Leucine rich amelogenin peptide prevents ovariectomy-induced bone loss in mice.
Amelogenins, major extra cellular matrix proteins of developing tooth enamel, are predominantly expressed by ameloblasts and play significant roles in the formation of enamel. Recently, amelogenin has been detected in various epithelial and mesenchymal tissues, implicating that it might have distinct functions in various tissues. We have previously reported that leucine rich amelogenin peptide (LRAP), one of the alternate splice forms of amelogenin, regulates receptor activator of NF-kappa B ligand (RANKL) expression in cementoblast/periodontal ligament cells, suggesting that the amelogenins, especially LRAP, might function as a signaling molecule in bone metabolism. The objective of this study was to identify and define LRAP functions in bone turnover. We engineered transgenic (TgLRAP) mice using a murine 2.3kb α1(I)-collagen promoter to drive expression of a transgene consisting of LRAP, an internal ribosome entry site (IRES) and enhanced green fluorescent protein (EGFP) to study functions of LRAP in bone formation and resorption. Calvarial cell cultures from the TgLRAP mice showed increased alkaline phosphatase (ALP) activity and increased formation of mineralized nodules compared to the cells derived from wild-type (WT) mice. The TgLRAP calvarial cells also showed an inhibitory effect on osteoclastogenesis in vitro. Gene expression comparison by quantitative polymerase chain reaction (Q-PCR) in calvarial cells indicated that bone formation makers such as Runx2, Alp, and osteocalcin were increased in TgLRAP compared to the WT cells. Meanwhile, Rankl expression was decreased in the TgLRAP cells in vitro. The ovariectomized (OVX) TgLRAP mice resisted bone loss induced by ovariectomy resulting in higher bone mineral density in comparison to OVX WT mice. The quantitative analysis of calcein intakes indicated that the ovariectomy resulted in increased bone formation in both WT and TgLRAP mice; OVX TgLRAP appeared to show the most remarkably increased bone formation. The parameters for bone resorption in tissue sections showed increased number of osteoclasts in OVX WT, but not in OVX TgLRAP over that of sham operated WT or TgLRAP mice, supporting the observed bone phenotypes in OVX mice. This is the first report identifying that LRAP, one of the amelogenin splice variants, affects bone turnover in vivo.


[Dynamics of interleukin 6 levels in the patients with cardiogenic and septic shock and in a control group of patients with uncomplicated AMI].
Cardiogenic shock (CS) is the leading cause of mortality in patients with acute myocardial infarction (AMI). Inflammatory response seems to be common response in patients with AMI, especially those with CS. We have therefore conducted a study to determine diagnostic and prognostic utility of interleukin 6 (IL6) levels in the cohort of patients with cardiogenic and septic shock (SS) and in a control group of patients with uncomplicated AMI. In this prospective study 71 patients fulfilled the inclusion criteria: 30 patients with cardiogenic shock, 21 patients with septic shock and 20 patients with ST elevation myocardial infarction (STEMI). Plasma levels of IL6 were measured at 8 time points. The main endpoint was 3 month mortality. We have shown that the highest IL6 levels during the first week were recorded in patients with septic shock with peak value at admission. The maximum level of IL6 was detected between 12 to 24 hours after the onset of MI among patients with cardiogenic shock. According to Receiver operating characteristic (ROC) statistics levels of IL6 > 357 pg/ml at admission (AUC 0.730, p = 0.031) were typical for patients with CS in comparison with control group of STEMI patients. Values of IL6 > 1 237 pg/ml at admission and > 1 071 pg/ml at 24 hours (after admission?) were typical for thouse in septic shock in comparison with CS patients. We found only a non-significant trend of IL6 for the prediction of mortality in the cohort of CS patients for levels 1 854 pg/ml (AUC 0.769, p = 0.066) sampled 12 hours after admission. There was no association of plasma levels of IL6 with mortality in septic shock patients. Patients with cardiogenic shock demonstrated more pronounced cytokine response as evidenced by increased levels of IL6 compared to patients with uncomplicated STEMI. Levels of IL6 peaked in SS patients at admission, in CS patients 12-24 hours after admission. In daily clinical practice routine measurement of IL6 levels for prediction of prognosis both in cardiogenic and septic shock are of little value mainly due to significant interindividual variability of IL6 values.


Thinking big: the tunability of bacterial cell size.
The determination of cell size is a fundamental challenge for all living organisms. In a given growth condition, cell size for a particular bacterial species typically falls within a narrow distribution. Nonetheless, size can vary enormously across species, and the size of a single bacterium can even vary substantially across growth conditions. Recent phenomenological studies have revived classic interest in how cells maintain their size and how they adjust their size with changes in growth rate. However, the mechanisms by which cells establish a particular size are relatively enigmatic. Here, we review existing knowledge on how size in rod-shaped bacteria is shaped by nutrient, mechanical, and genetic factors. We also examine obstacles to accurate size measurement and recent technologies that help to overcome these hurdles. Finally, we discuss the relevance of cell size to bacterial physiology.


Assessment of eosinophil cationic protein as a possible diagnostic marker for female genital schistosomiasis in women living in a Schistosoma haematobium endemic area.
Eosinophil cationic protein (ECP) levels were measured in vaginal lavage extracts from 518 Zimbabwean reproductive women, age range 15-49 years, to assess the potential use of ECP as a diagnostic marker for female genital schistosomiasis (FGS). One hundred and fifty women had confirmed FGS status. These included 77 (cases) women who had ova in genital tissue and 73 (controls) women who had no ova in genital tissue. Participants were examined at baseline, 3 and 15 months post-treatment with praziquantel. ECP levels were determined using the enzyme linked immunosorbent assay (ECP-ELISA). ECP levels from 18 Norwegian women were used to calculate the diagnostic values of the test. FGS was diagnosed from the study population using genital biopsy and smears. Women were also diagnosed for urinary schistosomiasis using the urine filtration technique. The prevalence of urinary schistosomiasis was 39 % at baseline and this declined to 8% and 6% at 3 and 15 month post-treatment surveys, respectively. There was a higher mean ECP level in women with FGS, 889.3 ng/mL (95% CI: 457.0-1327.5) compared to the endemic control group, 359.1 ng/mL (95%, CI: 227.3-490.9), P = 0.027. Mean ECP levels declined at 3 months following treatment of infected individuals. There was no correlation between ECP levels and tissue ova density, and urine egg intensity. The sensitivity, specificity, positive and negative predictive values for the ECP-ELISA test were 35%, 80%, 65% and 53%, respectively. Our results indicate that FGS causes an inflammatory immune response that increases ECP levels in genital fluid. Treatment of schistosomiasis results in a regression of pathology and a decline in ECP levels. However, other factors such as allergy and microbial infection could also be responsible for increased ECP levels in genital mucosa. These conditions will affect the validity of the test in diagnosis of FGS.


Daily Vegetables Intake and Response to COPD Rehabilitation. The Role of Oxidative Stress, Inflammation and DNA Damage.
Chronic obstructive pulmonary disease (COPD) is a respiratory disease associated with airways inflammation and lung parenchyma fibrosis. The primary goals of COPD treatment are to reduce symptoms and risk of exacerbations, therefore pulmonary rehabilitation is considered the key component of managing COPD patients. Oxidative airway damage, inflammation and reduction of endogenous antioxidant enzymes are known to play a crucial role in the pathogenesis of COPD. Recently, also natural antioxidants have been considered as they play an important role in metabolism, DNA repair and fighting the effects of oxidative stress. In this paper we evaluated the response of 105 elderly COPD patients to pulmonary rehabilitation (PR), based on high or low vegetable consumption, by analyzing clinical parameters and biological measurements at baseline and after completion of the three weeks PR. We found that daily vegetable intake in normal diet, without any specific intervention, can increase the probability to successfully respond to rehabilitation (65.4% of responders ate vegetables daily vs. 40.0% of non-responders, p = 0.033). The association was especially evident in subjects ≥ 80 year of age (OR = 17.0; p < 0.019). Three weeks of pulmonary rehabilitation are probably too short to reveal a reduction of the oxidative stress and DNA damage, but are enough to show an improvement in the patient's inflammatory state.


Knockdown of prolyl-4-hydroxylase domain 2 inhibits tumor growth of human breast cancer MDA-MB-231 cells by affecting TGF-β1 processing.
The prolyl-4-hydroxylase domain 1-3 (PHD1-3) enzymes are regulating the protein stability of the α-subunit of the hypoxia-inducible factor-1 (HIF-1), which mediates oxygen-dependent gene expression. PHD2 is the main isoform regulating HIF-1α hydroxylation and thus stability in normoxia. In human cancers, HIF-1α is overexpressed as a result of intratumoral hypoxia which in turn promotes tumor progression. The role of PHD2 for tumor progression is in contrast far from being thoroughly understood. Therefore, we established PHD2 knockdown clones of MDA-MB-231 breast cancer cells and analyzed their tumor-forming potential in a SCID mouse model. Tumor progression was significantly impaired in the PHD2 knockdown MDA-MB-231 cells, which could be partially rescued by re-establishing PHD2 expression. In a RNA profile screen, we identified the secreted phosphoprotein 1 (SPP1) as one target, which is differentially regulated as a consequence of the PHD2 knockdown. Knockdown of PHD2 drastically reduced the SPP1 expression in MDA-MB-231 cells. A correlation of SPP1 and PHD2 expression was additionally verified in 294 invasive breast cancer biopsies. In subsequent analyses, we identified that PHD2 alters the processing of transforming growth factor (TGF)-β1, which is highly involved in SPP1 expression. The altered processing capacity was associated with a dislocation of the pro-protein convertase furin. Thus, our data demonstrate that in MDA-MB-231 cells PHD2 might affect tumor-relevant TGF-β1 target gene expression by altering the TGF-β1 processing capacity.


