17β-Estradiol Protects Rat Annulus Fibrosus Cells Against Apoptosis via α1 Integrin-Mediated Adhesion to Type I Collagen: An In-vitro Study.
BACKGROUND 17β-Estradiol (E2) has been reported to protect annulus fibrosus (AF) cells in vitro against interleukin-1β (IL-1β)-induced apoptosis in a concentration-dependent manner. However, its time-response effect remains unexplored. In addition, integrin α2/collagen II interaction has been reported to influence the apoptosis of nucleus pulposus cells in vitro. Thus, we hypothesized that integrin α1/collagen II might play a role in exerting the anti-apoptosis effect by E2. The aim of the current study was to further investigate the anti-apoptotic effect of E2 and determine the role of integrin a1/collagen II interaction. MATERIAL AND METHODS Rat AF cells were primary cultured and used for the following experiments. AF cells were identified by immunocytochemistry of type I collagen. Cell apoptosis was detected by fluorescence-activated cell sorter (FACS) analysis. The activity of active caspase-3 was determined by use of a caspase-3 detection kit. AF cell adhesion to type I collagen was determined by cell adhesion assay. Protein level of integrin subunit α1 was quantified by Western blot and mRNA expression was determined by real-time qPCR. RESULTS The immunocytochemistry of type I collagen revealed that cell purity was eligible for the following experiments with 98% of purity. FACS analysis indicated time-dependent anti-apoptosis effect of E2 at time points of 6 h, 12 h, and 24 h, which was confirmed by Caspase-3 activity. Furthermore, cell adhesion assay showed that E2 significantly increased cell binding to 95% of control, and qPCR and Western blot analysis showed that E2 effectively upregulated integrin α1. However, estrogen receptor antagonist ICI182780 prohibited the effect of E2. CONCLUSIONS This study shows that E2 protects against apoptosis in a time-dependent manner, and α1 integrin-mediated adhesion to collagen II is essential for estrogen-dependent anti-apoptosis in rat annulus fibrosus cells in vitro.


Effects of simulation dimensionality on laser-driven electron acceleration and photon emission in hollow microchannel targets.
Using two-dimensional (2D) and three-dimensional (3D) kinetic simulations, we examine the impact of simulation dimensionality on the laser-driven electron acceleration and the emission of collimated γ-ray beams from hollow microchannel targets. We demonstrate that the dimensionality of the simulations considerably influences the results of electron acceleration and photon generation owing to the variation of laser phase velocity in different geometries. In a 3D simulation with a cylindrical geometry, the acceleration process of electrons terminates early due to the higher phase velocity of the propagating laser fields; in contrast, 2D simulations with planar geometry tend to have prolonged electron acceleration and thus produce much more energetic electrons. The photon beam generated in the 3D setup is found to be more diverged accompanied with a lower conversion efficiency. Our paper concludes that the 2D simulation can qualitatively reproduce the features in 3D simulation, but for quantitative evaluations and reliable predictions to facilitate experiment designs 3D modeling is strongly recommended.


Disruption of the Toxoplasma gondii parasitophorous vacuole by IFNgamma-inducible immunity-related GTPases (IRG proteins) triggers necrotic cell death.
Toxoplasma gondii is a natural intracellular protozoal pathogen of mice and other small mammals. After infection, the parasite replicates freely in many cell types (tachyzoite stage) before undergoing a phase transition and encysting in brain and muscle (bradyzoite stage). In the mouse, early immune resistance to the tachyzoite stage is mediated by the family of interferon-inducible immunity-related GTPases (IRG proteins), but little is known of the nature of this resistance. We reported earlier that IRG proteins accumulate on intracellular vacuoles containing the pathogen, and that the vacuolar membrane subsequently ruptures. In this report, live-cell imaging microscopy has been used to follow this process and its consequences in real time. We show that the rupture of the vacuole is inevitably followed by death of the intracellular parasite, shown by its permeability to cytosolic protein markers. Death of the parasite is followed by the death of the infected cell. The death of the cell has features of pyronecrosis, including membrane permeabilisation and release of the inflammatory protein, HMGB1, but caspase-1 cleavage is not detected. This sequence of events occurs on a large scale only following infection of IFNgamma-induced cells with an avirulent strain of T. gondii, and is reduced by expression of a dominant negative mutant IRG protein. Cells infected by virulent strains rarely undergo necrosis. We did not find autophagy to play any role in the key steps leading to the death of the parasite. We conclude that IRG proteins resist infection by avirulent T. gondii by a novel mechanism involving disruption of the vacuolar membrane, which in turn ultimately leads to the necrotic death of the infected cell.


Influence of chelate ring type on chelate-chelate and chelate-aryl stacking: the case of nickel bis(dithiolene).
Chelate-aryl and chelate-chelate stacking interactions of nickel bis(dithiolene) were studied at the CCSD(T)/CBS and DFT levels. The strongest chelate-aryl stacking interaction between nickel bis(dithiolene) and benzene has a CCSD(T)/CBS stacking energy of -5.60 kcal mol-1. The strongest chelate-chelate stacking interactions between two nickel bis(dithiolenes) has a CCSD(T)/CBS stacking energy of -10.34 kcal mol-1. The most stable chelate-aryl stacking has the benzene center above the nickel atom, while the most stable chelate-chelate dithiolene stacking has the chelate center above the nickel atom. Comparison of chelate-aryl stacking interactions of dithiolene and acac-type nickel chelate shows similar strength. However, chelate-chelate stacking is stronger for dithiolene nickel chelate than for acac-type nickel chelate, which has a CCSD(T)/CBS interaction energy of -9.50 kcal mol-1.


The psychopathology of schizophrenia: an integrated view on positive symptoms and negative symptoms.
Interest in the distinction between positive and negative symptoms has reached a peak in the last decade and has led to research in different fields like phenomenology, ethiopathogenesis, treatment, course and outcome. Which symptoms are considered positive or negative varies across different authors, although there seems to be agreement on a core syndrome. The definition problems can be also found in the rating scales used for measuring positive and negative symptoms. The positive/negative distinction may represent different manifestations of a common underlying process. It also may suggest the existence of different pathophysiologies in schizophrenia. Since both positive and negative symptoms are frequent in schizophrenia, they are most likely not completely independent. The negative/positive syndrome is not sufficient to describe the dimensions of the complex phenomenology of schizophrenia. Among others, a depressive syndrome needs to be integrated. There is much controversy concerning the course of positive and negative symptoms over time. In subacute and chronic patients the negative syndrome seems to be more stable than the positive syndrome. The differentiation between primary and secondary negative symptoms seems to have great relevance to clinical and research aspects. This differentiation is an important factor in the interpretation of neuroleptic trials on negative symptoms. One way of differentiating between direct and indirect drug effects on negative symptoms is to use sophisticated statistical procedures, for example path analysis.


Aromatase inhibitors induce spine synapse loss in the hippocampus of ovariectomized mice.
Recently, inhibition of estrogen synthesis by aromatase inhibitors has become a favored therapy for breast cancer in postmenopausal women. Estrogen is, however, important for synapse formation in the hippocampus. Inhibition of aromatase induces spine synapse loss in organotypic hippocampal slice cultures. We therefore studied the effect of systemic treatment with the potent aromatase inhibitor letrozole on spine synapse formation and synaptic proteins in the hippocampi of female mice for periods of 7 d and 4 wk. In cyclic, letrozole-treated females and in ovariectomized, letrozole-treated females, the number of spine synapses was significantly reduced in the hippocampus but not in the prefrontal or cerebellar cortex. Consequently, the expression of the N-methyl-D-aspartate receptor NR1 was significantly down-regulated after treatment with letrozole. In cyclic animals the expression of the synaptic proteins synaptophysin and spinophilin was down-regulated in response to letrozole. In ovariectomized animals, however, protein expression was down-regulated after 7 d of treatment, whereas the expression was up-regulated after 4 wk of treatment. Our results indicate that systemic inhibition of aromatase in mice affects structural synaptic plasticity in the hippocampus. This may contribute to cognitive deficits in postmenopausal women treated with aromatase inhibitors.


Nrf2-mediated neuroprotection in the MPTP mouse model of Parkinson's disease: Critical role for the astrocyte.
Oxidative stress has been implicated in the etiology of Parkinson's disease (PD) and in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) animal model of PD. It is known that under conditions of oxidative stress, the transcription factor NF-E2-related factor (Nrf2) binds to antioxidant response element (ARE) to induce antioxidant and phase II detoxification enzymes. To investigate the role of Nrf2 in the process of MPTP-induced toxicity, mice expressing the human placental alkaline phosphatase (hPAP) gene driven by a promoter containing a core ARE sequence (ARE-hPAP) were used. ARE-hPAP mice were injected (30 mg/kg) once per day for 5 days and killed 7 days after the last MPTP injection. In response to this design, ARE-dependent gene expression was decreased in striatum whereas it was increased in substantia nigra. The same MPTP protocol was applied in Nrf2(+/+) and Nrf2(-/-) mice; Nrf2 deficiency increases MPTP sensitivity. Furthermore, we evaluated the potential for astrocytic Nrf2 overexpression to protect from MPTP toxicity. Transgenic mice with Nrf2 under control of the astrocyte-specific promoter for the glial fribillary acidic protein (GFAP-Nrf2) on both a Nrf2(+/+) and Nrf2(-/-) background were administered MPTP. In the latter case, only the astrocytes expressed Nrf2. Independent of background, MPTP-mediated toxicity was abolished in GFAP-Nrf2 mice. These striking results indicate that Nrf2 expression restricted to astrocytes is sufficient to protect against MPTP and astrocytic modulation of the Nrf2-ARE pathway is a promising target for therapeutics aimed at reducing or preventing neuronal death in PD.


The incorporation of whole grain into pelleted broiler chicken diets. II. Gastrointestinal and digesta characteristics.
1. Pelleted diets, incorporating whole or ground wheat or barley in the pellets, were fed to broiler chickens and the performance, gastrointestinal development and digesta characteristics of those chickens recorded. 2. Body weight was similar with whole grain incorporation or enzyme application. Food conversion efficiency was improved by addition of enzyme to a full wheat diet. 3. Whole grain inclusion in pellets reduced proventriculus proportional mass and increased gizzard proportional mass with no apparent effects of exogenous feed enzyme addition. 4. Relative ileal mass was reduced by enzyme inclusion in a wheat diet and by inclusion of whole barley in the pellets. 5. Digesta viscosity was increased by whole wheat inclusion but reduced by enzyme inclusion irrespective of grain processing. Inclusion of 200 g/kg of barley did not alter viscosity of digesta beyond the duodenum. 6. Fresh excreta pH was higher with both cereals in the grower phase when whole grain was fed. On the barley diet, this was affected by enzyme addition, which created higher pH from a point earlier in the grower phase than when no enzyme was employed. 7. Evidence of a complex interaction between higher viscosity and pH being involved in differences in ileal relative mass was found through significant relationships being produced by enzyme use on the wheat diet alone.


