillus anthracis mutants resistant to infection by phage AP50c (AP50R) exhibit a mucoid colony phenotype and secrete an extracellular matrix.

Methods

Here we utilized a Roche/454-based whole genome sequencing approach to identify mutations that are candidates for conferring AP50c phage resistance, followed by genetic deletion and complementation studies to validate the whole genome sequence data and demonstrate that the implicated gene is necessary for AP50c phage infection.

Results

Using whole genome sequence data, we mapped the relevant mutations in six AP50R strains to csaB. Eleven additional spontaneous mutants, isolated in two different genetic backgrounds, were screened by PCR followed by Sanger sequencing of the csaB gene. In each spontaneous mutant, we found either a non-synonymous substitution, a nonsense mutation, or a frame-shift mutation caused by single nucleotide polymorphisms or a 5 base pair insertion in csaB. All together, 5 and 12 of the 17 spontaneous mutations are predicted to yield altered full length and truncated CsaB proteins respectively. As expected from these results, a targeted deletion or frame-shift mutations introduced into csaB in a different genetic background, in a strain not exposed to AP50c, resulted in a phage resistant phenotype. Also, substitution of a highly conserved histidine residue with an alanine residue (H270A) in CsaB resulted in phage resistance, suggesting that a functional CsaB is necessary for phage sensitivity. Conversely, introduction of the wild type allele of csaB in cis into the csaB deletion mutant by homologous recombination or supplying the wild type CsaB protein in trans from a plasmid restored phage sensitivity. The csaB mutants accumulated cell wall material and appeared to have a defective S-layer, whereas these phenotypes were reverted in the complemented strains.

Conclusions

Taken together, these data suggest an essential role for csaB in AP50c phage infection, most likely in phage adsorption. (The whole genome sequences generated from this study have been submitted to GenBank under SRA project ID: SRA023659.1 and sample IDs: AP50 R1: SRS113675.1, AP50 R2: SRS113676.1, AP50 R3: SRS113728.1, AP50 R4: SRS113733.1, AP50 R6: SRS113734.1, JB220 Parent: SRS150209.1, JB220 Mutant: SRS150211.1).
CRASH-3 - tranexamic acid for the treatment of significant traumatic brain injury: study protocol for an international randomized, double-blind, placebo-controlled trial
Authors: Dewan Yashbir , Komolafe Edward O , Mejía-Mantilla Jorge H , Perel Pablo , Roberts Ian , Shakur Haleema
Published: October 2012

Background

Worldwide, over 10 million people are killed or hospitalized because of traumatic brain injury each year. About 90% of deaths occur in low- and middle-income countries. The condition mostly affects young adults, and many experience long lasting or permanent disability. The social and economic burden is considerable. Tranexamic acid (TXA) is commonly given to surgical patients to reduce bleeding and the need for blood transfusion. It has been shown to reduce the number of patients receiving a blood transfusion by about a third, reduces the volume of blood transfused by about one unit, and halves the need for further surgery to control bleeding in elective surgical patients.

Methods/design

The CRASH-3 trial is an international, multicenter, pragmatic, randomized, double-blind, placebo-controlled trial to quantify the effects of the early administration of TXA on death and disability in patients with traumatic brain injury. Ten thousand adult patients who fulfil the eligibility criteria will be randomized to receive TXA or placebo. Adults with traumatic brain injury, who are within 8 h of injury and have any intracranial bleeding on computerized tomography (CT scan) or Glasgow Coma Score (GCS) of 12 or less can be included if the responsible doctor is substantially uncertain as to whether or not to use TXA in this patient. Patients with significant extracranial bleeding will be excluded since there is evidence that TXA improves outcome in these patients. Treatment will entail a 1 g loading dose followed by a 1 g maintenance dose over 8 h.

The main analyses will be on an ‘intention-to-treat’ basis, irrespective of whether the allocated treatment was received. Results will be presented as appropriate effect estimates with a measure of precision (95% confidence intervals). Subgroup analyses for the primary outcome will be based on time from injury to randomization, the severity of the injury, location of the bleeding, and baseline risk. Interaction tests will be used to test whether the effect of treatment differs across these subgroups. A study with 10,000 patients will have approximately 90% power to detect a 15% relative reduction from 20% to 17% in all-cause mortality.