Muscle activity of Bulgarian squat. Effects of additional vibration, suspension and unstable surface.
Practitioners of strength and conditioning are increasingly using vibration and unstable environments to enhance training effects. However, little evidence has been found comparing the use of suspension devices and vibratory platforms used in the Bulgarian squat. The purpose of this cross-sectional study was to examine the effect of suspension devices (TRX®), unstable surfaces (BOSU®), and vibration plates on muscle activity and force during the Bulgarian squat. Twenty physically active male students (age = 24.40 ± 3.63 years) performed a set of five repetitions of Bulgarian squats, suspended lunges, suspended lunges-BOSU, suspended lunges-Vibro30, and suspended lunges-Vibro40 (vibration 30 Hz or 40 Hz and 4 mm of amplitude). A randomized within-subject design was used to compare leg muscle activity, vertical ground reaction forces, and force exerted on the strap across the five exercises. Results showed no significant differences in muscle activity between the Bulgarian squat and suspended lunge (p = 0.109, d = 2.84). However, the suspended lunge significantly decreased muscle activation compared to the suspended lunge-BOSU (p = 0.012, d = 0.47), suspended lunge-Vibro30 (p = 0.001, d = 1.26), and suspended lunge-Vibro40 (p = 0.000, d = 1.51). Likewise, the Bulgarian squat achieved lower activity than the suspended lunge-Vibro40 (p = 0.010, d = 0.96). The force on the strap significantly decreased in the suspended lunge-BOSU compared to the suspended lunge-Vibro30 (p = 0.009, d = 0.56). The suspended lunge achieved higher front leg force production than the Bulgarian squat (p = 0.006, d = 0.48). In conclusion, leaning the rear leg on a suspension device does not provoke an increase in the activation of the front leg during the Bulgarian squat but increases the vertical ground reaction forces. Thus, the use of unstable surfaces or vibration plates for the front leg increased muscular activity when performing a suspended lunge.


[Early appearing neurofibromatosis (author's transl)].
Six cases of neurofibromatosis in children under seven years of age with other members of the family affected are reported. Mental retardation was observed in five patients, and one had convulsive crises. Growth and bone maturation retardation, without HGH deficiency after glucagon stimulation were observed.


PRISMA-Children (C) and PRISMA-Protocol for Children (P-C) Extensions: a study protocol for the development of guidelines for the conduct and reporting of systematic reviews and meta-analyses of newborn and child health research.
Paediatric systematic reviews differ from adult systematic reviews in several key aspects such as considerations of child tailored interventions, justifiable comparators, valid outcomes and child sensitive search strategies. Available guidelines, including PRISMA-P (2015) and PRISMA (2009), do not cover all the complexities associated with reporting systematic reviews in the paediatric population. Using a collaborative, multidisciplinary structure, we aim to develop evidence-based and consensus-based PRISMA-P-C (Protocol for Children) and PRISMA-C (Children) Extensions to guide paediatric systematic review protocol and completed review reporting. This project's methodology follows published recommendations for developing reporting guidelines and involves the following six phases; (1) establishment of a steering committee representing key stakeholder groups; (2) a scoping review to identify potential Extension items; (3) three types of consensus activities including meetings of the steering committee to achieve high-level decisions on the content and methodology of the Extensions, a survey of key stakeholders to generate a list of possible items to include in the Extensions and a formal consensus meeting to select the reporting items to add to, or modify for, the Extension; (4) the preliminary checklist items generated in phase III will be evaluated against the existing evidence and reporting practices in paediatric systematic reviews; (5) extension statements and explanation and elaboration documents will provide detailed advice for each item and examples of good reporting; (6) development and implementation of effective knowledge translation of the extension checklist, and an evaluation of the Extensions by key stakeholders. This protocol was considered a quality improvement project by the Hospital for Sick Children's Ethics Committee and did not require ethical review. The resultant checklists, jointly developed with all relevant stakeholders, will be disseminated through peer-reviewed journals as well as national and international conference presentations. Endorsement of the checklist will be sought simultaneously in multiple journals.


Trauma services for youth victims of sexual abuse- does one size fit all? A qualitative study among service providers in Ontario, Canada.
Despite a range of interventions available to treat mental health symptoms experienced by youth with a history of child sexual abuse (CSA), limited empirical work has examined practitioner delivery of these interventions in real-world practice. This paper aimed to qualitatively explore the delivery of trauma-based interventions in community settings in Ontario, Canada. Using qualitative description, a purposeful sample of service providers (N = 51; 92 % female) were recruited from nine community-based organizations located in Southern Ontario, Canada providing psychotherapeutic trauma-based interventions to youth with a history of child sexual abuse. Semi-structured one-on-one (n = 17), joint (n = 3) and focus group (n = 5) interviews elicited provider descriptions of their strategies and approaches for addressing trauma-related symptoms in this population. Data were interpreted using conventional content analyses. Eclectic delivery of interventions and multifactorial decision-making processes were identified as core elements of treatment planning and intervention delivery among providers. Eclectic treatment was described to involve the consideration of four core elements (provider judgement; youth voice; youth characteristics; and clinical team discussion) of intervention and three key principles (meeting youth needs; providing client-centered care; addressing safety and stability). Research capable of characterizing the efficacy of client-centered, eclectic approaches to treat symptoms experienced by youth with a history of CSA is needed.


Robust adenoviral and adeno-associated viral gene transfer to the in vivo murine heart: application to study of phospholamban physiology.
Viral gene transfer to the whole heart in vivo has been achieved in several mammalian species but remained difficult to accomplish in murine hearts. We postulated that a key impediment derives from the use of proximal aortic occlusion during virus injection, because this eliminates coronary perfusion gradients in mice as aortic root and left ventricle pressures equalize. Pressure-volume analysis confirmed these mechanics. In contrast, descending aortic occlusion with whole-body cooling (20 degrees C) preserved transmyocardial perfusion gradients and allowed for sustained (>10-minute) dwell times in an upper-body perfusion circuit. This approach yielded robust cardiac transfection with adenovirus (AdV) and adeno-associated virus (AAV) injected into the left ventricle cavity or more simply via a central vein. Cardio-specific expression was achieved with a myocyte-specific promotor. Optimal AdV transfection required 9-minute aortic occlusion, versus 5-minute occlusion for AAV. Using this method, we examined the in vivo function of phospholamban (PLB) by stably transfecting PLB-null mice with AAV encoding PLB (AAV(PLB)). AAV(PLB) restored PLB protein to near control levels that colocalized with SERCA2A in cardiomyocytes. At baseline, PLB-null hearts exhibited enhanced systolic and diastolic function, but frequency-dependent reserve was blunted versus wild-type controls. These properties, particularly the frequency response, returned toward control 3 months after AAV(PLB) transfection. The new simplified approach for murine whole-heart viral transfection should assist molecular physiology studies.


On the reconstruction of height functions and terrain maps from dense range data.
This paper describes a method for combining multiple, dense range images to create surface reconstructions of height functions. Height functions are a special class of three-dimensional (3-D) surfaces, where one 3-D coordinate is a function of the other two. They are relevant for application domains such as terrain modeling or two-and-half dimensional surface reconstruction. Dense range maps are produced by either a range measuring device combined with a scanning mechanism or a triangulation scheme, such as active or passive stereo. The proposed method follows from a statistical formulation that characterizes the optimal surface estimate as the one that maximizes the posterior probability conditional on the input data and prior information about the application domain. Because the domain of the reconstruction is a two-dimensional (2-D) scalar function, the optimal surface can be expressed as an image, and the variational form of that optimization produces a 2-D partial differential equation (PDE). The PDE consists of two parts: a first-order data term and a second-order smoothing term. Thus optimal surface reconstruction is formulated as the solution to a second-order, nonlinear, PDE on an image, which is related to the family of PDE-based image processing algorithms in the literature. This paper presents the theory for reconstruction and some particular aspects of the numerical implementation. It also analyzes results on both synthetic and real data sets, which show a 75%-95% reduction of the RMS sensor error.


The inhibitory potential of Fc receptor homolog 4 on memory B cells.
Fc receptor homolog 4 (FcRH4) is a B cell-specific member of the recently identified family of FcRHs whose intracellular domain contains three potential immunoreceptor tyrosine-based inhibitory motifs (ITIMs). The signaling potential of this receptor, shown here to be preferentially expressed by memory B cells, was compared with the inhibitory receptor FcgammaRIIb in B cells expressing either WT FcgammaRIIb or chimeric proteins in which the intracellular domain of FcRH4 was fused to the transmembrane and extracellular domains of FcgammaRIIb. Coligation of the FcgammaRIIb/FcRH4 chimeric protein with the B cell receptor (BCR) led to tyrosine phosphorylation of the two membrane-distal tyrosines and profound inhibition of BCR-mediated calcium mobilization, whole cell tyrosine phosphorylation, and mitogen-activated protein (MAP)-kinase activation. Mutational analysis of the FcRH4 cytoplasmic region indicated that the two membrane-distal ITIMs are essential for this inhibitory potential. Phosphopeptides corresponding to these ITIMs could bind the Src homology 2 (SH2) domain-containing tyrosine phosphatases SHP-1 and SHP-2, which associated with the WT FcRH4 and with mutants having inhibitory capability. These findings indicate the potential for FcRH4 to abort B cell receptor signaling by recruiting SHP-1 and SHP-2 to its two membrane distal ITIMs.


Sudden death victims <45 years: Agreement between cause of death established by the forensic physician and autopsy results.
The goal of this study was to ascertain accordance between cause of death established by the forensic physician and autopsy results in young sudden death victims in the Netherlands. Sudden death victims aged 1-45 years examined by forensic physicians operating in the participating regions which also underwent an autopsy between January 2006 and December 2011 were included (n = 70). Cause of death established by the forensic physician based on the external medicolegal examination was compared with autopsy findings using the ICD10-classification. Autopsy findings revealed that the majority of sudden death victims have died from a cardiac disease (n = 51, 73%). Most of the presumed heart disease related cases were confirmed by autopsy (n = 13, 87%). On the contrary, a large number of deaths caused by circulatory diseases were not recognised by the forensic physician (n = 38, 75%). In most of these cases, the forensic physician was forced to report an undetermined cause due to the lack of a solid explanation for death. Cause of death reported by the forensic physician appeared to be in agreement with the autopsy results in 12 cases (17%). Cause of death determination in young sudden death victims is a difficult task for forensic physicians due to the limited tools available during the medicolegal examination. An effort should be made to standardize extensive post-mortem investigation after sudden death in the young. Autopsy can provide valuable information regarding the cause of death, which is of great importance in view of the identification of inheritable diseases among decedents and their families.


Assessment of alternative mating strategies in Anopheles gambiae: Does mating occur indoors?
Mating in Anopheles gambiae has been observed only in outdoor swarms. Here we evaluate whether mating also occurs indoors. Mark-release-recapture of virgin males and females in natural houses showed that mating occurred over a single day even when mosquitoes can leave the house through exit traps and without adaptation to laboratory conditions. In these experiments, insemination rate in the M molecular form of An. gambiae (and An. arabiensis) was higher than that of the S form (15 versus 6%). Under these conditions, smaller females of the M form mated more frequently than larger females of that form. Sampling mosquitoes throughout the day showed that both sexes enter houses around sunrise and leave around sunset, staying indoors together from dawn to dusk. In an area dominated by the M form, the daily rate of insemination in samples from exit traps was approximately 5% higher than in those from entry traps, implying that mating occurred indoors. Importantly, frequency of cross mating between the molecular forms was as high as that between members of the same form, indicating that, indoors, assortative mating breaks down. Altogether, these results suggest that indoor mating is an alternative mating strategy of the M molecular form of An. gambiae. Because naturally occurring mating couples have not yet been observed indoors, this conclusion awaits validation.


