Anterior Tibial Artery Danger Zone During Anterolateral Plate Fixation of the Distal Tibia: A 3D Computed Tomography Angiogram Modeling Study.
The objective of this study was to define the danger zone at which the anterior tibial artery (ATA) is at risk during anterolateral plating of the distal tibia using a novel 3D computed tomography angiography (CTA) modeling technique. 116 patients (232 lower extremities) who underwent lower extremity CTAs between April 2020 and April 2022 were identified. Those with lower extremity trauma, evidence of a previously healed tibial fracture, or poor visualization of the ATA were excluded. The remaining 150 lower extremities (92 patients) were modeled with an anterolateral distal tibia plate using Sectra IDS7 software. The distance of the ATA from bony landmarks was measured perpendicular to the level at which the vessel intersected the plate. The ATA intersected the plate proximally at a mean distance of 10.5 cm (95% confidence intervals, 10.2-10.9) and at a mean distance of 4.6 cm (95% confidence intervals, 4.4-4.9) distally from the central tibial plafond. The ATA intersected with the plate as far distal as hole number 1 and as proximal as hole 14 of the plate. The greatest injury risk was associated with plate holes 3-8. In this region, the artery was at risk in 46-99 percent of specimens. The ATA is at risk when screws are placed percutaneously in an anterolateral distal tibia plate. The artery can be as close as 4.4 cm and as far as 10.9 cm proximal to the tibial plafond when crossing the plate, correlating to a risk of injury to the ATA at plate holes 1 through 14.


Effect of stimulated neutrophils on cyclic nucleotide content in isolated rat glomeruli.
In this study we examined the effect of cell-free supernatants from stimulated neutrophils on the adenosine 3',5'-cyclic monophosphate (cAMP) and guanosine 3',5'-cyclic monophosphate (cGMP) content in isolated rat glomeruli. Cell-free supernatants obtained from unstimulated and stimulated (with opsonized zymosan for 30 min at 37 degrees C) cells were incubated for 5 min with glomeruli and tubules. Cell-free supernatants from stimulated neutrophils significantly increased the cAMP content in the glomeruli from 34.7 +/- 2.3 to 99.7 +/- 7.0 pmol/mg protein (n = 23; P less than 0.001). The cAMP content in the tubules and the cGMP content in the glomeruli or tubules was not altered by the cell-free supernatants from stimulated neutrophils. The cAMP response of the glomeruli was not modified when supernatants were obtained from neutrophils stimulated in the presence of superoxide dismutase, a scavenger of superoxide anion. In contrast, the glomerular response to supernatants obtained from neutrophils stimulated in the presence of catalase, a scavenger of hydrogen peroxide, or in the presence of methionine or taurine, scavengers of hypochlorous acid, was significantly reduced (P less than 0.001). Additional experiments that used prostaglandin synthesis inhibitors (meclofenamate and ibuprofen) and phospholipase inhibitor (quinacrine) suggested that the reactive oxygen metabolites increase the cAMP content in glomeruli by stimulating phospholipase activity and thus enhancing prostaglandin synthesis. These data show that reactive oxygen metabolites generated by stimulated neutrophils increase cAMP content in glomeruli and suggest that neutrophils may modulate the glomerular function and the inflammatory response in glomerular disease by altering the cAMP content.


Application of a computable model of human spatial vision to phase discrimination.
We have used a computable model of human spatial vision to make predictions for phase-discrimination experiments. This model is being developed to deal with a broad range of problems in vision and was not specifically formulated to deal with phase discrimination. In the model, cross correlation of the stimuli with an array of sensors produces feature vectors that are operated on by a position-uncertain ideal observer to simulate detection and discrimination experiments. In this report the stimuli are compound sinusoidal gratings composed of a fundamental and a higher-frequency component added in various phases. We compare model predictions with three key results from the literature: the effect of the contrast of the fundamental on phase discrimination, threshold phase difference as a function of the fundamental frequency, and the contrast required for phase discrimination as a function of the frequency ratio of the two grating components. In the first two cases, the predictions capture the main features of the data, although quantitative discrepancies remain. In the third case, the model fails, and this failure suggests additional restrictions on the combination of information across sensors.


LiCHI - Liquid Crystal Hyperspectral Imager for simultaneous multispectral imaging in aeronomy.
A four channel hyperspectral imager using Liquid Crystal Fabry-Perot (LCFP) etalons has been built and tested. This imager is capable of making measurements simultaneously in four wavelength ranges in the visible spectrum. The instrument was designed to make measurements of natural airglow and auroral emissions in the upper atmosphere of the Earth and was installed and tested at the Poker Flat Research Range in Fairbanks, Alaska from February to April 2014. The results demonstrate the capabilities and challenges this instrument presents as a sensor for aeronomical studies.


Culture-negative septic arthritis and bacterial endocarditis. Diagnosis by synovial biopsy.
The capacity of bacterial endocarditis to mimic other systemic illnesses is well known. This report describes a patient with blood culture-negative bacterial endocarditis who presented with features suggestive of rheumatoid arthritis. Despite sterile synovial fluid, synovial biopsy culture resulted in identification of the causative organism and led to specific antibiotic therapy and cure. This is the first report of such a case.


Relevance of circulating tumor cells, extracellular nucleic acids, and exosomes in breast cancer.
Early detection of cancer is vital to improved overall survival rates. At present, evidence is accumulating for the clinical value of detecting occult tumor cells in peripheral blood, plasma, and serum specimens from cancer patients. Both molecular and cellular approaches, which differ in sensitivity and specificity, have been used for such means. Circulating tumor cells and extracellular nucleic acids have been detected within blood, plasma, and sera of cancer patients. As the presence of malignant tumors are clinically determined and/or confirmed upon biopsy procurement-which in itself may have detrimental effects in terms of stimulating cancer progression/metastases-minimally invasive methods would be highly advantageous to the diagnosis and prognosis of breast cancer and the subsequent tailoring of targeted treatments for individuals, if reliable panels of biomarkers suitable for such an approach exist. Herein, we review the current advances made in the detection of such circulating tumor cells and nucleic acids, with particular emphasis on extracellular nucleic acids, specifically extracellular mRNAs and discuss their clinical relevance.


Equilibrium and kinetic studies of oxygen binding to the haemocyanin from the freshwater snail Lymnaea stagnalis.
The binding of oxygen by the haemocyanin of the gastropod Lymnaea stagnalis was studied by equilibrium and kinetic methods. The studies were performed under conditions in which the haemocyanin molecule was in the native state. Over the pH range 6.8-7.6, in the presence of 10mM-CaCl2 the haemocyanin bound O2 cooperatively. Over this pH range the haemocyanin molecule displayed a normal Bohr effect whereby the O2 affinity of the molecule decreased with a fall in the pH of the solution. The maximum slope of the Hill plot (hmax.) was 3.5, obtained at pH 7.5. An increase in the CaCl2 concentration from 5 to 20 mM at pH 6.8 resulted in a slight increase in the oxygen affinity, with hmax. remaining virtually unchanged. At constant pH and CaCl2 concentration, an increase in NaCl concentration from 0 to 50 mM resulted in a small decrease in O2 affinity, but a significant increase in the value of hmax. from 3.5 to 8.6. Temperature-jump relaxation experiments over a range of O2 concentrations produced single relaxation times. The dependence of the relaxation time on the reactant concentrations indicated a simple bimolecular binding process. The calculated association and dissociation rate constants for this process at pH 7.5 are 29.5 X 10(6) M-1 X S-1 and 49 S-1 respectively. The association rate constant kon was found to be essentially independent of pH and CaCl2 concentration. The dissociation rate constant, koff, however, increased with a decrease in the pH, but was also independent of CaCl2 concentration. These results indicate that the stability of the haemocyanin-O2 complex is determined by the dissociation rate constant.


Structural and ultrastructural characteristics of the yolk syncytial layer in Prochilodus lineatus (Valenciennes, 1836) (Teleostei; Prochilodontidae).
The yolk syncytial layer (YSL) has been regarded as one of the main obstacles for a successful cryopreservation of fish embryos. The purpose of this study was to identify and characterize the YSL in Prochilodus lineatus, a fish species found in southeastern Brazil and considered a very important fishery resource. Embryos were obtained through artificial breeding by hormonal induction. After fertilization, the eggs were incubated in vertical incubators with a controlled temperature (28 degrees C). Embryos were collected in several periods of development up to hatching and then fixed with 2% glutaraldehyde and 4% paraformaldehyde in 0.1 M sodium phosphate buffer (pH 7.3). Morphological analyses were carried out under either light, transmission or scanning electron microscopy. The formation of the YSL in P. lineatus embryos starts at the end of the cleavage stage (morula), mainly at the margin of the blastoderm, and develops along the embryo finally covering the entire yolk mass (late gastrula) and producing a distinct intermediate zone between the yolk and the endodermal cells. The YSL was characterized by the presence of microvilli on the contact region with the yolk endoderm. A cytoplasmic mass, full of mitochondria, vacuoles, ribosomes, endomembrane nets and euchromatic nuclei, indicated a high metabolic activity. This layer is shown as an interface between the yolk and the embryo cells that, besides sustaining and separating the yolk, acts as a structure that makes it available for the embryo. The structural analyses identified no possible barriers to cryoprotectant penetration.


Structural dynamics of inosine triphosphate pyrophosphatase (ITPA) protein and two clinically relevant mutants: molecular dynamics simulations.
The inosine triphosphate pyrophosphatase (ITPA) protein is responsible for removing noncanonical purine nucleoside triphosphates from intracellular nucleotide pools. Absence of ITPA results in genomic instability and increased levels of inosine in DNA and RNA. The proline to threonine substitution at position 32 (P32T) affects roughly 15% of the global population and can modulate treatment outcomes for cancer, lupus, and hepatitis C patients. The substitution of arginine with cysteine at position 178 (R178C) is extremely uncommon and has only been reported in a small cohort of early infantile encephalopathy patients suggesting that a functional ITPA protein is required for life in humans. Here we present molecular dynamic simulations that describe the structure and dynamics of the wild-type ITPA homodimer and two of its clinically relevant mutants, P32T and R178C. The simulation results indicate that both the P32T and R178C mutations alter the structure and dynamic properties of the protein and provide a possible explanation of the experimentally observed effect of the mutations on ITPA activity. Specifically, the mutations increased the overall flexibility of the protein and changed the dominant collective motions of the top lobe as well as the helix 2 of the lower lobe. Moreover, we have identified key active-site residues that are classified as essential or intermediate for inosine triphosphate (ITP) hydrolyzing activity based on their hydrogen bond occupancy. Here we also present biochemical data indicating that the R178C mutant has very low ITP hydrolyzing activity.Communicated by Ramaswamy H. Sarma.