Trial registration

Current Controlled Trials ISRCTN15088122; Clinicaltrials.gov NCT01402882
Effects of lactobacillus plantarumZJ316 on pig growth and pork quality
Authors: Suo Cheng , Yin Yeshi , Wang Xiaona , Lou Xiuyu , Song Dafeng , Wang Xin , Gu Qing
Published: October 2012

Background

Lactobacillus plantarum is a plant-associated bacterial species but it has also been found in human, mouse and porcine gastrointestinal tracts. It can ferment a broad spectrum of plant carbohydrates; it is tolerant of bile salts and low pH, and it has antagonistic potential against intestinal pathogens. However, experiments reporting the use of L. plantarum as a probiotic are limited. In this study, the effects of L. plantarum ZJ316 isolated from infant fecal samples on pig growth and pork quality were investigated.

Results

One hundred and fifty newly weaned pigs were selected randomly and divided into five groups. Group 1 was fed a diet supplemented with the antibiotic mequindox; Groups 2, 3 and 4 were fed a diet supplemented with L. plantarum and no antibiotic; and Group 5 was fed a mixture of mequindox and L. plantarum. After a 60 days initial treatment, samples were collected for evaluation. The results showed that, the L. plantarum ZJ316 has probiotic effects on pig growth and that these effects are dose dependent. The effects of a dose of 1 × 109 CFU/d were more pronounced than those of a dose of 5 × 109 CFU/d or 1 × 1010 CFU/d. In Group 2 (1 × 109 CFU/d), the diarrhea (p = 0.000) and mortality rates (p = 0.448) were lower than in antibiotic-treated pigs (Group 1), and the daily weight gain (p = 0.001) and food conversion ratios were better (p = 0.005). Improved pork quality was associated with Lactobacillus treatment. pH (45 min, p = 0.020), hardness (p = 0.000), stickiness (p = 0.044), chewiness (p = 0.000), gumminess (p = 0.000) and restoring force (p = 0.004) were all significantly improved in Lactobacillus-treated pigs (Group 2). Although we found that L. plantarum exerted probiotic effects on pig growth and pork quality, the mechanisms underlying its action require further study. Polymerase chain reaction-denaturing gradient gel electrophoresis results showed that the gut bacterial communities in Lactobacillus- and antibiotic-treated pigs were very similar and the quantity of L. plantarum ZJ316 was below the detection limits of DGGE-band sequencing. The concentration of short-chain fatty acids in Lactobacillus- and antibiotic-treated fecal samples were not significantly different (p = 0.086). However, the villus height of ilea (p = 0.003), jejuna (p = 0.000) and duodena (p = 0.036) were found to be significantly improved by Lactobacillus treatment.

Conclusion

L. plantarum ZJ316 was found to have probiotic effects, improving pig growth and pork quality. The probiotic mechanism might not involve L. plantarum colonization and alteration of the gut bacterial community. Rather, it might be related to the inhibition of the growth of opportunistic pathogens and promotion of increased villus height.
Identification of estrogen responsive genes using esophageal squamous cell carcinoma (ESCC) as a model
Authors: Essack Magbubah , MacPherson Cameron Ross , Schmeier Sebastian , Bajic Vladimir B
Published: October 2012

Background

Estrogen therapy has positively impact the treatment of several cancers, such as prostate, lung and breast cancers. Moreover, several groups have reported the importance of estrogen induced gene regulation in esophageal cancer (EC). This suggests that there could be a potential for estrogen therapy for EC. The efficient design of estrogen therapies requires as complete as possible list of genes responsive to estrogen. Our study develops a systems biology methodology using esophageal squamous cell carcinoma (ESCC) as a model to identify estrogen responsive genes. These genes, on the other hand, could be affected by estrogen therapy in ESCC.