Literature survey on epidemiology and pathology of gangliocytic paraganglioma.
Although gangliocytic paraganglioma (GP) has generally been regarded as a neuroendocrine tumor, its origin remains unclear. We therefore aimed to investigate the details of this disease by carefully analyzing and extracting common features of the disease as presented in selected publications. We searched for English and Japanese cases of GP using the PubMed and IgakuChuoZasshi databases on August 2010. We then extracted and sampled raw data from the selected publications and performed appropriate statistical analyses. Additionally, we evaluated the expression of hormone receptors based on our previously reported case. 192 patients with GP were retrieved from the databases. Patient ages ranged from 15 y to 84 y (mean: 52.3 y). The gender ratio was 114:76 (male to female, 2 not reported). Maximum diameter of the tumors ranged from 5.5 mm to 100 mm (mean: 25.0 mm). The duodenum (90.1%, 173/192) was found to be the most common site of the disease. In 173 patients with duodenal GP, gastrointestinal bleeding (45.1%, 78/173) was found to be the most common symptom of the disease, followed by abdominal pain (42.8%, 74/173), and anemia (14.5%, 25/173). Rate of lymph node metastasis was 6.9% (12/173). Our statistical analysis indicated that significant differences were found for gender between GP within the submucosal layer and exceeding the submucosal layer. Furthermore, our immunohistochemical evaluation showed that both epithelioid and pancreatic islet cells showed positive reactivity for progesterone receptors. Our literature survey revealed that there were many more cases of GP exceeding the submucosal layer than were expected. Meanwhile, our statistical analyses and immunohistochemical evaluation supported the following two hypotheses. First, vertical growth of GP might be affected by progesterone exposure. Second, the origin of GP might be pancreatic islet cells. However, it is strongly suspected that our data have been affected by publication bias and to confirm these hypotheses, further investigation is required.


Biogenic synthesis of novel nanomaterials and their applications.
Despite the many benefits derived from the unique features and practicality of nanoparticles, the release of their toxic by-products or products from the synthesis stage into the environment could negatively impact natural resources and organisms. The physical and chemical methods for nanoparticle synthesis involve high energy consumption and the use of hazardous chemicals, respectively, going against the principles of green chemistry. Biological methods of synthesis that rely on extracts from a broad range of natural plants, and microorganisms, such as fungi, bacteria, algae, and yeast, have emerged as viable alternatives to the physical and chemical methods. Nanoparticles synthesized through biogenic pathways are particularly useful for biological applications that have high concerns about contamination. Herein, we review the physical and chemical methods of nanoparticle synthesis and present a detailed overview of the biogenic methods used for the synthesis of different nanoparticles. The major points discussed in this study are the following: (1) the fundamentals of the physical and chemical methods of nanoparticle syntheses, (2) the use of different biological precursors (microorganisms and plant extracts) to synthesize gold, silver, selenium, iron, and other metal nanoparticles, and (3) the applications of biogenic nanoparticles in diverse fields of study, including the environment, health, material science, and analytical chemistry.


Degradation characteristics of toluene, benzene, ethylbenzene, and xylene by Stenotrophomonas maltophilia T3-c.
Stenotrophomonas maltophilia T3-c, isolated from a biofilter for the removal of benzene, toluene, ethylbenzene, and xylene (BTEX), could grow in a mineral salt medium containing toluene, benzene, or ethylbenzene as the sole source of carbon. The effect of environmental factors such as initial toluene mass, medium pH, and temperature on the degradation rate of toluene was investigated. The cosubstrate interactions in the BTEX mixture by the isolate were also studied. Within the range of initial toluene mass (from 23 to 70 pmol), an increased substrate concentration increased the specific degradation of toluene by S. maltophilia T3-c. The toluene degradation activity of S. maltophilia T3-c could be maintained at a broad pH range from 5 to 8. The rates at 20 and 40 degrees C were 43 and 83%, respectively, of the rate at 30 degrees C. The specific degradation rates of toluene, benzene, and ethylbenzene by strain T3-c were 2.38, 4.25, and 2.06 micromol/g-DCW/hr. While xylene could not be utilized as a growth substrate by S. maltophilia T3-c, the presence of toluene resulted in the cometabolic degradation of xylene. The specific degradation rate of toluene was increased by the presence of benzene, ethylbenzene, or xylene in binary mixtures. The presence of toluene or xylene in binary mixtures with benzene increased the specific degradation rate of benzene. The presence of ethylbenzene in binary mixtures with benzene inhibited benzene degradation. The presence of more than three kinds of substrates inhibited the specific degradation rate of benzene. All BTEX mixtures, except tri-mixtures of benzene, ethylbenzene, and xylene or mixtures of all four substrates, had little effect on the degradation of ethylbenzene by S. maltophilia T3-c. The utilization preference of the substrates by S. maltophilia T3-c was as follows: ethylbenzene was degraded fastest, followed by toluene and benzene. However, the specific degradation rates of substrates, in order, were benzene, toluene, and ethylbenzene.


Long-Read-Based de novo Genome Assembly and Comparative Genomics of the Wheat Leaf Rust Pathogen Puccinia triticina Identifies Candidates for Three Avirulence Genes.
Leaf rust, caused by Puccinia triticina (Pt), is one of the most devastating diseases of wheat, affecting production in nearly all wheat-growing regions worldwide. Despite its economic importance, genomic resources for Pt are very limited. In the present study, we have used long-read sequencing (LRS) and the pipeline of FALCON and FALCON-Unzip (v4.1.0) to carry out the first LRS-based de novo genome assembly for Pt. Using 22.4-Gb data with an average read length of 11.6 kb and average coverage of 150-fold, we generated a genome assembly for Pt104 [strain 104-2,3,(6),(7),11; isolate S423], considered to be the founding isolate of a clonal lineage of Pt in Australia. The Pt104 genome contains 162 contigs with a total length of 140.5 Mb and N50 of 2 Mb, with the associated haplotigs providing haplotype information for 91% of the genome. This represents the best quality of Pt genome assembly to date, which reduces the contig number by 91-fold and improves the N50 by 4-fold as compared to the previous Pt race1 assembly. An annotation pipeline that combined multiple lines of evidence including the transcriptome assemblies derived from RNA-Seq, previously identified expressed sequence tags and Pt race 1 protein sequences predicted 29,043 genes for Pt104 genome. Based on the presence of a signal peptide, no transmembrane segment, and no target location to mitochondria, 2,178 genes were identified as secreted proteins (SPs). Whole-genome sequencing (Illumina paired-end) was performed for Pt104 and six additional strains with differential virulence profile on the wheat leaf rust resistance genes Lr26, Lr2a, and Lr3ka. To identify candidates for the corresponding avirulence genes AvrLr26, AvrLr2a, and AvrLr3ka, genetic variation within each strain was first identified by mapping to the Pt104 genome. Variants within predicted SP genes between the strains were then correlated to the virulence profiles, identifying 38, 31, and 37 candidates for AvrLr26, AvrLr2a, and AvrLr3ka, respectively. The identification of these candidate genes lays a good foundation for future studies on isolating these avirulence genes, investigating the molecular mechanisms underlying host-pathogen interactions, and the development of new diagnostic tools for pathogen monitoring.


[The impact of different fluid management on mortality in patients with septic shock].
To find out the influential effect of different fluid management on mortality of patients with septic shock in different phases. From March 2007 to December 2009, a retro spective controlled study was conducted on the clinical data of 107 adult patients with septic shock in the intensive care unit (ICU) of Subei Hospital of Jiangsu Province. The patients were divided into survival group ( n =68) and non survival group ( n =39) according to the final outcome. A number of demographic and variables were collected from the medical record. The acute physiology and chronic health evaluationII (APACHEII) score, sequential organ failure assessment (SOFA), liquid intake and output volume and its balance daily within 1 week, 24 hour early goal directed therapy (EGDT) and conservative late fluid management (CLFM) were compared between two groups. The Logistic regression statistics was used to determine the relationship between APACHEII, SOFA, EGDT, CLFM and survival. The single variable analysis showed that there was significant difference in the parameters of oxygenation index in 7 days ,arterial blood lactate clearance within 24 hours, acute lung injury, length of mechanical ventilation, length of ICU stay and in hospital, the goal of fluid management including 24 hour EGDT, 24 hour CLFM, fluid balance in 24 hours, total fluid input within 7 days, negative fluid balance and times during 7 days between two groups. Logistic regression showed that failure to achieve 24 hour EGDT and late CLFM,a negative balance of <2 000 ml, total fluid input of >20 000 ml within 1 week were independent risk factors of death, and odds ratio ( OR ) was 4.159, 4.431, 23.788 and 4.353, respectively, the P value was 0.035, 0.019, 0.000, 0.025, respectively. The 28 day mortality in 24 hour EGDT and CLFM group (12.5%) was significantly lower than that of 24 hour EGDT with liberal late fluid management (LLFM) group (46.2%) and that in the group of patients in whom with failure to have 24 hour EGDT with CLFM or LLFM (30.0%, 76.2%, P<0.05 or P <0.01). Both early achievement of 24 hour EGDT and late CLFM for the patients with septic shock can lower mortality.


Shape matters: lifecycle of cooperative patches promotes cooperation in bulky populations.
Natural cooperative systems take many forms, ranging from one-dimensional cyanobacteria arrays to fractal-like biofilms. We use in silico experimental systems to study a previously overlooked factor in the evolution of cooperation, physical shape of the population. We compare the emergence and maintenance of cooperation in populations of digital organisms that inhabit bulky (100 × 100 cells) or slender (4 × 2500) toroidal grids. Although more isolated subpopulations of secretors in a slender population could be expected to favor cooperation, we find the opposite: secretion evolves to higher levels in bulky populations. We identify the mechanistic explanation for the shape effect by analyzing the lifecycle and dynamics of cooperator patches, from their emergence and growth, to invasion by noncooperators and extinction. Because they are constrained by the population shape, the cooperator patches expand less in slender than in bulky populations, leading to fewer cooperators, less public good secretion, and generally lower cooperation. The patch dynamics and mechanisms of shape effect are robust across several digital cooperation systems and independent of the underlying basis for cooperation (public good secretion or a cooperation game). Our results urge for a greater consideration of population shape in the study of the evolution of cooperation across experimental and modeling systems.


