Ablation of the locus coeruleus increases oxidative stress in tg-2576 transgenic but not wild-type mice. Mice transgenic for production of excessive or mutant forms of beta-amyloid differ from patients with Alzheimer's disease in the degree of inflammation, oxidative damage, and alteration of intermediary metabolism, as well as the paucity or absence of neuronal atrophy and cognitive impairment. Previous observers have suggested that differences in inflammatory response reflect a discrepancy in the state of the locus coeruleus (LC), loss of which is an early change in Alzheimer's disease but which is preserved in the transgenic mice. In this paper, we extend these observations by examining the effects of the LC on markers of oxidative stress and intermediary metabolism. We compare four groups: wild-type or Tg2576 Aβ transgenic mice injected with DSP4 or vehicle. Of greatest interest were metabolites different between ablated and intact transgenics, but not between ablated and intact wild-type animals. The Tg2576_DSP4 mice were distinguished from the other three groups by oxidative stress and altered energy metabolism. These observations provide further support for the hypothesis that Tg2576 Aβ transgenic mice with this ablation may be a more congruent model of Alzheimer's disease than are transgenics with an intact LC.


Targeting the mechanisms of resistance to chemotherapy and radiotherapy with the cancer stem cell hypothesis. Despite advances in treatment, cancer remains the 2nd most common cause of death in the United States. Poor cure rates may result from the ability of cancer to recur and spread after initial therapies have seemingly eliminated detectable signs of disease. A growing body of evidence supports a role for cancer stem cells (CSCs) in tumor regrowth and spread after initial treatment. Thus, targeting CSCs in combination with traditional induction therapies may improve treatment outcomes and survival rates. Unfortunately, CSCs tend to be resistant to chemo- and radiation therapy, and a better understanding of the mechanisms underlying CSC resistance to treatment is necessary. This paper provides an update on evidence that supports a fundamental role for CSCs in cancer progression, summarizes potential mechanisms of CSC resistance to treatment, and discusses classes of drugs currently in preclinical or clinical testing that show promise at targeting CSCs.


Genome-wide association studies of hypertension: light at the end of the tunnel. Despite its significant genetic component, the study of hypertension by genome-wide association presents more challenges than other common complex diseases. Its high prevalence, heterogeneity, and somewhat unclear definition are the challenges that need to be overcome on one hand. On the other hand, there are issues of small effect sizes and pleiotropism that are not specific to hypertension alone but nonetheless magnify the problems of genetic dissection when coupled with phenotypic misclassification. We discuss issues of study design and summarise published genome-wide association studies (GWASs) of hypertension and blood pressure. With careful study design and analysis success is possible, as demonstrated by the recent large-scale studies. Following these, there is still further scope to advance the field through high fidelity phenotyping and deep sequencing.


Quasi-static and harmonic indentation of osteonal bone. The purpose of the study was to compare Quasi-Static (QS) and harmonic (CSM) methods of indentation testing. Bone sections were obtained from mid-femoral diaphyses of dogs which received a pair of calcein labels. Labeled (n = 35) and unlabeled (n = 112) osteons were identified. Indentation modulus (IM) and hardness (H) for the CSM method were collected during the entire loading cycle to peak depth, while IM and H for QS method were calculated at a peak depth of 500 nm. The mean (SD) of the IM and H for labeled osteons were as follows: QS IM = 15.3 GPa (3.85) versus CSM IM = 14.7 GPa (3.58); P = .52 and QS H = .39 GPa (.171) versus CSM H = .42 GPa (.146); P = .32. The mean (SD) of the IM and H for unlabeled osteons were as follows: QS IM = 21.5 GPa (2.80) versus CSM IM = 20.6 GPa (2.53); P = .054 and QS H = .64 GPa (.117) versus CSM H = .70 GPa (.120); P = .017. There was no difference in IM and H for the two methods, except for H of the unlabeled osteons. In addition, for the CSM method, IM at 100 nm, 200 nm, 300 nm, 400 nm and 500 nm were not statistically significant different (P = .06). Bone is viscoelastic at an organ level. However, this component of its behavior was not detected at the length scale examined.


Development of the first well-defined tungsten oxo alkyl derivatives supported on silica by SOMC: towards a model of WO3/SiO2 olefin metathesis catalyst. A well-defined, silica-supported tungsten oxo alkyl species prepared by the surface organometallic chemistry approach displays high and sustained activity in propene metathesis. Remarkably, its catalytic performances outpace those of the parent imido derivative, underlining the importance of the oxo ligand in the design of robust catalysts.