In silico identification and functional prediction of differentially expressed genes in South Asian populations associated with type 2 diabetes.
Type 2 diabetes (T2D) is one of the major metabolic disorders in humans caused by hyperglycemia and insulin resistance syndrome. Although significant genetic effects on T2D pathogenesis are experimentally proved, the molecular mechanism of T2D in South Asian Populations (SAPs) is still limited. Hence, the current research analyzed two Gene Expression Omnibus (GEO) and 17 Genome-Wide Association Studies (GWAS) datasets associated with T2D in SAP to identify DEGs (differentially expressed genes). The identified DEGs were further analyzed to explore the molecular mechanism of T2D pathogenesis following a series of bioinformatics approaches. Following PPI (Protein-Protein Interaction), 867 potential DEGs and nine hub genes were identified that might play significant roles in T2D pathogenesis. Interestingly, CTNNB1 and RUNX2 hub genes were found to be unique for T2D pathogenesis in SAPs. Then, the GO (Gene Ontology) showed the potential biological, molecular, and cellular functions of the DEGs. The target genes also interacted with different pathways of T2D pathogenesis. In fact, 118 genes (including HNF1A and TCF7L2 hub genes) were directly associated with T2D pathogenesis. Indeed, eight key miRNAs among 2582 significantly interacted with the target genes. Even 64 genes were downregulated by 367 FDA-approved drugs. Interestingly, 11 genes showed a wide range (9-43) of drug specificity. Hence, the identified DEGs may guide to elucidate the molecular mechanism of T2D pathogenesis in SAPs. Therefore, integrating the research findings of the potential roles of DEGs and candidate drug-mediated downregulation of marker genes, future drugs or treatments could be developed to treat T2D in SAPs.


Stepwise metal-ligand cooperation by a reversible aromatization/deconjugation sequence in ruthenium complexes with a tetradentate phenanthroline-based ligand.
The synthesis and reactivity of ruthenium complexes containing the tetradentate phenanthroline-based phosphine ligand 2,9-bis((di-tert-butylphosphino)methyl)-1,10-phenanthroline (PPhenP) is described. The hydrido chloro complex [RuHCl(PPhenP)] (2) undergoes facile dearomatization upon deprotonation of the benzylic position, to give [RuH(PPhenP-H)] (4). Addition of dihydrogen to 4 causes rearomatization of the phenanthroline moiety to trans-[Ru(H)(2)(PPhenP)] (5), followed by hydrogenation of an aromatic heterocycle in the ligand backbone, to give a new dearomatized and deconjugated complex [RuH(PPhenP*-H)] (6). These aromatization/deconjugation steps of the coordinated ligand were demonstrated to be reversible and operative in the dehydrogenation of primary alcohols without the need for a hydrogen acceptor. This aromatization/deconjugation sequence constitutes an unprecedented mode of a stepwise cooperation between the metal center and the coordinated ligand.


Is the use of colloids for fluid replacement harmless in children?
Albumin has been regarded as the gold standard for maintaining adequate colloid osmotic pressure in children, but increased cost, the lack of clear-cut benefits for survival, and fear of transmission of unknown viruses have contributed to its replacement by hydroxyethyl starch and gelatin preparations. Each of the synthetic colloids has unique physicochemical characteristics that determine their likely efficacy and adverse effect profile. This review will examine the advantages and disadvantages of the use of different colloid solutions in children with a particular focus on their safety profile. Dextrans are rarely used because of their negative effects on coagulation and potential for anaphylactic reactions. Gelatin and albumin have little effect on hemostasis, but the disadvantages of gelatin include its high anaphylactoid potential and limited beneficial volume effect. Tetrastarches have significantly fewer adverse effects on coagulation and renal function than the older hydroxyethyl starches and are now approved for children. Dissolving tetrastarches in a plasma-adapted, balanced solution rather than in saline further improves safety with regard to coagulation and acid-base balance. Tetrastarches offer the best currently available compromise between cost-effectiveness and safety profile in children with preexisting normal renal function and coagulation.


MiBiOmics: an interactive web application for multi-omics data exploration and integration.
Multi-omics experimental approaches are becoming common practice in biological and medical sciences underlining the need to design new integrative techniques and applications to enable the multi-scale characterization of biological systems. The integrative analysis of heterogeneous datasets generally allows to acquire additional insights and generate novel hypotheses about a given biological system. However, it can become challenging given the often-large size of omics datasets and the diversity of existing techniques. Moreover, visualization tools for interpretation are usually non-accessible to biologists without programming skills. Here, we present MiBiOmics, a web-based and standalone application that facilitates multi-omics data visualization, exploration, integration, and analysis by providing easy access to dedicated and interactive protocols. It implements classical ordination techniques and the inference of omics-based (multilayer) networks to mine complex biological systems, and identify robust biomarkers linked to specific contextual parameters or biological states. MiBiOmics provides easy-access to exploratory ordination techniques and to a network-based approach for integrative multi-omics analyses through an intuitive and interactive interface. MiBiOmics is currently available as a Shiny app at https://shiny-bird.univ-nantes.fr/app/Mibiomics and as a standalone application at https://gitlab.univ-nantes.fr/combi-ls2n/mibiomics .


Photolabile ubiquinone analogues for identification and characterization of quinone binding sites in proteins.
Quinones are essential components in most cell and organelle bioenergetic processes both for direct electron and/or proton transfer reactions but also as means to regulate various bioenergetic processes by sensing cell redox states. To understand how quinones interact with proteins, it is important to have tools for identifying and characterizing quinone binding sites. In this work three different photo-reactive azidoquinones were synthesized, two of which are novel compounds, and the methods of synthesis was improved. The reactivity of the azidoquinones was first tested with model peptides, and the adducts formed were analyzed by mass spectrometry. The added mass detected was that of the respective azidoquinone minus N(2). Subsequently, the biological activity of the three azidoquinones was assessed, using three enzyme systems of different complexity, and the ability of the compounds to inactivate the enzymes upon illumination with long wavelength UV light was investigated. The soluble flavodoxin-like protein WrbA could only use two of the azidoquinones as substrates, whereas respiratory chain Complexes I and II could utilize all three compounds as electron acceptors. Complex II, purified in detergent, was very sensitive to illumination also in the absence of azidoquinones, making the 'therapeutic window' in that enzyme rather narrow. In membrane bound Complex I, only two of the compounds inactivated the enzyme, whereas illumination in the presence of the third compound left enzyme activity essentially unchanged. Since unspecific labeling should be equally effective for all the compounds, this demonstrates that the observed inactivation is indeed caused by specific labeling.


Comparison of LMA Supreme, i-gel, and Baska Mask for Airway Management during Laparoscopic Cholecystectomy: A Prospective Randomized Comparative Study from North India.
The supraglottic airway device (SAD) has proved to be an appropriate alternative to endotracheal intubation in laparoscopic surgeries owing to various advantages, namely, decreased airway manipulation and stable hemodynamics. We compared the efficacy in terms of oropharyngeal leak pressure (OLP) and safety of laryngeal mask airway (LMA)-Supreme (LMA-S), i-gel, and Baska mask in patients undergoing laparoscopic cholecystectomy. Ninety patients posted for elective laparoscopic cholecystectomy were selected for a prospective randomized comparative study in a tertiary care center. The study comprised three groups of 30 each based on the different SADs used Group-LS with LMA-Supreme, Group-IG with i-gel, and Group-BM with Baska mask. The secondary objectives were device insertion time, ease of insertion, changes in the peak airway pressure (PAP), heart rate, mean arterial pressure, and airway complications (sore throat, dysphagia. dysphonia, lip/tongue or dental injury, etc.) between three groups. The quantitative data were analyzed using the one-way analysis of variance test and Bonferroni post hoc multiple comparison test. Qualitative data were compared using Chi.squared test. OLP was significantly higher (P = 0.005) in the Baska mask than i-gel and LMA-S groups just after insertion and during carboperitonium. There was no significant difference in time for device insertion, number of attempts, ease of insertion, and use of manipulation (P > 0.05). However, the gastric tube insertion time was significantly lower in Group BM (9.59 ± 2.78) than Group IG with 12.79 ± 3.47 and Group LS with 10.84 ± 3.68 (P < 0.05). There were no significant differences between the groups with regard to changes in the PAP, heart rate, mean arterial pressure at different time intervals, and complications. Baska mask provided a significantly higher OLP compared to i-gel and LMA-S without significant airway morbidity in laparoscopic surgeries.


Nocardia grenadensis sp. nov., isolated from sand of the Caribbean Sea.
A Gram-stain-positive, non-spore-forming bacterium (GW5-5797(T)) was isolated on soil extract agar from sand collected at a depth of 5 m in the Caribbean Sea near Grenada. 16S rRNA gene sequence analysis and similarity studies showed that strain GW5-5797(T) belongs to the genus Nocardia, and is most closely related to Nocardia speluncae N2-11(T) (99.2% similarity) and Nocardia jinanensis 04-5195(T) (99.2%) and more distantly related to Nocardia rhamnosiphila 202GMO(T) (98.6%) and other Nocardia species. Strain GW5-5797(T) could be distinguished from all other recognized Nocardia species by sequence similarity values less than 98.5%. The peptidoglycan diamino acid was meso-diaminopimelic acid. Strain GW5-5797(T) exhibited a quinone system with the predominant compounds MK-8(H(4)ω-cyclo) and MK-8(H(2)). The polar lipid profile of GW5-5797(T) consisted of the major compounds diphosphatidylglycerol, phosphatidylethanolamine and an unidentified glycolipid, moderate amounts of phosphatidylinositol and a phosphatidylinositol mannoside and minor amounts of several lipids including a second phosphatidylinositol mannoside. The polyamine pattern contained the major compound spermine and moderate amounts of spermidine. The major fatty acids were C(16:0,) C(18:1)ω9c and 10-methyl C(18:0). These chemotaxonomic traits are in excellent agreement with those of other Nocardia species. The results of DNA-DNA hybridizations and physiological and biochemical tests allowed genotypic and phenotypic differentiation of strain GW5-5797(T) from the most closely related species, showing 16S rRNA gene sequence similarities >98.5%. Strain GW5-5797(T) therefore merits separate species status, and we propose the name Nocardia grenadensis sp. nov., with the type strain GW5-5797(T) (=CCUG 60970(T) =CIP 110294(T)).