A role for the anaphase-promoting complex inhibitor Emi2/XErp1, a homolog of early mitotic inhibitor 1, in cytostatic factor arrest of Xenopus eggs.
Unfertilized vertebrate eggs are arrested in metaphase of meiosis II with high cyclin B/Cdc2 activity to prevent parthenogenesis. Until fertilization, exit from metaphase is blocked by an activity called cytostatic factor (CSF), which stabilizes cyclin B by inhibiting the anaphase-promoting complex (APC) ubiquitin ligase. The APC inhibitor early mitotic inhibitor 1 (Emi1) was recently found to be required for maintenance of CSF arrest. We show here that exogenous Emi1 is unstable in CSF-arrested Xenopus eggs and is destroyed by the SCF(betaTrCP) ubiquitin ligase, suggesting that endogenous Emi1, an apparent 44-kDa protein, requires a stabilizing factor. However, anti-Emi1 antibodies crossreact with native Emi2/Erp1/FBXO43, a homolog of Emi1 and conserved APC inhibitor. Emi2 is stable in CSF-arrested eggs, is sufficient to prevent CSF release, and is rapidly degraded in a Polo-like kinase 1-dependent manner in response to calcium-mediated egg activation. These results identify Emi2 as a candidate CSF maintenance protein.


The nucleotide sequence of Saccharomyces cerevisiae chromosome XII.
The yeast Saccharomyces cerevisiae is the pre-eminent organism for the study of basic functions of eukaryotic cells. All of the genes of this simple eukaryotic cell have recently been revealed by an international collaborative effort to determine the complete DNA sequence of its nuclear genome. Here we describe some of the features of chromosome XII.


The rate of deoxyribonucleic acid synthesis by cultured Chinese-hamster ovary cells. An application of isotope-dilution analysis.
The rate of DNA synthesis is exponentially growing cells was determined by isotopedilution analysis of the incorporation of [me-3H]thymidine. Thymidine concentrations greater than 7 micrometer were used so that the rate-limiting step governing incorporation would be at the level of DNA polymerase rather than at the level of thymidine kinase [Sjostrom & Forsdyke (1974) Biochem. J. 138, 253-262]. In early exponential phase the rate determined by isotope-dilution analysis closely correlated with the rates calculated either from growth curves or from known cell-cycle parameters. However, in late-exponential phase the rate calculated from the growth curve was less than that determined by isotope-dilution analysis. We conclude that, under certain conditions, the pool-corrected rate of incorporation of [me-3H]thymidine, as determined by isotope-dilution analysis, can accurately reflect the rate of DNA synthesis. Discrepancies between the observed rate of DNA synthesis and increase in cell number could reflect an exponential degeneration of post-S-phase cells.


Cytoplasmic retention and degradation of a mitotic inducer enable plant infection by a pathogenic fungus.
In the fungus Ustilago maydis, sexual pheromones elicit mating resulting in an infective filament able to infect corn plants. Along this process a G2 cell cycle arrest is mandatory. Such as cell cycle arrest is initiated upon the pheromone recognition in each mating partner, and sustained once cell fusion occurred until the fungus enter the plant tissue. We describe that the initial cell cycle arrest resulted from inhibition of the nuclear transport of the mitotic inducer Cdc25 by targeting its importin, Kap123. Near cell fusion to take place, the increase on pheromone signaling promotes Cdc25 degradation, which seems to be important to ensure the maintenance of the G2 cell cycle arrest to lead the formation of the infective filament. This way, premating cell cycle arrest is linked to the subsequent steps required for establishment of the infection. Disabling this connection resulted in the inability of fungal cells to infect plants.


[Treatment of local hyperkinesis].
Insufficient effectiveness of medicamentous therapy of local hyperkineses necessitated quest for other treatment options. In view of pathogenetic features of this pathological process we have chosen reflexotherapy to be instituted in our patients: auriculopuncture, electro-corporal- and acupuncture which have been shown to be expedient and effective in treating 65 patients with local hyperkinesis (blepharospasm, facial paraspasm, writer's spasm, spasmodic torticollis). Positive findings from clinical and paraclinical methods of investigation corroborate the results of the treatments administered.


The effect of weightlifting shoes on the kinetics and kinematics of the back squat.
Weightlifting shoes (WS) are often used by athletes to facilitate their squat technique; however, the nature of these benefits is not well understood. In this study, the effects of footwear and load on the mechanics of squatting were assessed for 32 participants (age: 25.4 ± 4.4 years; mass 72.87 ± 11.35 kg) grouped by sex and experience. Participants completed loaded and unloaded back squats wearing both WS and athletic shoes (AS). Data were collected utilising a 3D motion capture system synchronised with a force platform and used to calculate kinematic and kinetic descriptors of squatting. For both load conditions, WS gave significantly (P < 0.05) reduced ankle flexion and increased knee flexion than AS, as well as a more upright trunk and greater knee moment for the unloaded condition. In addition, the experienced group experienced a significantly greater increase in knee and hip flexion with WS than the novices when unloaded. These results are consistent with the idea that WS permit a more knee flexed, upright posture during squatting, and provide preliminary evidence that experienced squatters are more able to exploit this effect. Decisions about footwear should recognise the effect of footwear on movement and reflect an athlete's movement capabilities and training objectives.


Reliability and validity of the Spanish version of the Child Health and Illness Profile (CHIP) Child-Edition, Parent Report Form (CHIP-CE/PRF).
The objectives of the study were to assess the reliability, and the content, construct, and convergent validity of the Spanish version of the CHIP-CE/PRF, to analyze parent-child agreement, and compare the results with those of the original U.S. version. Parents from a representative sample of children aged 6-12 years were selected from 9 primary schools in Barcelona. Test-retest reliability was assessed in a convenience subsample of parents from 2 schools. Parents completed the Spanish version of the CHIP-CE/PRF. The Achenbach Child Behavioural Checklist (CBCL) was administered to a convenience subsample. The overall response rate was 67% (n = 871). There was no floor effect. A ceiling effect was found in 4 subdomains. Reliability was acceptable at the domain level (internal consistency = 0.68-0.86; test-retest intraclass correlation coefficients = 0.69-0.85). Younger girls had better scores on Satisfaction and Achievement than older girls. Comfort domain score was lower (worse) in children with a probable mental health problem, with high effect size (ES = 1.45). The level of parent-child agreement was low (0.22-0.37). The results of this study suggest that the parent version of the Spanish CHIP-CE has acceptable psychometric properties although further research is needed to check reliability at sub-domain level. The CHIP-CE parent report form provides a comprehensive, psychometrically sound measure of health for Spanish children 6 to 12 years old. It can be a complementary perspective to the self-reported measure or an alternative when the child is unable to complete the questionnaire. In general, the results are similar to the original U.S. version.


The sculpting of Jupiter's gossamer rings by its shadow.
Dust near Jupiter is produced when interplanetary impactors collide energetically with small inner moons, and is organized into a main ring, an inner halo, and two fainter and more distant gossamer rings. Most of these structures are constrained by the orbits of the moons Adrastea, Metis, Amalthea and Thebe, but a faint outward protrusion called the Thebe extension behaves differently and has eluded understanding. Here we report on dust impacts detected during the Galileo spacecraft's traversal of the outer ring region: we find a gap in the rings interior to Thebe's orbit, grains on highly inclined paths, and a strong excess of submicrometre-sized dust just inside Amalthea's orbit. We present detailed modelling that shows that the passage of ring particles through Jupiter's shadow creates the Thebe extension and fully accounts for these Galileo results. Dust grains alternately charge and discharge when traversing shadow boundaries, allowing the planet's powerful magnetic field to excite orbital eccentricities and, when conditions are right, inclinations as well.


Inhibition of Vps34 reprograms cold into hot inflamed tumors and improves anti-PD-1/PD-L1 immunotherapy.
One of the major challenges limiting the efficacy of anti-PD-1/PD-L1 therapy in nonresponding patients is the failure of T cells to penetrate the tumor microenvironment. We showed that genetic or pharmacological inhibition of Vps34 kinase activity using SB02024 or SAR405 (Vps34i) decreased the tumor growth and improved mice survival in multiple tumor models by inducing an infiltration of NK, CD8+, and CD4+ T effector cells in melanoma and CRC tumors. Such infiltration resulted in the establishment of a T cell-inflamed tumor microenvironment, characterized by the up-regulation of pro-inflammatory chemokines and cytokines, CCL5, CXCL10, and IFNγ. Vps34i treatment induced STAT1 and IRF7, involved in the up-regulation of CCL5 and CXCL10. Combining Vps34i improved the therapeutic benefit of anti-PD-L1/PD-1 in melanoma and CRC and prolonged mice survival. Our study revealed that targeting Vps34 turns cold into hot inflamed tumors, thus enhancing the efficacy of anti-PD-L1/PD-1 blockade.


Ventilation heterogeneity is a major determinant of airway hyperresponsiveness in asthma, independent of airway inflammation.
Airway hyperresponsiveness is the ability of airways to narrow excessively in response to inhaled stimuli and is a key feature of asthma. Airway inflammation and ventilation heterogeneity have been separately shown to be associated with airway hyperresponsiveness. A study was undertaken to establish whether ventilation heterogeneity is associated with airway hyperresponsiveness independently of airway inflammation in subjects with asthma and to determine the effect of inhaled corticosteroids on this relationship. Airway inflammation was measured in 40 subjects with asthma by exhaled nitric oxide, ventilation heterogeneity by multiple breath nitrogen washout and airway hyperresponsiveness by methacholine challenge. In 18 of these subjects with uncontrolled symptoms, measurements were repeated after 3 months of treatment with inhaled beclomethasone dipropionate. At baseline, airway hyperresponsiveness was independently predicted by airway inflammation (partial r2 = 0.20, p<0.001) and ventilation heterogeneity (partial r2 = 0.39, p<0.001). Inhaled corticosteroid treatment decreased airway inflammation (p = 0.002), ventilation heterogeneity (p = 0.009) and airway hyperresponsiveness (p<0.001). After treatment, ventilation heterogeneity was the sole predictor of airway hyperresponsiveness (r2 = 0.64, p<0.001). Baseline ventilation heterogeneity is a strong predictor of airway hyperresponsiveness, independent of airway inflammation in subjects with asthma. Its persistent relationship with airway hyperresponsiveness following anti-inflammatory treatment suggests that it is an important independent determinant of airway hyperresponsiveness. Normalisation of ventilation heterogeneity is therefore a potential goal of treatment that may lead to improved long-term outcomes.