Cellulose crystallinity index: measurement techniques and their impact on interpreting cellulase performance.
Although measurements of crystallinity index (CI) have a long history, it has been found that CI varies significantly depending on the choice of measurement method. In this study, four different techniques incorporating X-ray diffraction and solid-state 13C nuclear magnetic resonance (NMR) were compared using eight different cellulose preparations. We found that the simplest method, which is also the most widely used, and which involves measurement of just two heights in the X-ray diffractogram, produced significantly higher crystallinity values than did the other methods. Data in the literature for the cellulose preparation used (Avicel PH-101) support this observation. We believe that the alternative X-ray diffraction (XRD) and NMR methods presented here, which consider the contributions from amorphous and crystalline cellulose to the entire XRD and NMR spectra, provide a more accurate measure of the crystallinity of cellulose. Although celluloses having a high amorphous content are usually more easily digested by enzymes, it is unclear, based on studies published in the literature, whether CI actually provides a clear indication of the digestibility of a cellulose sample. Cellulose accessibility should be affected by crystallinity, but is also likely to be affected by several other parameters, such as lignin/hemicellulose contents and distribution, porosity, and particle size. Given the methodological dependency of cellulose CI values and the complex nature of cellulase interactions with amorphous and crystalline celluloses, we caution against trying to correlate relatively small changes in CI with changes in cellulose digestibility. In addition, the prediction of cellulase performance based on low levels of cellulose conversion may not include sufficient digestion of the crystalline component to be meaningful.


Tumour susceptibility in mice in relation to H-2 haplotype.
In many higher animal species, a major histocompatibility complex (MHC; in man: HLA; in mice: H-2) has been established and extensively studied. MHC products are essential in the recognition and destruction of cells carrying non-self antigenic determinants. Associations between specific HLA haplotypes and susceptibility towards nasopharyngeal carcinoma, breast cancer, acute lymphocytic leukaemia and Hodgkin's disease have been reported. A summary is made of the evidence for the involvement of H-2 genes in the development of virally induced tumours (leukaemia, mammary tumours and Rous sarcoma virus-induced fibrosarcomas). The formation of mouse lung tumours, for which there is no indication of a viral or hormonal etiology, has also proved to be significantly influenced by the H-2 haplotype. Similar results were obtained for spontaneous and chemically induced lung tumours. On closer analysis, more specific parameters, such as type of lung tumour and size, were found to be controlled by several regions of the H-2 complex.


Modulation of hepatic CYP2A1, CYP2C11, and CYP3A9 expression in adult rats by neonatal administration of tamoxifen.
To examine the effect of neonatal administration of tamoxifen on adult expression of hepatic cytochrome P-450 (CYP) enzymes and steroid 5alpha-reductase, male and female Sprague-Dawley rats were injected s.c. with tamoxifen (20 microg) or peanut oil (control) once daily at days 1 to 5 of age and sacrificed at 3 months of age. Neonatal tamoxifen treatment did not affect b.wt. or liver weight of adult male and female rats, but decreased testicular weight by approximately 40% in adult male rats. Neonatal administration of tamoxifen decreased hepatic microsomal testosterone 6beta- and 7alpha-hydroxylase activities in adult female rats whereas it did not alter steroid 5alpha-reductase activity. The same treatment increased testosterone 7alpha-hydroxylase activity, but did not affect testosterone 6beta-hydroxylase or steroid 5alpha-reductase activity in adult male rats. Immunoblot analysis indicated that neonatal tamoxifen treatment decreased CYP2C11 protein level by 26% and increased CYP2A1 protein content by 2.6-fold in adult male rats, whereas it had no effect on CYP3A or CYP2B protein expression. The reduction in the CYP3A-mediated testosterone 6beta-hydroxylase activity in adult female rats was accompanied by a decrease in CYP3A9 mRNA expression. Analysis of serum hormone levels indicated that neonatal exposure to tamoxifen resulted in a decrease in serum 17beta-estradiol concentration in adult female rats, whereas it did not alter serum testosterone concentration in adult male rats. In summary, treatment of neonatal rats with tamoxifen produced a long-lasting effect on hepatic CYP2A1, CYP2C11, and CYP3A9 expression in addition to testicular weight and serum 17beta-estradiol concentration.


Global unbalance in seaweed production, research effort and biotechnology markets.
Exploitation of the world's oceans is rapidly growing as evidenced by a booming patent market of marine products including seaweed, a resource that is easily accessible without sophisticated bioprospecting technology and that has a high level of domestication globally. The investment in research effort on seaweed aquaculture has recently been identified to be the main force for the development of a biotechnology market of seaweed-derived products and is a more important driver than the capacity of seaweed production. Here, we examined seaweed patent registrations between 1980 and 2009 to assess the growth rate of seaweed biotechnology, its geographic distribution and the types of applications patented. We compare this growth with scientific investment in seaweed aquaculture and with the market of seaweed production. We found that both the seaweed patenting market and the rate of scientific publications are rapidly growing (11% and 16.8% per year respectively) since 1990. The patent market is highly geographically skewed (95% of all registrations belonging to ten countries and the top two holding 65% of the total) compared to the distribution of scientific output among countries (60% of all scientific publications belonging to ten countries and the top two countries holding a 21%), but more homogeneously distributed than the production market (with a 99.8% belonging to the top ten countries, and a 71% to the top two). Food industry was the dominant application for both the patent registrations (37.7%) and the scientific publications (21%) followed in both cases by agriculture and aquaculture applications. This result is consistent with the seaweed taxa most represented. Kelp, which was the target taxa for 47% of the patent registrations, is a traditional ingredient in Asian food and Gracilaria and Ulva, which were the focus of 15% and 13% of the scientific publications respectively, that are also used in more sophisticated applications such as cosmetics, chemical industry or bioremediation. Our analyses indicate a recent interest of non-seaweed producing countries to play a part in the seaweed patenting market focusing on more sophisticated products, while developing countries still have a limited share in this booming market. We suggest that this trend could be reverted by promoting partnerships for R and D to connect on-going efforts in aquaculture production with the emerging opportunities for new biotech applications of seaweed products.


Fecal DNA testing for Colorectal Cancer Screening: the ColoSure™ test.
Colorectal cancer is the third most common cancer and the second leading cause of cancer-related deaths in the United States. Screening has been shown to be effective in reducing colorectal cancer incidence and mortality. Colonoscopy, sigmoidoscopy, and fecal occult blood tests are all recommended screening tests that have widespread availability. Nevertheless, many people do not receive the evidence-based recommended screening for colorectal cancer. Additional stool-based methods have been developed that offer more options for colorectal cancer screening, including a variety of fecal DNA tests. The only fecal DNA test that is currently available commercially in the United States is ColoSure(TM), which is marketed as a non-invasive test that detects an epigenetic marker (methylated vimentin) associated with colorectal cancer and pre-cancerous adenomas. We examined the published literature on the analytic validity, clinical validity, and clinical utility of ColoSure and we briefly summarized the current colorectal cancer screening guidelines regarding fecal DNA testing. We also addressed the public health implications of the test and contextual issues surrounding the integration of fecal DNA testing into current colorectal cancer screening strategies. The primary goal was to provide a basic overview of ColoSure and identify gaps in knowledge and evidence that affect the recommendation and adoption of the test in colorectal cancer screening strategies.


Genome sequence of an aflatoxigenic pathogen of Argentinian peanut, Aspergillus arachidicola.
Aspergillus arachidicola is an aflatoxigenic fungal species, first isolated from the leaves of a wild peanut species native to Argentina. It has since been reported in maize, Brazil nut and human sputum samples. This aflatoxigenic species is capable of secreting both B and G aflatoxins, similar to A. parasiticus and A. nomius. It has other characteristics that may result in its misidentification as one of several other section Flavi species. This study offers a preliminary analysis of the A. arachidicola genome. In this study we sequenced the genome of the A. arachidicola type strain (CBS 117610) and found its genome size to be 38.9 Mb, and its number of predicted genes to be 12,091, which are values comparable to those in other sequenced Aspergilli. A comparison of 57 known Aspergillus secondary metabolite gene clusters, among closely-related aflatoxigenic species, revealed nearly half were predicted to exist in the type strain of A. arachidicola. Of its predicted genes, 691 were identified as unique to the species and 60% were assigned Gene Ontology terms using BLAST2GO. Phylogenomic inference shows CBS 117610 sharing a most recent common ancestor with A. parasiticus. Finally, BLAST query of A. flavus mating-type idiomorph sequences to this strain revealed the presence of a single mating-type (MAT1-1) idiomorph. Based on A. arachidicola morphological, genetic and chemotype similarities with A. flavus and A. parasiticus, sequencing the genome of A. arachidicola will contribute to our understanding of the evolutionary relatedness among aflatoxigenic fungi.


Multicolor Imaging of Optic Disc Drusen.
Optic disc drusen (ODD) are calcified deposits at the anterior optic nerve that are often detectable by ophthalmic imaging, including optical coherence tomography and fundus autofluorescence imaging. Multicolor (MC) imaging is a novel modality that captures reflectance of blue, green, and near-infrared laser lights with confocal scanning laser ophthalmoscopy to rapidly acquire high-resolution reflectance images of the optic disc and retina. Here, we show an eye with 3 MC imaging features of ODD, including prominent green hyperreflectance of the optic disc, green sheathing of the papillary and peripapillary vasculature (arterioles > venules), and presence of orange superficial ODD. MC imaging can provide rapid high-resolution assessment of eyes with optic nerve head elevation to help distinguish pseudopapilledema vs papilledema in children and adults without dilation, and future large studies incorporating MC imaging will help determine its contribution in the diagnosis and monitoring of ODD and assessment of other causes of optic nerve head elevation.


Optic disk and cup segmentation from monocular color retinal images for glaucoma assessment.
Automatic retinal image analysis is emerging as an important screening tool for early detection of eye diseases. Glaucoma is one of the most common causes of blindness. The manual examination of optic disk (OD) is a standard procedure used for detecting glaucoma. In this paper, we present an automatic OD parameterization technique based on segmented OD and cup regions obtained from monocular retinal images. A novel OD segmentation method is proposed which integrates the local image information around each point of interest in multidimensional feature space to provide robustness against variations found in and around the OD region. We also propose a novel cup segmentation method which is based on anatomical evidence such as vessel bends at the cup boundary, considered relevant by glaucoma experts. Bends in a vessel are robustly detected using a region of support concept, which automatically selects the right scale for analysis. A multi-stage strategy is employed to derive a reliable subset of vessel bends called r-bends followed by a local spline fitting to derive the desired cup boundary. The method has been evaluated on 138 images comprising 33 normal and 105 glaucomatous images against three glaucoma experts. The obtained segmentation results show consistency in handling various geometric and photometric variations found across the dataset. The estimation error of the method for vertical cup-to-disk diameter ratio is 0.09/0.08 (mean/standard deviation) while for cup-to-disk area ratio it is 0.12/0.10. Overall, the obtained qualitative and quantitative results show effectiveness in both segmentation and subsequent OD parameterization for glaucoma assessment.