An advanced boundary element method (BEM) implementation for the forward problem of electromagnetic source imaging.
The forward problem of electromagnetic source imaging has two components: a numerical model to solve the related integral equations and a model of the head geometry. This study is on the boundary element method (BEM) implementation for numerical solutions and realistic head modelling. The use of second-order (quadratic) isoparametric elements and the recursive integration technique increase the accuracy in the solutions. Two new formulations are developed for the calculation of the transfer matrices to obtain the potential and magnetic field patterns using realistic head models. The formulations incorporate the use of the isolated problem approach for increased accuracy in solutions. If a personal computer is used for computations, each transfer matrix is calculated in 2.2 h. After this pre-computation period, solutions for arbitrary source configurations can be obtained in milliseconds for a realistic head model. A hybrid algorithm that uses snakes, morphological operations, region growing and thresholding is used for segmentation. The scalp, skull, grey matter, white matter and eyes are segmented from the multimodal magnetic resonance images and meshes for the corresponding surfaces are created. A mesh generation algorithm is developed for modelling the intersecting tissue compartments, such as eyes. To obtain more accurate results quadratic elements are used in the realistic meshes. The resultant BEM implementation provides more accurate forward problem solutions and more efficient calculations. Thus it can be the firm basis of the future inverse problem solutions.


Using in-situ environmental DNA sampling to detect the invasive New Zealand Mud Snail (Potamopyrgus antipodarum) in freshwaters.
Environmental DNA (eDNA) detection of aquatic invasive species is currently at the forefront of aquatic conservation efforts because the methodology provides a cost effective and sensitive means to detect animals at low densities. Developments in eDNA technologies have improved detection probabilities for rare, indicator, and invasive species over the past decade. However, standard lab analysis can take days or weeks before results are available and is prohibitive when rapid management decisions are required for mitigation. Here, we investigated the performance of a real-time quantitative PCR system for on-site eDNA detection of New Zealand mud snails (Potamopyrgus antipodarum). Six sites in western Washington, USA were sampled using the rapid eDNA technique and traditional methods, with five samples per site. On-site eDNA detection of mud snails resulted in a 10% increase in positive sites (16/30 = 53% positive) relative to visual surveys (13/30 = 43% positive). In addition, positive associations were observed between mud snail eDNA concentration (eDNA copies per reaction) and the number of mud snail individuals at each site (R 2 = 0.78). We show that the rapid on-site eDNA technology can be effective for detection and quantification of New Zealand mud snails in freshwaters. This on-site eDNA detection approach could possibly be used to initiate management protocols that allow for more rapid responses during the onset of biological invasions.


Allele frequency of inosine triphosphate pyrophosphatase gene polymorphisms in a Japanese population.
The enzyme inosine triphosphate pyrophosphatase (ITPase) catalyses the pyrophosphohydrolysis of ITP to IMP. ITPase deficiency is a clinically benign autosomal recessive condition characterised by the abnormal accumulation of ITP in erythrocytes. A deficiency of ITPase may predict adverse reactions to therapy with the thiopurine drug 6-mercaptopurine and its prodrug azathioprine. In this study, we examine the frequencies of ITPA polymorphisms in 100 healthy Japanese individuals. The allele frequency of the 94C > A variant in the Japanese sample was 0.135 (Caucasian allele frequency 0.06). The IV2 + 21A > C polymorphism was not found in Japanese (Caucasian allele frequency 0.130). Allele frequencies of the 138G > A, 561G > A and 708G > A polymorphisms were 0.57, 0.18 and 0.06 respectively in the Japanese population, and with the exception of the 138G > A polymorphism, similar to allele frequencies in Caucasians.


Tamm-Horsfall protein in human renal tumours.
Tamm-Horsfall Protein (THP) is found to be localised in the ascending loop of Henle and the distal tubules of normal and foetal kidneys. We have used an anti-THP monoclonal antibody (D2) to stain foetal, normal and kidney tumours. The dinitrophenyl hapten staining technique was the most specific and sensitive staining procedure. The staining of Tamm-Horsfall Protein in foetal and normal kidney was in agreement with most other investigators. The majority of renal cell carcinoma (22/24) and rhabdoid renal tumours (3/4) stained positively for THP. None of the Wilms' tumours, mesoblastic nephromas or bone metastasising renal tumours of childhood gave positive staining. The findings would suggest that renal cell carcinomas and rhabdoid kidney tumours arise from ascending loop of Henle or distal tubules. The lack of positive staining in the majority of childhood renal tumours raises the possibility of a different histogenesis for these neoplasms.


Long-term outcomes of tracheal stents removal under fluoroscopy guidance: comparison of tracheal fistulas and tracheal stenosis.
Endoscopic removal is the most common method for removal of tracheal stents. Few studies have reported the technique of fluoroscopy-guided stent removal for tracheal fistula and tracheal stenosis. We aimed to study the safety and efficacy of fluoroscopy-guided stent removal as well as the optimal duration for stent usage. We conducted a retrospective analysis of 152 patients who underwent fluoroscopy-guided stent removal from January 2011 to June 2017. Reasons for stent implantation were tracheal fistula in 85 patients (TF group), and tracheal stenosis in 67 patients (TS group). All patients underwent tracheal CT scans before stent removal and during follow up. The technical success rate, complications, and survival rate were compared between the two groups. The technical success rate of stent removal was 98.9 and 97.4%, respectively for the TF and TS group. Removal was routine for half of patients, and in the remainder, excessive granulation tissue was the common indications for stent removal, which was found after stenting at 142.1 ± 25.9 days in the TF group, and at 89.9 ± 15.0 day in the TS group. The total incidence of complications was 21.1 and 22.4%, respectively, for the TF and TS groups. Perioperative death occurred in one patient in the TF group, and two patients in the TS group. Recurrence of fistula or stenosis requiring re-stenting was the most comment complication in both groups. The 0.5-, 3-, 6-year survival rates were 90.3, 59.6, and 36.1% for TF group, and 80.4, 75.7, 75.7% for TS group. Fluoroscopic removal of tracheal stents is safe and effective for both tracheal fistula and tracheal stenosis, with no significant difference in outcomes. Clinicians should pay attention to the risk of hemoptysis for patients with malignant tumors and a combination with endoscopic hemostasis may help improve its safety.


Phage Life Cycles Behind Bacterial Biodiversity.
Bacteriophages (phages or bacterial viruses) are the most abundant biological entities in our planet; their influence reaches far beyond the microorganisms they parasitize. Phages are present in every environment and shape up every bacterial population in both active and passive ways. They participate in the circulation of organic matter and drive the evolution of microorganisms by horizontal gene transfer at unprecedented scales. The mass flow of genetic information in the microbial world influences the biosphere and poses challenges for science and medicine. The genetic flow, however, depends on the fate of the viral DNA injected into the bacterial cell. The archetypal notion of phages only engaging in predatorprey relationships is slowly fading. Because of their varied development cycles, environmental conditions, and the diversity of microorganisms they parasitize, phages form a dense and highly complex web of dependencies, which has important consequences for life on Earth. The sophisticated phage-bacteria interplay includes both aggressive action (bacterial lysis) and "diplomatic negotiations" (prophage domestication). Here, we review the most important mechanisms of interactions between phages and bacteria and their evolutionary consequences influencing their biodiversity.


Antismoking products.
Nicotine is the addictive substance in tobacco and its withdrawal is responsible for a range of unpleasant symptoms after smoking cessation. Although it produces acute physiological effects, nicotine alone is not carcinogenic and does not appear to cause the vascular disease associated with smoking. Nicotine replacement has been shown to be a safe and effective pharmacological treatment for tobacco dependence in certain smokers. Its efficacy is greatest when prescribed for those who are motivated and highly nicotine-dependent. It is probably not indicated for smokers with a low degree of nicotine dependence. Studies of nicotine chewing gum conducted in special referral clinics have generally produced positive results, whereas those conducted in community practice settings have shown a smaller benefit when compared with placebo. When the results of all published placebo-controlled trials are pooled the typical improvement in smoking cessation rate is 40% (odds ratio continued smoking 0.6; 95% confidence interval 0.5-0.71; P less than 0.00001). The best results with nicotine chewing gum have been obtained with multicomponent programmes which have included some counselling and ongoing follow up and support. Early reports of success with a transdermal nicotine preparation suggest that it may have similar efficacy to nicotine gum. Clonidine administered orally or transdermally has also been shown to reduce tobacco withdrawal symptoms but requires more convincing evidence of long-term efficacy before it can be recommended for routine use. Currently available over-the-counter products, apart from nicotine chewing gum, have not been shown to be effective.


Two-dimensional phase unwrapping using a minimum spanning tree algorithm.
Phase unwrapping refers to the determination of phase from modulo 2pi data, some of which may not be reliable. In 2D, this is equivalent to confining the support of the phase function to one or more arbitrarily shaped regions. A phase unwrapping algorithm is presented which works for 2D data known only within a set of nonconnected regions with possibly nonconvex boundaries. The algorithm includes the following steps: segmentation to identify connectivity, phase unwrapping within each segment using a Taylor series expansion, phase unwrapping between disconnected segments along an optimum path, and filling of phase information voids. The optimum path for intersegment unwrapping is determined by a minimum spanning tree algorithm. Although the algorithm is applicable to any 2D data, the main application addressed is magnetic resonance imaging (MRI) where phase maps are useful.


[Lumbar diskectomy without or with spondylodesis? Revival of an old dilemma].
Indications for spine fusion in combination with removal of a lumbar intervertebral disc are not as well defined or as widely accepted. Extreme opinions have been expressed on both side of this issue, but it seems unreasonable that every segment should be fused after removal of a disc or that none should be. The indication for fusion or for no fusion is often based on the specialist to whom the patient is referred. Orthopedists perform often fusion, neurosurgeons rarely. The problem is not the superiority of combined operation or simple disc excision, but the right indication for one or other procedure. It is clear that for the patient with acute disc displacement with leg-pain as the predominant symptom, simple laminectomy and disc excision will yield good results in most cases. Basically the are two indications for combined operation: the first of this is a strong history of instability troubles prior to the disc prolapse; second indication is the bilateral hemilaminectomy and discectomy, which can lead the spine quite instable. Indication for secondary spinal fusion are: 1) the presence after disc excision of complain of pain in the back with relatively little sciatic radiation, sometimes as intermittent claudication; 2) the overproduction of scar tissue is seen very often in instable segment after disc excision and partial or complete facetectomy. Decompression of the nerve root and fusion may result in a great benefit. Finally we recall the possibility to perform simple fusion in flexion without excision of the disc and without laminectomy in cases with median protrusion of the disc, seen in CT in patients with chronic low back pain and inconstant radicular pain radiation. We describe our own technic of combined operation.