Therapeutic potential of miR-21 regulation by human peripheral blood derived-small extracellular vesicles in myocardial infarction.
Small extracellular vesicles (sEVs) as natural membranous vesicles are on the frontiers of nanomedical research, due to their ability to deliver therapeutic molecules such as microRNAs (miRNAs). The miRNA-21 (miR-21) is thought to be involved in the initiation and development of myocardial infarction (MI). Here, we examined whether miR-21 regulation using human peripheral blood-derived sEVs (PB-sEVs) could serve as a potential therapeutic strategy for MI. First, we examined miR-21 levels in hypoxic conditions and validated the ability of PB-sEVs to serve as a potential delivery system for miRNAs. Further, bioinformatics analysis and luciferase assay were performed to identify target genes of miR-21 mechanistically. Among numerous target pathways, we focused on nitrogen metabolism, which remains relatively unexplored compared with other possible miR-21-mediated pathways; hence, we aimed to determine novel target genes of miR-21 related to nitrogen metabolism. In hypoxic conditions, the expression of miR-21 was significantly up-regulated and correlated with nitric oxide synthase 3 (NOS3) levels, which in turn influences cardiac function. The down-regulation of miR-21 expression by PB-sEVs loaded with anti-miR-21 significantly improved survival rates, consistent with the augmentation of cardiac function. However, the up-regulation of miR-21 expression by PB-sEVs loaded with miR-21 reversed these effects. Mechanistically, miR-21 targeted and down-regulated the mRNA and protein expression of striatin (STRN), which could regulate NOS3 expression. In conclusion, we identified a novel therapeutic strategy to improve cardiac function by regulating the expression of miR-21 with PB-sEVs as an miR-21 or anti-miR-21 delivery vehicle and confirmed the miR-21-associated nitrogen metabolic disorders in MI.


Ischemia induces closure of gap junctional channels and opening of hemichannels in heart-derived cells and tissue.
Gap junction intercellular communication (GJIC) and hemichannel permeability may have important roles during an ischemic insult. Our aim was to evaluate the effect of ischemia on gap junction channels and hemichannels. We used neonatal rat heart myofibroblasts and simulated ischemia with a HEPES buffer with high potassium, low pH, absence of glucose, and oxygen tension was reduced by dithionite. Microinjection, western blot, immunofluorescence, cell viability and dye uptake were used to evaluate the effects induced by dithionite. Isolated perfused rat hearts were used to analyse infarct size. Short period with simulated ischemia reduced the ability to transfer a dye between neighbouring cells, which indicated reduced GJIC. Prolonged exposure to simulated ischemia caused opening of hemichannels, and cell death was apparent while gap junction channels remained closed. Connexin 43 became partially dephosphorylated and the total amount decreased during simulated ischemia. We were not able to detect the alternative hemichannel-forming protein, Pannexin 1, in these cells. The potential importance of Connexin 43 or Pannexin 1 hemichannels in ischemia-induced infarct in the intact heart was studied by perfusion of the heart in the presence of peptides that block one or the other type of hemichannels. The connexin-derived peptide, Gap26, significantly reduced the infract/risk zone ratio (control 48.7±4.2% and Gap26 19.4±4.1%, p<0.001), while the pannexin-derived peptide, (10)Panx1, did not change infarct/risk ratio. Connexin 43 is most likely responsible for both closure of gap junction channels and opening of hemichannels during simulated ischemia in neonatal rat heart myofibroblasts. Opening of connexin 43 hemichannels during ischemia-reperfusion seems to be an important mechanism for ischemia-reperfusion injury in the heart. By preventing the opening of these channels during early ischemia-reperfusion the infarct size becomes significantly reduced.


An easy game for frauds? Effects of professional experience and time pressure on passport-matching performance.
Despite extensive research on unfamiliar face matching, little is known about factors that might affect matching performance in real-life scenarios. We conducted 2 experiments to investigate the effects of several such factors on unfamiliar face-matching performance in a passport-check scenario. In Experiment 1, we assessed the effect of professional experience on passport-matching performance. The matching performance of 96 German Federal Police officers working at Munich Airport was compared with that of 48 novices without specific face-matching experience. Police officers significantly outperformed novices, but nevertheless missed a high ratio of frauds. Moreover, the effects of manipulating specific facial features (with paraphernalia like glasses and jewelry, distinctive features like moles and scars, and hairstyle) and of variations in the physical distance between the faces being matched were investigated. Whereas manipulation of physical distance did not have a significant effect, manipulations of facial features impaired matching performance. In Experiment 2, passport-matching performance was assessed in relation to time constraints. Novices matched passports either without time constraints, or under a local time limit (which is typically used in laboratory studies), or under a global time limit (which usually occurs during real-life border controls). Time pressure (especially the global time limit) significantly impaired matching performance. (PsycINFO Database Record


Apolipoprotein E, Receptors, and Modulation of Alzheimer's Disease.
Apolipoprotein E (apoE) is a lipid carrier in both the peripheral and the central nervous systems. Lipid-loaded apoE lipoprotein particles bind to several cell surface receptors to support membrane homeostasis and injury repair in the brain. Considering prevalence and relative risk magnitude, the ε4 allele of the APOE gene is the strongest genetic risk factor for late-onset Alzheimer's disease (AD). ApoE4 contributes to AD pathogenesis by modulating multiple pathways, including but not limited to the metabolism, aggregation, and toxicity of amyloid-β peptide, tauopathy, synaptic plasticity, lipid transport, glucose metabolism, mitochondrial function, vascular integrity, and neuroinflammation. Emerging knowledge on apoE-related pathways in the pathophysiology of AD presents new opportunities for AD therapy. We describe the biochemical and biological features of apoE and apoE receptors in the central nervous system. We also discuss the evidence and mechanisms addressing differential effects of apoE isoforms and the role of apoE receptors in AD pathogenesis, with a particular emphasis on the clinical and preclinical studies related to amyloid-β pathology. Finally, we summarize the current strategies of AD therapy targeting apoE, and postulate that effective strategies require an apoE isoform-specific approach.


3-Aroyl-1,4-diarylpyrroles Inhibit Chronic Myeloid Leukemia Cell Growth through an Interaction with Tubulin.
We designed 3-aroyl-1,4-diarylpyrrole (ARDAP) derivatives as potential anticancer agents having different substituents at the 1- or 4-phenyl ring. ARDAP compounds exhibited potent inhibition of tubulin polymerization, binding of colchicine to tubulin, and cancer cell growth. ARDAP derivative 10 inhibited the proliferation of BCR/ABL-expressing KU812 and LAMA84 cells from chronic myeloid leukemia (CML) patients in blast crisis and of hematopoietic cells ectopically expressing the imatinib mesylate (IM)-sensitive KBM5-WT or its IM-resistant KBM5-T315I mutation. Compound 10 minimally affected the proliferation of normal blood cells, indicating that it may be a promising agent to overcome broad tyrosine kinase inhibitor resistance in relapsed/refractory CML patients. Compound 10 significantly decreased CML proliferation by inducing G2/M phase arrest and apoptosis via a mitochondria-dependent pathway. ARDAP 10 augmented the cytotoxic effects of IM in human CML cells. Compound 10 represents a robust lead compound to develop tubulin inhibitors with potential as novel treatments for CML.


The remarkable environmental rebound effect of electric cars: a microeconomic approach.
This article presents a stepwise, refined, and practical analytical framework to model the microeconomic environmental rebound effect (ERE) stemming from cost differences of electric cars in terms of changes in multiple life cycle environmental indicators. The analytical framework is based on marginal consumption analysis and hybrid life cycle assessment (LCA). The article makes a novel contribution through a reinterpretation of the traditional rebound effect and methodological refinements. It also provides novel empirical results about the ERE for plug-in hybrid electric (PHE), full-battery electric (FBE), and hydrogen fuel cell (HFC) cars for Europe. The ERE is found to have a remarkable impact on product-level environmental scores. For the PHE car, the ERE causes a marginal increase in demand and environmental pressures due to a small decrease in the cost of using this technology. For FBE and HFC cars, the high capital costs cause a noteworthy decrease in environmental pressures for some indicators (negative rebound effect). The results corroborate the concern over the high influence of cost differences for environmental assessment, and they prompt sustainable consumption policies to consider markets and prices as tools rather than as an immutable background.


[Optimization of treatment of acute pancreatitis in elderly and senile].
The purpose of this study was to evaluate the efficacy of Reamberin as a component of intensive care edematous form of acute pancreatitis in elderly and senile patients. There were analysed the treatment data of 78 patients of this category diagnosed with «acute pancreatitis edematous form». Based on the regimens, patients were divided into 2 groups: 42 patients of the main group received Reamberin in addition to the standard treatment; patients in the control group (36 patients) received standard basic therapy. Inclusion in Reamberin regimens edematous form of acute pancreatitis in patients older than 60 years increases the effectiveness of treatment due to more rapid relief of symptoms of endogenous intoxication. The drug has a membrane stabilizing action, on the one hand, preventing the progression of the destruction of the pancreas and hence increase endogenous intoxication, the other - limiting structural disorders of the liver, normalizes its detoxification function. In addition, increasing the effectiveness of anticoagulant and fibrinolytic systems Reamberin corrects disturbances in the hemostatic system, contributing to the improvement of organ blood flow hepatopancreatoduodenal zone.


[Ecological conditions of exclusion zone biocenoses 20 years after the accident on Chernobyl NPP].
In present work are introduced perennial ecological process studies, accrue in different exclusion zone (EZ) biocenoses. Main factors have an influence on biocenoses ecological condition--the radioactive contamination of territory and the absence of economic activity. A conclusion on increasing adjusting dug useful entomofauna and on relative stabilizations of ecological situations of the fallow lands and in gardens of EZ is made. Pinetrees in conditions of EZ are the most unstable biological system and require a constant checking and undertaking forestry actions.