Incarceration and perinatal smoking: a missed public health opportunity.
Incarceration is simultaneously a public health opportunity and a public health concern. We examined the association between maternal/partner incarceration in the year prior to birth and perinatal smoking. We pooled 2006-2010 data from the Centers for Disease Control and Prevention's Pregnancy Risk Assessment and Monitoring System. Controlling for age, race/ethnicity, education, marital status and other stressors, we assessed prevalence and heaviness of perinatal smoking. Women who reported incarceration of themselves or their partners in the year prior to delivery were more likely to smoke during the last trimester of pregnancy (adjusted OR (AOR) 1.51 (95% CI 1.36 to 1.67)), and they were more likely to smoke more than 10 cigarettes a day compared to smokers who did not report incarceration (AOR 1.35 (95% CI 1.10 to 1.65)). Patterns were similar for the 3 months prior to pregnancy and postbirth smoking. Incarceration of a parent in the 12 months before birth is associated with increased risk of fetal and newborn exposure to smoking. The criminal justice system can be utilised by public health practitioners to target perinatal smoking reduction interventions.


Self-reported job responsibilities of public school adapted physical educators.
The purpose was to survey adapted physical educators, teaching in the public schools, concerning the nature of their work and the percentage of time spent weekly in 14 specific job roles or responsibilities. Of 102 respondents solicited from national conferences, 66 teachers representing 20 states provided usable data. Most respondents worked in urban settings (77%), served an average of 8 schools per week, had an average caseload of 76 students, and saw each student an average of two times a week. Percentages of time spent each week were greatest in direct instruction (43%), traveling (9%), planning instruction (9%), and assessing students (7%). Findings were similar to those reported previously and discussed in relation to job competencies taught in university classes designed to prepare specialists in adapted physical education.


Enhanced electrochemiluminescence of CdS quantum dots capped with mercaptopropionic acid activated by EDC for Zika virus detection.
Enhanced electrochemiluminescence (ECL) signals of CdS quantum dots capped with 3-mercaptopropionic acid (MPA@CdS QDs) have been observed after using N-(3-dimethylaminopropyl)-N'-ethylcarbodiimide (EDC) to activate the carboxyl groups. The generated ECL signals are strong enough that their images can be captured using a Huawei mobile phone. A possible mechanism for the generation of enhanced ECL signals has been proposed. Then, a sandwich immunosensor platform for detecting Zika virus (ZIKV) was fabricated with silica microspheres as the carrier and MPA@CdS QDs as ECL signal labels. Due to the dual signal amplification of EDC activation and microsphere enrichment, good linearity from 1.0 fg mL-1 to 1.0 ng mL-1 was exhibited by the QD-based ECL immunosensor for ZIKV detection. The detection limit was 0.3 fg mL-1.


Oral and dermal toxicity of alkenones extracted from Isochrysis species.
Isochrysis is commercially available marine algae used for animal feed, human nutrient supplements, and biodiesel. The Isochrysis species is one of five genera of haptophytes that produces unique, long-chain lipids known as alkenones that are promising new ingredients for green cosmetics, personal care products and pharmaceutical delivery. However, there is a lack of toxicity data for alkenones in animals, thus limiting their use in humans. In this study, we performed acute oral, acute dermal, and repeated 28-day dermal toxicity studies, using female SAS Sprague Dawley Rats. Our behavioral studies indicated that the specific alkenones had no overt behavioural effects at oral doses up to 4000 mg/kg. In the acute and chronic dermal toxicity studies, the alkenones produced less irritation and did not significantly damage the skin based on the Draize skin reaction scale and trans-epidermal water loss readings compared to the positive control, 1% sodium lauryl sulfate. Overall, our results indicated that alkenones are safe in Sprague Dawley rats, suggesting that they could be used for both oral and dermal formulations, although additional studies will be required.


Fenestration in endovascular grafts for aortic aneurysm repair: new horizons for preserving blood flow in branch vessels.
To describe techniques for deploying fenestrated stent-grafts that use partial graft deployment and guided tracking of the fenestration to the arterial orifice. Fenestrations have been added to custom-made tube grafts and commercially manufactured Zenith stent-graft systems to preserve perfusion of aortic side branches. Partial device deployment, orientation markers on the endograft, and intraoperative angiography enable maneuvering of the fenestration over the orifice of the target vessel with the aid of guiding catheters. Placement of a Palmaz stent overlapping the fenestration and vessel orifice secures the junction. Two variations of fenestration have preserved blood flow in renal arteries during endovascular repair of abdominal aortic aneurysms (AAAs); similar techniques have maintained flow to the celiac axis in a thoracic aortic aneurysm. Accurate placement of a fenestration over the orifice of a target vessel is feasible, but long-term maintenance of position is dependent on secure graft fixation. This capability brings us a step closer to overcoming the problem of inadequate necks in infra-renal AAAs, especially when the neck is foreshortened by asymmetry of the renal origins. It may also pave the way for the eventual replacement of the entire aorta with an endoluminal graft.


FMN binding site of yeast NADPH-cytochrome P450 reductase exposed at the surface is highly specific.
NADPH-cytochrome P450 reductase (CPR) transfers two reducing equivalents derived from NADPH via FAD and FMN to microsomal P450 monooxygenases in one-electron transfer steps. The crystal structure of yeast CPR (yCPR) contains a surface-exposed FMN binding site (FMN2 site) at the interface of the FMN binding and connecting domains, in addition to the single buried site that has been observed in rat CPR. This finding provides a testable hypothesis of how intramolecular (between FAD and FMN) and intermolecular (between FMN and P450) electron transfer may occur in CPR. To verify that occupancy of the FMN2 site is not an artifact of crystallization, a surface plasmon resonance (SPR) biosensor technique has been applied to probe the selectivity of this site under functional conditions. A series of kinetic and equilibrium binding experiments involving yCPR immobilized on different sensor chip surfaces was performed using FMN and FAD, as well as FMN-derived compounds, including riboflavin, dimethylalloxazine, and alloxazine, and other molecules that resemble the planar isoalloxazine ring structure. Only FMN and FAD showed stoichiometric binding responses. Binding affinity for FMN was in the submicromolar range, 30 times higher than that for FAD. Association kinetic rates for the yCPR/FMN complex were up to 60-fold higher than for the yCPR/FAD complex. Taken together, these data indicate that (i) the surface-exposed site in yCPR is highly selective toward binding flavins, (ii) binding of FMN in this site is notably favored, and finally, (iii) both the phosphate group and the isoalloxazine ring of FMN are essential for binding.


Female sexual victimization predicts psychosis: a case-control study based on the Danish Registry System.
An increasing research literature has identified a statistical association between trauma exposure and psychosis. Methodological limitations, primarily relating to failures to establish the temporal ordering of events and relying on retrospective self-reports, have made the argument for a causal association difficult to establish. A case-control study was conducted based on data from the Danish Civil Registration System and the Danish Psychiatric Central Register. All female visitors to a rape center during the index year (2003) were matched with controls based on age and area of residence. Information on previous and subsequent diagnoses of psychosis was extracted from the registers for cases and controls. A hierarchical binary logistic regression was used with demographic variables, preindex psychosis, and rape center attendance as predictor variables, and the dependent variable was a postindex year diagnosis of psychosis. The OR associated with sexual victimization (OR = 10.04; 95% CI 2.50-40.33) indicted an increased likelihood of psychosis while controlling for the other predictors in the model. This study found that sexual victimization significantly increased the likelihood of a diagnosis of psychosis and therefore suggests that there may be a role for traumatic experiences in the etiology of psychosis.


Clinical Applications of Nanosized Drug-Delivery Systems in Lung Cancer Imaging and Therapy.
Globally, lung cancer is one of the most frequently diagnosed and deadliest types of cancer. Lung cancer imaging can be performed using both invasive and noninvasive techniques, including magnetic resonance, positron emission tomography, single photon emission computed tomography, chest radiography, and computed tomography. But nonspecific contrast agents and radiopharmaceuticals are insufficient for early and specific diagnoses and imaging. In the case of lung cancer therapy, conventional therapeutic agents and radiotherapy may cause severe and systemic adverse and toxic effects and fail to eradicate all tumor tissue. Therefore, formulation of novel, targeted, and specific agents is critically important to overcome these challenges. In this review, we summarize lung cancer classification, current methods for lung cancer imaging and therapy, and future options containing nanosized systems for lung cancer imaging and/or therapy.


Hydrogen and deuterium charging of lifted-out specimens for atom probe tomography.
Hydrogen embrittlement can cause a dramatic deterioration of the mechanical properties of high-strength metallic materials. Despite decades of experimental and modelling studies, the exact underlying mechanisms behind hydrogen embrittlement remain elusive. To unlock understanding of the mechanism and thereby help mitigate the influence of hydrogen and the associated embrittlement, it is essential to examine the interactions of hydrogen with structural defects such as grain boundaries, dislocations and stacking faults. Atom probe tomography (APT) can, in principle, analyse hydrogen located specifically at such microstructural features but faces strong challenges when it comes to charging specimens with hydrogen or deuterium. Here, we describe three different workflows enabling hydrogen/deuterium charging of site-specific APT specimens: namely cathodic, plasma and gas charging. All the experiments in the current study have been performed on a model twinning induced plasticity steel alloy. We discuss in detail the caveats of the different approaches in order to help future research efforts and facilitate further studies of hydrogen in metals. Our study demonstrates successful cathodic and gas charging, with the latter being more promising for the analysis of the high-strength steels at the core of our work.