[Tubal pregnancy after a previous tubal ligation and hysterectomy].
This is a case report on extra-uterine pregnancy occurring several years after hysterectomy. The special aspect of this particular case is that years before hysterectomy the patient had been subjected to sterilization surgery with partial tubal resection. Such cases can be expected more often in future in view of today's liberal indications for hysterectomy and also for tubal sterilization.


Effects of insulin infusion on human skeletal muscle pyruvate dehydrogenase, phosphofructokinase, and glycogen synthase. Evidence for their role in oxidative and nonoxidative glucose metabolism.
To determine whether activation by insulin of glycogen synthase (GS), phosphofructokinase (PFK), or pyruvate dehydrogenase (PDH) in skeletal muscle regulates intracellular glucose metabolism, subjects were studied basally and during euglycemic insulin infusions of 12, 30, and 240 mU/m2 X min. Glucose disposal, oxidative and nonoxidative glucose metabolism were determined. GS, PFK, and PDH were assayed in skeletal muscle under each condition. Glucose disposal rates were 2.37 +/- 0.11, 3.15 +/- 0.19, 6.71 +/- 0.44, and 11.7 +/- 1.73 mg/kg X min; glucose oxidation rates were 1.96 +/- 0.18, 2.81 +/- 0.28, 4.43 +/- 0.32, and 5.22 +/- 0.52. Nonoxidative glucose metabolism was 0.39 +/- 0.13, 0.34 +/- 0.26, 2.28 +/- 0.40, and 6.52 +/- 1.21 mg/kg X min. Both the proportion of active GS and the proportion of active PDH were increased by hyperinsulinemia. PFK activity was unaffected. Activation of GS was correlated with nonoxidative glucose metabolism, while activation of PDH was correlated with glucose oxidation. Sensitivity to insulin of GS was similar to that of nonoxidative glucose metabolism, while the sensitivity to insulin of PDH was similar to that of glucose oxidation. Therefore, the activation of these enzymes in muscle may regulate nonoxidative and oxidative glucose metabolism.


Study of Weight Patterns in Exclusively Breast Fed Neonates- Does the Route of Delivery have an Impact?
Physiological weight loss is seen in all breast fed neonates. The route of delivery may have an effect on the neonatal weight loss/gain in these exclusively breast fed babies. Additional assistance and support for exclusive breast feeding is needed by mothers who undergo cesarean section. To study and compare the weight patterns in full term exclusively breast fed neonates born by normal vaginal route versus cesarean section in the first month of life. It is a prospective observational study. Healthy, full term neonates born by normal vaginal route or cesarean section in a rural tertiary hospital with uneventful perinatal periods were included. Exclusive breast feeding was given to all neonates with supervision and encouragement to the mothers. Primary outcome measure- Weight loss of the neonates at 24 hours and 72 hours of life. Neonates delivered by cesarean section showed a higher weight loss (% of birth weight) at 24 hours {mean(sd)} than those delivered vaginally {3.2 (1.9) vs 2.2 (1.2); p-value=0.0016}. At 72 hours, the cesarean neonates had higher weight loss than vaginally delivered neonates {5.9 (3.1) vs 4.7 (2.5); p-value=0.0314}. At 28 days of life, the neonates born by cesarean section showed lower weight gain than those delivered by vaginal route {10.9 (2.1) vs 11.9 (2.3); p-value=0.0244}. The route of delivery has a significant impact on the physiological weight loss seen in exclusively breast fed neonates. Babies delivered by cesarean section showed significantly higher weight loss in the first week of life, and lower weight gain at the end of first month than babies born by vaginal route.


High-resolution total-internal-reflection fluorescence microscopy using periodically nanostructured glass slides.
We compare the performance of a total-internal-reflection fluorescence microscope under varying illumination and substrate conditions. The samples are deposited on a standard homogeneous glass slide or on a grating and illuminated by one or two interfering beams at various incident angles. A conjugate gradient with positivity a priori information is used to reconstruct the fluorophore density from the images. Numerical studies demonstrate that when the sample lies on an optimized grating, the lateral resolution of the microscope is greatly improved, up to fourfold, the best result being obtained when the grating is illuminated by two interfering beams.


Off to the park: a geospatial investigation of adapted ride-on car usage.
Adapted ride-on cars (ROC) are an affordable, power mobility training tool for young children with disabilities. Previous qualitative research has identified environmental factors, such as weather and adequate drive space, as barriers to families' adoption of their ROC. However, we do not currently know the relationship between the built environment and ROC usage. In our current study, we quantified the driving patterns of 14 children (2.5 ± 1.45 years old, 8 male: 6 female) using ROCs outside and inside of their homes over the course of a year using a custom datalogger and geospatial data. To measure environmental accessibility, we used the AccessScore from Project Sidewalk, an open-source accessibility mapping initiative, and the Walk Score, a measure of neighborhood pedestrian-friendliness. The number of play sessions with the ROC ranged from 1 to 76; 4 participants used it less than 10 times and 4 participants used it more than 50 times. Our findings indicate that more play sessions took place indoors, within the participants' homes. However, when the ROC was used outside the home, children engaged in longer play sessions, actively drove for a larger portion of the session, and covered greater distances. Most children tended to drive their ROCs in close proximity to their homes, with an average maximum distance from home of 181 meters. Most notably, we found that children drove more in pedestrian-friendly neighborhoods and when in proximity to accessible paths. The accessibility of the built environment is paramount when providing any form of mobility device to a child. Providing an accessible place for a child to move, play, and explore is critical in helping a child and family adopt the mobility device into their daily life.


Shear degradation as a probe of microalgal exopolymer structure and rheological properties.
The bulk theological properties of exopolymers produced by three species of microalgae are destroyed by shear stress. The properties are drag reduction in capillary pressure flow and low shear rate viscosity. As such, shear stress constitutes an experimental probe into the macromolecular structure which effects bulk Theological properties. Native and sheared exopolymer solutions were subjected to analysis by electrophoresis, size exclusion chromatography, hydrolysis, dialysis, and reducing end-group analysis. The evidence indicates that shearing did not break the glycoside backbone of these exopolymers, rather shearing disrupted subtle interactions between copolymers. The interactions necessary for bulk rheological properties are likely at the quaternary level of macromolecular organization, specifically weak aggregations.


Powdery mildew fungal effector candidates share N-terminal Y/F/WxC-motif.
Powdery mildew and rust fungi are widespread, serious pathogens that depend on developing haustoria in the living plant cells. Haustoria are separated from the host cytoplasm by a plant cell-derived extrahaustorial membrane. They secrete effector proteins, some of which are subsequently transferred across this membrane to the plant cell to suppress defense. In a cDNA library from barley epidermis containing powdery mildew haustoria, two-thirds of the sequenced ESTs were fungal and represented approximately 3,000 genes. Many of the most highly expressed genes encoded small proteins with N-terminal signal peptides. While these proteins are novel and poorly related, they do share a three-amino acid motif, which we named "Y/F/WxC", in the N-terminal of the mature proteins. The first amino acid of this motif is aromatic: tyrosine, phenylalanine or tryptophan, and the last is always cysteine. In total, we identified 107 such proteins, for which the ESTs represent 19% of the fungal clones in our library, suggesting fundamental roles in haustoria function. While overall sequence similarity between the powdery mildew Y/F/WxC-proteins is low, they do have a highly similar exon-intron structure, suggesting they have a common origin. Interestingly, searches of public fungal genome and EST databases revealed that haustoria-producing rust fungi also encode large numbers of novel, short proteins with signal peptides and the Y/F/WxC-motif. No significant numbers of such proteins were identified from genome and EST sequences from either fungi which do not produce haustoria or from haustoria-producing Oomycetes. In total, we identified 107, 178 and 57 such Y/F/WxC-proteins from the barley powdery mildew, the wheat stem rust and the wheat leaf rust fungi, respectively. All together, our findings suggest the Y/F/WxC-proteins to be a new class of effectors from haustoria-producing pathogenic fungi.


Five anthocyanin polymorphisms are associated with an R2R3-MYB cluster in Mimulus guttatus (Phrymaceae).
Botanists have long been interested in the reasons for genetic variation among individuals, populations, and species of plants. The anthocyanin pathway is ideal for studying the evolution of such phenotypic variation. We used a combination of quantitative trait loci mapping and association studies to understand the genetic basis of variation in five anthocyanin phenotypes including calyx, corolla, and leaf coloration patterns that vary within and among populations of Mimulus guttatus. We then examined what genes might be responsible for this phenotypic variation and whether one of the traits, calyx spotting, is randomly distributed across the geographic range of the species. All five phenotypes in M. guttatus were primarily controlled by the same major locus (PLA1), which contains a tandem array of three R2R3-MYB genes known to be involved in the evolution of flower color in a related species of Mimulus. Calyx spotting was nonrandomly distributed across the range of M. guttatus and correlated with multiple climate variables. The results of this study suggest that variation in R2R3-MYB genes is the primary cause of potentially important anthocyanin phenotypic variation within and among populations of M. guttatus, a finding consistent with recent theoretical and empirical research on flower color evolution.


[Comparative study of the composition and nutritional value of the seeds and protein concentrations in legumes].
The nutritional properties of three legumes: pea (Pisum sativum), faba bean (Vicia faba) and soya (Glycine max) have been characterized. From these seeds, protein concentrates were elaborated by wet processing and two different procedures of drying were followed (freeze-drying and alcohol washing). The composition and content of several antinutritional factors (phytates, tannins, trypsin inhibitors and lectins) were assessed in all of them. Also some functional properties regarding their potential use in food technology were evaluated, such as protein solubility at different pH, as well as water and oil absorption capacities. All the obtained concentrates showed high protein contents, nevertheless protein extraction efficiency was smaller in alcohol-washed concentrates than in the lyophilized ones. In the other hand, the concentrates obtained from pea and faba bean showed higher yields than those obtained from soya. The content of antinutritional factors were markedly reduced after the concentration process. Furthermore, the functional properties of pea and faba bean protein concentrates point out their suitability for food preparation as previously reported for soya.


