Antrochoanal polyp: clinical presentation and retrospective comparison of endoscopic sinus surgery and endoscopic sinus surgery plus mini-Caldwell surgical procedures.
Antrochoanal polyp is a benign polypoid lesion orginating from the maxillary sinus antrum and extending to the choana. Our aim was to assess the clinical presentation and associated rhinological findings of antrochoanal polyp patients and to evaluate results of 2 surgical treatments termed endoscopic sinus surgery (ESS) and ESS plus mini-Caldwell operation. The study included 46 patients. Factors such as patient age, sex, history of chronic sinusitis, allergic rhinitis, septal deviations, chonca bullosa, turbinate hypertrophy, and the origin of the polyp were assessed. We also evaluated ESS and ESS plus mini-Caldwell surgical procedures for recurrences, synechia, bleeding, and ostium stenosis. Overall, there were 27 men and 19 women. The ESS approach was used in 26 cases, and 20 cases had combined ESS and mini-Caldwell procedures. The statistical significant difference between the 2 groups was only recurrence (P < 0.05). In the ESS group, bleeding, synechia, and ostium stenosis were seen more than in the ESS + mini-Caldwell group, but there was no significant difference between the 2 groups in bleeding, synechia, and ostium stenosis (P > 0.05). We thought that lower rate of recurrence found in ESS + Caldwell group in this study was associated with better visualization of the maxillary sinus walls and, therefore, easier resection of the remnant polyp. We concluded that higher incidences of bleeding and synechia were related to the mucosal damage occurring in the septum and the inferior concha due to excessive manipulation of endoscope and surgical instruments.


Coherent addition of fiber-amplified ultrashort laser pulses.
We report on a novel approach of performance scaling of ultra-fast lasers by means of coherent combination. Pulses from a single mode-locked laser are distributed to a number of spatially separated fiber amplifiers and coherently combined after amplification. Splitting and combination is achieved by polarization cubes, i.e. the approach bases on polarization combining. A Hänsch-Couillaud detector measures the polarization state at the output. The error signal (deviation from linear polarization) is used to stabilize the synchronization of different channels. In a proof-of-principle experiment the combination of two femtosecond fiber-based CPA systems is presented. A combining efficiency as high as 97% has been achieved. The technique offers a unique scaling potential and can be applied to all ultrafast amplification schemes independent of the architecture of the gain medium.


Variable extent of emperipolesis in the evolution of Rosai Dorfman disease: Diagnostic and pathogenetic implications.
This study examines variation of morphologic features, including emperipolesis, during the evolution of a case of Rosai Dorfman Disease (RDD). A 44-year-old male patient with RDD affecting the salivary glands, cervical lymph nodes, nasal and maxillary sinus mucosa had a waxing and waning course over two and a half years, with episodic sudden increase in size followed by involution and then a static course with moderate sized swellings. Multiple aspirations and biopsies were performed, which form the basis of this study. Four classical cases of RDD on aspirates and another four on biopsy were analyzed for comparison, with quantification of the number of lymphocytes engulfed by histiocytes (emperipolesis). Three nasal biopsies and one salivary gland excision of the index case, performed during acute exacerbation, showed chronic inflammation and foamy histiocytes without emperipolesis, the aspirate showing emperipolesis nil in 45%, 1-3 lymphocytes in 15%, 4-10 in 36% and > 10 in 4%. Two aspirations and one lymph node biopsy done from static phase showed classical features of RDD with extensive emperipolesis, the aspirate from left cervical lymph node showing emperipolesis nil in 2%, 1-3 in 5%, 4-10 in 35% and > 10 in 58% while right cervical lymph node aspirate showed emperipolesis nil in 9%, 1-3 in 21%, 4-10 in 29% and > 10 in 41%. A biopsy performed from involuting cervical lymph node showed extensive apoptosis and vasculitis without foamy histiocytes or emperipolesis. For comparison, eight classical RDD cases showed abundant emperipolesis with mild variation. Emperipolesis is variable in RDD depending on disease activity, which has differential diagnostic relevance and demonstrates the natural history of this rare disease.


The beta-defensin gallinacin-6 is expressed in the chicken digestive tract and has antimicrobial activity against food-borne pathogens.
Food-borne pathogens are responsible for most cases of food poisoning in developed countries and are often associated with poultry products, including chicken. Little is known about the role of beta-defensins in the chicken digestive tract and their efficacy. In this study, the expression of chicken beta-defensin gallinacin-6 (Gal-6) and its antimicrobial activity against food-borne pathogens were investigated. Reverse transcription-PCR analysis showed high expression of Gal-6 mRNA in the esophagus and crop, moderate expression in the glandular stomach, and low expression throughout the intestinal tract. Putative transcription factor binding sites for nuclear factor kappa beta, activator protein 1, and nuclear factor interleukin-6 were found in the Gal-6 gene upstream region, which suggests a possible inducible nature of the Gal-6 gene. In colony-counting assays, strong bactericidal and fungicidal activity was observed, including bactericidal activity against food-borne pathogens Campylobacter jejuni, Salmonella enterica serovar Typhimurium, Clostridium perfringens, and Escherichia coli. Treatment with 16 mug/ml synthetic Gal-6 resulted in a 3 log unit reduction in Clostridium perfringens survival within 60 min, indicating fast killing kinetics. Transmission electron microscopy examination of synthetic-Gal-6-treated Clostridium perfringens cells showed dose-dependent changes in morphology after 30 min, including intracellular granulation, cytoplasm retraction, irregular septum formation in dividing cells, and cell lysis. The high expression in the proximal digestive tract and broad antimicrobial activity suggest that chicken beta-defensin gallinacin-6 plays an important role in chicken innate host defense.


Manganese transport in eukaryotes: the role of DMT1.
Manganese (Mn) is a transition metal that is essential for normal cell growth and development, but is toxic at high concentrations. While Mn deficiency is uncommon in humans, Mn toxicity is known to be readily prevalent due to occupational overexposure in miners, smelters and possibly welders. Excessive exposure to Mn can cause Parkinson's disease-like syndrome; patients typically exhibit extrapyramidal symptoms that include tremor, rigidity and hypokinesia [Calne DB, Chu NS, Huang CC, Lu CS, Olanow W. Manganism and idiopathic parkinsonism: similarities and differences. Neurology 1994;44(9):1583-6; Dobson AW, Erikson KM, Aschner M. Manganese neurotoxicity. Ann NY Acad Sci 2004;1012:115-28]. Mn-induced motor neuron diseases have been the subjects of numerous studies; however, this review is not intended to discuss its neurotoxic potential or its role in the etiology of motor neuron disorders. Rather, it will focus on Mn uptake and transport via the orthologues of the divalent metal transporter (DMT1) and its possible implications to Mn toxicity in various categories of eukaryotic systems, such as in vitro cell lines, in vivo rodents, the fruitfly, Drosophila melanogaster, the honeybee, Apis mellifera L., the nematode, Caenorhabditis elegans and the baker's yeast, Saccharomyces cerevisiae.


Parent involvement and student academic performance: a multiple mediational analysis.
Parent involvement in a child's education is consistently found to be positively associated with a child's academic performance. However, there has been little investigation of the mechanisms that explain this association. The present study examines two potential mechanisms of this association: the child's perception of cognitive competence and the quality of the student-teacher relationship. This study used a sample of 158 seven-year-old participants, their mothers, and their teachers. Results indicated a statistically significant association between parent involvement and a child's academic performance, over and above the impact of the child's intelligence. A multiple mediation model indicated that the child's perception of cognitive competence fully mediated the relation between parent involvement and the child's performance on a standardized achievement test. The quality of the student-teacher relationship fully mediated the relation between parent involvement and teacher ratings of the child's classroom academic performance. Limitations, future research directions, and implications for public policy initiatives are discussed.


The activity reaction core and plasticity of metabolic networks.
Understanding the system-level adaptive changes taking place in an organism in response to variations in the environment is a key issue of contemporary biology. Current modeling approaches, such as constraint-based flux-balance analysis, have proved highly successful in analyzing the capabilities of cellular metabolism, including its capacity to predict deletion phenotypes, the ability to calculate the relative flux values of metabolic reactions, and the capability to identify properties of optimal growth states. Here, we use flux-balance analysis to thoroughly assess the activity of Escherichia coli, Helicobacter pylori, and Saccharomyces cerevisiae metabolism in 30,000 diverse simulated environments. We identify a set of metabolic reactions forming a connected metabolic core that carry non-zero fluxes under all growth conditions, and whose flux variations are highly correlated. Furthermore, we find that the enzymes catalyzing the core reactions display a considerably higher fraction of phenotypic essentiality and evolutionary conservation than those catalyzing noncore reactions. Cellular metabolism is characterized by a large number of species-specific conditionally active reactions organized around an evolutionary conserved, but always active, metabolic core. Finally, we find that most current antibiotics interfering with bacterial metabolism target the core enzymes, indicating that our findings may have important implications for antimicrobial drug-target discovery.