Phylogenetic analysis and rapid identification of the whitefly, Bemisia afer, in China.
The phylogenetic relationship between the whitefly Bemisia afer (Priesner & Hosny) (Hemiptera: Aleyrodidae) from China and other populations among the world were analyzed based on the mitochondrial cytochrome oxidase I (mtCOI) gene. Phylogenetic analysis of mtCOI sequences and those of reference B. afer sequences showed that the populations of the species could be separated into 5 clades (I-V). There were at least two clades of the species from China (IV and V). These data suggested that B. afer might be a species complex. The Chinese B. afer populations were most divergent with B. afer from the United Kingdom and African countries. The distance between the Chinese B. afer (IV and V) and clades I, II, and III is more than 32%, while the distance among clades I, II, III is lower than 7.7%. A new set of primers specific to B. afer was designed to amplify a region of approximately 400 bp to discriminate B. afer from other Bemisia species in China based on mtCOI sequences.


[Hepatopathy with a progressive course after one-time administration of (chloro-2-ethyl)-1-cyclohexyl-3-nitroso-1-uréa (CCNU) in rats].
A few cases of liver involvement have been reported in patients receiving treatment with CCNU. Nitrosourea CCNU is an antitumoral agent largely used in the treatment of some types of leukemia, Hodgkin's disease, bronchial or cerebral tumors. It was shown that CCNU induced pericholangitis and intra-hepatic cholestasis in rat: moderate after 20 mg/kg CCNU, these hepatic lesions were maximal on day 8. In the present report we were interested in the evolution of hepatic alterations a long time after cessation of drug administration. So we studied hepatic ultrastructure three months after a unique 20 mg/kg or 50 mg/kg CCNU administration. Lesions were stable after 20 mg/kg CCNU and no reversibility was observed 3 months after 50 mg/kg CCNU: evolution to cholangiolysis, to adenomatous transformation of parenchyma or biliary cirrhosis were noted.


Anti-inflammatory properties of human milk.
An hypothesis was developed which predicts that human milk protects against infections of the alimentary tract of the breast-fed infant by non-inflammatory mechanisms. Human milk is poor in the initiators and mediators of inflammation and rich in anti-inflammatory agents. Furthermore, many of the anti-inflammatory agents are comparatively resistant to digestive enzymes and therefore might be expected to remain active in the gastrointestinal tract of the recipient. Further studies of these factors in in vivo models will be required to validate the hypothesis.


A Novel Lipase from Streptomyces exfoliatus DSMZ 41693 for Biotechnological Applications.
Genome mining of Streptomyces exfoliatus DSMZ 41693 has allowed us to identify four different lipase-encoding sequences, and one of them (SeLipC) has been successfully cloned and extracellularly expressed using Rhodococcus sp. T104 as a host. SeLipC was purified by one-step hydrophobic interaction chromatography. The enzyme is a monomeric protein of 27.6 kDa, which belongs to subfamily I.7 of lipolytic enzymes according to its phylogenetic analysis and biochemical characterization. The purified enzyme shows the highest activity at 60 °C and an optimum pH of 8.5, whereas thermal stability is significantly improved when protein concentration is increased, as confirmed by thermal deactivation kinetics, circular dichroism, and differential scanning calorimetry. Enzyme hydrolytic activity using p-nitrophenyl palmitate (pNPP) as substrate can be modulated by different water-miscible organic cosolvents, detergents, and metal ions. Likewise, kinetic parameters for pNPP are: KM = 49.6 µM, kcat = 57 s-1, and kcat/KM = 1.15 × 106 s-1·M-1. SeLipC is also able to hydrolyze olive oil and degrade several polyester-type polymers such as poly(butylene succinate) (PBS), poly(butylene succinate)-co-(butylene adipate) (PBSA), and poly(ε-caprolactone) (PCL). Moreover, SeLipC can catalyze the synthesis of different sugar fatty acid esters by transesterification using vinyl laurate as an acyl donor, demonstrating its interest in different biotechnological applications.


N-ethylmaleimide-induced changes in agonist affinity for histamine H1-receptors in the guinea pig brain.
The effect of the thiol-alkylating agent, N-ethylmaleimide (NEM), on histamine (HA) H1-receptors from guinea pig cerebellum, labeled with [3H]mepyramine, was investigated. The properties of [3H]mepyramine binding (apparent dissociation constant and maximal number of sites) were not modified by prior treatment of the membranes with 2 or 5 mM NEM. This treatment did not change either the inhibition curves of d-chlorpheniramine or mianserin, two H1-receptor antagonists. In contrast, treatments of membranes with NEM significantly decreased the IC50 values of HA and the slope indexes (pseudo Hill coefficients) of HA inhibition curves, which became inferior to unity. These effects were irreversible, and their extent related to the NEM treatment duration and the NEM concentration. A computer analysis of the data indicated that part of the H1-receptors were converted from a state of low affinity for the amine (IC50 value of 75 microM) into a high agonist affinity state (IC50 value of 2 microM). The change was less marked for partial agonists than for HA. The NEM-induced change was observed in the presence and in the absence of Na+ ions, known to decrease the affinity of HA for H1-receptors. Agonists or antagonists did not protect against the modification of HA affinity induced by NEM. The digitonin-solubilized receptors retained their sensitivity to NEM. Among other thiol reagents, iodoacetamide and iodoacetic acid were ineffective, and organic mercurial agents strongly reduced the number of [3H]mepyramine-binding sites. NEM treatment might alkylate a critical thiol group located outside the ligand-binding domain of the H1 receptor and thereby stabilize the latter in a conformation distinct from that of the activated state.


Expression of the human leukocyte adhesion molecule, LAM1. Identity with the TQ1 and Leu-8 differentiation antigens.
The LAM1 molecule is a member of the new family of cellular adhesion/homing molecules that contain a lectin-like domain at their amino-terminal end followed by an epidermal growth factor-like domain and short consensus repeat units like those found in C3/C4 binding proteins. Two mAb that react with the leukocyte adhesion molecule 1 (LAM1) were produced and used to examine the cell-surface expression of LAM1. The anti-LAM1 antibodies were reactive with the majority of blood lymphocytes, NK cells, neutrophils, and monocytes. LAM1 was also expressed by subpopulations of phenotypically immature and mature thymocytes. Blood lymphocytes rapidly modulated LAM1 from the cell surface during PMA exposure for 60 min. Coordinate with the loss of LAM1 from the cell surface, PMA-treated lymphocytes lost the ability to bind to lymph node high endothelial venules, indicating that expression of LAM1 may play a role in lymphocyte homing. Mitogen stimulation of blood T and B lymphocytes also resulted in decreased LAM1 expression, but at a slower rate. LAM1 was only weakly expressed by a minority of spleen lymphocytes. However, culturing spleen lymphocytes in media alone resulted in increased expression of LAM1 by a subpopulation of the cells (40 to 60%). Concomitant mitogen stimulation of spleen lymphocytes resulted initially in down-regulation of LAM1 expression followed by increased expression of LAM1 and then subsequent loss of LAM1 from the cell surface. The pattern of anti-LAM1 antibody reactivity was identical to that reported for the TQ1 and Leu-8 antibodies, and all of these antibodies reacted with cells transfected with the LAM1 cDNA. Thus, LAM1 is broadly expressed by leukocytes, and binding of LAM1 may participate in the process of leukocyte extravasation into lymphoid organs or sites of acute inflammation with subsequent loss of LAM1 from the cell surface.


Balancing selection is the main force shaping the evolution of innate immunity genes.
The evolutionarily recent geographic expansion of humans, and the even more recent development of large, relatively dense human settlements, has exposed our species to new pathogenic environments. Potentially lethal pathogens are likely to have exerted important selective pressures on our genome, so immunity genes can be expected to show molecular signatures of the adaptation of human populations to these recent conditions. While genes related to the acquired immunity system have indeed been reported to show traces of local adaptation, little is known about the response of the innate immunity system. In this study, we analyze the variability patterns in different human populations of fifteen genes related to innate immunity. We have used both single nucleotide polymorphism and sequence data, and through the analysis of interpopulation differentiation, the linkage disequilibrium pattern, and intrapopulation diversity, we have discovered some signatures of positive and especially balancing selection in these genes, thus confirming the importance of the immune system genetic plasticity in the evolutionary adaptive process. Interestingly, the strongest evidence is found in three TLR genes and CD14. These innate immunity genes play a pivotal role, being involved in the primary recognition of pathogens. In general, more evidences of selection appear in the European populations, in some case possibly related to severe population specific pressures. However, we also describe evidence from African populations, which may reflect parallel or long-term selective forces acting in different geographic areas.


Interleukin-6 at the Host-Tumor Interface: STAT3 in Biomolecular Condensates in Cancer Cells.
It was recognized over 30 years ago that the polyfunctional cytokine interleukin-6 (IL-6) was an almost invariant presence at the host-tumor interface. The IL-6 in the tumor microenvironment was produced either by the cancer cell or by host stromal cells, or by tumor-infiltrating immune cells, or all of them. IL-6 effects in this context included local changes in tumor cell-cell and cell-substrate adhesion, enhanced motility, epithelial to mesenchymal transformation (EMT), and changes in cell proliferation rates in both solid tumors as well as hematologic dyscrasias. Locally produced IL-6 enhanced cancer-targeting functions of tumor-infiltrating macrophages and immune cells. Additionally, the sex-biased phenotype of certain cancers [e.g., hepatocellular carcinoma (HCC) which is 3-5-fold more common in men] was related to the inhibition of macrophage-derived IL-6 production by estradiol-17β (E2). In many circumstances, locally produced IL-6 reached the peripheral circulation and elicited systemic effects such as cachexia and paraneoplastic syndrome (including fever, increased erythrocyte sedimentation rate, increased levels of C-reactive protein in serum, hypoalbuminemia). This review highlights the EMT produced by IL-6 in cancer cells, as well as mechanisms underlying sex bias in HCC, enhanced IL-6 expression in cancer cells resulting from mutations in p53, consequent alterations in STAT3 transcriptional signaling, and the newer understanding of STAT3 nuclear bodies in the cancer cell as phase-separated biomolecular condensates and membraneless organelles (MLOs). Moreover, the perplexing issue of discrepant measurements of IL-6 in human circulation using different assays, especially in patients undergoing immunotherapy, is discussed. Additionally, the paradoxical chaperone (enhancing) effect of anti-IL-6 "neutralizing" antibodies on IL-6 in vivo and consequent limitations of immunotherapy using anti-IL-6 mAb is considered.