Expression of O-Alkylguanine-DNA Alkyltransferase in Normal and Malignant Bladder Tissue of Egyptian Patients. Bladder tumour tissues and corresponding uninvolved mucosa (normal tissue) of Egyptian bladder cancer patients were assessed for O(6)-alkylguanine-DNA-alkyltransferase (MGMT) activity by functional assay of tissue extracts (36 paired samples), and distribution by immunofluorescence (IF) microscopy of fixed material (24 paired samples). MGMT varied widely from 42-253 fmoles/mg protein and from 3.2-40 fmoles/μg DNA in normal and 58-468 fmoles/mg protein and 2.5-49.5 fmoles/mg protein, in the tumour tissues; only one tumour had undetectable activity. Pairwise comparison of MGMT activity in tumour and adjacent normal tissue showed no significant difference based on DNA content but was 1.75-fold higher in tumour (P < .01) based on protein. There was no effect of gender or bilharzia infection status. IF showed that in tumours, both the mean percentage of positive nuclei (57.3 ± 20.3%) and mean integrated IF (5.47 ± 3.66) were significantly higher than those in uninvolved tissues (42.8 ± 13.5% P = .04) and (1.89 ± 1.42; P < .01), respectively. These observations suggest that, overall, MGMT levels are increased during human bladder carcinogenesis and that MGMT downregulation is not a common feature of bladder cancers. Based on this, bladder cancers would be expected to be relatively resistant to chemotherapy which involved O(6)-guanine alkylating antitumour agents.


Single exposure fabrication and manipulation of 3D hydrogel cell microcarriers. We present a simple and high-throughput method for fabricating free-floating hydrogel cell microcarriers using single exposure UV patterning. We also demonstrate magnetic manipulation of the free-floating cell microcarriers using a magnetic nanoparticle-embedded structure for an active agitation and a solution exchange.


Probing magnetic and gold nanoparticles by using MAClevers® as ultrasensitive sensors. Magnetic AFM probes known as MAClevers® were employed for sensing picogram amounts of magnetic nanoparticles, based on the cantilever frequency shifts resulting from the magnetically induced adsorption of mass. By using organothiol functionalized magnetic nanoparticles, this analytical strategy was successfully extended to the detection of gold nanoparticles, as confirmed by confocal Raman microscopy.


Transition metal induced magnetism in smaller fullerenes (Cn for n≤36). The magnetic properties of 3d transition metals (TM) encapsulated inside smaller fullerenes ranging from C20 to C36 have been investigated using spin polarized density functional theory. The TM impurities stabilize asymmetrically at an off-center position for n≥28. The total magnetic moment (MM) of TM@Cn complexes are largely contributed by TMs and a small amount of MM of 0.12-0.50 μB is induced on the cage carbon atoms. The 3d TM atoms interact with C atoms of C20 and C28 cage ferromagnetically (FM) except for Ni@C28 which shows antiferromagnetic (AFM) interaction. The magnetic interactions change from FM to AFM in C32 cage for Ti, V, Cr and Mn. The MM gets quenched in Ni@Cn for n≥32. The total MM of Mn@Cn does not show any change although the nature of magnetic interactions changes from FM to AFM at n=32. Ti and V are the only TMs which show positive cohesive energy in all fullerenes considered. The smallest fullerene which can encapsulate all 3d TM are Cn for n≥32, consistent with available experimental and theoretical results.


Photofragmentation in selected tautomers of protonated adenine. The photofragmentation by UV excitation of selectively prepared 1(+) and 3(+) tautomers of protonated adenine is studied after excitation at a 266 and 263 nm wavelengths with two different experimental set-ups located in Seoul and Orsay. While the production of 1(+) tautomers with an electrospray ion source is now well accepted, calculations were used to ascribe the preparation of 3(+) tautomers from cold adenine dimers. The fragmentation patterns are rather similar for both tautomers, suggesting similar mechanisms as a statistical fragmentation in the ground electronic state after internal conversion.


SR-FTIR spectroscopy of renal epithelial carcinoma side population cells displaying stem cell-like characteristics. It is hypothesized that cells with stem cell-like properties may be influential in carcinogenesis, possessing the ability to self-renew, produce differentiated daughter cells and resist environmental or therapeutic injury. This has led to a surge in interest in identifying and characterizing the tumour initiating or cancer stem cell (CSC) with the aim of discovering novel diagnostic and prognostic markers and of understanding the basic biology with the ultimate aim of generating new therapeutic approaches and biomarkers. However, a major hurdle to this process has been the lack of a truly specific cancer stem cell biomarker allied to the rarity of these cells. This has led to problems in characterising these CSCs by traditional '-omic' techniques. Using a renal carcinoma cell line model, we show that synchrotron radiation-Fourier transform infrared (SR-FTIR) spectroscopy is a suitable tool to measure discrete differences in the biochemistry of small numbers of single-cells. Using the chemometric techniques of Principal Component and Linear Discriminant Analysis (PCA and LDA) for multivariate reduction, biochemical differences between the cells from different sub-populations were evaluated. Results found lipid and phosphodiester vibrations to be particularly good discriminating markers in the spectra of these stem-like cells, relative to the more differentiated, proliferating cells that make up the majority of the cell population.