Results

Based on different sources of information we identified 418 genes implicated in ESCC. Putative estrogen responsive elements (EREs) mapped to the promoter region of the ESCC genes were used to initially identify candidate estrogen responsive genes. EREs mapped to the promoter sequence of 30.62% (128/418) of ESCC genes of which 43.75% (56/128) are known to be estrogen responsive, while 56.25% (72/128) are new candidate estrogen responsive genes. EREs did not map to 290 ESCC genes. Of these 290 genes, 50.34% (146/290) are known to be estrogen responsive. By analyzing transcription factor binding sites (TFBSs) in the promoters of the 202 (56+146) known estrogen responsive ESCC genes under study, we found that their regulatory potential may be characterized by 44 significantly over-represented co-localized TFBSs (cTFBSs). We were able to map these cTFBSs to promoters of 32 of the 72 new candidate estrogen responsive ESCC genes, thereby increasing confidence that these 32 ESCC genes are responsive to estrogen since their promoters contain both: a/mapped EREs, and b/at least four cTFBSs characteristic of ESCC genes that are responsive to estrogen. Recent publications confirm that 47% (15/32) of these 32 predicted genes are indeed responsive to estrogen.

Conclusion

To the best of our knowledge our study is the first to use a cancer disease model as the framework to identify hormone responsive genes. Although we used ESCC as the disease model and estrogen as the hormone, the methodology can be extended analogously to other diseases as the model and other hormones. We believe that our results provide useful information for those interested in genes responsive to hormones and in the design of hormone-based therapies.
Matching positive end-expiratory pressure to intra-abdominal pressure improves oxygenation in a porcine sick lung model of intra-abdominal hypertension
Authors: Regli Adrian , Mahendran Rohan , Fysh Edward T , Roberts Brigit , Noffsinger Bill , De Keulenaer Bart L , Singh Bhajan , van Heerden Peter V
Published: October 2012

Introduction

Intra-abdominal hypertension (IAH) causes atelectasis, reduces lung volumes and increases respiratory system elastance. Positive end-expiratory pressure (PEEP) in the setting of IAH and healthy lungs improves lung volumes but not oxygenation. However, critically ill patients with IAH often suffer from acute lung injury (ALI). This study, therefore, examined the respiratory and cardiac effects of positive end-expiratory pressure in an animal model of IAH, with sick lungs.

Methods

Nine pigs were anesthetized and ventilated (48 +/- 6 kg). Lung injury was induced with oleic acid. Three levels of intra-abdominal pressure (baseline, 18, and 22 mmHg) were randomly generated. At each level of intra-abdominal pressure, three levels of PEEP were randomly applied: baseline (5 cmH2O), moderate (0.5 × intra-abdominal pressure), and high (1.0 × intra-abdominal pressure). We measured end-expiratory lung volumes, arterial oxygen levels, respiratory mechanics, and cardiac output 10 minutes after each new IAP and PEEP setting.

Results

At baseline PEEP, IAH (22 mmHg) decreased oxygen levels (-55%, P <0.001) and end-expiratory lung volumes (-45%, P = 0.007). At IAP of 22 mmHg, moderate and high PEEP increased oxygen levels (+60%, P = 0.04 and +162%, P <0.001) and end-expiratory lung volume (+44%, P = 0.02 and +279%, P <0.001) and high PEEP reduced cardiac output (-30%, P = 0.04). Shunt and dead-space fraction inversely correlated with oxygen levels and end-expiratory lung volumes. In the presence of IAH, lung, chest wall and respiratory system elastance increased. Subsequently, PEEP decreased respiratory system elastance by decreasing chest wall elastance.

Conclusions

In a porcine sick lung model of IAH, PEEP matched to intra-abdominal pressure led to increased lung volumes and oxygenation and decreased chest wall elastance shunt and dead-space fraction. High PEEP decreased cardiac output. The study shows that lung injury influences the effects of IAH and PEEP on oxygenation and respiratory mechanics. Our findings support the application of PEEP in the setting of acute lung injury and IAH.
Efficacy and mood conversion rate during long-term fluoxetine v. lithium monotherapy in rapid- and non-rapid-cycling bipolar II disorder
Authors: Amsterdam Jay D. , Luo Lola , Shults Justine
Published: October 2012

Background

Controversy exists over antidepressant use in rapid-cycling bipolar disorder.