Prophylactic antibiotics for preventing Gram positive infections associated with long-term central venous catheters in oncology patients.
This is an updated version of the review which was first published in the Cochrane Database of Systematic Reviews in 2006. Long-term central venous catheters (CVCs), including tunnelled CVCs (TCVCs) and totally implanted devices or ports (TIDs), are increasingly used when treating oncology patients. Despite international guidelines on sterile insertion and appropriate CVC maintenance and use, infection remains a common complication. These infections are mainly caused by Gram positive bacteria. Antimicrobial prevention strategies aimed at these micro-organisms could potentially decrease the majority of CVC infections. The aim of this review was to evaluate the efficacy of antibiotics in the prevention of Gram positive infections in long-term CVCs. To determine the efficacy of administering antibiotics prior to the insertion of long-term CVCs, or flushing or locking long-term CVCs with a combined antibiotic and heparin solution, or both, to prevent Gram positive catheter-related infections in adults and children receiving treatment for cancer. We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (to June 2013) and the MEDLINE and EMBASE databases (1966 to 2013). Randomised controlled trials (RCTs) comparing prophylactic antibiotics given prior to long-term CVC insertion with no antibiotics, RCTs comparing a combined antibiotic and heparin solution with a heparin-only solution to flush or lock newly inserted long-term CVCs, and RCTs comparing a combination of these interventions in adults and children receiving treatment for cancer. Two authors independently selected studies, classified them and extracted data on to a pre-designed data collection form. We pooled data using the RevMan software version 5.2 and used random-effects (RE) model methods for meta-analyses. We included 11 trials with a total of 828 oncology patients (adults and children). We assessed most included studies to be at a low or unclear risk of bias. Five trials compared the use of antibiotics (vancomycin, teicoplanin or ceftazidime) given before the insertion of the long-term CVC with no antibiotics, and six trials compared antibiotics (vancomycin, amikacin or taurolidine) and heparin with a heparin-only solution for flushing or locking the long-term CVC after use. Administering an antibiotic prior to insertion of the CVC did not significantly reduce Gram positive catheter-related sepsis (CRS) (five trials, 360 adults; risk ratio (RR) 0.72, 95% confidence interval (CI) 0.33 to 1.58; I² = 5 2%; P = 0.41).Flushing and locking long-term CVCs with a combined antibiotic and heparin solution significantly reduced the risk of Gram positive catheter-related sepsis compared with a heparin-only solution (468 participants, mostly children; RR 0.47, 95% CI 0.28 to 0.80; I² = 0%; P = 0.005). For a baseline infection rate of 15%, this reduction translated into a number needed to treat (NNT) of 12 (95% CI 9 to 33) to prevent one catheter-related infection. We considered this evidence to be of a moderate quality. There was no benefit to administering antibiotics before the insertion of long-term CVCs to prevent Gram positive catheter-related infections. Flushing or locking long-term CVCs with a combined antibiotic and heparin solution appeared to reduce Gram positive catheter-related sepsis experienced in people at risk of neutropenia through chemotherapy or disease. Due to insufficient data it was not clear whether this applied equally to TCVCs and totally implanted devices (TIDs), or equally to adults and children. The use of a combined antibiotic and heparin solution may increase microbial antibiotic resistance, therefore it should be reserved for high risk people or where baseline CVC infection rates are high (> 15%). Further research is needed to identify high risk groups most likely to benefit.


A spectroscopic and calorimetric investigation on the thermal stability of the Cys3Ala/Cys26Ala azurin mutant.
The disulfide bond connecting Cys-3 and Cys-26 in wild type azurin has been removed to study the contribution of the -SS- bond to the high thermal resistance previously registered for this protein (. J. Phys. Chem. 99:14864-14870). Site-directed mutagenesis was used to replace both cysteines for alanines. The characterization of the Cys-3Ala/Cys-26Ala azurin mutant has been carried out by means of electron paramagnetic resonance spectroscopy at 77 K, UV-VIS optical absorption, fluorescence emission and circular dichroism at room temperature. The results show that the spectral features of the Cys-3Ala/Cys-26Ala azurin resemble those of the wild type azurin, indicating that the double mutation does not affect either the formation of the protein's overall structure or the assembly of the metal-binding site. The thermal unfolding of the Cys-3Ala/Cys-26Ala azurin has been followed by differential scanning calorimetry, optical absorption variation at lambda(max) = 625 nm, and fluorescence emission using 295 nm as excitation wavelength. The analysis of the data shows that the thermal transition from the native to the denaturated state of the modified azurin follows the same multistep unfolding pathway as observed in wild type azurin. However, the removal of the disulfide bridge results in a dramatic reduction of the thermodynamic stability of the protein. In fact, the transition temperatures registered by the different techniques are down-shifted by about 20 degrees C with respect to wild type azurin. Moreover, the Gibbs free energy value is about half of that found for the native azurin. These results suggest that the disulfide bridge is a structural element that significantly contributes to the high stability of wild type azurin.


Interactions of surfactants (edge activators) and skin penetration enhancers with liposomes.
Incorporating edge activators (surfactants) into liposomes was shown previously to improve estradiol vesicular skin delivery; this phenomenon was concentration dependent with low or high concentrations being less effective. Replacing surfactants with limonene produced similar behaviour, but oleic acid effects were linear with concentration up to 16% (w/w), beyond which it was incompatible with the phospholipid. This present study thus employed high sensitivity differential scanning calorimetry to probe interactions of additives with dipalmitoylphosphatidylcholine (DPPC) membranes to explain such results. Cholesterol was included as an example of a membrane stabiliser that removed the DPPC pre-transition and produced vesicles with a higher transition temperature (T(m)). Surfactants also removed the lipid pre-transition but reduced T(m) and co-operativity of the main peak. At higher concentrations, surfactants also formed new species, possibly mixed micelles with a lower T(m). The formation of mixed micelles may explain reduced skin delivery from liposomes containing high concentrations of surfactants. Limonene did not remove the pre-transition but reduced T(m) and co-operativity of the main peak, apparently forming new species at high concentrations, again correlating with vesicular delivery of estradiol. Oleic acid obliterated the pre-transition. The T(m) and the co-operativity of the main peak were reduced with oleic acid concentrations up to 33.2mol%, above which there was no further change. At higher concentrations, phase separation was evident, confirming previous skin transport findings.


Conformational investigation of the structure-activity relationship of GdFFD and its analogues on an achatin-like neuropeptide receptor of Aplysia californica involved in the feeding circuit.
Proteins and peptides in nature are almost exclusively made from l-amino acids, and this is even more absolute in the metazoan. With the advent of modern bioanalytical techniques, however, previously unappreciated roles for d-amino acids in biological processes have been revealed. Over 30 d-amino acid containing peptides (DAACPs) have been discovered in animals where at least one l-residue has been isomerized to the d-form via an enzyme-catalyzed process. In Aplysia californica, GdFFD and GdYFD (the lower-case letter "d" indicates a d-amino acid residue) modulate the feeding behavior by activating the Aplysia achatin-like neuropeptide receptor (apALNR). However, little is known about how the three-dimensional conformation of DAACPs influences activity at the receptor, and the role that d-residues play in these peptide conformations. Here, we use a combination of computational modeling, drift-tube ion-mobility mass spectrometry, and receptor activation assays to create a simple model that predicts bioactivities for a series of GdFFD analogs. Our results suggest that the active conformations of GdFFD and GdYFD are similar to their lowest energy conformations in solution. Our model helps connect the predicted structures of GdFFD analogs to their activities, and highlights a steric effect on peptide activity at position 1 on the GdFFD receptor apALNR. Overall, these methods allow us to understand ligand-receptor interactions in the absence of high-resolution structural data.


Mapping Underwater Sound in the Dutch Part of the North Sea.
The European Union requires member states to achieve or maintain good environmental status for their marine territorial waters and explicitly mentions potentially adverse effects of underwater sound. In this study, we focused on producing maps of underwater sound from various natural and anthropogenic origins in the Dutch North Sea. The source properties and sound propagation are simulated by mathematical methods. These maps could be used to assess and predict large-scale effects on behavior and distribution of underwater marine life and therefore become a valuable tool in assessing and managing the impact of underwater sound on marine life.


Cannabis Systematics at the Levels of Family, Genus, and Species.
New concepts are reviewed in Cannabis systematics, including phylogenetics and nomenclature. The family Cannabaceae now includes Cannabis, Humulus, and eight genera formerly in the Celtidaceae. Grouping Cannabis, Humulus, and Celtis actually goes back 250 years. Print fossil of the extinct genus Dorofeevia (=Humularia) reveals that Cannabis lost a sibling perhaps 20 million years ago (mya). Cannabis print fossils are rare (n=3 worldwide), making it difficult to determine when and where she evolved. A molecular clock analysis with chloroplast DNA (cpDNA) suggests Cannabis and Humulus diverged 27.8 mya. Microfossil (fossil pollen) data point to a center of origin in the northeastern Tibetan Plateau. Fossil pollen indicates that Cannabis dispersed to Europe by 1.8-1.2 mya. Mapping pollen distribution over time suggests that European Cannabis went through repeated genetic bottlenecks, when the population shrank during range contractions. Genetic drift in this population likely initiated allopatric differences between European Cannabis sativa (cannabidiol [CBD]>Δ9-tetrahydrocannabinol [THC]) and Asian Cannabis indica (THC>CBD). DNA barcode analysis supports the separation of these taxa at a subspecies level, and recognizing the formal nomenclature of C. sativa subsp. sativa and C. sativa subsp. indica. Herbarium specimens reveal that field botanists during the 18th-20th centuries applied these names to their collections rather capriciously. This may have skewed taxonomic determinations by Vavilov and Schultes, ultimately giving rise to today's vernacular taxonomy of "Sativa" and "Indica," which totally misaligns with formal C. sativa and C. indica. Ubiquitous interbreeding and hybridization of "Sativa" and "Indica" has rendered their distinctions almost meaningless.


Transcriptomic and Functional Screens Reveal MicroRNAs That Modulate Prostate Cancer Metastasis.
Identifying new mechanisms that underlie the complex process of metastasis is vital to combat this fatal step in prostate cancer (PCa) progression. Small non-coding RNAs are emerging as important regulators of tumor cell biology. Here we take an integrative approach to elucidate the contribution of microRNAs to metastatic progression, combining transcriptomic analysis with functional screens for migration and morphology. We developed high-content microscopy, high-throughput functional screens for migration and morphology in PCa cells using a microRNA library. RNA-Seq analysis of paired epithelial and mesenchymal PCa cells identified differential expression of 200 microRNAs. Data integration identified two microRNAs that inhibited migration, induced an epithelial-like morphology and were increased in epithelial PCa cells. An overrepresentation of the AAGUGC seed sequence was detected in all three datasets. Analysis of published datasets of patients with PCa identified microRNAs of clinical relevance. The integration of high-throughput functional and expression analyses identifies microRNAs with clinical significance that modulate metastatic behavior in PCa.


Family-focused prevention with Latinos: What about sisters and brothers?
Using a randomized, intent-to-treat design, this pilot study examined the feasibility and short-term effects of Siblings Are Special (SIBS) with a sample of 54 low-income Latino families (91% Mexican-origin). Participants were older (M = 10.8 years; SD = .46) and younger siblings (M = 8.4 years; SD = 1.13), and their parents (94% biological mothers), who were randomly assigned within school to the intervention (n = 28) or no-attention control (n = 26) condition. The intervention condition included 12 weekly afterschool sessions (90 min each) for sibling pairs and 3 family nights for parents and siblings (2 hr each). SIBS was designed to enhance sibling relationships via 2 primary intervention targets: (a) children's capacities that underlie positive sibling dynamics, including relationship skills, cognitions, and shared activities; and (b) parenting of siblings, specifically, enhancing positive guidance and involvement and discouraging authoritarian control. Pre- and posttest data were gathered from siblings and parents. Recruitment and implementation data revealed high rates of attendance and completion, and high ratings of parent satisfaction with the program. Further, analyses suggested the program had positive effects of small to modest magnitude on posttest measures of sibling and parent–child relationship quality, parenting of siblings, older siblings' emotional efficacy, and parents' depressive symptoms and parenting stress, controlling for pretest levels of all outcomes and family background characteristics. Discussion addresses the feasibility of sibling-focused programs with low-income Latino families and makes recommendations for future research.