A microfluidic approach for investigating the temperature dependence of biomolecular activity with single-molecule resolution. We present a microfluidic approach for single-molecule studies of the temperature-dependent behavior of biomolecules, using a platform that combines microfluidic sample handling, on-chip temperature control, and total internal reflection fluorescence (TIRF) microscopy of surface-immobilized biomolecules. With efficient, rapid, and uniform heating by microheaters and in situ temperature measurements within a microfluidic flowcell by micro temperature sensors, closed-loop, accurate temperature control is achieved. To demonstrate its utility, the temperature-controlled microfluidic flowcell is coupled to a prism-based TIRF microscope and is used to investigate the temperature-dependence of ribosome and transfer RNA (tRNA) structural dynamics that are required for the rapid and precise translocation of tRNAs through the ribosome during protein synthesis. Our studies reveal that the previously characterized, thermally activated transitions between two global conformational states of the pre-translocation (PRE) ribosomal complex persist at physiological temperature. In addition, the temperature-dependence of the rates of transition between these two global conformational states of the PRE complex reveal well-defined, measurable, and disproportionate effects, providing a robust experimental framework for investigating the thermodynamic activation parameters that underlie transitions across these barriers.


Enantioselective synthesis of spirooxoindoles via chiral auxiliary (bicyclic lactam) controlled SNAr reactions. A highly efficient enantioselective S(N)Ar reaction of chiral acyl bicyclic lactam with substituted-2,4-dinitrobenzenes was developed, affording products containing quarternary stereogenic centers. They are further utilized towards an enantioselective synthesis of spirooxoindoles.


Nucleotidylation of unsaturated carbasugar in validamycin biosynthesis. Validamycin A is a member of microbial-derived C(7)N-aminocyclitol family of natural products that is widely used as crop protectant and the precursor of the antidiabetic drug voglibose. Its biosynthetic gene clusters have been identified in several Streptomyces hygroscopicus strains, and a number of genes within the clusters have been functionally analyzed. Of these genes, valB, which encodes a sugar nucleotidyltransferase, was found through inactivation study to be essential for validamycin biosynthesis, but its role was unclear. To characterize the role of ValB in validamycin biosynthesis, four carbasugar phosphate analogues were synthesized and tested as substrate for ValB. The results showed that ValB efficiently catalyzes the conversion of valienol 1-phosphate to its nucleotidyl diphosphate derivatives, whereas other unsaturated carbasugar phosphates were found to be not the preferred substrate. ValB requires Mg(2+), Mn(2+), or Co(2+) for its optimal activity and uses the purine-based nucleotidyltriphosphates (ATP and GTP) more efficiently than the pyrimidine-based NTPs (CTP, dTTP, and UTP) as nucleotidyl donor. ValB represents the first member of unsaturated carbasugar nucleotidyltransferases involved in natural products biosynthesis. Its characterization not only expands our understanding of aminocyclitol-derived natural products biosynthesis, but may also facilitate the development of new tools for chemoenzymatic synthesis of carbohydrate mimetics.


Reversible phase transfer and fractionation of Au nanoparticles by pH change. The reversible transfer of Au nanoparticles between water and chloroform phases by pH change was achieved by using a long-chain amine derivative. Further, we demonstrated that the phase transfer method was very effective for the fractionation of Au nanoparticles according to their crystal facet distinction.


Chiral separation and determination of ofloxacin enantiomers by ionic liquid-assisted ligand-exchange chromatography. A simple and accurate method for the separation and determination of ofloxacin enantiomers was developed by ionic liquid-assisted ligand-exchange high performance liquid chromatography. Both achiral and chiral ionic liquids were tested for their efficiency of ofloxacin enantiomeric separation. The effects of ligands, concentration of metal ion, organic modifier, pH of the mobile phase, and temperature were also investigated and evaluated. Optimal conditions were obtained on a conventional C(18) column, where the mobile phase consisted of methanol/water (20 : 80, v/v) (containing 4.0 mmol L(-1) amino acid ionic liquid and 3.0 mmol L(-1) copper sulfate) at a flow rate of 0.5 mL min(-1). Under this condition, the ofloxacin enantiomers could be baseline separated within 14 minutes; the proposed method was used to analyze different commercial ofloxacin medicines.