[Usefulness of IPC continuous monitoring in shunt dysfunction].
Shunt dysfunction is a common situation in neurosurgery. Often symptoms, physical examination and radiology are not enough to set a diagnosis. ICP continuous monitoring is a safe and reliable tool that provides valuable information about CSF dynamics in these patients. Not only quantitative analysis is needed but also a qualitative one that enables pathological waves identification, because high amplitude B waves are strongly related to shunt dysfunction. In this paper experience about ICP continuous monitoring in patients with shunt dysfunction suspect is presented. Quantitative and qualitative data analysis led to a correct diagnosis, improving all the patients treated according to this criterion. An intraparenchymatous Camino® sensor and neuroPICture software (developed by first author) for data collection and graphic representation were used. Complications related to monitoring were absent and graphics obtained useful for qualitative analysis.


Kerr effect in all-fiber cavities of optical gyros.
The transmission spectrum of an all-fiber cavity is theoretically analyzed, in order to evaluate the perturbation induced in the eigenfrequency measurement by the Kerr effect. Existence of a threshold separating the bistable operation region from the monostable is shown. In the weakly nonlinear operation, the asymmetry of the line is evaluated and the resulting error in the frequency measurement is analytically derived.


Zinc deficiency in adult rats reduces the relative abundance of testis-specific angiotensin-converting enzyme mRNA.
Zinc deficiency results in reduced testicular angiotensin-converting enzyme (ACE) activity and reduced amounts of ACE protein in the testes of young rats. In the present study, we examined the effect of zinc deficiency on the relative abundance of testicular ACE mRNA and its relationship to ACE activity over time. Forty-five male rats at 7 wk of age were placed on one of three feeding regimens: 1) a diet adequate in zinc, 2) a diet deficient in zinc and 3) a diet adequate in zinc that was fed in an amount equal to that consumed by a paired mate fed the zinc-deficient diet. Rats were killed after 3, 5 and 7 wk. Rats fed the zinc-deficient diet had significantly lower (P < 0.01) body weight gain and testis weight at each week sampled than the other groups. They also showed compromised zinc status as evidenced by significantly lower (P < 0.01) serum and testis zinc concentrations. At each period, rats fed the zinc-deficient diet had significantly lower (P < 0.01) testicular ACE activity than rats fed either of the zinc-adequate diets. Coinciding with low ACE activity, there was a lower (P < 0.01) relative abundance of ACE mRNA in the group for the zinc-deficient diet than in either of the zinc-adequate groups. The results suggest that much of the low ACE activity in the testis of rats in the latter stages of zinc deficiency is attributable to a reduction in ACE gene transcription. However, an effect of the deficiency on ACE mRNA turnover is not ruled out.


An ultra-stretchable, highly sensitive and biocompatible capacitive strain sensor from an ionic nanocomposite for on-skin monitoring.
Flexible strain sensors that can be comfortably attached onto the skin for real-time and accurate detection of physiological signals are particularly important for the realization of healthcare, soft robotics and human-machine interfacing. It is still challenging to develop strain sensors that satisfy both high stretchability and high sensitivity. Here, we demonstrate an ultra-stretchable, highly sensitive and biocompatible capacitive-type strain sensor based on a nanocomposite containing ionic hydrogels and silver nanofibers (AgNFs). The sensor exhibits an ultra-high stretchability of 1000% and high sensitivity with a maximum gauge factor (GF) of up to 165. We find that the incorporation of AgNFs greatly increases the electrical-double layer (EDL) area at the hydrogel/metal interface and hence enhances by 3 orders of magnitude the strain sensitivity. With a short response time and good operation stability, the sensor and its matrix were successfully applied to monitor various physiological signals such as arm and finger motions, pulse, electrocardiographs (ECG), breath, speaking and emotion changes.


ICD harm and benefit: risk scores applied to the Swedish ICD-treated LQTS population.
Objectives. The use of implantable cardioverter defibrillators (ICDs) in long QT syndrome (LQTS) patients is essential in high-risk patients. However, it is sometimes used in patients without high-risk profiles for whom the expected benefit may be lower than the risk of ICD harm. Here, we evaluated ICD benefit and harm by assessing risk according to risk scores and pre-ICD clinical characteristics. Design. We studied 109 Swedish LQTS patients drawn from the Swedish ICD and Pacemaker Registry with data collected from medical records. In addition to clinical characteristics, we used two risk scores to assess pre-ICD risk, and evaluated ICD benefit and harm. Results. Twenty percent of all patients received ≥1 appropriate shock with a first appropriate shock incidence rate of 4.3 per 100 person-years. A long QTc (≥550 ms) and double mutations were significantly associated with appropriate shock. Low risk scores among patients without pre-ICD aborted cardiac arrest were not significantly associated with low risk of first appropriate shock. The incidence rates of a first inappropriate shock and first complication were 3.0 and 7.6 per 100 person-years, respectively. Conclusion. Our findings on ICD harm emphasize the importance of careful individual pre-ICD consideration. When we applied two risk scores to patients without pre-ICD aborted cardiac arrest, we could not validate their ability to identify patients with low risk of appropriate shocks and patients who were assessed as having a low risk still received appropriate shocks. This further supports the complexity of risk stratification and the difficulty of using risk scores.


Purification and characteristics of a gamma-glutamyl kinase involved in Escherichia coli proline biosynthesis.
gamma-Glutamyl kinase, the first enzyme of the proline biosynthetic pathway, was purified to homogeneity from an Escherichia coli strain resistant to the proline analog 3,4-dehydroproline. The enzyme had a native molecular weight of 236,000 and was apparently comprised of six identical 40,000-dalton subunits. Enzymatic activity of the protein was detectable only in assays containing highly purified gamma-glutamyl phosphate reductase, the second enzyme of the proline pathway. Plots of gamma-glutamyl kinase activity as a function of glutamate concentration were sigmoidal, with a half-saturation value for glutamate of 33 mM, whereas plots of enzyme activity as a function of ATP concentration displayed typical Michaelis-Menten kinetics with a Km for ATP of 4 X 10(-4) M. Enzyme activity was insensitive to the glutamate analog L-methionine-DL-sulfoximine, but ADP was a potent competitive inhibitor. Characteristics of the enzyme were compared with those of a gamma-glutamyl kinase partially purified from a 3,4-dehydroproline-sensitive E. coli. These results indicated that the only major difference was that the enzyme from the 3,4-dehydroproline-resistant strain was 100-fold less sensitive to feedback inhibition by proline.


Gas chromatographic-mass spectrometric assay of four indole alkylamines of rat pineal.
Gas chromatography-mass spectrometry was used to quantitate serotonin, N-acetylserotonin, 5-methoxytryptamine, and melatonin in single rat pineal glands. After gas chromatographic separation, the ion density of specific fragments of each indole was measured with mass spectrometry. Sensitivity of this indole assay is of the order of 10(-12) to 10(-13) mole. Routinely, specificity is based on gas chromatographic retention time and the recording of the ion density generated by specific fragments. Absolute identification of the extracted indoles was based on multiple ion detection.


Differentiation of human umbilical cord mesenchymal stromal cells into low immunogenic hepatocyte-like cells.
Mesenchymal stromal cells (MSC) isolated from several human tissues have been known to differentiate into the hepatic lineage in vitro, but the immunogenicity of the differentiated hepatocyte-like cells (DHC) has not been reported. Umbilical cord (UC) MSC are thought to be an attractive cell source for cell therapy because of their young age and low infection rate compared with adult tissue MSC. Hepatic differentiation of UC-MSC was induced with a 2-step protocol. The expressions of hepatic markers were detected by RT-PCR and immunofluorescence staining. Albumin production and urea secretion were measured by ELISA and colorimetric assay respectively. The immunosuppressive properties of DHC was detected by mixed lymphocyte culture. After incubation with specific growth factors, including hepatocyte growth factor (HGF) and basic fibroblast growth factor (bFGF), UC MSC exhibited a high hepatic differentiation ability in an adherent culture condition. The differentiated UC MSC showed hepatocyte-like morphology and expressed several liver-specific markers at gene and protein levels. Furthermore, the DHC exhibited hepatocyte-specific functions, including albumin secretion, low-density lipoprotein uptake and urea production. More importantly, DHC did not express major histocompatibility complex (MHC) II antigen and were not able to induce lymphocyte proliferation in mixed lymphocyte culture, as undifferentiated UC MSC did. Our results indicate that UC MSC are able to differentiate into functional hepatocyte-like cells that still retain their low immunogenicity in vitro. More importantly, DHC incorporated into the parenchyma of liver when transplanted into mice with CCl(4)-induced liver injury. Therefore, DHC may be an ideal source for cell therapy of liver diseases.


Dabigatran vs warfarin for radiofrequency catheter ablation of atrial fibrillation.
It is not clear whether dabigatran is as safe and effective as uninterrupted anticoagulation with warfarin during radiofrequency catheter ablation (RFA) of atrial fibrillation (AF). To compare the safety and efficacy of dabigatran by using a novel administration protocol and uninterrupted anticoagulation with warfarin for periprocedural anticoagulation in patients undergoing RFA of AF. In this case-control analysis, 763 consecutive patients (mean age 61±10 years) underwent RFA of AF using dabigatran (N = 191) or uninterrupted warfarin (N = 572) for periprocedural anticoagulation. In all patients, anticoagulation was started≥4 weeks before RFA. Dabigatran was held after the morning dose on the day before the procedure and resumed 4 hours after vascular hemostasis was achieved. A transesophageal echocardiogram performed in all patients receiving dabigatran did not demonstrate an intracardiac thrombus. There were no thromboembolic complications in either group. The prevalence of major (4 of 191, 2.1%) and minor (5 of 191, 2.6%) bleeding complications in the dabigatran group were similar to those in the warfarin group (12 of 572, 2.1%; P = 1.0 and 19 of 572, 3.3%; P = .8, respectively). Pericardial tamponade occurred in 2 of 191 (1%) patients in the dabigatran group and in 7 of 572 (1.2%) patients in the warfarin group (P = 1.0). All patients who had a pericardial tamponade, including 2 in the dabigatran group, had uneventful recovery after perdicardiocentesis. On multivariate analysis, international normalized ratio (odds ratio [OR] 4.0; 95% confidence interval [CI] 1.1-15.0; P = .04), clopidogrel use (OR 4.2; 95% CI 1.5-12.3; P = .01), and CHA2DS2-VASc score (OR 1.4; 95% CI 1.1-1.8; P = .01) were the independent risk factors of bleeding complications only in the warfarin group. When held for approximately 24 hours before the procedure and resumed 4 hours after vascular hemostasis, dabigatran appears to be as safe and effective as uninterrupted warfarin for periprocedural anticoagulation in patients undergoing RFA of AF.