Magnetic Nanotweezers for Interrogating Biological Processes in Space and Time.
The ability to sense and manipulate the state of biological systems has been extensively advanced during the past decade with the help of recent developments in physical tools. Unlike standard genetic and pharmacological perturbation techniques-knockdown, overexpression, small molecule inhibition-that provide a basic on/off switching capability, these physical tools provide the capacity to control the spatial, temporal, and mechanical properties of the biological targets. Among the various physical cues, magnetism offers distinct advantages over light or electricity. Magnetic fields freely penetrate biological tissues and are already used for clinical applications. As one of the unique features, magnetic fields can be transformed into mechanical stimuli which can serve as a cue in regulating biological processes. However, their biological applications have been limited due to a lack of high-performance magnetism-to-mechanical force transducers with advanced spatiotemporal capabilities. In this Account, we present recent developments in magnetic nanotweezers (MNTs) as a useful tool for interrogating the spatiotemporal control of cells in living tissue. MNTs are composed of force-generating magnetic nanoparticles and field generators. Through proper design and the integration of individual components, MNTs deliver controlled mechanical stimulation to targeted biomolecules at any desired space and time. We first discuss about MNT configuration with different force-stimulation modes. By modulating geometry of the magnetic field generator, MNTs exert pulling, dipole-dipole attraction, and rotational forces to the target specifically and quantitatively. We discuss the key physical parameters determining force magnitude, which include magnetic field strength, magnetic field gradient, magnetic moment of the magnetic particle, as well as distance between the field generator and the particle. MNTs also can be used over a wide range of biological time scales. By simply adjusting the amplitude and phase of the applied current, MNTs based on electromagnets allow for dynamic control of the magnetic field from microseconds to hours. Chemical design and the nanoscale effects of magnetic particles are also essential for optimizing MNT performance. We discuss key strategies to develop magnetic nanoparticles with improved force-generation capabilities with a particular focus on the effects of size, shape, and composition of the nanoparticles. We then introduce various strategies and design considerations for target-specific biomechanical stimulations with MNTs. One-to-one particle-receptor engagement for delivering a defined force to the targeted receptor and the small size of the nanoparticles are important. Finally, we demonstrate the utility of MNTs for manipulating biological functions and activities with various spatial (single molecule/cell to organisms) and temporal resolution (microseconds to days). MNTs have the potential to be utilized in many exciting applications across diverse biological systems spanning from fundamental biology investigations of spatial and mechanical signaling dynamics at the single-cell and systems levels to in vivo therapeutic applications.


Analyzing array data using supervised methods.
Pharmacogenomics is the application of genomic technologies to drug discovery and development, as well as for the elucidation of the mechanisms of drug action on cells and organisms. DNA microarrays measure genome-wide gene expression patterns and are an important tool for pharmacogenomic applications, such as the identification of molecular targets for drugs, toxicological studies and molecular diagnostics. Genome-wide investigations generate vast amounts of data and there is a need for computational methods to manage and analyze this information. Recently, several supervised methods, in which other information is utilized together with gene expression data, have been used to characterize genes and samples. The choice of analysis methods will influence the results and their interpretation, therefore it is important to be familiar with each method, its scope and limitations. Here, methods with special reference to applications for pharmacogenomics are reviewed.


3D-Printed PCL/PLA Composite Stents: Towards a New Solution to Cardiovascular Problems.
Biodegradable stents (BRS) offer enormous potential but first they must meet five specific requirements: (i) their manufacturing process must be precise; (ii) degradation should have minimal toxicity; (iii) the rate of degradation should match the recovery rate of vascular tissue; (iv) ideally, they should induce rapid endothelialization to restore the functions of vascular tissue, but at the same time reduce the risk of restenosis; and (v) their mechanical behavior should comply with medical requirements, namely, the flexibility required to facilitate placement but also sufficient radial rigidity to support the vessel. Although the first three requirements have been comprehensively studied, the last two have been overlooked. One possible way of addressing these issues would be to fabricate composite stents using materials that have different mechanical, biological, or medical properties, for instance, Polylactide Acid (PLA) or Polycaprolactone (PCL). However, fashioning such stents using the traditional stent manufacturing process known as laser cutting would be impossible. Our work, therefore, aims to produce PCL/PLA composite stents using a novel 3D tubular printer based on Fused Deposition Modelling (FDM). The cell geometry (shape and area) and the materials (PCL and PLA) of the stents were analyzed and correlated with 3T3 cell proliferation, degradation rates, dynamic mechanical and radial expansion tests to determine the best parameters for a stent that will satisfy the five strict BRS requirements. Results proved that the 3D-printing process was highly suitable for producing composite stents (approximately 85⁻95% accuracy). Both PCL and PLA demonstrated their biocompatibility with PCL stents presenting an average cell proliferation of 12.46% and PLA 8.28% after only 3 days. Furthermore, the PCL/PLA composite stents demonstrated their potential in degradation, dynamic mechanical and expansion tests. Moreover, and regardless of the order of the layers, the composite stents showed (virtually) medium levels of degradation rates and mechanical modulus. Radially, they exhibited the virtues of PCL in the expansion step (elasticity) and those of PLA in the recoil step (rigidity). Results have clearly demonstrated that composite PCL/PLA stents are a highly promising solution to fulfilling the rigorous BRS requirements.


Variation of chemical composition of essential oils in wild populations of Thymus algeriensis Boiss. et Reut., a North African endemic species.
ABSBACKGROUND: Thymus algeriensis is an endemic aromatic plant to Tunisia largely used in folk medicine and as a culinary herb. The bulks aromatic plants come from wild populations whose essential oils compositions as well as their biological properties are severely affected by the geographical location and the phase of the plant development. Therefore, the aim of the present work is to provide more information on the variation of essential oil composition of T. algeriensis collected during the vegetative and the flowering phases and from eight different geographical regions. Besides, influence of population location and phenological stage on yield and metal chelating activity of essential oils is also assessed. The essential oil composition of Thymus algeriensis was determined mainly by GC/FID and GC/MS. The chemical differentiation among populations performed on all compounds was assessed by linear discriminate analysis and cluster analysis based on Euclidean distance. A total of 71 compounds, representing 88.99 to 99.76% of the total oil, were identified. A significant effect of the population location on the chemical composition variability of T. algeriensis oil was observed. Only 18 out of 71 compounds showed a statistically significant variation among population locations and phenological stages. Chemical differentiation among populations was high. Minor compounds play an important role to distinguish between chemical groups. Five chemotypes according to the major compounds have been distinguished. Chemotypes distribution is linked to the population location and not to bioclimate, indicating that local selective environmental factors acted on the chemotype diversity. The major compounds at the species level were α-pinene (7.41-13.94%), 1,8-cineole (7.55-22.07%), cis-sabinene hydrate (0.10-12.95%), camphor (6.8-19.93%), 4-terpineol (1.55-11.86%), terpenyl acetate (0-14.92%) and viridiflorol (0-11.49%). Based on major compounds, the populations were represented by (α-pinene/1,8-cineole/cis-sabinene hydrate/camphor/viridiflorol), (1,8-cineole/camphor/terpenyl acetate), (α-pinene/1,8-cineole/camphor), (1,8-cineole/camphor/4-terpineol) and (α-pinene/1,8-cineole/cis-sabinene hydrate/camphor/4-terpineol) chemotypes. Variation of phenological stage did not have a statistically significant effect on the yield and metal chelating activity of the essential oil. These results can be used to investigate the geographical location and the harvesting time of this plant for relevant industries.


Pro12Ala polymorphism of the PPARγ2 gene interacts with a mediterranean diet to prevent telomere shortening in the PREDIMED-NAVARRA randomized trial.
The gene variant Pro/Ala (rs1801282) in the PPARγ2 has been associated with lower cardiovascular risk and greater benefit from lifestyle interventions. This polymorphism also seems to be associated with longer lifespan, but no information on telomere length (TL) is available. Our aim was to study the association between the Ala allele and changes in TL in high cardiovascular risk subjects and the potential interaction with a Mediterranean dietary pattern. A total of 521 subjects (55-80 years) participating in the Prevención con Dieta Mediterránea randomized trial were genotyped. Changes in TL, measured by quantitative real-time polymerase chain reaction (PCR), were assessed over 5 years of a nutritional intervention, which promoted adherence to the Mediterranean diet (MeDiet). Interestingly, Ala carriers showed lower telomere shortening after 5 years compared with the Pro/Pro genotype (P=0.031). This association was modulated by MeDiet because those Ala carriers who reported better conformity to the MeDiet exhibited increased TL (P<0.001). Moreover, a reduction in carbohydrate intake (≤9.5 g/d) resulted in increased TL among Ala carriers. Notably, an apparent gene-diet interaction was found through the observed changes in the MUFA+PUFA/carbohydrates ratio: as this ratio increased, TL lengthening was detected to a greater extent in the Ala carriers compared with the Pro/Pro subjects (P for interaction <0.001). The Pro12Ala polymorphism is associated with TL homeostasis after 5 years follow-up in subjects at high cardiovascular risk. In addition, a higher adherence to the MeDiet pattern strengthens the prevention of telomere shortening among Ala carriers. www.controlled-trials.com; Unique Identifier: ISRCTN35739639.