Aims

Exploratory analysis of safety and efficacy of fluoxetine v. lithium monotherapy in individuals with rapid- v. non-rapid-cycling bipolar II disorder.

Method

Randomised, double-blind, placebo-controlled comparison of fluoxetine v. lithium monotherapy in patients initially stabilised on fluoxetine monotherapy (trial registration NCT0O044616).

Results

The proportion of participants with depressive relapse was similar between the rapid- and non-rapid-cycling groups (P=0.20). The odds of relapse were similar between groups (P=0.36). The hazard of relapse was similar between groups (hazard ratio 0.87, 95% CI 0.40-1.91). Change in mania rating scores was similar between groups (P=0.86). There was no difference between groups in the rate of syndromal (P-0.27) or subsyndromal (P=0.82) hypomania.

Conclusions

Depressive relapse and treatment-emergent mood conversion episode rates were similar for lithium and fluoxetine monotherapy and placebo during long-term, relapse-prevention therapy of rapid- and non-rapid-cycling bipolar II disorder.
Electrochemical and Photophysical Study in Solution and on Ruthenium(II) Polypyridyl Complexes Containing Thiophenylethynylphenanthrolines Self-assembled on Gold Surfaces
Authors: Shiotsuka Michito , Kondo Hiroshi , Inomata Tomohiko , Sako Katsuya , Masuda Hideki
Published: October 2012

Novel ruthenium(II) polypyridyl complexes with diethynylphenanthrolines containing acetylthiophenyl unit(s) have been prepared and characterized by photophysical measurements. These complexes showed the MLCT and the lowest energy π–π* absorption bands, and also intensive broad emission bands assignable to a triplet MLCT transition were observed in the deaerated solution. The electrochemistry of these complexes in the solution and on self-assembled monolayers on the gold electrode clearly showed Ru(II)/R(III) redox waves.
C–C Coupling Promoted by a NiCl2/bpy/Mg System in DMF and Its Application to Dehalogenative Polycondensation
Authors: Yamamoto Takakazu
Published: October 2012

A mixture of NiCl2, 2,2′-bipyridine (bpy), and Mg in DMF promoted dehalogenative homocoupling of RX (e.g., bromobenzene and p-tolyl bromide) efficiently. This basic coupling reaction was applied for polycondensation of dihaloorganic compounds, X–R′–X, to give poly(9,9-dioctylfluorene-2,7-diyl), poly(9,10-dioctyl-9,10-dihydrophenanthrene-2,7-diyl), and poly(pyridine-2,5-diyl).
Monte Carlo Simulation of Polymer–Nanoparticle Composites
Authors: Terao Takamichi
Published: October 2012

The structural formation of polymer–nanoparticle composites (PNC), which are also called polymer spherical brushes, is investigated by Monte Carlo simulations. Based on an osmotic model, the solid–liquid transition of PNC systems due to the steric effect between PNCs is studied by employing the Lindemann criterion and the Hansen–Verlet criterion. The phase diagram of PNC systems is also clarified by the free-energy analysis of the system. These results indicate the existence of PNC crystals with sufficiently high density and the large number of polymer chains per each particle.
Formation of Nanocrystals of a Zinc Pillared-layer Porous Coordination Polymer Using Microwave-assisted Coordination Modulation
Authors: Sakata Yoko , Furukawa Shuhei , Kim Chiwon , Kitagawa Susumu
Published: October 2012

Nanocrystals of three-dimensional pillared-layer type porous coordination polymers, [Zn2(ndc)2(dabco)]n, were fabricated by microwave-assisted coordination modulation, and its morphology was controlled by changing the modulator concentration. Adsorption measurement supported that the crystallinity and intrinsic porosity were maintained even for nanosized crystals, comparable to the corresponding micrometer-sized bulk powder crystals.
Entropy Coherent and Entropy Convex Measures of Risk
Authors: Laeven Roger J. A. , Stadje Mitja
Published: October 2012