Interactive Voice Response-Based Self-management for Chronic Back Pain: The COPES Noninferiority Randomized Trial.
Recommendations for chronic pain treatment emphasize multimodal approaches, including nonpharmacologic interventions to enhance self-management. Cognitive behavioral therapy (CBT) is an evidence-based treatment that facilitates management of chronic pain and improves outcomes, but access barriers persist. Cognitive behavioral therapy delivery assisted by health technology can obviate the need for in-person visits, but the effectiveness of this alternative to standard therapy is unknown. The Cooperative Pain Education and Self-management (COPES) trial was a randomized, noninferiority trial comparing IVR-CBT to in-person CBT for patients with chronic back pain. To assess the efficacy of interactive voice response-based CBT (IVR-CBT) relative to in-person CBT for chronic back pain. We conducted a noninferiority randomized trial in 1 Department of Veterans Affairs (VA) health care system. A total of 125 patients with chronic back pain were equally allocated to IVR-CBT (n = 62) or in-person CBT (n = 63). Patients treated with IVR-CBT received a self-help manual and weekly prerecorded therapist feedback based on their IVR-reported activity, coping skill practice, and pain outcomes. In-person CBT included weekly, individual CBT sessions with a therapist. Participants in both conditions received IVR monitoring of pain, sleep, activity levels, and pain coping skill practice during treatment. The primary outcome was change from baseline to 3 months in unblinded patient report of average pain intensity measured by the Numeric Rating Scale (NRS). Secondary outcomes included changes in pain-related interference, physical and emotional functioning, sleep quality, and quality of life at 3, 6, and 9 months. We also examined treatment retention. Of the 125 patients (97 men, 28 women; mean [SD] age, 57.9 [11.6] years), the adjusted average reduction in NRS with IVR-CBT (-0.77) was similar to in-person CBT (-0.84), with the 95% CI for the difference between groups (-0.67 to 0.80) falling below the prespecified noninferiority margin of 1 indicating IVR-CBT is noninferior. Fifty-four patients randomized to IVR-CBT and 50 randomized to in-person CBT were included in the analysis of the primary outcome. Statistically significant improvements in physical functioning, sleep quality, and physical quality of life at 3 months relative to baseline occurred in both treatments, with no advantage for either treatment. Treatment dropout was lower in IVR-CBT with patients completing on average 2.3 (95% CI, 1.0-3.6) more sessions. IVR-CBT is a low-burden alternative that can increase access to CBT for chronic pain and shows promise as a nonpharmacologic treatment option for chronic pain, with outcomes that are not inferior to in-person CBT. clinicaltrials.gov Identifier: NCT01025752.


Feasibility of applying a noninvasive method for sleep monitoring based on mouse behaviors.
Currently, electroencephalogram (EEG)/electromyogram (EMG) system is widely regarded as the "golden standard" for sleep monitoring. Imperfectly, its invasive monitoring may somehow interfere with the natural state of sleep. Up to now, noninvasive methods for sleep monitoring have developed, which could preserve the undisturbed and naïve sleep state of mice to the greatest extent, but the feasibility of their application under different conditions should be extensive validated. Based on existing research, we verified the feasibility of a sleep monitoring system based on mouse behaviors under different conditions. The experimental mice were exposed to various stresses and placed into a combined device comprising noninvasive sleep monitoring equipment and an EEG/EMG system, and the sleep status was recorded under different physiological, pharmacological, and pathophysiological conditions. The consistency of the parameters obtained from the different systems was calculated using the Bland-Altman statistical method. The results demonstrated that the physiological sleep times determined by noninvasive sleep monitoring system were highly consistent with those obtained from the EEG/EMG system, and the coefficients were 94.4% and 95.1% in C57BL/6J and CD-1 mice, respectively. The noninvasive sleep monitoring system exhibited high sensitivity under the sleep-promoting effect of diazepam and caffeine-induced wakefulness, which was indicated by its ability to detect the effect of dosage on sleep times, and accurate determination of the sleep/wakeful status of mice under different pathophysiological conditions. After combining the data obtained from all the mice, the coefficient between the sleep times detected by behavior-based sleep monitoring system and those obtained from the EEG/EMG equipment was determined to .94. The results suggested that behavior-based sleep monitoring system could accurately evaluate the sleep/wakeful states of mice under different conditions.


Brachioplasty technique with the use of molds.
Over previous years many surgical techniques have been developed to correct lipodystrophy and brachial skin laxity while providing a natural, discreet contour and symmetrical scars, a goal that has not always been achieved. In this study, the authors classify the alterations of the arm into three degrees and propose a different surgical treatment, to be used alone or associated with another procedure, for each classification. They developed a new technique that uses a mold to mark the incision in an italic double S-shape. From 1996 to 1998, 20 patients who underwent this surgery showed symmetrical and smaller scars with better results and minimal complications.


A Wnt-ow of opportunity: targeting the Wnt/beta-catenin pathway in breast cancer.
Aberrant activation of the Wnt/beta-catenin signaling pathway is a hallmark of many tumors, including breast cancer. In the normal breast, tightly regulated expression of Wnt/beta-catenin pathway components, including Wnts and the APC tumor suppressor, dictates its role in balancing stem cell self-renewal, maintenance and differentiation during embryonic and postnatal development. Therefore, not surprisingly, dysregulation of Wnt/beta-catenin signaling through overexpression of pathway activators, such as Wnts or stabilized beta-catenin, or targeted disruption of inhibitors, such as APC, leads to mammary tumorigenesis in several genetically engineered mouse (GEM) models. These models are powerful tools to dissect the importance of Wnt/beta-catenin signaling in human breast cancer because they recapitulate some of the histological features of human breast cancers that demonstrate pathway dysregulation. Over the last decade, numerous approaches have been developed to target the Wnt/beta-catenin pathway in tumor cells, from antagonizing Wnt ligand secretion or binding to promoting beta-catenin degradation to specifically blocking beta-catenin-mediated transcriptional activity. Despite sizeable hurdles because of gaps in our knowledge of most efficacious ways to inhibit the pathway, the breast cancer subtypes to target and how pathway antagonists might be used in combination therapy, crippling Wnt/beta-catenin signaling offers a tremendous opportunity to impact breast cancer pathogenesis. This review will provide an overview of the current understanding of Wnt/beta-catenin pathway involvement in regulating normal breast development and morphogenesis, the generation of Wnt/beta-catenin-dependent GEM models of human breast cancer, upregulation of signaling in human breast cancers and the compelling therapeutic strategies aimed at targeting the Wnt/beta-catenin pathway that show promising anti-tumor activity.


Barriers and opportunities to oral health in Dutch-Moroccan children in the Netherlands: a narrative report.
Previous studies showed that 5-year-old Dutch-Moroccan children had significantly higher dmft scores compared to Dutch children of the same age, even after correction for socio-economic status. The mechanisms underlying this difference are little understood. To explore cultural factors involved in poorer oral health of Dutch-Moroccan children by identifying knowledge, attitudes and behaviour of their mothers concerning their children's oral health. In 2012 mothers of Dutch-Moroccan preschool children in two cities in the Netherlands were interviewed in two focus groups (n = 16) or individual semi-structured interviews (n = 13). Semi structured interviews were also c onducted with three oral health professionals, working with Dutch-Moroccan children, and one physician from an under-five-clinic. All interviews were voice recorded, transcribed and inductively coded. MAXQDA software was used for data analysis. All mothers mentioned pain complaints, swelling and black front teeth as oral health problems in their children. Although mothers were aware that brushing teeth and reducing sugary snacks are effective preventative strategies, they did not sufficiently implement these measures. This was due to lack of brushing skills, insufficient awareness of the daily sugar intake of their children and their childrearing concerning these measures. Most mothers indicated they felt empowered in making dental care decisions. This research revealed the presence of knowledge on preventive strategies regarding their children's oral health in Dutch-Moroccan mothers, but an inadequate implementation of these measures in their daily lives. Additional qualitative research is needed to gain deeper insight for broader exposure of values, knowledge and culture.


The Relationship Between Resting State Network Connectivity and Individual Differences in Executive Functions.
The brain is organized into a number of large networks based on shared function, for example, high-level cognitive functions (frontoparietal network), attentional capabilities (dorsal and ventral attention networks), and internal mentation (default network). The correlations of these networks during resting-state fMRI scans varies across individuals and is an indicator of individual differences in ability. Prior work shows higher cognitive functioning (as measured by working memory and attention tasks) is associated with stronger negative correlations between frontoparietal/attention and default networks, suggesting that increased ability may depend upon the diverging activation of networks with contrasting function. However, these prior studies lack specificity with regard to the higher-level cognitive functions involved, particularly with regards to separable components of executive function (EF). Here we decompose EF into three factors from the unity/diversity model of EFs: Common EF, Shifting-specific EF, and Updating-specific EF, measuring each via factor scores derived from a battery of behavioral tasks completed by 250 adult participants (age 28) at the time of a resting-state scan. We found the hypothesized segregated pattern only for Shifting-specific EF. Specifically, after accounting for one's general EF ability (Common EF), individuals better able to fluidly switch between task sets have a stronger negative correlation between the ventral attention network and the default network. We also report non-predicted novel findings in that individuals with higher Shifting-specific abilities exhibited more positive connectivity between frontoparietal and visual networks, while those individuals with higher Common EF exhibited increased connectivity between sensory and default networks. Overall, these results reveal a new degree of specificity with regard to connectivity/EF relationships.


[Occupational injuries in Oslo: a study of occupational injuries treated by the Oslo Emergency Ward and Oslo Ambulance Service].
There is little reliable information about the incidence and severity of occupational injuries in Norway. Occupational injuries occurring at worksites in Oslo and treated by Oslo Emergency Ward or Oslo Ambulance Service were recorded over a period of three months. Patients with serious injuries were interviewed about the accident. 1153 injury incidents were registered, 229 (20%) of which were considered serious. Median age of patients was 32 years. Estimated annual incidence of injuries at worksites in Oslo treated by Oslo Emergency Ward/Oslo Ambulance Service was 14 per 1000 employees, for all injuries in Oslo requiring treatment, 20 per 1000 employees. Men had three times the incidence of women. The incidence was highest in the youngest age groups. Of those with serious injuries, 30% had a non-Scandinavian language as their first language. Electricians, carpenters and police officers had the highest observed incidences. 87 injuries (8%) were caused by violence. The incidence of occupational injuries in Oslo is reduced by about 40% since the 1970s. There is, however, no reduction for women. Construction workers are still at high risk. Workers of non-Scandinavian origin are also at high risk, probably because of selection into high-risk occupations. The injury register provides a good overview, but in-depth studies are needed to identify specific risk factors.