Foodborne Disease Outbreaks Associated with Organic Foods in the United States.
Consumer demand for organically produced foods is increasing in the United States as well as globally. Consumer perception often credits organic foods as being safer than conventionally produced foods, although organic standards do not directly address safety issues such as microbial or chemical hazards. We reviewed outbreaks reported to the Centers for Disease Control and Prevention's Foodborne Disease Outbreak Surveillance System where the implicated food was reported to be organic. Information collected for each outbreak included the year, state, number of illnesses, pathogen, and implicated food. We identified 18 outbreaks caused by organic foods from 1992 to 2014, resulting in 779 illnesses, 258 hospitalizations, and 3 deaths; 56% of outbreaks occurred from 2010 to 2014. Nine outbreaks occurred in a single state, and nine outbreaks were multistate. Salmonella sp. (44% of outbreaks) and Escherichia coli O157:H7 (33%) were the most commonly occurring pathogens. Eight of the outbreaks were attributed to produce items, four to unpasteurized dairy products, two to eggs, two to nut and seed products, and two to multi-ingredient foods. Fifteen (83%) outbreaks were associated with foods that were definitely or likely U.S. Department of Agriculture certified. More foodborne outbreaks associated with organic foods in the United States have been reported in recent years, in parallel with increases in organic food production and consumption. We are unable to assess risk of outbreaks due to organic foods compared with conventional foods because foodborne outbreak surveillance does not systematically collect food production method. Food safety requires focused attention by consumers, regardless of whether foods are produced organically or conventionally. Consumers should be aware of the risk of milk and produce consumed raw, including organic.


[Trends of nursing science inquiry in doctoral dissertations].
The purpose of this study was to identify the theoretical characteristics and direction of inquiry in the discipline of nursing by analyzing doctoral dissertations. The materials used in this study were 277 doctoral dissertations from five universities in Korea. The framework for the study was derived from Kim's(1993) alternative linkage among philosophy, theory, and method in nursing science. Of the 277 dissertations it was found that there were 13 types of linkages out of a possible 54 types. Most of the dissertations (128 of 277) were done within the linkage of realism/etic/quantitative/explanatory knowledge type. Of the 218 dissertations within scientific realism, 42 were within relativism, and 17 within practicism. There were 134 dissertations of the explanatory knowledge type, 112 descriptive ones, and 31 prescriptive ones. Studies done within the etic quantitative methodology included 209 dissertations and within the emic perspective, 43 with qualitative methodology, and 7 with quantitative. The results show that it is necessary to develop more alternative linkages for nursing practice and this will lead to expanding nursing knowledge.


Incidence of food anaphylaxis in Piemonte region (Italy): data from registry of Center for Severe Allergic Reactions.
There are wide differences in estimated incidence and prevalence of anaphylaxis because of the absence, until recently, of a universal consensus on the definition of anaphylaxis and the different source of collected data. We aimed to estimate the incidence of food anaphylaxis based on the database of Piemonte Region (Italy) Reference Center for Severe Allergic Reactions. All cases of severe food allergic reactions reported in 2010 were studied. Clinical data associated to the reports were evaluated according to National Institute of Allergy and Infectious Disease and Food Allergy and Anaphylaxis Network diagnostic criteria of anaphylaxis. 75 % of the 778 cases were classified as food anaphylaxis (incidence of 13/100,000 person-years, ranging from 9.9 in adults to 29/100,000 person-years in children). Nuts were the most frequent foods causing anaphylaxis. Milk and eggs were responsible for anaphylaxis more often in children, while peach, vegetables and crustaceans were in adults. Cardiovascular symptoms were more frequent in adults. Gastrointestinal involvement was more frequent in children. A high prevalence of respiratory allergic comorbidities was observed. Food is an important cause of anaphylaxis, particularly in subjects with respiratory allergic comorbidities. Children and adults differ in triggers and clinical presentation of anaphylaxis.


Breast Cancer Screening Practices for High-Risk Women: A Cross-Sectional Survey of Primary Care Providers.
Background: Little literature exists on primary care providers' knowledge and preferences toward breast cancer screening for high-risk women. Materials and Methods: A cross-sectional web-based survey of primary care providers in Minnesota was conducted in 2016. The primary aim was to determine the breast cancer screening practices of primary care providers for women at high risk for breast cancer. A multipart questionnaire focused on breast cancer screening practices for high-risk women and perceived risks/benefits of breast cancer screening was administered. Statistical analyses, included descriptive statistics and tests of differences in screening practices and knowledge across key professional characteristics, were conducted. Results: Eight hundred five primary care providers completed the survey (7.7% response). Participants were predominantly female (72.2%); 43.9% were physicians, 11.4% physician assistants, and 44.8% advanced practice registered nurses. One-quarter of providers recommended mammography and breast magnetic resonance imaging (MRI) for high-risk women ages 40-49 years. There were no differences in breast MRI recommendations based on years of experience or practice setting. In high-risk women with prior chest radiation and an increased risk of breast cancer, for whom guidelines recommend mammography and MRI, 75.0% of providers recommended mammography, but only 44.3% recommended breast MRI. Recent continuing education on breast cancer screening was associated with providers being more comfortable giving high-risk screening recommendations (p = 0.002). Conclusions: Most primary care providers believe mammography is helpful in women at high risk for breast cancer. Less than half of practitioners, however, recommend breast MRI to screen women at high risk for breast cancer, despite guidelines promoting the use of breast MRI. Increased provider education is warranted.


Sex allocation in relation to host races in the brood-parasitic common cuckoo (Cuculus canorus).
Sex allocation theory and empirical evidence both suggest that natural selection should favour maternal control of offspring sex ratio in relation to their ability to invest in the offspring. Generalist parasites constitute a particularly interesting group to test this theory as different females commonly utilize different host species showing large variation in provisioning ability. The common cuckoo (Cuculus canorus) is a generalist brood parasite that lays its eggs in the nest of many different passerine birds, but each female tends to specialize on one particular host species giving rise to highly specialized host races. The different host species show large variation in their ability to invest in the parasitic offspring, presenting an opportunity for female cuckoos to bias offspring sex ratio in relation to host species quality. Here, we investigate host-race specific sex allocation controlling for maternal identity in the common cuckoo. We found no evidence of any significant relationship between host race and sex ratio in one sympatric population harbouring three different host races, or in a total of five geographically separated populations. There was also no significant association between host quality, as determined by species-specific female host body mass, and cuckoo sex ratio. Finally, we found no significant relationship between individual cuckoo maternal quality, as determined by her egg volume, and sex ratio within each host race. We conclude that the generalist brood-parasitic common cuckoo show no significant sex-ratio bias in relation to host race and discuss this finding in light of gene flow and host adaptations.


[Experience with conservative therapy in primary breast cancer: experiences Northern Israel Oncology Center, 1981-1990].
Between 1981 and 1990, 346 patients with primary breast cancer were treated using breast conservation. Mean age was 55 +/- 13 years and median follow-up 53 months. 36.5% were in pathological Stage I, 55% in Stage II, and 4% in Stage III, while 4.5% were in clinical Stages I-II. 60% of the lesions were excised with good margins, 12% with close margins (0.5 cm), 2.5% with macroscopic residuals, 7.5% with microscopic residuals and 18% with margins that could not be determined. Level II lymph node dissection was performed in 334 patients (97%). Adjuvant therapy (combination of chemotherapy and/ or hormones) was given to 223 (64%). Radiotherapy, usually 50-55 Gy tangential photon irradiation to the whole breast, was given to 335 (97%); electron or photon "boost" to the tumor bed was given to 234 (70%); most patients received 20 Gy. Most node-positive patients received 50 Gy to the lymphatic drainage system. A year after completion of radiotherapy cosmetic results were rated as good in 195/212 (92%), moderate in 17/212 (8%), but in none as poor. 5-year actuarial survival was 90% for Stage I and 81% for Stage II disease. 24 (7%) developed breast recurrence, 8 of whom (2%) also had distant metastases; 5 (1.5%) developed supraclavicular lymph node metastases and 59 (17%) distant metastases. Predictors of poor survival or local recurrence were: age under 40 years, premenopausal status, multifocality, and blood/lymph vessel infiltration by tumor cells. The satisfactory level of local control achieved is attributed to the high doses of radiation administered in high-risk lesions (up to 70 Gy total tumor dose).


Tempol reduces oxidative stress, improves insulin sensitivity, decreases renal dopamine D1 receptor hyperphosphorylation, and restores D1 receptor-G-protein coupling and function in obese Zucker rats.
Oxidative stress plays a pathogenic role in hypertension, particularly the one associated with diabetes and obesity. Here, we test the hypothesis that renal dopamine D1 receptor dysfunction in obese Zucker rats is caused by oxidative stress. One group each from lean and obese Zucker rats received tempol, a superoxide dismutase mimetic in drinking water for 2 weeks. Obese animals were hypertensive, hyperglycemic, and hyperinsulinemic, exhibited renal oxidative stress, and increased protein kinase C activity. Also, there was hyperphosphorylation of D1 receptor, defective receptor-G-protein coupling, blunted dopamine-induced Na+-K+-ATPase inhibition, and diminished natriuretic response to D1 receptor agonist, SKF-38393. However, obese animals had elevated levels of plasma nitric oxide and urinary cGMP. In addition, L-N-nitroarginine and sodium nitroprusside showed similar effect on blood pressure in lean and obese rats. In obese animals, tempol reduced blood pressure, blood glucose, insulin, renal oxidative stress, and protein kinase C activity. Tempol also decreased D1 receptor phosphorylation and restored receptor G-protein coupling. Dopamine inhibited Na+-K+-ATPase activity, and SKF-38393 elicited a natriuretic response in tempol-treated obese rats. Thus in obese Zucker rats, tempol ameliorates oxidative stress and improves insulin sensitivity. Consequently, hyperphosphorylation of D1 receptor is reduced, leading to restoration of receptor-G-protein coupling and the natriuretic response to SKF-38393.


Insecticide treated nets: impact on vector populations and relevance of initial intensity of transmission and pyrethroid resistance.
Insecticide treated bednets locate a deposit of a quick-acting insecticide of low human toxicity between a sleeper and host-seeking mosquitoes. Thus a chemical barrier is added to the often incomplete physical barrier provided by the net. Treated nets may be considered as mosquito traps baited by the odour of the sleeper. Trials in Assam, Tanzania and elsewhere have shown that when a whole community is provided with treated nets, so many mosquitoes of anthropophilic species are killed by contact with the nets that the density and/or sporozoite rate of the vector population is reduced. In order to gain this "mass" or community effect, in addition to widespread personal protection, and thus to achieve the full potential of the treated net method, a high per cent coverage of the community is needed. This suggests that organised free provision of treated nets, comparable to a house spraying programme, is likely to be more cost-effective than trying to market nets and insecticide to very poor rural people. In areas with high malaria transmission, where acquisition of immunity to malaria is very important, it has been argued that vector control (without vector eradication) could, in the long run, make the situation worse by preventing the normal build-up of immunity. However, our data from Tanzania do not support this idea--3-4 years after provision of nets (which are re-treated annually) young children are still showing clear health benefits; older children are not "paying" for this by showing worse impact of malaria. There is less malaria morbidity in a highland area where malaria transmission is about 15x less intense than in a nearby lowland area. The per cent impact of treated nets malaria morbidity in both area was very similar. At present only pyrethroids are used for net treatment which suggested that emergence of pyrethroid resistance would have a disastrous effect. However, in West Africa, where there is now a high frequency of the kdr resistance gene in Anopheles gambiae, it is reported that treated nets continue to have a powerful impact on vector populations. In Tanzania, pyrethroid resistance has not been detected in malaria vectors, but it has emerged in bedbugs after seven years use of treated nets.