Eight-Year Outcomes of Bilateral Lateral Rectus Recessions versus Unilateral Recession-Resection in Childhood Basic-Type Intermittent Exotropia.
To report 8-year outcomes from a randomized controlled trial (RCT) comparing bilateral lateral rectus muscle recession (BLRc) with unilateral recession-resection (R&R) for childhood intermittent exotropia (IXT). Eight-year follow-up of RCT cohort. Of 197 randomized participants, 123 agreed to continue follow-up after the 3-year outcome visit (baseline age, 3-< 11 years; basic-type IXT, 15-40 prism diopters [Δ] by prism and alternate cover test [PACT]; baseline stereoacuity, ≤ 400 arcsec; no prior surgery). After the RCT primary outcome at 3 years, annual follow-up from 4 through 8 years with treatment at investigator discretion. Suboptimal surgical outcome by 8 years after randomization, defined as any of the following at any visit: exotropia of 10 Δ or more by simultaneous prism cover test (SPCT) at distance or near, constant esotropia (ET) of 6 Δ or more by SPCT at distance or near, loss of near stereoacuity by 0.6 log arcsec or more from baseline, or reoperation. Secondary outcomes included (1) reoperation by 8 years and (2) complete or near-complete resolution at 8 years, defined as exodeviation of less than 10 Δ by SPCT and PACT at distance and near and 10 Δ or more reduction from baseline by PACT at distance and near, ET of less than 6 Δ at distance and near, no decrease in stereoacuity by 0.6 log arcsec or more from baseline, and no reoperation or nonsurgical treatment for IXT. The Kaplan-Meier cumulative probability of suboptimal surgical outcome through 8 years was 68% (55 events among 101 at risk) for BLRc and 53% (42 events among 96 at risk) for R&R (difference, 15%; 95% confidence interval [CI], -2% to 32%; P = 0.08). Complete or near-complete resolution at 8 years occurred in 15% (7/46) for BLRc and 37% (16/43) for R&R (difference, -22%; 95% CI, -44% to -0.1%; P = 0.049). The cumulative probability of reoperation was 30% for BLRc and 11% for R&R (difference, 19%; 95% CI, 2%-36%; P = 0.049). Despite no significant difference for the primary outcome, the 95% CI did not exclude a moderate benefit of R&R, which together with secondary outcomes suggests that unilateral R&R followed by usual care may yield better long-term outcomes than BLRc followed by usual care for basic-type childhood IXT using these surgical doses. Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.


Kaposi's sarcoma in renal transplant patients: predisposing factors and prognosis.
Among 772 kidney transplant recipients in two centers 25 patients developed Kaposi's sarcoma (KS) (3.2%). The twenty-two of 25 recipients with regular follow-up records were compared for predisposing factors with another group of 22 renal transplant recipients. All patients received cyclosporine (CsA), azathioprine, or mycophenolate mofetil and steroids; patients who received cadaver donor organs additionally received antilymphocyte globulin for induction. KS was diagnosed at a mean of 25.8 months after transplantation. The male to female ratio; mean age; mean follow-up period; hepatitis B, hepatitis C, cytomegalovirus status; and other infection rates were similar in the two groups. Some HLA-DR antigens were detected only in patients with KS. All patients had mucocutaneous involvement, which was multiple in 54.5%. Visceral involvement, and lymph node involvement, or both was detected in seven patients. First-line treatment was to stop CsA and reduce the doses of the other drugs. Three patients underwent additional surgical excision. Fourteen (63.6%) patients experienced complete remissions, including six who required additional chemotherapy or radiotherapy after incomplete or lack of responses to first-line treatment. Two patients died with functioning grafts due to generalized KS. Seven patients returned to hemodialysis at a mean of 36 months after the diagnosis of KS. No significant predisposing factor was observed other than the prevalence of specific HLA-DR antigens. Chemotherapy or radiotherapy should be initiated for patients with multiple, diffuse, and rapidly progressive lesions or organ dysfunction in addition to withdrawal of CsA and tapering of other drugs. Generalized KS displays the poorest prognosis.


Tube radial distribution phenomenon with a two-phase separation solution of a fluorocarbon and hydrocarbon organic solvent mixture in a capillary tube and metal compounds separation.
A fluorocarbon and hydrocarbon organic solvent mixture is known as a temperature-induced phase-separation solution. When a mixed solution of tetradecafluorohexane as a fluorocarbon organic solvent and hexane as a hydrocarbon organic solvent (e.g., 71:29 volume ratio) was delivered in a capillary tube that was controlled at 10°C, the tube radial distribution phenomenon (TRDP) of the solvents was clearly observed through fluorescence images of the dye, perylene, dissolved in the mixed solution. The homogeneous mixed solution (single phase) changed to a heterogeneous solution (two phases) with inner tetradecafluorohexane and outer hexane phases in the tube under laminar flow conditions, generating the dynamic liquid-liquid interface. We also tried to apply TRDP to a separation technique for metal compounds. A model analyte mixture, copper(II) and hematin, was separated through the capillary tube, and detected with a chemiluminescence detector in this order within 4 min.


Titin and myosin, but not desmin, are linked during myofibrillogenesis in postmitotic mononucleated myoblasts.
Monoclonal antibodies specific for the muscle protein titin have been used in conjunction with muscle-specific antibodies against myofibrillar myosin heavy chains (MHCs) and desmin to study myogenesis in cultured cells. Desmin synthesis is initiated in replicating presumptive myoblasts, whereas the synthesis of titin and MHC is initiated simultaneously in their progeny, the postmitotic, mononucleated myoblasts. Both titin and MHC are briefly localized to nonstriated and thereafter to definitively striated myofibrils. At no stage during myofibrillogenesis is either protein observed as part of a sequence of mini-sarcomeres. Titin antibodies bind to the A-I junction, MHC antibodies to the A bands in nascent, maturing, and mature myofibrils. In contrast, desmin remains distributed as longitudinal filaments until well after the definitive myofibrils have aligned laterally. This tight temporal and topographical linkage between titin and myosin is also observed in postmitotic, mononucleated myoblasts and multinucleated myotubes when myofibrillogenesis is perturbed with Colcemid or taxol. Colcemid induces elongating postmitotic mononucleated myoblasts and multinucleated myotubes to round up and form Colcemid myosacs. The myofibrils that emerge in these rounded cells are deployed in convoluted circles. The time required for their nonstriated myofibrils to transform into striated myofibrils is greatly protracted. Furthermore, as Colcemid induces immense desmin intermediate filament cables, the normal spatial relationships between emerging individual myofibrils is distorted. Despite these disturbances at all stages, the characteristic temporal and spatial relationship observed in normal myofibrils between titin and MHC is observed in myofibrils assembling in Colcemid-treated cells. Newly born postmitotic mononucleated myoblasts, or maturing myotubes, reared in taxol acquire a star-shaped configuration and are induced to assemble "pseudo-striated myofibrils." Pseudo-striated myofibrils consist of laterally aggregated 1.6-micron long, thick filaments that interdigitate, not with thin filaments, but with long microtubules. These atypical myofibrils lack Z bands. Despite the absence of thin filaments and Z bands, titin localizes with its characteristics sarcomeric periodicity in pseudo-striated myofibrils. We conclude that the initiation and subsequent regulation of titin and myosin synthesis, and their spatial deployment within developing sarcomeres are tightly coupled events. These findings are discussed in terms of a model that proposes interaction between two relatively autonomous "organizing centers" in the assembly of each sarcomere.


Identification of intrinsic and extrinsic membrane proteins bearing surface epitopes of Mycoplasma hyopneumoniae.
A library of monoclonal antibodies (McAbs) raised against Mycoplasma hyopneumoniae was screened to select McAbs that bound both to surface epitopes on intact organisms and to corresponding proteins identified by immunoblot analysis. Four proteins (indicated by MW in kilodaltons) were established as surface antigens: p65, p50, p44 and p41. Triton X-114 detergent phase fractionation of whole organisms clearly distinguished p65, p50 and p44 as hydrophobic integral membrane proteins, whereas p41 was identified as a hydrophilic surface protein apparently extrinsic to the membrane. This technique also provided a rapid and efficient method for isolating the relatively small number of hydrophobic proteins associated with M. hyopneumoniae. Preliminary evidence suggests that p65, p50 and p44 are linked covalently to lipids, which may be important in dictating their interaction with the membrane. Immunoblot analysis of antibodies from swine immunized with M. hyopneumoniae also suggests that p65 and p44 may be "immunodominant" antigens in this host.


Traditional versus internet bullying in junior high school students.
To examine the prevalence of traditional and Internet bullying and the personal, family, and school environment characteristics of perpetrators and victims. Students (12-14 years old) in 35 junior high schools were randomly selected from the Jerusalem Hebrew (secular and religious) and Arab educational system (n = 2,610). Students answered an anonymous questionnaire, addressing personal, family, and school characteristics. Traditional bullying and Internet bullying for perpetrators and victims were categorized as either occurring at least sometimes during the school year or not occurring. Twenty-eight percent and 8.9 % of students were perpetrators of traditional and Internet bullying, respectively. The respective proportions of victims were 44.9 and 14.4 %. Traditional bullies presented higher Odds Ratios (ORs) for boys, for students with poor social skills (those who had difficulty in making friends, were influenced by peers in their behavior, or were bored), and for those who had poor communication with their parents. Boys and girls were equally likely to be Internet bullies and to use the Internet for communication and making friends. The OR for Internet bullying victims to be Internet bullying perpetrators was 3.70 (95 % confidence interval 2.47-5.55). Victims of traditional bullying felt helpless, and victims of traditional and Internet bullying find school to be a frightening place. There was a higher OR of Internet victimization with reports of loneliness. Traditional bully perpetrators present distinctive characteristics, while Internet perpetrators do not. Victims of traditional and Internet bullying feel fear in school. Tailored interventions are needed to address both types of bullying.


Excretion of glutathione conjugates by primary cultured rat hepatocytes.
Conjugation of xenobiotics with glutathione occurs commonly within the liver, and these glutathione conjugates are then preferentially excreted into bile. We have characterized this excretory process using primary cultured hepatocytes (24 h). 1-Chloro-2,4-dinitrobenzene rapidly entered the cells and formed a glutathione conjugate, S-(dinitrophenyl)glutathione, irrespective of the temperature of incubation. In contrast, the efflux of the glutathione conjugate was essentially absent in the cold but recovered rapidly upon rewarming of the cells. Therefore, initial rates of efflux of the conjugate at 37 degrees C were measured from cells preloaded biosynthetically at 10 degrees C. Efflux was a saturable process with respect to intracellular S-(dinitrophenyl)glutathione with an apparent Km of 0.58 +/- 0.12 mM and Vmax of 0.15 +/- 0.05 nmol/min/mg of protein. The excretion of S-(dinitrophenyl)glutathione had an energy of activation of 15.3 kcal/mol. The glutathione conjugate of p-nitrobenzylchloride when formed within the hepatocytes acted as a competitive inhibitor of S-(dinitrophenyl)glutathione efflux. Cultured hepatocytes, therefore, appeared to have a specific transport process for the excretion of glutathione conjugates. The addition of S-(dinitrophenyl)glutathione, but not GSH, GSSG, or methionine, to the medium caused a decrease in the rate of efflux of radiolabeled S-(dinitrophenyl)glutathione. The hepatocytes were able, however, to excrete the glutathione conjugate against an excess of extracellular S-(dinitrophenyl)glutathione. This observation suggested that extracellular S-(dinitrophenyl)glutathione, although capable of binding to the carrier, entered the hepatocytes quite slowly relative to rates of efflux. This carrier may function in a manner that would minimize the reuptake by hepatocytes of conjugates that have been excreted into the bile.