Chromosome shattering: a mitotic catastrophe due to chromosome condensation failure.
Chromosome shattering has been described as a special form of mitotic catastrophe, which occurs in cells with unrepaired DNA damage. The shattered chromosome phenotype was detected after application of a methanol/acetic acid (MAA) fixation protocol routinely used for the preparation of metaphase spreads. The corresponding phenotype in the living cell and the mechanism leading to this mitotic catastrophe have remained speculative so far. In the present study, we used V79 Chinese hamster cells, stably transfected with histone H2BmRFP for live-cell observations, and induced generalized chromosome shattering (GCS) by the synergistic effect of UV irradiation and caffeine posttreatment. We demonstrate that GCS can be derived from abnormal mitotic cells with a parachute-like chromatin configuration (PALCC) consisting of a bulky chromatin mass and extended chromatin fibers that tether centromeres at a remote, yet normally shaped spindle apparatus. This result hints at a chromosome condensation failure, yielding a "shattered" chromosome complement after MAA fixation. Live mitotic cells with PALCCs proceeded to interphase within a period similar to normal mitotic cells but did not divide. Instead they formed cells with highly abnormal nuclear configurations subject to apoptosis after several hours. We propose a factor depletion model where a limited pool of proteins is involved both in DNA repair and chromatin condensation. Chromosome condensation failure occurs when this pool becomes depleted.


Multiple transitions induced by light intensity fluctuations in illuminated chemical systems.
The influence of external noise on the steady-state properties of a chemical system with very simple kinetics was studied. We dealt with an isomerization reaction, in a closed system, coupled to a light absorption and radiationless deexcitation process involving only one of the isomers. The theoretical analysis established that external noise deeply modified the macroscopic properties of the system and even induced transition phenomena that are totally unexpected from the usual deterministic description.


The impact of palliative irradiation on the management of patients with acquired immune deficiency syndrome.
We have studied the natural history of the acquired immune deficiency syndrome (AIDS), and the part that irradiation plays in the management of this devastating and fatal disease. The radioresponsiveness of the two most common malignancies associated with AIDS, Kaposi's sarcoma (KS) and malignant lymphoma (ML), has been demonstrated. We have documented satisfactory time-dose relationships for the management of multiple manifestations of KS, including cutaneous and deep subcutaneous extremity involvement, visceral lesions, and AIDS-associated lymphadenopathy. A similar time-dose construct has been documented for ML, involving the brain and both central and peripheral lymph nodes. Irradiation can provide good to excellent palliation with only minimal side effects, and will produce a lesser impact on the hematological and immunological systems than chemotherapy. Therefore, we advocate the liberal employment of palliative radiation therapy in patients with AIDS.


Social class variation, the effect of the economic recession and childhood obesity at 3 years of age in Ireland.
Many studies have reported a social class gradient within overweight prevalence ( 1-4 ). Additionally, cross-country comparisons report high overweight trends and a change in food consumption patterns in countries affected by an economic crisis ( 5-11 ). The aim of this study was to assess the association between social class and recession on obesity levels in 3-year-old Irish children. The population-based infant cohort of the national Growing Up in Ireland (GUI) study was used. Prevalence rates of overweight and obesity were calculated and logistic regression models, adjusting for confounders, were used to examine the relationship between social class, effects of the recession and childhood obesity. In 2008, 19.5% of 9-month-olds were obese and 19.4% overweight increasing to 22.7% and 20.4%, respectively by 2011 when the infants were 3 years old (World Health Organization (WHO) criteria). The prevalence of obesity increased by 2.3% to 10.1% for various social classes (unadjusted). However, adjusting for confounders, there was no evidence of a difference in obesity of 3-year-old children across social classes. There was evidence that obesity was 22-27% higher for families who perceived a very significant crisis effect on their family, compared with those significantly affected. Increases in obesity were found to be significantly associated with perceived recession effects on the family, but not with social class. Policy makers should be aware that in times of economic downturn, public health efforts to promote healthy weight are needed at a population level rather than for specific social classes.


Secretory galectin-3 induced by glucocorticoid stress triggers stemness exhaustion of hepatic progenitor cells.
Adult progenitor cell populations typically exist in a quiescent state within a controlled niche environment. However, various stresses or forms of damage can disrupt this state, which often leads to dysfunction and aging. We built a glucocorticoid (GC)-induced liver damage model of mice, found that GC stress induced liver damage, leading to consequences for progenitor cells expansion. However, the mechanisms by which niche factors cause progenitor cells proliferation are largely unknown. We demonstrate that, within the liver progenitor cells niche, Galectin-3 (Gal-3) is responsible for driving a subset of progenitor cells to break quiescence. We show that GC stress causes aging of the niche, which induces the up-regulation of Gal-3. The increased Gal-3 population increasingly interacts with the progenitor cell marker CD133, which triggers focal adhesion kinase (FAK)/AMP-activated kinase (AMPK) signaling. This results in the loss of quiescence and leads to the eventual stemness exhaustion of progenitor cells. Conversely, blocking Gal-3 with the inhibitor TD139 prevents the loss of stemness and improves liver function. These experiments identify a stress-dependent change in progenitor cell niche that directly influence liver progenitor cell quiescence and function.


Molecular basis of cytoplasmic male sterility and fertility restoration in rice.
Cytoplasmic male sterility (CMS) is a maternally inherited trait that causes dysfunctions in pollen and anther development. CMS is caused by the interaction between nuclear and mitochondrial genomes. A product of a CMS-causing gene encoded by the mitochondrial genome affects mitochondrial function and the regulation of nuclear genes, leading to male sterility. In contrast, the RESTORER OF FERTILITY gene (Rf gene) in the nuclear genome suppresses the expression of the CMS-causing gene and restores male fertility. An alloplasmic CMS line is often bred as a result of nuclear substitution, which causes the removal of functional Rf genes and allows the expression of a CMS-causing gene in mitochondria. The CMS/Rf system is an excellent model for understanding the genetic interactions and cooperative functions of mitochondrial and nuclear genomes in plants, and is also an agronomically important trait for hybrid seed production. In this review article, pollen and anther phenotypes of CMS, CMS-associated mitochondrial genes, Rf genes, and the mechanism that causes pollen abortion and its agronomical application for rice are described.


The structure of an insect chymotrypsin.
The South American imported fire ant (Solenopsis invicta), without natural enemies in the United States, widely infests the southern United States, causing more than a half billion dollars in health and agriculture-related damage annually in Texas alone. Fire ants are resistant to most insecticides, so control will require a more fundamental understanding of their biochemistry and metabolism leading to the design of selective, ecologically safe insecticides. The 4th instar larvae play a crucial role in the nutrition of the colony by secreting proteinases (especially chymotrypsin) which digest food products for the entire colony. The first structure of an ant proteolytic enzyme, fire ant chymotrypsin, was determined to atomic resolution (1.7 A). A structural comparison of the ant and mammalian structures confirms the "universality" of the serine proteinase motif and reveals a difference at residues 147-148, which are proteolytically removed in the bovine enzyme but are firmly intact in the ant chymotrypsin, suggesting a different activation mechanism for the latter. Likewise, the absence of the covalently attached propeptide domain (1-15) further suggests an uncharacteristic activation mechanism. The presence of Gly189 in the S1 site is an atypical feature of this chymotrypsin and is comparable only to human leukocyte elastase, hornet chymotrypsin and fiddler crab collagenase. Binding studies confirm the chymotrypsin nature of this novel enzyme.


BMI and physical activity among at-risk sixth- and ninth-grade students, Hillsborough County, Florida, 2005-2006.
During the past 3 decades, the number of overweight adolescents increased while adolescent engagement in physical activity decreased. We investigated the prevalence of overweight and physical activity levels among economically disadvantaged and minority middle- and high-school students in a school district in Florida. In particular, data on physical activity levels of middle-school students are limited and needed for prevention and intervention planning. In addition, because of state education policies, students in Florida are less likely than students nationally to enroll in physical education, placing them at a higher risk for decreased physical activity levels. We used multivariate methodology to analyze physical activity levels among 526 students from 3 middle and 2 high schools in southwest Florida. Forty percent of students met criteria for overweight or obesity. Overall, less than 45% of students reported engaging in daily physical activity. Boys reported higher levels of physical activity than did girls, and a decline in physical activity levels was observed between grades 6 and 9, especially among minority girls (ie, African American and Latino). Lack of time was identified as the greatest barrier to engaging in physical activity. This study documents health disparities among minority students from economically disadvantaged backgrounds in an urban school district. Participation in daily physical activity was below recommended guidelines across grades. We found numerous barriers to engaging in physical activity, which will enable local education agencies to evaluate their current physical activity policies and identify alternative physical activities for these youth.


Agricultural adaptation in the native North American weed waterhemp, Amaranthus tuberculatus (Amaranthaceae).
There is increasing interest in documenting adaptation of weedy plant species to agricultural ecosystems, beyond the evolution of herbicide resistance. Waterhemp (Amaranthus tuberculatus) is a native plant of the Midwestern U.S. that began infesting agricultural fields in the 20th century within the central portion of its range. We hypothesized that the vegetative growth and reproductive traits of waterhemp from this heavily infested central region provide differential fitness benefits in agricultural environments. We collected seeds from across the species' native range, representing regions with varying degrees of waterhemp infestation, and planted them together in common garden soybean plots. A 2010 common garden experiment was conducted within the range of agriculturally weedy waterhemp (in Missouri), and a 2011 common garden experiment was conducted outside of this range (in Ohio). Days to flowering and flowering plant height, mature plant size data (height, number of branches, and length of the longest branch), and above-ground biomass were measured to estimate relative fitness. In both common garden locations, plants from regions where waterhemp occurs as an agricultural weed - including those from the heavily infested Mississippi Valley region (Iowa, Illinois, and Missouri) and the less severely infested Plains region (Nebraska, Kansas, and Oklahoma) - had higher relative performance in almost all fitness-related measures than plants from the Northeast region (Ohio, Michigan, and Ontario), which had little to no agriculturally weedy waterhemp at the time of our study. Further analysis revealed that fewer days to flowering in the Northeast populations can be largely accounted for by latitude of origin, suggesting a strong genetic influence on this reproductive trait. These findings suggest intraspecific variation in agricultural adaptation in a native U.S. weed, and support the use of agricultural weeds to study adaptation.