Contraindications for external cephalic version in breech position at term: a systematic review.
External cephalic version (ECV) is a safe and effective intervention that can prevent breech delivery, thus reducing the need for cesarean delivery. It is recommended in national guidelines. These guidelines also mention contraindications for ECV, and thereby restrict the application of ECV. We assessed whether the formulation of these contraindications in guidelines are based on empiric data. Systematic review. Pregnant women with a singleton breech presentation from 34 weeks. We searched the National Guideline Clearinghouse, the Cochrane Central Register of Controlled Trials, MEDLINE (1953-2009), EMBASE (1980-2009), TRIP database (until 2011), NHS (National Health Services, until 2011), Diseases database (until 2011) and NICE guidelines (until 2011) for existing guidelines on ECV and studied the reproducibility of the contraindications stated in the guidelines. Furthermore, we systematically reviewed the literature for contraindications and evidence on these contraindications. Contraindications of ECV. We found five guidelines mentioning 18 contraindications, varying from five to 13 per guideline. The contraindications were not reproducible between the guidelines with oligohydramnios as the only contraindication mentioned in all guidelines. The literature search yielded 60 studies reporting on 39 different contraindications, of which we could only assess evidence of six of them. The present study shows that there is no general consensus on the eligibility of patients for ECV. Therefore we propose to limit contraindications for ECV to clear empirical evidence or to those with a clear pathophysiological relevance.


Use of simulated epithelial lung fluid in assessing the human health risk of Pb in urban street dust.
In many urban contexts, non-dietary Pb exposure from street dusts may add to the overall exposure burden, and the presence of high total Pb content is well documented in urban street dust from across the globe. Given the increasing recognition of the potential adverse health effects from both the quantity and the chemical and physical composition of the inhaled fraction, and the recognition that it is the soluble fraction rather than the total element content that has more direct links to health effects, attention has focused in this study on the human health risks via this exposure pathway. In order to investigate the environmental exposure to Pb from the inhalation of urban street dusts, a newly developed in vitro simulated epithelium lung fluid (SELF) has been applied to the <10μm fraction of urban street dusts. In this context, 21 urban street dust samples, across five UK cities, were selected based on their high pseudo-total Pb content. The work revealed that inhalation bioaccessibility, and hence inhalation dose, varied across the cities but was generally found to be low (<10%). Indeed, the lung bioaccessibility was far lower (% lung bioaccessibility ranged from 1.2 to 8.8) than is currently applied in two of the most commonly employed risk assessment models i.e. the Integrated Exposure Uptake Biokinetic model (IEUBK, USA) and the Contaminated Land Exposure Assessment model (CLEA, UK). The estimated inhalation dose (for adults) calculated from the PM10 bioaccessibility ranged from 7ngkg-1BWday-1 (Edinburgh) to 1.3ngkg-1BWday-1 (Liverpool). The results indicate a low potential inhalation bioaccessibility for Pb in these urban street dust samples when modelled using the neutral pH conditions of the SELF.


Species-wide whole genome sequencing reveals historical global spread and recent local persistence in Shigella flexneri.
Shigella flexneri is the most common cause of bacterial dysentery in low-income countries. Despite this, S. flexneri remains largely unexplored from a genomic standpoint and is still described using a vocabulary based on serotyping reactions developed over half-a-century ago. Here we combine whole genome sequencing with geographical and temporal data to examine the natural history of the species. Our analysis subdivides S. flexneri into seven phylogenetic groups (PGs); each containing two-or-more serotypes and characterised by distinct virulence gene complement and geographic range. Within the S. flexneri PGs we identify geographically restricted sub-lineages that appear to have persistently colonised regions for many decades to over 100 years. Although we found abundant evidence of antimicrobial resistance (AMR) determinant acquisition, our dataset shows no evidence of subsequent intercontinental spread of antimicrobial resistant strains. The pattern of colonisation and AMR gene acquisition suggest that S. flexneri has a distinct life-cycle involving local persistence.


Doping-Induced Electron Transfer at Organic/Oxide Interfaces: Direct Evidence from Infrared Spectroscopy.
Charge transfer at organic/inorganic interfaces critically influences the properties of molecular adlayers. Although for metals such charge transfers are well documented by experimental and theoretical results, in the case of semiconductors, clear and direct evidence for a transfer of electrons or holes from oxides with their typically high ionization energy is missing. Here, we present data from infrared reflection-absorption spectroscopy demonstrating that despite a high ionization energy, electrons are transferred from ZnO into a prototype strong molecular electron acceptor, hexafluoro-tetracyano-naphthoquinodimethane (F6-TCNNQ). Because there are no previous studies of this type, the interpretation of the pronounced vibrational red shifts observed in the experiment was aided by a thorough theoretical analysis using density functional theory. The calculations reveal that two mechanisms govern the pronounced vibrational band shifts of the adsorbed molecules: electron transfer into unoccupied molecular levels of the organic acceptor and also the bonding between the surface Zn atoms and the peripheral cyano groups. These combined experimental data and the theoretical analysis provide the so-far missing evidence of interfacial electron transfer from high ionization energy inorganic semiconductors to molecular acceptors and indicates that n-doping of ZnO plays a crucial role.


Lactobacillus equigenerosi strain Le1 invades equine epithelial cells.
Lactobacillus equigenerosi strain Le1, a natural inhabitant of the equine gastrointestinal tract, survived pH 3.0 and incubation in the presence of 1.5% (wt/vol) bile salts for at least 2 h. Strain Le1 showed 8% cell surface hydrophobicity, 60% auto-aggregation, and 47% coaggregation with Clostridium difficile C6. Only 1% of the cells adhered to viable buccal epithelial cells and invaded the cells within 20 min after contact. Preincubation of strain Le1 in a buffer containing pronase prevented adhesion to viable epithelial cells. Preincubation in a pepsin buffer delayed invasion from 20 min to 1 h. Strain Le1 did not adhere to nonviable epithelial cells. Administration of L. equigenerosi Le1 (1 × 10(9) CFU per 50 kg body weight) to healthy horses did not increase white blood cell numbers. Differential white blood cell counts and aspartate aminotransferase levels remained constant. Glucose, lactate, cholesterol, and urea levels remained constant during administration with L. equigenerosi Le1 but decreased during the week after administration.


Cloning of a novel receptor expressed in rat prostate and ovary.
We have cloned a novel member of the nuclear receptor superfamily. The cDNA of clone 29 was isolated from a rat prostate cDNA library and it encodes a protein of 485 amino acid residues with a calculated molecular weight of 54.2 kDa. Clone 29 protein is unique in that it is highly homologous to the rat estrogen receptor (ER) protein, particularly in the DNA-binding domain (95%) and in the C-terminal ligand-binding domain (55%). Expression of clone 29 in rat tissues was investigated by in situ hybridization and prominent expression was found in prostate and ovary. In the prostate clone 29 is expressed in the epithelial cells of the secretory alveoli, whereas in the ovary the granuloma cells in primary, secondary, and mature follicles showed expression of clone 29. Saturation ligand-binding analysis of in vitro synthesized clone 29 protein revealed a single binding component for 17beta-estradiol (E2) with high affinity (Kd= 0.6 nM). In ligand-competition experiments the binding affinity decreased in the order E2 > diethylstilbestrol > estriol > estrone > 5alpha-androstane-3beta,17beta-diol >> testosterone = progesterone = corticosterone = 5alpha-androstane-3alpha,17beta-diol. In cotransfection experiments of Chinese hamster ovary cells with a clone 29 expression vector and an estrogen-regulated reporter gene, maximal stimulation (about 3-fold) of reporter gene activity was found during incubation with 10 nM of E2. Neither progesterone, testosterone, dexamethasone, thyroid hormone, all-trans-retinoic acid, nor 5alpha-androstane-3alpha,I7beta-diol could stimulate reporter gene activity, whereas estrone and 5alpha-androstane-3beta,17beta-diol did. We conclude that clone 29 cDNA encodes a novel rat ER, which we suggest be named rat ERbeta to distinguish it from the previously cloned ER (ERalpha) from rat uterus.


Non-Hodgkin's lymphoma: is India ready to incorporate recent advances in day to day practice?
Non Hodgkin's Lymphoma (NHL) cure rates are increasing and morbidities are decreasing, with more active pharmacological agents and technological advancements. In spite of this, India is still battling with the prejudices of an economically and educationally impoverished patient base. We analyzed NHL cases from 2000 to 2006 using data from case sheets. Of 303 cases, only 100 patients had complete workup and received some form of treatment. For 203 patients, reasons for non-compliance were: financial constraint (119), distance from center (38), inability of physician to provide guarantees of cure (13), poor prognosis/fear of recurrence (28)), preferences for alternate medicine (5). Most common investigations that could not be afforded for staging were whole body CT scans and bone marrow aspiration and biopsy. Thirteen patients were in stage III and 53 in Stage IV. The most common regimen was CHOP (Cyclophosphamide, Adriamycin, Vincristine, Prednisolone). Forty-five patients did not complete six courses of CHOP and 35 patients had significant delay. Reasons for delay were intermittent availability of cash (35), intolerable toxicities (30), absence of supportive care (21), given-up attitudes (17). Eighty-three patients suffered Grade III/IV debilitating toxicities. Overall survival at five years was 50%. NHL in India is no different from the developed world. However, there are disparities in survivorship and outcomes, due to un-affordability and attitudes of the patients. Therefore, we suggest the development of Community Health Insurance Schemes (CHIs), with the hospital as the nodal center to address the above mentioned issues.