The role of carbohydrate and protein parts of extracellular polymeric substances on the dewaterability of biological sludges.
There are many factors affecting the biological sludge dewaterability such as particle size distribution, floc structure, extracellular polymeric substances (EPS), etc. In this research, the role of the protein and carbohydrate parts of EPS (EPS(carbohydrate), and EPS(protein)) on the dewaterability of biological sludges was investigated. The sludge EPS composition was altered by feeding the sludges of same origin, in different reactors, with synthetic media having carbon to nitrogen (C/N) ratios of 8, 19 and 30 (in terms of COD/NH3-N), respectively. EPS in sludge samples were extracted by a cation exchange resin (CER). The characteristics of EPS were investigated by analytical methods and by using FT-IR spectroscopy. The dewaterability of the sludges was determined in terms of filterability and compactibility. Filterability, as filterability constant (X), and compactibility, as cake solids concentration, of sludges were determined by using the capillary suction time (CST) test and the centrifugation, respectively. The floc structure of sludge samples was also observed microscopically. Filterability and compactibility of the sludge samples were improved considerably with the increasing carbohydrate part and the decreasing protein part of the sludge EPS. EPS(protein) was inversely related to the cake solids concentration, which might be explained by the water holding capacity of EPS(protein). Filterability and compactibility of sludges improved by the increase of the size and strength of the flocs.


Content uniformity of microdose tablets (dosage 1 microgram--10 mg) produced by fluid bed granulation of interactive mixtures.
Tablets (100 mg), containing microdose quantities of micronized model drug (1 microgram--10 mg), were produced from interactive powder mixtures which had been fluid bed granulated. Granulation prevents adhesion unit and constituent segregation occurring during compression. Single tablet assays were performed on 100 tablets from each batch. The content of tablets fell within +/- 15% of the mean, and the coefficient of variation was less than 5% (99% confidence) for all batches. Skewness in the content distribution showed little evidence of superpotent tablets and indicated the absence of significant agglomerates of particles of the micronized component. However, there was some indication that the mixtures produced were not totally agglomerate free. These results demonstrate that the true potential of interactive mixing may be realized, provided segregation in the mixture can be eliminated. The distribution of micronized model drug, as a function of carrier particle size, was determined for the different concentration mixtures before and after granulation. When 0.1-2% interactive mixtures were sieved gently, the proportions of micronized material adhering to the different size fractions of carrier were similar. However, the very low concentration mixtures (0.001-0.03%) proved to be relatively unstable, a significant proportion of the micronized component being transferred from the mixtures to the metal surfaces of the sieves. Granulation of the mixtures in a fluidized bed produced a uniform distribution of micronized material throughout the different sized granules. These granules were stable during vibration on the sieves and when compressed. All samples of tablets met the United States Pharmacopeia XXI content uniformity requirements.


Deacetylepoxyazadiradione ameliorates diabesity in in-vivo zebrafish larval model by influencing the level of regulatory adipokines and oxidative stress.
Obesity and diabetes constitute significant global health issues associated with one another. In contrast to diabetes, which is characterised by oxidative stress that enhances cellular damage and the following complications. Obesity dynamics involve chronic inflammation that promotes insulin resistance and metabolic disruptions. Anti-inflammatory and antioxidant agents, therefore, hold promise for synergistic effects, addressing inflammation and oxidative stress, key factors in managing obesity and diabetes. These agents can be utilized in novel drug delivery approaches. The complex interactions between deacetylepoxyazadiradione (DEA) and zebrafish larva subjected to metabolic impairment due to a high-fat diet (HFD) are examined in this study. The survival assay showed a significantly lower rate (79% survival rate) in the larvae exposed to HFD. Contrastingly, DEA treatment showed significant results with survival rates increasing dose-dependently (84%, 89%, and 94% at concentrations of 50 μM, 100 μM, and 150 μM, respectively). Further investigations revealed that DEA could reduce hyperlipidemic and hyperglycemic conditions in zebrafish larvae. Glucose levels significantly dropped in the DEA treatment, which was associated with a decline in larval weight, lipid accumulation, oxidative stress and apoptosis. Enzyme assays revealed higher antioxidant enzyme concentrations in DEA treated in-vivo larval models, which were associated with reduced expression of pro-inflammatory genes. In conclusion, the results demonstrate that DEA can alleviate oxidative stress and inflammation, effectively easing the diabesity-like state in zebrafish larvae. This offers potential avenues for developing DEA as a valuable drug candidate to manage the intricate diabesity condition.


IDH1-Mutation in Diffuse Gliomas in Persons Age 55 Years and Over.
Diffuse astrocytoma (DA), anaplastic astrocytoma (AA), and glioblastoma (GBM) are defined by the World Health Organization (WHO) based on IDH-mutational status. The vast majority of IDH-mutated gliomas (90% of which involve a mutation in IDH1 R132H, which can be assessed by IDH1 immunohistochemistry [IHC]) occur in persons younger than 55 years of age. This raises the question as to the prevalence of IDH-mutant tumors in older persons and whether the gliomas in older patients should be routinely tested. Since January 1, 2014, we have employed a standard screening panel for all gliomas regardless of patient age. From 578 total gliomas tested, 88 were IDH-mutant DA/AA/GBMs and 11 IDH-mutant tumors were in persons age 55 and older. Of the 11 IDH-mutant examples in the older group, 9 were first clinical presentations of the tumor, 4 of which were in persons age 70 or older (oldest, 76 years). We assessed whether the typical profile of nuclear ATRX loss with or without strong nuclear p53 IHC occurred in these and younger patients and found that ATRX/p53 IHC patterns paralleled those in younger patients. We conclude that, although infrequent, IDH IHC is strongly recommended for all ages of adult patients with diffuse gliomas.


Children's perspectives on their relationships with their nonresident fathers: influences, outcomes and implications.
Children's relationships with their nonresident fathers, and associations between these relationships, children's relationships with mothers and stepfathers, and the children's adjustment were studied in 162 children from single-parent and stepfamilies, selected from a representative community sample in the UK, studied at 2 time points two years apart. Children were interviewed about their relationships with their nonresident fathers, mothers and stepfathers; mothers reported on children's adjustment, and other family variables. Positive child-nonresident father relationships were correlated with (a) contact between child and father, (b) the quality of the mother-child relationship, and (c) the frequency of contact between the mother and her former partner. Conflict between child and father was correlated with conflict between child and mother, and child and stepfather. Child-nonresident father contact and relationships were stable over 2 years, and related to children's adjustment; these associations were stronger for children from single-parent families than for those with stepfathers, and for those whose mothers had been first pregnant as teenagers. Associations between the quality of children's relationships with nonresident fathers and their adjustment need to be considered within the framework of the larger family system; child-father relationships are particularly important for children from 'high risk' families.


A comparison of biomedical databases.
Various published bibliographic and abstract services covering the period 1970-1988 were compared to analyze scope and coverage. A total of 7,281 articles and book titles (1,655 Soviet and 5,626 foreign) were selected on forty-one topics in different medical fields. The titles originated from three different samples but included all Soviet medical literature on the subjects. A distribution of biomedical serials from five databases is given by country, and twelve indices to assess the quality of biomedical databases are suggested.


[Critical evaluation of the Abbott MS-2 automatic system in the rapid determination of antibiograms].
The Abbott MS-2 system for rapid determinations of the bacterial growths in the kinetic mode is briefly described. Some details of the operations of the apparatus and about the experimental procedure are given by referring to a phenomenological description for the bacterial growth. A critical analysis of the antimicrobic susceptibilities and of the minimum inhibiting concentrations (MIC) provided by the apparatus is also carried out. In particular the problems arising for cephalosporins is emphasized.


Weyl nodes in periodic structures of superconductors and spin-active materials.
Motivated by recent progress in epitaxial growth of proximity structures of s-wave superconductors (S) and spin-active materials (M), in this paper we show that certain periodic structures of S and M can behave effectively as superconductors with pairs of point nodes, near which the low-energy excitations are Weyl fermions. A simple model, where M is described by a Kronig-Penney potential with both spin-orbit coupling and exchange field, is proposed and solved to obtain the phase diagram of the nodal structure, the spin texture of the Weyl fermions, as well as the zero-energy surface states in the form of open Fermi lines (Fermi arcs). As a second example, a lattice model with alternating layers of S and magnetic Z2 topological insulators is solved. The calculated spectrum confirms previous predictions of Weyl nodes based on the tunnelling Hamiltonian of Dirac electrons. Our results provide further evidence that periodic structures of S and M are well suited for engineering gapless topological superconductors.This article is part of the theme issue 'Andreev bound states'.


Atomic structure of the trypsin-A90720A complex: a unified approach to structure and function.
A90720A is a potent serine proteinase inhibitor produced by the terrestrial blue-green alga Microchaete loktakensis. Most of its structure has been defined by spectroscopic and degradative studies, but the configurations of several stereochemical centers are unknown, and its mode of inhibition of serine proteinases is not understood. We therefore examined the structure of the compound in a complex with trypsin. We have crystallized the bovine trypsin-A90720A complex and determined its three-dimensional structure at 1.90 A resolution using single crystal X-ray diffraction. The structure of the bound inhibitor is clearly shown in the electron density. The structure defines the absolute stereostructure of A90720A, establishes its bound conformation and illuminates its mode of inhibition. A90720A interacts with trypsin in a substrate-like manner through an extensive series of hydrogen bonds, hydrophobic interactions and steric complementarity. The compound uses a mixture of peptidal and nonpeptidal elements to imitate the canonical conformation of the exposed binding loop of 'small' proteinase inhibitors.