A generalized linear mixed model for longitudinal binary data with a marginal logit link function.
Longitudinal studies of a binary outcome are common in the health, social, and behavioral sciences. In general, a feature of random effects logistic regression models for longitudinal binary data is that the marginal functional form, when integrated over the distribution of the random effects, is no longer of logistic form. Recently, Wang and Louis (2003) proposed a random intercept model in the clustered binary data setting where the marginal model has a logistic form. An acknowledged limitation of their model is that it allows only a single random effect that varies from cluster to cluster. In this paper, we propose a modification of their model to handle longitudinal data, allowing separate, but correlated, random intercepts at each measurement occasion. The proposed model allows for a flexible correlation structure among the random intercepts, where the correlations can be interpreted in terms of Kendall's τ. For example, the marginal correlations among the repeated binary outcomes can decline with increasing time separation, while the model retains the property of having matching conditional and marginal logit link functions. Finally, the proposed method is used to analyze data from a longitudinal study designed to monitor cardiac abnormalities in children born to HIV-infected women.


Kidney injury molecule-1 staining in renal allograft biopsies 10 days after transplantation is inversely correlated with functioning proximal tubular epithelial cells.
Kidney injury molecule-1 (KIM-1) and neutrophil gelatinase-associated lipocalin (NGAL) are promising biomarkers for monitoring delayed graft function (DGF) after kidney transplantation. Here we investigated localization and distribution of KIM-1 and NGAL staining in renal allograft biopsies and studied their association with histological features, functional DGF (fDGF) and the tubular function slope (TFS), a functioning proximal tubular epithelial cell (PTEC) marker. Day 10 protocol biopsies of 64 donation after circulatory death recipients were stained for KIM-1 and NGAL and the positive area was quantified using ImageJ software. Biopsies were scored according to Banff and acute tubular necrosis (ATN) criteria. A 99mtechnetium-mercaptoacetyltriglycine (99mTc-MAG3)-renography was performed to calculate TFS. KIM-1 staining was located on the brush border of tubular epithelial cells (TECs) and correlated with denudation, while NGAL was present more focally in a cytoplasmic distribution. KIM-1 and NGAL staining were not correlated and no co-localization was observed. Quantitative stainings were not associated with fDGF, but KIM-1 tended to be higher in patients with prolonged fDGF (≥21 days; P = 0.062). No correlation was observed between the quantitative tissue stainings and urinary KIM-1 or NGAL. Quantitative KIM-1 staining was inversely correlated with the TFS (Spearman's ρ = -0.53; P < 0.001), whereas NGAL was not. The latter finding might be because cortical NGAL staining is dependent on filtration and subsequent reabsorption by functioning PTECs. Staining of NGAL was indeed restricted to PTECs, as shown by co-localization with a PTEC-specific lectin. KIM-1 and NGAL staining showed different localization and distribution. Quantitative KIM-1 staining was inversely correlated with functioning PTECs.


L-methionine supplementation modulates IgM+ B cell responses in rainbow trout.
The interest in dietary amino acids (AAs) as potential immunomodulators has been growing the recent years, since specific AAs are known to regulate key metabolic pathways of the immune response or increase the synthesis of some immune-related proteins. Methionine, tryptophan and lysine are among the ten essential AAs for fish, meaning that they cannot be produced endogenously and must be provided through the diet. To date, although dietary supplementation of fish with some of these AAs has been shown to have positive effects on some innate immune parameters and disease resistance, the effects that these AAs provoke on cells of the adaptive immune system remained unexplored. Hence, in the current study, we have investigated the effects of these three AAs on the functionality of rainbow trout (Oncorhynchus mykiss) IgM+ B cells. For this, splenic leukocytes were isolated from untreated adult rainbow trout and incubated in culture media additionally supplemented with different doses of methionine, tryptophan or lysine in the presence or absence of the model antigen TNP-LPS (2,4,6-trinitrophenyl hapten conjugated to lipopolysaccharide). The survival, IgM secreting capacity and proliferation of IgM+ B cells was then studied. In the case of methionine, the phagocytic capacity of IgM+ B cells was also determined. Our results demonstrate that methionine supplementation significantly increases the proliferative effects provoked by TNP-LPS and also up-regulates the number of cells secreting IgM, whereas tryptophan or lysine have either minor or even negative effects on rainbow trout IgM+ B cells. This increase in the number of IgM-secreting cells in response to methionine surplus was further verified in a feeding experiment, in which the beneficial effects of methionine on the specific response to anal immunization were also confirmed. The results presented demonstrate the beneficial effects of dietary supplementation with methionine on the adaptive immune responses of fish.


CD117⁺ CD3⁻ CD56⁻ OX40Lhigh cells express IL-22 and display an LTi phenotype in human secondary lymphoid tissues.
Here, we identify cells within human adult secondary lymphoid tissues that are comparable in phenotype and location to the lymphoid tissue inducer (LTi) cells that persist in the adult mouse. Identified as CD117(+) CD3(-) CD56(-) cells, like murine LTi cells, they lack expression of many common lineage markers and express CD127, OX40L and TRANCE. These cells were detected at the interface between the B- and T- zones, as well as at the subcapsular sinus in LNs, the location where LTi cells reside in murine spleen and LNs. Furthermore, like murine LTi cells, these cells expressed high levels of IL-22 and upregulated IL-22 expression upon IL-23 stimulation. Importantly, these cells were not an NK cell subset since they showed no expression of IFN-γ and perforin. Interestingly, a subset of the CD117(+) CD3(-) CD56(-) OX40L(+) population expressed NKp46, again similar to recent findings in mice. Finally, these cells supported memory CD4(+) T-cell survival in an OX40L-dependent manner. Combined, these data indicate that the CD117(+) CD3(-) CD56(-) OX40L(+) cells in human secondary lymphoid tissues are comparable in phenotype, location and function to the LTi cells that persist within adult murine secondary lymphoid tissues.


The potential use of chickpeas in development of infant follow-on formula.
Undernutrition during childhood is a common disorder in the developing countries, however most research has focussed much on its treatment rather than its prevention. We investigated the potential of using chickpeas in infant follow-on formula production against the requirements of WHO/FAO on complementary foods and EU regulations on follow-on formula. Chickpeas were germinated for 72 hours followed by boiling, drying and dehulling in order to minimise associated anti-nutrition factors. Saccharifying enzymes were used to hydrolyse starch to maltose and the resulting flours were analysed for their protein content and amino acid profile. The protein content (percentage) increased from 16.66 ± 0.35 and 20.24 ± 0.50 to 20.00 ± 0.15 and 21.98 ± 0.80 for the processed desi and kabuli cultivar compared to raw chickpeas, respectively (P < 0.05). There was insignificant change (P = 0.05) in amino acid profile following processing and the resulting flour was found to meet the amino acid requirements of WHO/FAO protein reference for 0-24 month's children. The designed chickpea based infant follow-on formula meets the WHO/FAO requirements on complementary foods and also the EU regulations on follow-on formula with minimal addition of oils, minerals and vitamins. It uses chickpea as a common source of carbohydrate and protein hence making it more economical and affordable for the developing countries without compromising the nutrition quality.


Induction of interleukin 8 by American cockroach allergens from human airway epithelial cells via extracellular signal regulatory kinase and jun N-terminal kinase but not p38 mitogen-activated protein kinase.
Cockroaches are potent aeroallergens associated with asthma. Several reports suggest that a novel group of G protein-linked receptors, protease-activated receptors (PARs), may be involved in the intracellular signaling pathway induced by aeroallergens of the epithelial cells. To investigate the mechanisms of American cockroach allergens (CraA) on interleukin 8 (IL-8) in human pulmonary epithelial cells. Protease activities of CraA were quantified by the Azocoll method. The gene and protein expressions of IL-8 from CraA-stimulated A549 cells were quantified by real-time polymerase chain reaction and enzyme-linked immunosorbent assay, respectively. The activity of different mitogen-activated protein kinases (MAPKs) was assessed by Western blot. CraA-induced A549 cell IL-8 secretion in a dose-dependent manner at both the messenger RNA and protein levels. CraA-induced IL-8 secretion can be blocked by serine protease inhibitors, phenylmethane sulfonyl fluoride, and aprotinin but not by other protease inhibitors. Blocking antibodies against the cleavage sites of PAR-2 and PAR-3, but not of PAR-1, inhibited CraA-induced IL-8 production. CraA induced significant PAR-2 and PAR-3 messenger RNA upregulation and extracellular-regulated kinase (ERK/1/2) and Jun N-terminal kinase (JNK) phosphorylation but not p38 MAPK. Furthermore, ERK1/2 (U0126) and JNK (SP600125) inhibitors inhibited CraA-induced IL-8 secretion by 100% and 45%, respectively. Both PAR-2 and PAR-3 might play a role in CraA-induced IL-8 secretion from human airway epithelial cells. It signals mainly through the ERK1/2 and partly from the JNK pathways. The key receptors and signaling molecules mediate cytokine release from the respiratory epithelium and can be potential therapeutic targets in treating cockroach allergy.


Validity of a Neurological Scoring System for Canine X-Linked Myotubular Myopathy.
A simple clinical neurological test was developed to evaluate response to gene therapy in a preclinical canine model of X-linked myotubular myopathy (XLMTM). This devastating congenital myopathy is caused by mutation in the myotubularin (MTM1) gene. Clinical signs include muscle weakness, early respiratory failure, and ventilator dependence. A spontaneously occurring canine model has a similar clinical picture and histological abnormalities on muscle biopsy compared with patients. We developed a neuromuscular assessment score, graded on a scale from 10 (normal) to 1 (unable to maintain sternal recumbency). We hypothesize that this neurological assessment score correlates with genotype and established measures of disease severity and is reliable when performed by an independent observer. At 17 weeks of age, there was strong correlation between neurological assessment scores and established methods of severity testing. The neurological severity score correctly differentiated between XLMTM and wild-type dogs with good interobserver reliability, on the basis of strong agreement between neurological scores assigned by independent observers. Together, these data indicate that the neurological scoring system developed for this canine congenital neuromuscular disorder is reliable and valid. This scoring system may be helpful in evaluating response to therapy in preclinical testing in this disease model, such as response to gene therapy.