Splenic peliosis with spontaneous splenic rupture: report of two cases.
Peliosis is a rare condition characterised by multiple cyst-like, blood-filled cavities within the parenchyma of solid organs. Most commonly affecting the liver, isolated splenic peliosis is an even more unique phenomenon. Patients with the condition are often asymptomatic. However, this potentially lethal condition can present with spontaneous organ rupture. We present two such cases, discuss their management and review what is currently known in the existing literature. A previously well twenty-six year old woman presented with abdominal pain following a trivial episode of coughing. A diagnosis of spontaneous splenic rupture was made following clinical and radiological examination. She underwent emergency splenectomy and made a full, uneventful recovery. Histopathological examination confirmed splenic peliosis. The second case describes an eighty six year old lady who sustained a trivial fall and developed pain in her left side. A CT confirmed splenic rupture. She became haemodynamically unstable during her admission and underwent emergency splenectomy. Histopathological examination revealed splenic peliosis. She went on to make an uneventful recovery. Splenic peliosis is very rare. It has a number of associations including immunosuppression, drug therapy and infection. Although patients are often asymptomatic, life-threatening spontaneous organ rupture may occur. If the diagnosis of peliosis is confirmed, additional investigations should be considered to detect its presence in other organs. Furthermore, the presence of the condition may be relevant if further medical or surgical intervention is planned.


Probing the proteasome cavity in three steps: bio-orthogonal photo-reactive suicide substrates.
Tri-functional activity-based protein probes that encompass an electrophilic trap, a photo-reactive group and a bio-orthogonal ligation handle are described. With these, and in a three-step chemical proteomics approach, proteasomal catalytic sites are covalently and irreversibly modified, followed by photocrosslinking of these to flanking subunits and Staudinger-Bertozzi ligation for visualization and identification of the resulting conjugates.


DISTq: An Iterative Analysis of Glucose Data for Low-Cost, Real-Time and Accurate Estimation of Insulin Sensitivity.
Insulin sensitivity (SI) estimation has numerous uses in medical and clinical situations. However, highresolution tests that are useful for clinical diagnosis and monitoring are often too intensive, long and costly for regular use. Simpler tests that mitigate these issues are not accurate enough for many clinical diagnostic or monitoring scenarios. The gap between these tests presents an opportunity for new approaches. The quick dynamic insulin sensitivity test (DISTq) utilises the model-based DIST test protocol and a series of population estimates to eliminate the need for insulin or C-peptide assays to enable a high resolution, low-intensity, real-time evaluation of SI. The method predicts patient specific insulin responses to the DIST test protocol with enough accuracy to yield a useful clinical insulin sensitivity metric for monitoring of diabetes therapy. The DISTq method replicated the findings of the fully sampled DIST test without the use of insulin or C-peptide assays. Correlations of the resulting SI values was R=0.91. The method was also compared to the euglycaemic hyperinsulinaemic clamp (EIC) in an in-silico Monte-Carlo analysis and showed a good ability to re-evaluate SI(EIC) (R=0.89), compared to the fully sampled DIST (R=0.98) Population-derived parameter estimates using a-posteriori population-based functions derived from DIST test data enables the simulation of insulin profiles that are sufficiently accurate to estimate SI to a relatively high precision. Thus, costly insulin and C-peptide assays are not necessary to obtain an accurate, but inexpensive, real-time estimate of insulin sensitivity. This estimate has enough resolution for SI prediction and monitoring of response to therapy. In borderline cases, re-evaluation of stored (frozen) blood samples for insulin and C-peptide would enable greater accuracy where necessary, enabling a hierarchy of tests in an economical fashion.


Fusarium graminearum Species Complex Associated with Maize Crowns and Roots in the KwaZulu-Natal Province of South Africa.
Thirty-three isolates of the Fusarium graminearum species complex obtained from diseased maize (Zea mays) crowns and roots in the Winterton district, KwaZulu-Natal province of South Africa were identified to species level. Their pathogenicity and virulence to maize 'PHI 32D96B' seedlings were determined under glasshouse conditions, with seedling survival and growth and crown and root rot as criteria. Phylogenetic analyses using the 3-O-acetyltransferase (Tri101) gene region sequences revealed the presence of F. boothii (2 isolates), F. graminearum sensu stricto (26 isolates), and F. meridionale (5 isolates) in the F. graminearum species complex associated with diseased maize crowns and roots. Pathogenicity results showed that F. boothii was the most and F. meridionale the least virulent of the three species. F. boothii and F. graminearum sensu stricto significantly reduced survival of seedlings and all three species caused significant reduction in growth and significantly more crown and root rot than the control (uninoculated). This is the first report of F. boothii, F. graminearum sensu stricto, and F. meridionale associated with diseased maize crowns and roots and their pathogenicity and virulence as soilborne pathogens on maize seedlings in South Africa.


Back-to-Germline (B2G) Procedure for Antibody Devolution.
Bispecific antibodies (bsAbs) with avidity-enhanced specificity can be used to address target cells with increased specificity, ideally binding efficiently to cells that express two cognate antigens, yet not to cells that express only one of those. Building blocks required to generate such bsAbs are binders that recognize the two antigens with high specificity yet with various (including very low monovalent) affinities. The herein described 'back-to-germline' (B2G) procedure defines such derivatives. It converts parent antibodies with high specificity to derivatives that retain specificity but modulate affinity. The approach defines mutations to be introduced into antibody complementarity-determining regions (CDRs) regions without requiring structures of antibody-antigen complexes. Instead, it reverses the B-cell maturation process that increases affinities, with preference on CDR residues with high antigen contact probability. Placing germline residues at those positions generates VH and VL domains and Fv-combinations thereof that retain specificities but are 'de-matured' to different degrees. De-maturation influences on-rates and off-rates, and can produce entities with extremely low affinity for which binding can only be detected in bivalent formats. A comparison with alanine replacement in CDRs (so far, the most frequently applied technology) indicates that B2G may be more reliable/predictable without introduction of stickiness or poly-reactivity. The applicability for generating sets of affinity-modulated monospecific variants is exemplarily shown for antibodies that bind CD138, Her2/neu, and EGFR.


Adaptive control of saccades via internal feedback.
Ballistic movements like saccades require the brain to generate motor commands without the benefit of sensory feedback. Despite this, saccades are remarkably accurate. Theory suggests that this accuracy arises because the brain relies on an internal forward model that monitors the motor commands, predicts their sensory consequences, and corrects eye trajectory midflight. If control of saccades relies on a forward model, then the forward model should adapt whenever its predictions fail to match sensory feedback at the end of the movement. Using optimal feedback control theory, we predicted how this adaptation should alter saccade trajectories. We trained subjects on a paradigm in which the horizontal target jumped vertically during the saccade. With training, the final position of the saccade moved toward the second target. However, saccades became increasingly curved, i.e., suboptimal, as oculomotor commands were corrected on-line to steer the eye toward the second target. The adaptive response had two components: (1) the motor commands that initiated the saccades changed slowly, aiming the saccade closer to the jumped target. The adaptation of these earliest motor commands displayed little forgetting during the rest periods. (2) Late in saccade trajectory, another adaptive response steered it still closer to the jumped target, producing curvature. Adaptation of these late motor commands showed near-complete forgetting during the rest periods. The two components adapted at different timescales, with the late-acting component displaying much faster rates. It appears that in controlling saccades, the brain relies on an internal feedback that has the characteristics of a fast-adapting forward model.


Neuroeconomic approaches to mental disorders.
The pervasiveness of decision-making in every area of human endeavor highlights the importance of understanding choice mechanisms and their detailed relationship to underlying neurobiological function. This review surveys the recent and productive application of game-theoretic probes (economic games) to mental disorders. Such games typically possess concrete concepts of optimal play, thus providing quantitative ways to track when subjects' choices match or deviate from optimal. This feature equips economic games with natural classes of control signals that should guide learning and choice in the agents that play them. These signals and their underlying physical correlates in the brain are now being used to generate objective biomarkers that may prove useful for exposing and understanding the neurogenetic basis of normal and pathological human cognition. Thus, game-theoretic probes represent some of the first steps toward producing computationally principled, objective measures of cognitive function and dysfunction useful for the diagnosis, treatment, and understanding of mental disorders.


Surgical management of giant posterior communicating artery aneurysms.
Giant posterior communicating artery (PCoA) aneurysms (> 25 mm) are rare lesions associated with a poor prognosis and high rates of morbidity and mortality. To review the clinical results of giant PCoA aneurysms surgically treated at our institution, focusing on operative nuances. All cases of giant PCoA aneurysms treated surgically at our institution were identified from a prospectively maintained patient database. Patient demographic factors, medical comorbidities, rupture status, neurological presentation, clinical outcomes, and surgical records were critically reviewed. From 1989 to 2010, 11 patients (10 women) underwent surgical clipping of giant PCoA aneurysms. Presenting signs and symptoms included cranial nerve palsies, diminished mental status, headache, visual changes, and seizures. Five aneurysms were ruptured on admission. All aneurysms were clipped primarily except 1, which was treated by parent artery sacrifice and extracranial-to-intracranial bypass after intraoperative aneurysm rupture. Perioperative morbidity and mortality rates were 36% (4 of 11) and 18.3% (2 of 11), respectively. Excellent or good clinical outcomes, defined as modified Rankin Scale scores ≤ 2, were achieved in 86% (5 of 6) of patients available for long-term clinical follow-up (mean, 12.5 ± 13.6 months). Giant PCoA aneurysms are rare vascular lesions that may present with a variety of neurological signs and symptoms. These lesions can be successfully managed surgically with satisfactory morbidity and mortality rates. To the best of our knowledge, this is the largest surgical series of giant PCoA aneurysms published to date.