We introduce two subclasses of convex measures of risk, referred to as entropy coherent and entropy convex measures of risk. Entropy coherent and entropy convex measures of risk are special cases of φ-coherent and φ-convex measures of risk. Contrary to the classical use of coherent and convex measures of risk, which for a given probabilistic model entails evaluating a financial position by considering its expected loss, φ-coherent and φ-convex measures of risk evaluate a financial position under a given probabilistic model by considering its normalized expected φ-loss. We prove that (i) entropy coherent and entropy convex measures of risk are obtained by requiring φ-coherent and φ-convex measures of risk to be translation invariant; (ii) convex, entropy convex, and entropy coherent measures of risk emerge as certainty equivalents under variational, homothetic, and multiple priors preferences upon requiring the certainty equivalents to be translation invariant; and (iii) φ-convex measures of risk are certainty equivalents under variational and homothetic preferences if and only if they are convex and entropy convex measures of risk. In addition, we study the properties of entropy coherent and entropy convex measures of risk, derive their dual conjugate function, and characterize entropy coherent and entropy convex measures of risk in terms of properties of the corresponding acceptance sets.
Noncooperative Games for Subcontracting Operations
Authors: Vairaktarakis George L.
Published: October 2012

Consider a set of manufacturers, all of which can subcontract part of their workload to a third party. For simplicity, we assume that every manufacturer as well as the third party each possess a single production facility. Each manufacturer has to decide the amount of workload to be subcontracted so as to minimize the completion time of his in-house and subcontracted workloads. In an effort to provide good service to all, the third party gives priority to manufacturers whose subcontracted workload is small. This incentive scheme forces manufacturers to compete for position in the third-party processing sequence. We develop pure Nash equilibria schedules under three distinct protocols for production.
Cost and Quality Implications of Opioid-Based Postsurgical Pain Control in Total Abdominal Hysterectomy: A Study of Cost Outliers and Opioid-Related Adverse Events
Authors: Reitan John , Moleski Ron , Van Breda Arletta , Adamson Robert , Lew Indu
Published: October 2012

Objective

A retrospective medical record review, case-control study of patients undergoing total abdominal hysterectomy was conducted to determine the relationship between opioid burden, related adverse drug effects (ADEs), and extended length of stay (LOS) and acute care costs cause(s) of LOS outliers.

Methods

Ninety-seven case patients with extended LOS (≥ 5 days) met the study eligibility criteria and were matched with case controls (patients with a LOS <5 days). The medical records of cases and controls were reviewed to collect information describing pre-established data points: opioid doses and opioid-related ADEs. Difference between cases and controls were compared using McNemar's test for matched pairs, paired t test, and signed rank test.

Results

Comparisons of opioid-related ADEs revealed the following statistically significant differences compared with controls: respiratory ADEs (eg, hypoxia) in 12% of cases versus 1% of controls ( P < .01) and gastrointestinal ADEs (eg, nausea/vomiting) in 44% of cases versus 19% of controls ( P < .01). Cases received higher doses during the 72 hours following postanesthesia care unit (PACU) discharge ( P = .04). By hospital discharge, cases had received 2.5 times the total opioid dose of controls and, on average, remained hospitalized 132 hours (5.5 days) longer than controls. Approximately 33% of LOS difference between cases and controls occurred prior to operating room admission, whereas approximately 66% occurred between PACU admission and hospital discharge.