Effect of age at weaning on the physiological stress response and temperament of two beef cattle breeds.
The study was conducted to evaluate the effect of age at weaning and breed on the stress response of calves to weaning and their temperament. At calving, 14 Parda de Montaña calves and 14 Pirenaica calves were randomly assigned to either early weaning (at 90 days) or traditional weaning (at 150 days) treatment. During nursing, calves were allowed to suckle their dams twice a day for 30 min. After weaning, calves were placed in an adjacent barn without access to their dams, where they remained for 7 days. On day 8 after weaning, they were transported to a feedlot where they received an intensive diet. Blood samples were taken 168 h before weaning (baseline) and 6, 24, 48 and 168 h after weaning for cortisol, fibrinogen and haematology analyses, and temperament was measured 90 and 180 days after weaning with the flight speed test. Cortisol concentration increased after weaning, irrespective of age at weaning. Early-weaned calves had a lower fibrinogen baseline and a greater increase in fibrinogen concentrations 48 h after weaning than traditionally weaned calves. Moreover, fibrinogen concentration returned to baseline values 168 h after weaning in traditionally weaned calves, whereas it remained high in early-weaned calves. Concerning breed effects, Pirenaica calves had higher cortisol concentration and fibrinogen increments after weaning than Parda de Montaña calves. Slight alterations occurred after weaning in haematology, but all parameters returned to baseline values 168 h after weaning, with no significant effects of age at weaning or breed. Despite the absence of clinical signs, early-weaned calves of both breeds suffered marginal anaemia, according to haemoglobin values. Regardless of age at weaning, Pirenaica calves had greater reactivity to human presence than Parda de Montaña calves, according to their higher flight speed values measured. Finally, early-weaned calves were lighter than traditionally weaned calves at weaning, but had similar weight gains in the feedlot. Consequently, they needed an additional 40 days to reach the target weight, irrespective of breed. Therefore, age at weaning had no major effects on the stress response to weaning or temperament, but early weaning increased the length of the feedlot period. On the other hand, Pirenaica calves were more reactive than Parda de Montaña calves to the stress of weaning and human presence.


Light and heat control over secondary structure and amyloid-like fiber formation in an overcrowded-alkene-modified Trp zipper.
The external photocontrol over peptide folding, by the incorporation of molecular photoswitches into their structure, provides a powerful tool to study biological processes. However, it is limited so far to switches that exhibit only a rather limited geometrical change upon photoisomerization and that show thermal instability of the photoisomer. Here we describe the use of an overcrowded alkene photoswitch to control a model β-hairpin peptide. This photoresponsive unit undergoes a large conformational change and has two thermally stable isomers which has major influence on the secondary structure and the aggregation of the peptide, permitting the phototriggered formation of amyloid-like fibrils.


Lafora progressive Myoclonus Epilepsy mutation database-EPM2A and NHLRC1 (EPM2B) genes.
Progressive Myoclonus Epilepsy (PME) of the Lafora type is an autosomal recessive disease, which presents in teenage years with myoclonia and generalized seizures leading to death within a decade of onset. It is characterized by pathognomonic inclusions, Lafora bodies (LB), in neurons and other cell types. Two genes causing Lafora disease (LD), EPM2A on chromosome 6q24 and NHLRC1 (EPM2B) on chromosome 6p22.3 have been identified, and our recent results indicate there is at least one other gene causing the disease. The EPM2A gene product, laforin, is a protein tyrosine phosphatase (PTP) with a carbohydrate-binding domain (CBD) in the N-terminus. NHLRC1 encodes a protein named malin, containing a zinc finger of the RING type in the N-terminal half and 6 NHL-repeat domains in the C-terminal direction. To date 43 different variations in EPM2A and 23 in NHLRC1 are known, including missense, nonsense, frameshift, and deletions. We have developed a human LD mutation database using a new generic biological database cross-referencing platform. The database, which currently contains 66 entries is accessible on the World Wide Web (http://projects.tcag.ca/lafora). Entries can be submitted via the curator of the database or via a web-based form.


[Adenoma of the liver in man].
The authors report the case of a 28-year-old man with a solitary adenoma of the liver. The tumor was detected because of a raised erythrocyte sedimentation rate and serum fibrinogen. Review of the literature shows that adenoma of the liver is an uncommon tumor in man since only 30 other cases have been reported. The tumor is often multiple (55 p. 100) and the clinical manifestations are quite different from those observed in women: the adenoma is often asymptomatic (45 p. 100) and rupture is rare (10 p. 100). Androgens seem to be implicated in the development of adenoma in man since 8 out of 31 patients had received androgens for a long period of time; androgens also seem to favor the tumor's rupture.


Lysine pyrrolation is a naturally-occurring covalent modification involved in the production of DNA mimic proteins.
Covalent modification of proteins exerts significant effects on their chemical properties and has important functional and regulatory consequences. We now report the identification and verification of an electrically-active form of modified proteins recognized by a group of small molecules commonly used to interact with DNA. This previously unreported property of proteins was initially discovered when the γ-ketoaldehydes were identified as a source of the proteins stained by the DNA intercalators. Using 1,4-butanedial, the simplest γ-ketoaldehyde, we characterized the structural and chemical criteria governing the recognition of the modified proteins by the DNA intercalators and identified N(ε)-pyrrolelysine as a key adduct. Unexpectedly, the pyrrolation conferred an electronegativity and electronic properties on the proteins that potentially constitute an electrical mimic to the DNA. In addition, we found that the pyrrolated proteins indeed triggered an autoimmune response and that the production of specific antibodies against the pyrrolated proteins was accelerated in human systemic lupus erythematosus. These findings and the apparent high abundance of N(ε)-pyrrolelysine in vivo suggest that protein pyrrolation could be an endogenous source of DNA mimic proteins, providing a possible link connecting protein turnover and immune disorders.


The determination of air/water partition coefficients for alkyl carboxylic acids by a new indirect method.
The air/water partition coefficients of carboxylic acids, Kw, especially those of high molecular weight, are very difficult to determine directly. Values of Kw can be obtained by an indirect method as Kw = K/P where K is an air/solvent partition coefficient and P is the corresponding water/solvent partition coefficient. In the present method, gas-liquid chromatographic data and water/solvent partition data are used to obtain 'descriptors' of carboxylic acids that can then be used to determine the required K, P, and thus Kw values. These are reported for all the 24 n-alkyl carboxylic acids from formic acid to n-tetracosanoic acid, and for seven branched chain alkyl carboxylic acids. There is good agreement with literature values of Kw, where available, although the present data on the n-alkyl carboxylic acids is much more self consistent than the literature data.


Cocatalysts-Photoanode Interface in Photoelectrochemical Water Splitting: Understanding and Insights.
Sluggish oxygen evolution reactions on photoanode surfaces severely limit the application of photoelectrochemical (PEC) water splitting. The loading of cocatalysts on photoanodes has been recognized as the simplest and most efficient optimization scheme, which can reduce the surface barrier, provide more active sites, and accelerate the surface catalytic reaction kinetics. Nevertheless, the introduction of cocatalysts inevitably generates interfaces between photoanodes and oxygen evolution cocatalysts (Ph/OEC), which causes severe interfacial recombination and hinders the carrier transfer. Recently, many researchers have focused on cocatalyst engineering, while few have investigated the effect of the Ph/OEC interface. Hence, to maximize the advantages of cocatalysts, interfacial problems for designing efficient cocatalysts are systematically introduced. In this review, the interrelationship between the Ph/OEC and PEC performance is classified and some methods for characterizing Ph/OEC interfaces are investigated. Additionally, common interfacial optimization strategies are summarized. This review details cocatalyst-design-based interfacial problems, provides ideas for designing efficient cocatalysts, and offers references for solving interfacial problems.


Coagulation, fibrinolysis, and fibrin deposition in acute lung injury.
To review: a) the role of extravascular fibrin deposition in the pathogenesis of acute lung injury; b) the abnormalities in the coagulation and fibrinolysis pathways that promote fibrin deposition in the acutely injured lung; and c) the pathways that contribute to the regulation of the fibrinolytic system via the lung epithelium, including newly recognized posttranscriptional and urokinase-dependent pathways. Another objective was to determine how novel anticoagulant or fibrinolytic strategies may be used to protect against acute inflammation or accelerated fibrosis in acute lung injury. Published medical literature. Alveolar fibrin deposition is characteristic of diverse forms of acute lung injury. Intravascular thrombosis or disseminated intravascular coagulation can also occur in the acutely injured lung. Extravascular fibrin deposition promotes lung dysfunction and the acute inflammatory response. In addition, transitional fibrin in the alveolar compartment undergoes remodeling leading to accelerated pulmonary fibrosis similar to the events associated with wound healing, or desmoplasia associated with solid neoplasms. In acute lung injury, alveolar fibrin deposition is potentiated by consistent changes in endogenous coagulation and fibrinolytic pathways. Procoagulant activity is increased in conjunction with depression of fibrinolytic activity in the alveolar compartment. Initiation of the procoagulant response occurs as a result of local overexpression of tissue factor associated with factor VII. Depression of fibrinolytic activity occurs as a result of inhibition of urokinase plasminogen activator (uPA) by plasminogen activators, or series inhibition of plasmin by antiplasmins. Locally increased amplification of plasminogen activator inhibitor-1 (PAI-1) is largely responsible for this fibrinolytic defect. Newly described pathways by which lung epithelial cells regulate expression of uPA, its receptor uPAR, and PAI-1 at the posttranscriptional level have been identified. These pathways operate by cis-trans interactions between mRNA binding proteins; regulatory sequences within these mRNAs control their stability. The regulatory mechanisms seem to involve multiple protein-mRNA interactions, and the phosphorylation state of the proteins appears to determine whether complex formation of, or dissociation from, the regulatory sequences occurs. uPA is capable of inducing its own expression in lung epithelial cells as well as that of uPAR and PAI-1-the effects involve posttranscriptional regulatory components. These and related observations have led to the implementation of anticoagulant or fibrinolytic strategies to protect the lung against acute lung injury. The success of new fibrinolytic strategies to block pleural loculation suggests that a similar approach might be used to prevent accelerated pulmonary fibrosis, which can occur in association with many forms of acute lung injury. Disordered coagulation and fibrinolysis promote extravascular fibrin deposition in acute lung injury. It is this deposition that characterizes acute lung injury and repair. Expression of uPA, uPAR, and PAI-1 by the lung epithelium, as well as the ability of uPA to induce other components of the fibrinolytic system, involves posttranscriptional regulation. These pathways may contribute to disordered fibrin turnover in the injured lung. The success of anticoagulant or fibrinolytic strategies designed to reverse the abnormalities of local fibrin turnover in acute lung injury supports the inference that abnormalities of coagulation, fibrinolysis, and fibrin deposition have a critical role in the pathogenesis of acute lung injury.