Biomechanical Analysis of the Cross, Hook, and Uppercut in Junior vs. Elite Boxers: Implications for Training and Talent Identification.
Punching in boxing requires a combination of force and velocity of the acting arm, originating from an optimal synchronization of the different body segments. However, it is not well-understood what kinematic parameters of the punching execution influence boxing performance the most. This study aimed to investigate the differences in punching execution between 15 potential Olympic medalist boxers (Elite group) and 8 younger well trained boxers (Junior group). Each athlete was equipped with an instrumented suit composed of 17 inertial measurement units (IMU) and were asked to perform several series of 3 standardized punch types (cross, hook, and uppercut) with maximal force. Linear velocity, stability, and punch forces were computed from the different sensors. Our findings show that Elite boxers systematically produced more force and at a higher velocity for the three punch types compared to Juniors. Further analysis revealed differences in joint contributions between Elite and Juniors, Juniors presenting a higher contribution of the shoulder for the three punch types. Finally ground reaction force imbalance between the front and rear foot was revealed in the cross only, in all boxers (60.6 ± 24.9 vs. 39.4 ± 24.9% and 54.1 ± 7.1 vs. 45.9 ± 7.1%, p ≤ 0.05, for the front vs. rear foot in Elite and Juniors, respectively) but not different between groups. These results have important implications for practitioners involved in the talent identification process, longitudinal follow-up, and training of boxers.


The regulation of anion loading to the maize root xylem.
The regulation of anion loading to the shoot in maize (Zea mays) was investigated via an electrophysiological characterization of ion conductances in protoplasts isolated from the root stele. Two distinct anion conductances were identified. In protoplasts from well-watered plants, Z. mays xylem-parenchyma quickly-activating anion conductance (Zm-X-QUAC) was the most prevalent conductance and is likely to load the majority of NO(3)(-) and Cl(-) ions to the xylem in nonstressed conditions. Z. mays xylem-parenchyma inwardly-rectifying anion conductance was found at a lower frequency in protoplasts from well-watered plants than Zm-X-QUAC, was much smaller in magnitude in all observed conditions, and is unlikely to be such a major pathway for anion loading into the xylem. Activity of Z. mays xylem-parenchyma inwardly-rectifying anion conductance increased following a water stress prior to protoplast isolation, but the activity of the putative major anion-loading pathway, Zm-X-QUAC, decreased. Addition of abscisic acid (ABA) to protoplasts from well-watered plants also inhibited Zm-X-QUAC activity within minutes, as did a high free Ca(2+)concentration in the pipette. ABA was also seen to activate a Ca(2+)-permeable conductance (Z. mays xylem-parenchyma hyperpolarization activated cation conductance) in protoplasts from well-watered plants. It is postulated that the inhibition of anion loading into the xylem (an important response to a water stress) due to down-regulation of Zm-X-QUAC activity is mediated by an ABA-mediated rise in free cytosolic Ca(2+).


Parthenogenetic activation and somatic cell nuclear transfer of porcine oocytes activated by an electric pulse and AZD5438 treatment.
We examined the in vitro developmental competence of parthenogenetic activation (PA) oocytes activated by an electric pulse (EP) and treated with various concentrations of AZD5438 for 4 h. Treatment with 10 µM AZD5438 for 4 h significantly improved the blastocyst formation rate of PA oocytes in comparison with 0, 20, or 50 µM AZD5438 treatment (46.4% vs. 34.5%, 32.3%, and 24.0%, respectively; P 0.05). Furthermore, 66.67% of blastocysts derived from these AZD5438-treated PA oocytes had a diploid karyotype. The blastocyst formation rate of PA and somatic cell nuclear transfer (SCNT) embryos was similar between oocytes activated by an EP and treated with 2 mM 6-dimethylaminopurine for 4 h and those activated by an EP and treated with 10 µM AZD5438 for 4 h (11.11% vs. 13.40%, P > 0.05). In addition, the level of maturation-promoting factor (MPF) was significantly decreased in oocytes activated by an EP and treated with 10 µM AZD5438 for 4 h. Finally, the mRNA expression levels of apoptosis-related genes (Bax and Bcl-2) and pluripotency-related genes (Oct4, Nanog, and Sox2) were checked by RT-PCR; however, there were no differences between the AZD5438-treated and non-treated control groups. Our results demonstrate that porcine oocyte activation via an EP in combination with AZD5438 treatment can lead to a high blastocyst formation rate in PA and SCNT experiments.


Impulsive personality predicts dopamine-dependent changes in frontostriatal activity during component processes of working memory.
Dopaminergic drugs affect a variety of cognitive processes, but the direction and extent of effects vary across individuals and tasks. Paradoxical effects are observed, by which the same drug causes cognitive enhancing as well as adverse effects. Here, we demonstrate that individual differences in impulsive personality account for the contrasting effects of dopaminergic drugs on working memory and associated frontostriatal activity. We observed that the dopamine D2 receptor agonist bromocriptine improved the flexible updating (switching) of relevant information in working memory in high-impulsive subjects, but not in low-impulsive subjects. These behavioral effects in high-impulsive subjects accompanied dissociable effects on frontostriatal activity. Bromocriptine modulated the striatum during switching but not during distraction from relevant information in working memory. Conversely, the lateral frontal cortex was modulated by bromocriptine during distraction but not during switching. The present results provide a key link between dopamine D2 receptor function, impulsivity, and frontostriatal activity during component processes of working memory.


A break from pain! Interruption management in the context of pain.
Activity interruptions, namely temporary suspensions of an ongoing task with the intention to resume it later, are common in pain. First, pain is a threat signal that urges us to interrupt ongoing activities in order to manage the pain and its cause. Second, activity interruptions are used in chronic pain management. However, activity interruptions by pain may carry costs for activity performance. These costs have recently started to be systematically investigated. We review the evidence on the consequences of activity interruptions by pain for the performance of the interrupted activity. Further, inspired by literature on interruptions from other research fields, we suggest ways to improve interruption management in the field of pain, and provide a future research agenda.


Differential optical absorption spectroscopy (DOAS) system for urban atmospheric pollution monitoring.
We describe a fully computer-controlled differential optical absorption spectroscopy system for atmospheric air pollution monitoring. A receiving optical telescope can sequentially tune in to light beams from a number of distant high-pressure Xe lamp light sources to cover the area of a medium-sized city. A beam-finding servosystem and automatic gain control permit unattended long-time monitoring. Using an astronomical code, we can also search and track celestial sources. Selected wavelength regions are rapidly and repetitively swept by a monochromator to sensitively record the atmospheric absorption spectrum while avoiding the detrimental effects of atmospheric turbulence. By computer fitting to stored laboratory spectra, we can evaluate the path-averaged concentration of a number of important pollutants such as NO(2), SO(2), and O(3). A measurement of NH(3) and NO close to the UV limit is also demonstrated.


A dosage-dependent requirement for Sox9 in pancreatic endocrine cell formation.
We have previously shown the transcription factor SOX9 to be required for the maintenance of multipotential pancreatic progenitor cells in the early embryonic pancreas. However, the association of pancreatic endocrine defects with the Sox9-haploinsufficiency syndrome campomelic dysplasia (CD) implies additional later roles for Sox9 in endocrine development. Using short-term lineage tracing in mice, we demonstrate here that SOX9 marks a pool of multipotential pancreatic progenitors throughout the window of major cell differentiation. During mid-pancreogenesis, both endocrine and exocrine cells simultaneously arise from the SOX9(+) epithelial cords. Our analysis of mice with 50%-reduced Sox9 gene dosage in pancreatic progenitors reveals endocrine-specific defects phenocopying CD. By birth, these mice display a specific reduction in endocrine cell mass, while their exocrine compartment and total organ size is normal. The decrease in endocrine cells is caused by reduced generation of endocrine progenitors from the SOX9(+) epithelium. Conversely, formation of exocrine progenitors is insensitive to reduced Sox9 gene dosage, thus explaining the normal organ size at birth. Our results show that not only is SOX9 required for the maintenance of early pancreatic progenitors, but also governs their adoption of an endocrine fate. Our findings therefore suggest that defective endocrine specification might underlie the pancreatic phenotype of individuals with CD.


Cardiac Effects of Antiretroviral-Naïve versus Antiretroviral-Exposed HIV Infection in Children.
Cardiac involvement in HIV infected children has been frequently reported, but whether this is due to HIV infection itself or to antiretroviral treatment (ART) is unknown. This cross sectional study involved 114 vertically-acquired HIV-infected (56 ART-naive, 58 ART-exposed) and 51 healthy children in Jakarta, Indonesia. Echocardiography was performed to measure dimensions of the left ventricle (LV) and systolic functions. We applied general linear modeling to evaluate the associations between HIV infection/treatment status and cardiac parameters with further adjustment for potential confounders or explanatory variables. Findings are presented as (adjusted) mean differences between each of the two HIV groups and healthy children, with 95% confidence intervals and p values. Compared to healthy children, ART-naïve HIV-infected children did not show significant differences in age-and-height adjusted cardiac dimensions apart from larger LV internal diameter (difference 2.0 mm, 95%CI 0.2 to 3.7), whereas ART exposed HIV infection showed thicker LV posterior walls (difference = 1.1 mm, 95%CI 0.5 to 1.6), larger LV internal diameter (difference = 1.7 mm, 95%CI 0.2 to 3.2) and higher LV mass (difference = 14.0 g, 7.4 to 20.5). With respect to systolic function, reduced LV ejection fraction was seen in both ART-naïve HIV infected (adjusted difference = -6.7%, -11.4 to -2.0) and, to a lesser extent, in ART-exposed HIV infected children (difference = -4.5%, -8.5 to -0.4). Inflammation level seemed to be involved in most associations in ART-exposed HIV-infected, but few, if any, for decreased function in the ART-naive ones, whereas lower hemoglobin appeared to partially mediate chamber dilation in both groups and reduced function, mainly in ART-exposed children. ART-naive HIV infected children have a substantial decrease in cardiac systolic function, whereas the ART-exposed have thicker ventricular walls with larger internal diameter and higher mass, but less functional impairment.


Are Serum Mac 2-Binding Protein Levels Elevated in Esophageal Cancer? A Control Study of Esophageal Squamous Cell Carcinoma Patients.
Elevated serum Mac 2-binding protein (M2BP) levels have been observed in some cancers. As far as we know, its importance has not been investigated in esophageal squamous cell carcinoma (ESCC). The investigated problem of this study was to evaluate whether there was a difference between ESCC patients and the control group in terms of M2BP. Also, we evaluated the diagnostic performance of serum M2BP alone or in combination with the CEA for patients with ESCC. Blood serum samples were collected from 50 healthy donors and 150 patients with ESCC. M2BP levels of all 200 samples were quantified by ELISA (enzyme-linked immunosorbent assay). Patients who had been diagnosed with ESCC and did not have any other malignancies were enrolled to study. The two groups did not significantly differ in terms of age (p > 0.05). In the control group, the mean serum M2BP level was 14.97 ± 3.46 ng/mL. The mean serum M2BP level of the ESCC patients was 176.65 ± 22.14 ng/mL. The serum M2BP level was significantly higher in patients with ESCC than in the control group (p < 0.001). Gender was also comparable in both groups (p = 0.695). Our analysis demonstrated that this marker may be associated with the mechanism of the disease. Despite that serum M2BP is not a specific marker for ESCC, it can be used as an adjuvant biomarker for the diagnosis of ESCC.