The Cost Implications in Ontario, Alberta, and British Columbia of Early Versus Delayed External Cephalic Version in the Early External Cephalic Version 2 (EECV2) Trial.
According to the Early External Cephalic Version (EECV2) Trial, planning external cephalic version (ECV) early in pregnancy results in fewer breech presentations at delivery compared with delayed external cephalic version. A Cochrane review conducted after the EECV2 Trial identified an increase in preterm birth associated with early ECV. We examined whether a policy of routine early ECV (i.e., before 37 weeks' gestation) is more or less costly than a policy of delayed ECV. We undertook this analysis from the perspective of a third-party payer (Ministry of Health). We applied data, using resources reported in the EECV2 Trial, to the Canadian context using 10 hospital unit costs and 17 physician service/procedure unit costs. The data were derived from the provincial health insurance plan schedule of medical benefits in three Canadian provinces (Ontario, Alberta, and British Columbia). The difference in mean total costs between study groups was tested for each province separately. We found that planning early ECV results in higher costs than planning delayed ECV. The mean costs of all physician services/procedures and hospital units for planned ECV compared with delayed ECV were $7997.32 versus $7263.04 in Ontario (P < 0.001), $8162.82 versus $7410.55 in Alberta (P < 0.001), and $8178.92 versus $7417.04 in British Columbia (P < 0.001), respectively. From the perspective of overall cost, our analyses do not support a policy of routinely planning ECV before 37 weeks' gestation.


Effects of Atomic Ratio on the Mechanical Properties of Amorphous Silicon Carbon Nitride.
This paper evaluates the mechanical properties of amorphous silicon carbon nitride (a-SiCxNy) films with different atomic ratios via molecular dynamics simulation. The Si-C-N ternary amorphous model is constructed using ReaxFF potential and melt-quenching method. The results demonstrate that the density range of constructed model spans a wide range of densities (2.247-2.831 g/cm3). The short- and medium-range order of the constructed a-SiCxNy structures show a good correlation with the experimental observations. Based on the structural feasibility, the elastoplastic performance is analyzed. There is significant ductility during the uniaxial tension process of a-SiCxNy, except for Si(CN2)2. The calculated elastic modulus ranges from 206.80 GPa to 393.58 GPa, close to the experimental values of coating films. In addition, the elastic modulus of a-SiCxNy does not change monotonically with the carbon or silicon content but is related to the atomic ratio. This article provides an understanding of the chemical composition dependence of the mechanical properties of amorphous compounds at the molecular level.


[Scientific medical forum as important source of scientific-information provision for innovation processes in the healthcare sector of Ukraine].
The article made a retrospective analysis of the scientific medical forums (congresses, symposia and scientific conferences) in the healthcare sector of Ukraine in 2008-2012, planned by higher medical schools and post-graduate medical education schools, scientific institutions of Ministry of Healthcare of Ukraine, National Academy of Medical Science of Ukraine, medical associations and scientific and medical societies. Quantitative and qualitative assessment was carried out of the effectiveness of their implementation, provided suggestions for improving the planning and conducting of medical research forums.


The prothrombin time does not predict the risk of recurrent venous thromboembolism or major bleeding in rivaroxaban-treated patients.
For treatment of deep vein thrombosis (DVT) and pulmonary embolism (PE), rivaroxaban is given in fixed doses without routine coagulation monitoring. To determine whether monitoring would enhance its benefit-risk profile, we examined whether peak and trough prothrombin time (PT) values measured in 3797 rivaroxaban-treated patients included in the EINSTEIN DVT and PE studies correlated with subsequent recurrent VTE and major bleeding. In addition, we examined the stability of PT values over time and the impact of clinical variables on PT values. The mean peak PT values at months 3 and 6 or 12 were 21.9 ± 5 and 21.7 ± 6.0 s, respectively, while the mean trough PT values at months 2 and 6 were 15.1 ± 5.1 and 15.3 ± 2.9 s, respectively. Although peak and through PT values were higher in females, and with older age, frailty, active cancer, low body weight, impaired renal function and use of moderate to strong inhibitors of CYP3A4 and/or P-glycoprotein, and were lower in patients taking strong CYP 3A4 inducers, the differences were small and results were overlapping. Neither peak nor trough PT values correlated with recurrent VTE or major bleeding. PT monitoring is unlikely to improve the benefit-risk profile of rivaroxaban in patients with DVT or PE. The study was registered at www.clinicaltrials.gov as #NCT00440193 (EINSTEIN-DVT) and #NCT00439777 (EINSTEIN-PE).


'Entering a New World': empathic awareness as the key to positive family/staff relationships in care homes.
Despite an almost universal policy of community care, placing a relative in a care home will be an increasingly common event as population ageing continues. Studies suggest that most families wish to remain involved in care following placement but that they often experience difficulties in establishing relationships with staff. This paper reports on the fifth phase of a Swedish study exploring the experience of placement from a temporal perspective and including the views of all the key actors (relatives, staff in the community, staff in care homes). The focus here is placed on the perceptions of care home staff and their perceived role in relation to spouses who have recently placed a partner. The study adopted a grounded theory approach and data were collected from in-depth interviews with 16 staff members of varying grades and positions. Analysis of the data suggested 3 levels of awareness amongst staff: empathic awareness, guarded awareness and limited awareness. The characteristics of empathic awareness are outlined and its implications briefly considered.


Lessons Learned: Beta-Testing the Digital Health Checklist for Researchers Prompts a Call to Action by Behavioral Scientists.
Digital technologies offer unique opportunities for health research. For example, Twitter posts can support public health surveillance to identify outbreaks (eg, influenza and COVID-19), and a wearable fitness tracker can provide real-time data collection to assess the effectiveness of a behavior change intervention. With these opportunities, it is necessary to consider the potential risks and benefits to research participants when using digital tools or strategies. Researchers need to be involved in the risk assessment process, as many tools in the marketplace (eg, wellness apps, fitness sensors) are underregulated. However, there is little guidance to assist researchers and institutional review boards in their evaluation of digital tools for research purposes. To address this gap, the Digital Health Checklist for Researchers (DHC-R) was developed as a decision support tool. A participatory research approach involving a group of behavioral scientists was used to inform DHC-R development. Scientists beta-tested the checklist by retrospectively evaluating the technologies they had chosen for use in their research. This paper describes the lessons learned because of their involvement in the beta-testing process and concludes with recommendations for how the DHC-R could be useful for a variety of digital health stakeholders. Recommendations focus on future research and policy development to support research ethics, including the development of best practices to advance safe and responsible digital health research.


Rules and values: a coordinated regulatory and educational approach to the public health crises of chronic pain and addiction.
Chronic pain and opioid addiction are 2 pressing public health problems, and prescribing clinicians often lack the skills necessary to manage these conditions. Our study sought to address the benefits of a coalition of an academic medical center pain faculty and government agencies in addressing the high unintentional overdose death rates in New Mexico. New Mexico's 2012-2013 mandated chronic pain and addiction education programs studied more than 1000 clinicians. Positive changes were noted in precourse and postcourse surveys of knowledge, self-efficacy, and attitudes. Controlled substance dispensing data from the New Mexico Board of Pharmacy also demonstrated safer prescribing. The total morphine and Valium milligram equivalents dispensed have decreased continually since 2011. There was also a concomitant decline in total drug overdose deaths.


Unique Patterns of Bilingual Speech: Factors Affecting Disfluency Rates in Russian-Hebrew Bilingual Children.
Bilingual children often demonstrate a high rate of disfluencies, which might impact the diagnostic evaluation of fluency disorders; however, research on the rates and types of disfluencies in bilinguals' two languages is limited. The purpose of this research is to profile disfluencies of two types, stuttering-like disfluencies (SLDs) and other disfluencies (ODs), in the speech of Russian-Hebrew bilingual typically developing children, focusing on cross-linguistic differences and the effect of language proficiency in both languages. Spontaneous narratives based on the Frog, Where Are You? (Mayer, 1969) picture book were collected in both languages from 40 bilingual Russian-Hebrew children aged 5;6-6;6 (years;months). The transcribed narratives were coded for SLD (sound, syllable, and monosyllabic word repetitions) and OD (multisyllabic word/phrase repetitions, interjections, and revisions), and their frequencies per 100 syllables were calculated. Overall, most children had a percentage of SLD and OD below the cutoff point and within the existing criteria for stuttering diagnosis established based on monolingual data, but several children exceeded this stuttering criterion. Monosyllabic word repetitions (part of SLD) and interjections (part of OD) were more frequent in Hebrew than in Russian. Lower proficiency was associated with a higher percentage of monosyllabic word repetitions and of interjections in both languages. Bilingual disfluency criteria are needed, since based on the existing monolingual criteria, some children might be erroneously assessed as children who stutter, thus leading to overdiagnosis. The results support the claim that proficiency is an important factor in the production of disfluencies.


Purpose of esthetic risk assessment in prosthetic rehabilitations with gingiva-shade ceramics.
Esthetic predictability and the possibility to reduce the need for more aggressive surgical interventions have been two strong reasons for the growing acceptance of gingiva shade ceramics in dental treatments. However this type of rehabilitation also has several esthetic constraints. The aim of this paper is to present an assessment system that may serve as a clinician's guideline to clearly identify the risk factors influencing the esthetic result of gum-shade ceramics and, in the end, to grade these clinical situations as high, medium or low esthetic risk. Over several years of clinical experience, the authors have identified different factors that influence the achievement of satisfactory esthetic results using gumshade ceramics: smile line, extension of the prosthetic rehabilitation, anatomical area, vertical and horizontal transition between the prosthesis and the natural gingiva, contact surface, framework material, and color. In conclusion, despite the great applicability of gingiva-shade ceramics in the resolution of clinical cases involving complex architecture of the hard and soft tissues, this procedure should not be considered one free of esthetic risk. There are different factors that should be evaluated when considering the esthetic results with gingiva-shade ceramics.