Incidental findings in MRI of the paranasal sinuses in adults: a population-based study (HUNT MRI).
Diagnostic imaging of the head is used with increasing frequency, and often includes the paranasal sinuses, where incidental opacifications are found. To determine the clinical relevance of such findings can be challenging, and for the patient such incidental findings can give rise to concern if they are over-reported. Studies of incidental findings in the paranasal sinuses have been conducted mostly in patients referred for diagnostic imaging, hence the prevalence in the general population is not known. The purpose of this study was to determine the prevalence and size of incidental opacification in the paranasal sinuses in a non-selected adult population using magnetic resonance imaging (MRI) without medical indication, and to relate the results to sex and season. Randomly and independent of medical history, 982 participants (518 women) with a mean age of 58.5 years (range, 50-66) underwent MRI of the head as part of a large public health survey in Norway. The MRIs included 3D T1 weighted volume data and 2D axial T2 weighted image (WI). Opacifications, indicating mucosal thickenings, polyps, retention cysts, or fluid, were recorded if measuring more than 1 mm. Opacifications were found in 66% of the participants. Mucosal thickenings were found in 49%, commonly in the maxillary sinuses (29%) where 25% had opacifications that were less than 4 mm in size. Other opacifications occurred in the anterior ethmoid (23%), posterior ethmoid (21%), frontal sinus (9%), and sphenoid (8%). Polyps and retention cysts were also found mainly in the maxillary sinuses in 32%. Fluid was observed in 6% of the MRIs. Mucosal thickening was observed more frequently in men than in women (P <0.05). No seasonal variation was found. In this large non-selected sample, incidental opacification in the paranasal sinuses was seen in two out of three participants, and mucosal thickening was seen in one out of two. Fluid was rare. Knowledge of incidental opacification is important because it can affect clinical practice.


Coping with employee, family, and student roles: evidence of dispositional conflict and facilitation tendencies.
Balancing multiple roles is a challenge for individuals in many sectors of the population. The purpose of this study was to test the hypothesis that individuals have dispositional tendencies to experience interrole conflict and facilitation. We also aimed to show that coping styles and life satisfaction are correlates of dispositional conflict and facilitation tendencies. Two survey studies were conducted with individuals involved in 3 life roles (i.e., employee, student, and family member; Study 1: N = 193; Study 2: N = 284). The hierarchical structure of conflict and facilitation was examined in both studies. Support for the dispositional model was found in both cases through the use of hierarchical confirmatory factor analyses. In Study 2, a longitudinal assessment of the nomological network surrounding conflict and facilitation tendencies was conducted with structural equation modeling analyses; we found that coping styles had synchronous relations with dispositional conflict and facilitation; dispositional conflict had a lagged and negative relation with life satisfaction.


Tracheostomy-Assisted Foreign Body Removal: Insights From a Case Series and Literature Review.
Foreign body aspiration into the trachea is a common occurrence in children. While most foreign bodies in the airways can be removed using rigid tracheoscopy, there are instances where tracheostomy or tracheotomy is needed. This article presents a series of cases in which tracheostomy was necessary to remove foreign bodies, and summarizes the relevant experiences and lessons learned. We reviewed a total of 7 cases in which tracheostomy and rigid tracheoscopy were combined for foreign body removal out of a larger cohort of 1559 cases at Shenzhen Children's Hospital in Guangdong, China over a 20-year period. The combined use of tracheostomy and rigid tracheoscopy resulted in successful removal of foreign bodies in all 7 patients reviewed in this study. Six patients developed complications of tracheotomy, mainly including mediastinal emphysema (5/7), subcutaneous emphysema (3/7), and pneumothorax (1/7). Tracheotomy was temporary in all patients. In cases where a foreign body in the trachea is too large or has irregular, sharp edges, is embedded in submucosal tissues with edema, cannot be passed smoothly through the vocal cords, or local endoscopic facilities are inadequate, a tracheotomy may be necessary. However, this approach should be used with caution, and close collaboration with anesthesiologists and careful management of intraoperative emergencies are crucial for improving the success rate of the procedure. Additionally, the complications should be noted, paying particular attention to early complications such as pneumothorax, pneumomediastinum, and bleeding.


Fibrin glues in combination with mesenchymal stem cells to develop a tissue-engineered cartilage substitute.
Damage of cartilage due to traumatic or pathological conditions results in disability and severe pain. Regenerative medicine, using tissue engineering-based constructs to enhance cartilage repair by mobilizing chondrogenic cells, is a promising approach for restoration of structure and function. Fresh fibrin (FG) and platelet-rich fibrin (PR-FG) glues produced by the CryoSeal(®) FS System, in combination with human bone marrow-derived mesenchymal stem cells (BM-hMSCs), were evaluated in this study. We additionally tested the incorporation of heparin-based delivery system (HBDS) into these scaffolds to immobilize endogenous growth factors as well as exogenous transforming growth factor-β(2). Strongly, CD90+ and CD105+ hMSCs were encapsulated into FG and PR-FG with and without HBDS. Encapsulation of hMSCs in PR-FG led to increased expression of collagen II gene at 2.5 weeks; however, no difference was observed between FG and PR-FG at 5 weeks. The incorporation of HBDS prevented the enhancement of collagen II gene expression. BM-hMSCs in FG initially displayed enhanced aggrecan gene expression and increased accumulation of Alcian blue-positive extracellular matrix; incorporation of HBDS into these glues did not improve aggrecan gene expression and extracellular matrix accumulation. The most significant effect on cartilage marker gene expression and accumulation was observed after encapsulation of hMSCs in FG. We conclude that FG is more promising than PR-FG as a scaffold for chondrogenic differentiation of hMSCs; however, immobilization of growth factors inside these fibrin scaffolds with the HBDS system has a negative impact on this process. In addition, BM-hMSCs are valid and potentially superior alternatives to chondrocytes for tissue engineering of articular cartilage.


Partial expression of endogenous mouse mammary tumor virus in mammary tumors induced in BALB/c mice by chemical, hormonal, and physical agents.
The possible interaction of environmental factors with the endogenous mouse mammary tumor virus (MMTV) genome in the development of mammary tumors in the low-tumor-incidence BALB/c mouse strain was examined. Tumors were induced in virgin female animals by treatment with chemical carcinogen 7,12- dimethylbenz[alpha]anthracene or urethan, with or without prolonged hormonal stimulation, or by X-irradiation. Concomitant hormonal stimulation resulted in increased tumor incidences compared with those induced by chemical carcinogen treatment alone. The frequency of tumor induction by irradiation alone or in combination with urethan or prolactin stimulation was very low. MMTV expression in the mammary tumors was assayed by nucleic acid hybridization and by immunohistochemical staining. Depending upon the treatment group, 0 to 89% of the tumors contained detectable levels of MMTV RNA (>/=0.0005% of the total cellular RNA). Tumors which contained detectable viral transcripts exhibited only low levels of MMTV RNA, which did not appear to represent the accumulation of RNA sequences homologous to the entire MMTV genome; synthesis of MMTV structural proteins was detected in only one tumor. Viral RNA-positive tumors were generally associated with a longer latent period. MMTV RNA expression occurred in tumors classified histologically as adenoacanthomas, as well as in mammary adenocarcinomas, although the cell types in the adenoacanthomas expressing viral RNA were not identified. It does not appear that expression of the endogenous MMTV genome is required for maintenance of all mammary tumors in BALB/c mice, although partial genome expression undetectable by the methods employed cannot be ruled out. Linear regression analyses were performed. The mean time to tumor appearance and the percentage of tumors which were MMTV RNA positive were found to vary linearly as a function of the total dose of 7,12-dimethylbenz[alpha]anthracene administered. The percentage of tumors which were MMTV RNA positive was also shown to be linearly related to the mean time to tumor appearance. These relationships provide a basis for predictions in the BALB/c system related to these parameters.


Kidney of giraffes.
This study focuses on certain aspects of the renal structure of the giraffe, with some implications as to its function. About 4,000 collecting ducts open at the truncated end of a curved crest that juts into the renal pelvis as the inner medulla (IM). Extensions of the pelvis pass between the medullary (MP) and vascular (VP) processes almost to the corticomedullary border. The MPs contain an IM and an outer medulla (OM) containing clusters of capillaries (vascular bundles). The VPs contain the interlobar arteries and veins. All of the IM and almost all of the OM, with its vascular bundles, are bathed with pelvic urine. The cortex comprises 63% of the parenchyma. The OM has nine times the mass of the IM. The IM comprises 4% of the parenchyma. The ratio of mass of the adult cortex to the medulla is 1.7:1.0, and the number of glomeruli per kidney is 6.6 x 10(6). Glomerular mass is 6.2-6.7% of renal mass in the adult and 5.2% in the 6-month-old calf. The dimensions of the glomerular capsules are the same across the thickness of the cortex. Every terminal collecting duct drains an estimated 1,650 nephrons. In the adult giraffe the ratio of thickness of the muscularis of the main renal artery (RA) to its diameter is 0.117 (right RA) and 0.132 (left RA). These ratios are close to those in rhinoceros and ox but greater than in man. The visceral arteries (celiac, anterior mesenteric, and renal) have about the same muscularis : diameter ratio. Giraffes have arterial hypertension, but atherosclerosis is apparently absent and serum lipid fractions are low.


Prevalence of disability in Tamil Nadu, India.
Information on disability is essential for the government to formulate policies, allocate adequate resources and implement appropriate programmes. We aimed to estimate the prevalence of disability and describe the types of disability by gender, age and geographical regions in Tamil Nadu, India. We analysed the 2011 Census cross-sectional survey data of Tamil Nadu. Age-adjusted disability rates and disability rates per 100 000 population were calculated. There were 1 179 963 disabled individuals in Tamil Nadu in 2011, a disability rate of 1635 per 100 000 population. Disability in movement, hearing and sight individually accounted for 24%, 19% and 11% of the total disability, respectively. Sixteen districts had disability rates above the state average. As age advanced, disability rates increased; the highest disability rate of 2533 per 100 000 was among people aged 60 years and above. The disability rates were higher in males compared to females (1819 v. 1451 per 100 000). Rural areas had higher disability areas compared to urban (1670 v. 1599 per 100 000). Currently married, working populations and literate populations had lower disability rates. Disability rate in the Scheduled Castes was higher at 1763 per 100 000 compared to the Scheduled Tribes and other social groups. Multiple disability was high in the age groups 0-19 years and 60 years and above. Physical or mental disability was observed in 1.6% of the population of Tamil Nadu. Research is warranted to identify underlying causes and interventions to reduce the burden of disability in the state.