Wnt/β-catenin Signaling Contributes to Tumor Malignancy and Is Targetable in Gastrointestinal Stromal Tumor.
Gastrointestinal stromal tumor (GIST) is the most common type of sarcoma and usually harbors either a KIT or PDGFRA mutation. However, the molecular basis for tumor malignancy is not well defined. Although the Wnt/β-catenin signaling pathway is important in a variety of cancers, its role in GIST is uncertain. Through analysis of nearly 150 human GIST specimens, we found that some human GISTs expressed β-catenin and contained active, dephosphorylated nuclear β-catenin. Furthermore, advanced human GISTs expressed reduced levels of the Wnt antagonist DKK4. Accordingly, in human GIST T1 cells, Wnt stimulation increased β-catenin-mediated transcriptional activity in a reporter assay as well as transcription of the downstream target genes Axin2 and CCND1 In contrast, DKK4 overexpression in GIST T1 cells reduced Wnt/β-catenin signaling. In addition, we showed that nuclear β-catenin stability was partially regulated by the E3 ligase COP1, as demonstrated with coimmunoprecipitation and COP1 knockdown. Three molecular inhibitors of the Wnt/β-catenin pathway demonstrated antitumor efficacy in various GIST models, both in vitro and in vivo Notably, the tankyrase inhibitor G007-LK alone had substantial activity against tumors of genetically engineered KitV558Δ/+ mice, and the effect was increased by the addition of the Kit inhibitor imatinib mesylate. Collectively, our findings demonstrate that Wnt/β-catenin signaling is a novel therapeutic target for selected untreated or imatinib-resistant GISTs. Mol Cancer Ther; 16(9); 1954-66. ©2017 AACR.


An improved selective culture medium enhances the isolation of Burkholderia pseudomallei from contaminated specimens.
Burkholderia pseudomallei is a Gram-negative environmental bacterium found in tropical climates that causes melioidosis. Culture remains the diagnostic gold standard, but isolation of B. pseudomallei from heavily contaminated sites, such as fecal specimens, can be difficult. We recently reported that B. pseudomallei is capable of infecting the gastrointestinal tract of mice and suggested that the same may be true in humans. Thus, there is a strong need for new culture techniques to allow for efficient detection of B. pseudomallei in fecal and other specimens. We found that the addition of norfloxacin, ampicillin, and polymyxin B to Ashdown's medium (NAP-A) resulted in increased specificity without affecting the growth of 25 B. pseudomallei strains. Furthermore, recovery of B. pseudomallei from human clinical specimens was not affected by the three additional antibiotics. Therefore, we conclude that NAP-A medium provides a new tool for more sensitive isolation of B. pseudomallei from heavily contaminated sites.


Universality in network dynamics.
Despite significant advances in characterizing the structural properties of complex networks, a mathematical framework that uncovers the universal properties of the interplay between the topology and the dynamics of complex systems continues to elude us. Here we develop a self-consistent theory of dynamical perturbations in complex systems, allowing us to systematically separate the contribution of the network topology and dynamics. The formalism covers a broad range of steady-state dynamical processes and offers testable predictions regarding the system's response to perturbations and the development of correlations. It predicts several distinct universality classes whose characteristics can be derived directly from the continuum equation governing the system's dynamics and which are validated on several canonical network-based dynamical systems, from biochemical dynamics to epidemic spreading. Finally, we collect experimental data pertaining to social and biological systems, demonstrating that we can accurately uncover their universality class even in the absence of an appropriate continuum theory that governs the system's dynamics.


[Coverage of the Emergency Health Care Law and the Compulsory Insurance against Road Traffic Crashes (SOAT)].
The aim of this study was to ascertain, from patients' perspective, the degree of knowledge and the actual coverage of the Emergency Health Care Law and the Compulsory Insurance against Road Traffic Crashes (SOAT). A cross-sectional, active surveillance of emergency wards of selected health facilities in three Peruvian cities (Lima, Pucallpa y Ayacucho) was conducted. Out of 644 surveyed victims, 77% did not know about the law about provision of emergency health care (81% in Lima, 64% in Pucallpa y 93% in Ayacucho; p<0.001). Following the explanation of what this law entails, 46% reported to have received care according to the law specifications. As for SOAT, the health care related costs of 237 persons (37.2%) were not covered by any insurance scheme (74% in Pucallpa, 34% in Ayacucho and 26% in Lima: p<0.001). In this study, the lack of knowledge about the provision of emergency health care law was important, and the coverage of care was deficient as nearly half of participants reported not to be treated by one or more of the entitlements stated in such law. Road traffic injuriesrelated health care costs were not covered by any insurance scheme in one of three victims. Improvements on citizens' information about their rights and of effective law enforcement are badly needed to reach a universal and more equitable coverage in the health care of road traffic-related victims.


Sublingual endothelial glycocalyx and atherosclerosis. A cross-sectional study.
Damage to endothelial glycocalyx is thought to be an early marker of atherosclerosis and measuring reduced glycocalyx size clinically via the Perfused Boundary Region (PBR) may allow early detection of cardiovascular disease. However, the true value of the glycocalyx in estimating cardiovascular risk or detecting cardiovascular disease is uncertain. We therefore investigated whether small glycocalyx size is associated with cardiovascular risk or disease in a large multi-ethnic cohort. In a multi-ethnic community-based sample (N = 6169, 42.4% male, mean age 43.6 ±13) we applied multiple imputation for missing data and used logistic regression and odds ratios to cross-sectionally investigate the relationship of small glycocalyx size as estimated by highest quartile of PBR with, on the one hand, classical risk factors for atherosclerosis including age, sex, diastolic and systolic blood pressure, LDL, HDL, triglycerides, BMI, diabetes, smoking status, and antihypertensive and lipid-lowering medication; on the other hand, prevalent cardiovascular disease. Analyses were additionally adjusted for ethnicity. With PBR divided in quartiles, the highest PBR quartile (smallest glycocalyx size) as dependent variable was independently associated with female sex (OR for male versus female: 0.61, 95% CI: 0.53, 0.70) and diabetes (OR: 1.28, 95% CI: 1.03-1.59) in a model adjusted for all classical risk factors of atherosclerosis and for ethnicity. With regard to cardiovascular disease, no association was found between the smallest glycocalyx size as independent variable and overall cardiovascular disease, coronary heart disease and revascularization procedures, or stroke. Small glycocalyx size as estimated by highest PBR is associated with female sex and diabetes, which do not completely reflect a high cardiovascular risk profile. At the same time, glycocalyx size is not associated with prevalent cardiovascular disease.


WO3-x sensitized TiO2 spheres with full-spectrum-driven photocatalytic activities from UV to near infrared.
To make full use of solar energy for photocatalytic reactions, in this work, we developed full-spectrum-responsive photocatalysts with noteworthy photocatalytic activities under either UV, visible or even near infrared irradiation for the photodegradation of methylene blue. The core-shell structure of TiO2@WO3-x is designed from the consideration of combining the full-spectrum photo-absorption properties of WO3-x with the excellent semiconductor properties of TiO2. As expected, the WO3-x sensitized TiO2 sphere gives rise to a prominently strong optical absorption in the whole region of 300-2500 nm and thus displays desired photocatalytic properties for the full utilization of all solar energy, especially in the unexploited NIR part, which accounts for most of the sunlight. Encouraged by the above exciting photocatalytic outcome, we then go further to propose a plausible mechanism for interpreting the NIR-driven photocatalytic properties, which is based on the hypothesis of low-valent W5+ site induced free electrons and evidence-based ESR results.


Usability Testing of an Electronic Patient-Reported Outcome System for Survivors of Critical Illness.
Web-based electronic patient-reported outcomes (ePRO) measures are increasingly used to facilitate patient-centered health assessments. However, it is unknown if ePRO completion is feasible for recently ill intensive care unit (ICU) survivors and their families. To develop and evaluate the usability of a novel ePRO system (ePRO to Support People and Enhance Recovery [ePROSPER]) among ICU survivors and their families within an ongoing clinical trial. Paper-based PROs were iteratively adapted to electronic forms (ePROs). Then, the usability of ePROSPER was assessed among 60 patients, their family members, and PRO and programming experts via questionnaires (eg, Systems Usability Scale), "think aloud" open-ended feedback, task completion times, and error rates. Input from patients and their families was used to incorporate user-experience modifications into ePROSPER. This feedback also led to inclusion of automated reminders for questionnaire completion and real-time alerts for staff triggered by high symptom levels. Median usability scores increased over testing cycles from 40 to 73 to 95, nearing the maximum score and showing excellent usability. All users completed ePROSPER within 20 minutes; 87% preferred it to a written version. ePROSPER was then implemented in a clinical trial without data errors. Automated ePRO systems can be successfully integrated in a post-ICU clinical trial setting. The value of integrating such systems in direct clinical care should be assessed in future studies.


Developing health information literacy: a needs analysis from the perspective of preprofessional health students.
The research identified the skills, if any, that health preprofessional students wished to develop after receiving feedback on skill gaps as well as any strategies they intended to use to address these gaps. A qualitative approach was used to elicit students' reflections on building health information literacy skills. First, the students took the Research Readiness Self-Assessment instrument, which measured their health information literacy, and then they received individually tailored feedback about their scores and skill gaps. Second, students completed a post-assessment survey asking how they intended to close identified gaps in their skills on these. Three trained coders analyzed qualitative comments by 181 students and grouped them into themes relating to "what skills to improve" and "how to improve them." Students intended to develop library skills (64% of respondents), Internet skills (63%), and information evaluation skills (63%). Most students reported that they would use library staff members' assistance (55%), but even more respondents (82%) planned to learn the skills by practicing on their own. Getting help from librarians was a much more popular learning strategy than getting assistance from peers (20%) or professors (17%). The study highlighted the importance of providing health preprofessional students with resources to improve skills on their own, remote access to library staff members, and instruction on the complexity of building health literacy skills, while also building relationships among students, librarians, and faculty.