Conclusions

Case patients with unusually long length of hospital stay (LOS outliers) received higher opioid doses and experienced more opioid-related ADEs than controls. These factors appear to contribute to outlier status but cannot completely explain all LOS outliers.
Phenotypic plasticity of plant response to herbivore eggs: effects on resistance to caterpillars and plant development
Authors: Pashalidou Foteini G. , Lucas-Barbosa Dani , van Loon Joop J. A. , Dicke Marcel , Fatouros Nina E.
Published: October 2012

Herbivory induces direct resistance responses in plants that negatively affect subsequently colonizing herbivores. Moreover, eggs of herbivorous insects can also activate plant resistance, which in some cases prevents hatching larvae from feeding. Until now, plant‐mediated effects of eggs on subsequent herbivory, and the specificity of such responses, have remained poorly understood. We studied the specificity and effects of plant resistance induced by herbivore egg deposition against lepidopteran larvae of species with different dietary breadths, feeding on a wild annual plant, the crucifer Brassica nigra. We examined whether this plant‐mediated response affects the growth of caterpillars of a specialist (Pieris brassicae) that feeds on B. nigra leaves and flowers, and a generalist (Mamestra brassicae) that rarely attacks this wild crucifer. We measured growth rates of neonate larvae to the end of their second instar after the larvae had hatched on plants exposed to eggs vs. plants without eggs, under laboratory and semi‐field conditions. Moreover, we studied the effects of egg deposition by the two herbivore species on plant height and flowering rate before and after larval hatching. Larvae of both herbivore species that developed on plants previously infested with eggs of the specialist butterfly P. brassicae gained less mass compared with larvae that developed on egg‐free plants. Plants exposed to butterfly eggs showed accelerated plant growth and flowering compared to egg‐free plants. Egg deposition by the generalist moth M. brassicae, in contrast, had no effect on subsequent performance by either herbivore species, or on plant development. Our results demonstrate that B. nigra plants respond differently to eggs of two herbivore species in terms of plant development and induced resistance to caterpillar attack. For this annual crucifer, the retardation of caterpillar growth in response to deposition of eggs by P. brassicae in combination with enhanced growth and flowering likely result in reproductive assurance, after being exposed to eggs from an herbivore whose larvae rapidly reduce the plant's reproductive potential through florivory.
Geomechanical Considerations in Hydraulic Fracturing Designs
Authors: Rafiee Mehdi , Soliman M. Y. , Pirayesh Elias , Emami Meybodi Hamid
Published: October 2012

The role of geomechanics in design and evaluation of hydraulic fracture stimulations in unconventional reservoirs has become more important than ever. Microcosmic mapping provides a good estimation of fracture geometry and stimulated reservoir volume (SRV); however, without geomechanical considerations, the predictions may not be completely accurate. By understanding reservoir rock mechanics and those parameters that have a major impact on the performance of fracture treatments, more reliable decisions in fracturing design and optimization can be made. This paper presents the results of an analytical model that predicts the changes in stress anisotropy in the neighborhood of the fractures of different designs in an elastic-static medium. Also, a numerical model has been used to investigate the effect of different geomechanical parameters on the geometry of the fractures. Results show that the spacing between fractures has a major impact on the changes in stresses. The effect of well spacing on fracture geometry in modified zipper frac design has been investigated. The results of this study give valuable insight into optimization of fracture placement in newly developed designs of hydraulic fractures in horizontal wellbores.
The Values of Empowerment and Citizenship and the Experience of Children and Adolescents with a Chronic Disease
Authors: Pais Sofia C. , Guedes Margarida , Menezes Isabel
Published: October 2012

In spite of becoming progressively common, chronic diseases are quite invisible in modern societies, as these silent diseases are relatively absent from public socio-political debates. As a consequence, social agents and institutions seem to reveal significant difficulties in coping with the singularities of children and adolescents with a chronic disease and their parents. This article stresses the importance of recognising children and adolescents with a chronic disease as citizens who have both special needs and special rights, and emphasises the important role of support associations as mediators among various actors in the health sphere (private, public, political, medical institutions …). This research focuses on the empowerment, well-being and participation behind the experience of chronic conditions as perceived by children and adolescents with chronic illnesses, their families, and health and educational professionals. The data collected includes interviews, focus group discussions, questionnaires and a family narrative. The results suggest that there is a strong need for alternative discourses about citizenship and participation in the life experiences of people with a chronic disease, especially because the quality of their life contexts appears to be a determinant factor for well-being and empowerment.