The influence of focal spot size, shape, emission profile and position on field coverage in a Gulmay D3300 Kilovoltage X-ray therapy unit.
An important characteristic of kilovoltage therapy is the narrow penumbra obtainable with a well designed collimator system. A graphical illustration of applicator geometry is used to show that undesirable penumbral broadening and consequent reduction of field coverage could result if the upper aperture in an applicator is smaller than a critical size or if the applicator is not sufficiently well aligned with the focal spot. This concept is applied in an investigation of the formation of penumbra in the Gulmay D3300, in which the influence of the focal spot size, shape and emission profile, obtained from an image of the focal spot produced using a pin-hole in a sheet of lead, is elucidated. The effective focal spot of the Varian X-ray tube was observed to be rectangular, significantly longer in the front-back direction (6 mm) than in the anode-cathode direction (3.5 mm) and quite non-uniform in emission intensity over its length, with pronounced hot-spots at each end. It is shown that this results in a penumbra which is slightly broadened in the front-back direction when the alignment is perfect, but significantly broadened asymmetrically even when the alignment just meets the manufacturer's stated tolerance. Consequently the alignment, which is performed with an alignment jig supplied by the manufacturer, needs to be very precise to obtain acceptable field coverage, which needs to be checked following an X-ray tube change.


Exploring urinary catheters: the perspectives of patients and nurses.
This literature review is part of a larger dissertation project that explores the lived experience of patients using long-term urinary catheters and nurses' attitudes towards urinary catheters. Systematic examination of the literature revealed six relevant primary research studies. These were critically appraised to assess their worth. Further studies were also reviewed, although these were often from neighbouring fields as relatively little research has been undertaken in this field. Findings suggest that there is a disparity between the care that nurses provide to patients with long-term catheters and the holistic care that patients need. Furthermore, nurses' decision-making skills are hampered by poor multidisciplinary documentation practices in the acute sector. It is concluded that nurses' attitudes towards urinary catheters do affect the care that patients receive.


A wavelet packet model of evoked potentials.
The standard methods for decomposition and analysis of evoked potentials are bandpass filtering, identification of peak amplitudes and latencies, and principal component analysis (PCA). We discuss the limitations of these and other approaches and introduce wavelet packet analysis. Then we propose the "single-channel wavelet packet model," a new approach in which a unique decomposition is achieved using prior time-frequency information and differences in the responses of the components to changes in experimental conditions. Orthogonal sets of wavelet packets allow a parsimonious time-frequency representation of the components. The method allows energy in some wavelet packets to be shared among two or more components, so the components are not necessarily orthogonal. The single-channel wavelet packet model and PCA both require constraints to achieve a unique decomposition. In PCA, however, the constraints are defined by mathematical convenience and may be unrealistic. In the single-channel wavelet packet model, the constraints are based on prior scientific knowledge. We give an application of the method to auditory evoked potentials recorded from cats. The good frequency resolution of wavelet packets allows us to separate superimposed components in these data. Our present approach yields estimates of component waveforms and the effects of experiment conditions on the amplitude of the components. We discuss future extensions that will provide confidence intervals and p values, allow for latency changes, and represent multichannel data.


Downsizing and purchases of psychotropic drugs: A longitudinal study of stayers, changers and unemployed.
The evidence is insufficient regarding the association between organizational downsizing and employee mental health. Our aim was to analyze trajectories of prescribed sedatives and anxiolytics with a sufficiently long follow-up time to capture anticipation, implementation and adaption to a downsizing event among stayers, changers and those who become unemployed compared to unexposed employees. Residents in Sweden aged 20-54 years in 2007, with stable employment between 2004 and 2007, were followed between 2005 and 2013 (n = 2,305,795). Employment at a workplace with staff reductions ≥18% between two subsequent years in 2007-2011 (n = 915,461) indicated exposure to, and timing of, downsizing. The unexposed (n = 1,390,334) were randomized into four corresponding sub-cohorts. With generalized estimating equations, we calculated the odds ratios (OR) of purchasing prescribed anxiolytics or sedatives within nine 12-month periods, from four years before to four years after downsizing. In order to investigate whether the groups changed their probability of purchases over time, odds ratios (OR) and their 95% confidence intervals (95% CI) were calculated contrasting the prevalence of purchases during the first and the last 12-month period within four time periods for each exposure group. The odds of purchasing psychotropic drugs increased more for changers (sedatives OR 1.08, 95% CI 1.05-1.11) and unemployed (anxiolytics OR 1.08, 95% CI 1.03-1.14), compared to unexposed before downsizing, while for stayers purchases increased more than for unexposed during and after downsizing. Among those without previous sickness absence, stayers increased their purchases of psychotropic drugs from the year before the event up to four years after the event. This study indicates that being exposed to downsizing is associated with increased use of sedatives and anxiolytics, before the event among those who leave, but especially thereafter for employees who stay in the organization.


Persistence of pulmonary tertiary lymphoid tissues and anti-nuclear antibodies following cessation of cigarette smoke exposure.
Formation of pulmonary tertiary immune structures is a characteristic feature of advanced COPD. In the current study, we investigated the mechanisms of tertiary lymphoid tissue (TLT) formation in the lungs of cigarette smoke-exposed mice. We found that cigarette smoke exposure led to TLT formation that persisted following smoking cessation. TLTs consisted predominantly of IgM positive B cells, while plasma cells in close proximity to TLTs expressed IgM, IgG, and IgA. The presence of TLT formation was associated with anti-nuclear autoantibody (ANA) production that also persisted following smoking cessation. ANAs were observed in the lungs, but not the circulation of cigarette smoke-exposed mice. Similarly, we observed ANA in the sputum of COPD patients where levels correlated with disease severity and were refractory to steroid treatment. Both ANA production and TLT formation were dependent on interleukin-1 receptor 1 (IL-1R1) expression. Contrary to TLT and ANA, lung neutrophilia resolved following smoking cessation. These data suggest a differential regulation of innate and B cell-related immune inflammatory processes associated with cigarette smoke exposure. Moreover, our study further emphasizes the importance of interleukin-1 (IL-1) signaling pathways in cigarette smoke-related pulmonary pathogenesis.


Transcriptional regulation of steroid receptor coactivator-1 (SRC-1) in glucocorticoid action.
Diverse mechanisms of steroid receptor action have been clarified in recent years, as a consequence of the discovery of multiple coactivators. Among them, steroid receptor coactivator-1 (SRC-1) is a member of the p160 coactivator families, which are 160 kDa proteins that interact with steroid receptors in a hormone-sensitive manner. Since coactivators function as transcriptional power boosters, subtle changes in coactivator expression levels in certain cells markedly change of receptor-mediated transcriptional activity. Expression of the glucocorticoid receptor (GR) has been shown to be autoregulated in glucocorticoid action, i.e., GR is downregulated by its cognate ligand, indicating that this autoregulation of GR may protect target cells against excessive hormone action. In the present study, we examined whether coactivator expression levels are also regulated by glucocorticoids. Among several coactivators, the SRC-1 mRNA level was downregulated by dexamethasone treatment in rat tissues, such as liver, heart, kidney, stomach, and cerebrum, in vivo. We also demonstrated dexamethasone-mediated downregulation of SRC-1 mRNA and its protein levels in rat renal mesangial cells in vitro. These results suggest that ligand-mediated downregulation of SRC-1 is crucial in the physiology of glucocorticoid action.


Computer-controlled delivery versus syringe delivery of local anesthetic injections for therapeutic scaling and root planing.
The authors conducted a study to compare administration of local anesthetic using a computer-controlled delivery device with an aspirating syringe for therapeutic scaling and root planing. The anterior middle superior alveolar, or AMSA, injection was compared with other maxillary injections. Twenty healthy adults with moderate periodontal disease participated in this single-blind crossover study. Subjects were evaluated by a trained examiner and were treated by experienced dental hygienists. Subjects provided written and verbal pain ratings via a visual analog scale, or VAS, and a verbal rating scale, or VRS. AMSA injections were compared with syringe-delivered injections--greater palatine, or GP, and nasopalatine, or NP, blocks, and anterior superior alveolar and middle superior alveolar injections--in maxillary quadrants. Bleeding and changes in attachment were evaluated after one month. VAS and VRS scores for AMSA were significantly lower for computer-controlled delivery when compared with NP injections and combined maxillary injections (VAS scores) and with GP and combined maxillary injections (VRS scores). Mean injection times were similar for both groups. Mean gains in attachment were equal, 0.19 millimeters for quadrants anesthetized using computer-controlled injections and 0.22 mm for syringe injections. Subjects reported having less pain with GP and NP injections delivered using the computer-controlled device, and total injection time was similar to that required for syringe injections. Both techniques provided adequate anesthesia for therapeutic scaling and root planing. Clinical Implications. The two anesthetic delivery techniques were therapeutically equivalent for mandibular injections, and the AMSA injection has clinically significant advantages for maxillary injections.


Relations between implementation of new treatments and improved outcomes in patients with non-ST-elevation myocardial infarction during the last 20 years: experiences from SWEDEHEART registry 1995 to 2014.
We assessed the changes in short- and long-term outcomes and their relation to implementation of new evidence-based treatments in all patients with non-ST-elevation myocardial infarction (NSTEMI) in Sweden over 20 years. Cases with NSTEMI (n = 205 693) between 1995 and 2014 were included from the nationwide Swedish Web-System for Enhancement and Development of Evidence-Based Care in Heart Disease Evaluated According to Recommended Therapies (SWEDEHEART) registry. During 20 years in-hospital invasive procedures increased from 1.9% to 73.2%, percutaneous coronary intervention or coronary artery bypass grafting 6.5% to 58.1%, dual antiplatelet medication 0% to 72.7%, statins 13.3% to 85.6%, and angiotensin-converting enzyme inhibitors/angiotensin II receptor blocker 36.8% to 75.5%. The standardized 1-year mortality ratio compared with a control population decreased from 5.53 [95% confidence interval (CI) 5.30-5.75] to 3.03 (95% CI 2.89-3.19). If patients admitted the first 2 years were modelled to receive the same invasive treatments as the last 2 years the expected mortality/myocardial infarction (MI) rate would be reduced from 33.0% to 25.0%. After adjusting for differences in baseline characteristics, the change of 1-year cardiovascular death/MI corresponded to a linearly decreasing odds ratio trend of 0.930 (95% CI 0.926-0.935) per 2-year period. This trend was substantially attenuated [0.970 (95% CI 0.964-0.975)] after adjusting for changes in coronary interventions, and almost eliminated [0.988 (95% CI 0.982-0.994)] after also adjusting for changes in discharge medications. In NSTEMI patients during the last 20 years, there has been a substantial improvement in long-term survival and reduction in the risk of new cardiovascular events. These improvements seem mainly explained by the gradual uptake and widespread use of in-hospital coronary interventions and evidence-based long-term medications.


Detection of radical species in haematin-catalysed retinoic acid 5,6-epoxidation by using h.p.l.c.-e.p.r. spectrometry.
E.p.r. signals were detected in an all-trans-retinoic acid/haematin incubation mixture by using an e.p.r. spin-trapping technique. The spin adducts are presumably attributable to some intermediates in haematin-catalysed retinoic acid 5,6-epoxidation, since addition of nitrosobenzene to the reaction mixture dose-dependently inhibited the epoxidation. Analysing the reaction mixture by h.p.l.c.-e.p.r. spectrometry resulted in the detection of three peaks (III-1, III-2, IV) ascribable to the radical species. Two (peaks III-1 and -2) of the three peaks, which appeared 10 min after the reaction had started, seem to be attributable to the radical species directly participating in the epoxidation. The radicals trapped by nitrosobenzene do not appear to be derived from active oxygen, since none of these peaks were detected in a similar h.p.l.c. analysis of O2- and OH.-generating systems. They are presumably derived from retinoic acid. This view is also supported by the following results: none of these peaks were detected in the h.p.l.c. elution profile of the reaction mixture when retinoic acid was absent; peaks III-1 and 2 were detected even under anaerobic conditions, and their peak heights were unchanged under aerobic conditions.


National risk prediction model for elective abdominal aortic aneurysm repair.
Mortality results for elective abdominal aortic aneurysm (AAA) repair are published by the Vascular Society of Great Britain and Ireland. These mortality results are not currently risk-adjusted. The objective of this study was to develop a national risk prediction model for elective AAA repair. Data for consecutive patients undergoing elective AAA repair from the National Vascular Database between April 2008 and March 2011 were analysed. Multiple logistic regression and backwards model selection were used for model development. The study outcome measure was in-hospital mortality. Model calibration and discrimination were assessed for all AAA repairs, and separately for open repair and endovascular aneurysm repair (EVAR) subgroups. There were 312 in-hospital deaths among 11,423 AAA repairs (2.7 (95 per cent confidence interval (c.i.) 2.4 to 3.0) per cent): 230 after 4940 open AAA repairs (4.7 (4.1 to 5.3) per cent) and 82 after 6483 EVARs (1.3 (1.0 to 1.6) per cent). Variables associated with in-hospital death included in the final model were: open repair, increasing age, female sex, serum creatinine level over 120 µmol/l, cardiac disease, abnormal electrocardiogram, previous aortic surgery or stent, abnormal white cell count, abnormal serum sodium level, AAA diameter and American Society of Anesthesiologists fitness grade. The area under the receiver operating characteristic (ROC) curve was 0.781 (95 per cent c.i. 0.756 to 0.806) with a bias-corrected value of 0.774. Model calibration was good (P = 0.963) based on the Hosmer-Lemeshow goodness-of-fit test, (bias-corrected) calibration curves, risk group assessment and recalibration regression. This multivariable model for elective AAA repair can be used to risk-adjust outcome analyses and provide patient-specific estimates of in-hospital mortality risk for open AAA repair or EVAR.


Predictors of High-cost Patients With Noninfectious Inflammatory Eye Diseases.
Noninfectious inflammatory eye diseases (NIIEDs), such as uveitis, is a general term used to describe a complex mix of acute, chronic, allergic, and inflammatory disorders. Prior literature has established that, in addition to severe clinical burden, NIIEDs is associated with significant economic burden for US payers; however, no literature provides a current estimate of the economic burden associated with patients with high-cost NIIEDs. This study aimed to better understand the cost and resource use distribution and predictors of patients with high-cost NIIEDs. This retrospective cohort study selected adult patients with NIIEDs from a large US administrative claims database between 2006 and 2015. Among the included patients, total all-cause health care costs were calculated for a randomly selected 12-month period. Patients in the top 20% of total all-cause health care costs were identified as high-cost patients; the remaining patients were identified as lower-cost patients. Patient demographic characteristics, clinical characteristics, cost, and health care resource utilization (HRU) were compared. Logistic regression models were used to determine characteristics associated with high-cost patients. Patients with NIIEDs (n = 14,879) were categorized into 2976 high-cost and 11,903 lower-cost patients. High-cost patients with NIIEDs were significantly more likely to experience blindness, cataract, cystoid macular degeneration, retinal detachment, and visual disturbances during the follow-up period than the lower-cost patients (all P < 0.05). The high-cost patients accounted for ~77% of the total all-cause health care spend. High-cost patients incurred an average annual total health care cost of $59,873, and the top 1 percentile incurred $349,967 during the follow-up period. Hospitalization was a key cost driver among the high-cost patients, accounting for 50% of the total cost among the top 1 percentile of patients. High-cost patients were more likely to have specific autoimmune diseases, inpatient admission, and use of biologic and immunosuppressant agents. A small segment of patients with NIIEDs consumed most resources. This study identified several predictors based on patient characteristics and HRU that may help inform the profile of patients with NIIEDs with the highest health care needs. As such, patients with a given profile can be selected for targeted interventions by clinicians to potentially help improve quality of care and to reduce costs.


Early results of the Ponseti method for the treatment of clubfoot in distal arthrogryposis.
Clubfoot occurs in approximately one in 1000 live births and is one of the most common congenital birth defects. Although there have been several reports of successful treatment of idiopathic clubfoot with the Ponseti method, the use of this method for the treatment of other forms of clubfoot has not been reported. The purpose of the present study was to evaluate the early results of the Ponseti method when used for the treatment of clubfoot associated with distal arthrogryposis. Twelve consecutive infants (twenty-four feet) with clubfoot deformity associated with distal arthrogryposis were managed with the Ponseti method and were retrospectively reviewed at a minimum of two years. The severity of the foot deformity was classified according to the grading system of Diméglio et al. The number of casts required to achieve correction was compared with published data for the treatment of idiopathic clubfoot. Recurrent clubfoot deformities or complications during treatment were recorded. Twenty-two clubfeet in eleven patients were classified as Diméglio grade IV, and two clubfeet in one patient were classified as Diméglio grade II. Initial correction was achieved in all clubfeet with a mean of 6.9 +/- 2.1 casts (95% confidence interval, 5.6 to 8.3 casts), which was significantly greater than the mean of 4.5 +/- 1.2 casts (95% confidence interval, 4.3 to 4.7 casts) needed in a cohort of 219 idiopathic clubfeet that were treated during the same time period by the senior author with use of the Ponseti method (p = 0.002). Six feet in three patients had a relapse after initial successful treatment. All relapses were related to noncompliance with prescribed brace wear. Four relapsed clubfeet in two patients were successfully treated with repeat casting and/or tenotomy; the remaining two relapsed clubfeet in one patient were treated with extensive soft-tissue-release operations. Our early-term results support the use of the Ponseti method for the initial treatment of distal arthrogrypotic clubfoot deformity. Longer follow-up will be necessary to assess the risk of recurrence and the potential need for corrective clubfoot surgery in this patient population, which historically has been difficult to treat nonoperatively.


Causal indicators in quality of life research.
Quality of Life (QOL) questionnaires contain two different types of items. Some items, such as assessments of symptoms of disease, may be called causal indicators because the occurrence of these symptoms can cause a change in QOL. A severe state of even a single symptom may suffice to cause impairment of QOL, although a poor QOL need not necessarily imply that a patient suffers from all the symptoms. Other items, for example anxiety and depression, can be regarded as effect indicators which reflect the level of QOL. These indicators usually have a more uniform relationship with QOL, and therefore a patient with poor QOL is likely to have low scores on all effect indicators. In extreme cases it may seem intuitively obvious which items are causal and which are effect indicators, but often it is less clear. We propose a model which includes these two types of indicators and show that they behave in markedly different ways. Formal quantitative methods are developed for distinguishing them. We also discuss the impact of this distinction upon instrument validation and the design and analysis of summary subscales.


Near-Complete Genome Sequence of Ralstonia solanacearum T523, a Phylotype I Tomato Phytopathogen Isolated from the Philippines.
Ralstonia solanacearum strain T523 is the major phytopathogen causing tomato bacterial wilt in the Philippines. Here, we report the complete chromosome and draft megaplasmid genomes with predicted gene inventories supporting rhizosphere processes, extensive plant virulence effectors, and the production of bioactive signaling metabolites, such as ralstonin, micacocidin, and homoserine lactone.


Practical management of catheter-associated UTIs.
In the long-term catheterized elderly, damage to the epithelial wall is primarily responsible for bladder infections, due to the presence of the catheter as a foreign body and its frequent manipulations. The presence of bacteriuria, a classic sign of infection in the non-catheterized patient, is of little diagnostic importance in the long-term catheterized patient, since it is both permanent and inevitable. Routine preventive measures--eg, frequent catheter changes, prophylactic antibiotics--are of no value. Other measures are worth considering and, if instituted, will reduce the frequency of severe complications from long-term catheterization and improve quality of life.


Distinct Patterns of Gene Expression Changes in the Colon and Striatum of Young Mice Overexpressing Alpha-Synuclein Support Parkinson's Disease as a Multi-System Process.
Evidence supports a role for the gut-brain axis in Parkinson's disease (PD). Mice overexpressing human wild type α- synuclein (Thy1-haSyn) exhibit slow colonic transit prior to motor deficits, mirroring prodromal constipation in PD. Identifying molecular changes in the gut could provide both biomarkers for early diagnosis and gut-targeted therapies to prevent progression. To identify early molecular changes in the gut-brain axis in Thy1-haSyn mice through gene expression profiling. Gene expression profiling was performed on gut (colon) and brain (striatal) tissue from Thy1-haSyn and wild-type (WT) mice aged 1 and 3 months using 3' RNA sequencing. Analysis included differential expression, gene set enrichment and weighted gene co-expression network analysis (WGCNA). At one month, differential expression (Thy1-haSyn vs. WT) of mitochondrial genes and pathways related to PD was discordant between gut and brain, with negative enrichment in brain (enriched in WT) but positive enrichment in gut. Linear regression of WGCNA modules showed partial independence of gut and brain gene expression changes. Thy1-haSyn-associated WGCNA modules in the gut were enriched for PD risk genes and PD-relevant pathways including inflammation, autophagy, and oxidative stress. Changes in gene expression were modest at 3 months. Overexpression of haSyn acutely disrupts gene expression in the colon. While changes in colon gene expression are highly related to known PD-relevant mechanisms, they are distinct from brain changes, and in some cases, opposite in direction. These findings are in line with the emerging view of PD as a multi-system disease.