SAXS in combination with a free liquid jet for improved time-resolved in situ studies of the nucleation and growth of nanoparticles. A new setup for fast in situ SAXS studies of early stages in the nucleation and growth of colloidal nanoparticles is presented. Evading the disturbing influence of container walls and minimizing the possibility of beam-induced reactions, the benefits of the setup are demonstrated exemplarily for the well-known synthesis of gold nanoparticles via the Turkevich method. Analysis with the new experimental setup reveals the initial rate of particle formation, and enables analysis of particle growth rates.


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


Highly sensitive naked-eye and fluorescence "turn-on" detection of Cu(2+) using Fenton reaction assisted signal amplification. Increase of pH induced by Cu(2+)-catalyzed Fenton reaction promoted ring-opening of triazole-linked fluorescein lactone, which enabled selective "turn-on" fluorescent detection of Cu(2+), along with ultralow naked-eye detection limit down to 200 nM.


Scavenger receptors and their potential as therapeutic targets in the treatment of cardiovascular disease. Scavenger receptors act as membrane-bound and soluble proteins that bind to macromolecular complexes and pathogens. This diverse supergroup of proteins mediates binding to modified lipoprotein particles which regulate the initiation and progression of atherosclerotic plaques. In vascular tissues, scavenger receptors are implicated in regulating intracellular signaling, lipid accumulation, foam cell development, and cellular apoptosis or necrosis linked to the pathophysiology of atherosclerosis. One approach is using gene therapy to modulate scavenger receptor function in atherosclerosis. Ectopic expression of membrane-bound scavenger receptors using viral vectors can modify lipid profiles and reduce the incidence of atherosclerosis. Alternatively, expression of soluble scavenger receptors can also block plaque initiation and progression. Inhibition of scavenger receptor expression using a combined gene therapy and RNA interference strategy also holds promise for long-term therapy. Here we review our current understanding of the gene delivery by viral vectors to cells and tissues in gene therapy strategies and its application to the modulation of scavenger receptor function in atherosclerosis.


Local defects enhanced dehydrogenation kinetics of the NaBH(4)-added Li-Mg-N-H system. A mechanistic understanding on the enhanced kinetics of hydrogen storage in the NaBH(4)-added Mg(NH(2))(2)-2LiH system is provided by carrying out experimental investigations associated with first-principles calculations. It is found that the operating temperatures for hydrogen desorption of the Mg(NH(2))(2)-2LiH system are reduced by introducing NaBH(4), and the NaBH(4) species seems almost unchanged during dehydrogenation/hydrogenation process. First-principles calculations reveal that the presence of NaBH(4) in the Mg(NH(2))(2)-2LiH system facilitates the formation of Mg vacancies in Mg(NH(2))(2). The appearance of Mg vacancies not only weakens the N-H bonds but also promotes the diffusion of atoms and/or ions, consequently resulting in the improvement of the reaction kinetics of hydrogen desorption/absorption of the NaBH(4)-added Mg(NH(2))(2)-2LiH system. This finding provides us with a deep insight into the role played by NaBH(4) in the Li-Mg-N-H system, as well as ideas for designing high-performance catalysts for metal-N-H-based hydrogen storage media.


Advanced X-ray absorption and emission spectroscopy: in situ catalytic studies. Knowledge of the structure of catalysts is essential to understand their behavior, which further facilitates development of an active, selective, and stable catalyst. Determining the structure of a functioning catalyst is essential in this regard. The structure of a catalyst is prone to change during the catalytic process and needs to be determined in its working conditions. In this tutorial review, we have summarized studies done at synchrotron radiation facilities that illustrate the capability to determine catalyst structure using X-ray absorption spectroscopy (XAS) and X-ray emission spectroscopy (XES). These studies aim at facilitating the determination of the dynamic structure-performance relationships during a catalytic process.


Combined XRD and infrared studies of pyridinium species in (PyH)(3)[PW(12)O(40)] single crystals. The pyridinium salts of 12-tungstophosphoric acid (PyH)(3)[PW(12)O(40)]·2CH(3)CN (1) and (PyH)(3)[PW(12)O(40)] (2) have been prepared and studied by single crystal and powder X-ray diffraction (XRD) in order to characterize the crystallographic sites occupied by the pyridinium species. The three PyH(+) species are located on two unequivalent sites. Two species are linearly H-bonded to the oxygen atoms of the Keggins unit (α species), whereas the third one (β) forms a bent H-bond. In order to determine the infrared bands characterizing each type of pyridinium species in the 1650-1300 cm(-1) range, infrared spectra have been recorded from room temperature to 100 K. They reveal that only α pyridinium species give rise to the unusual splitting of the PyH(+)ν8b and ν19b modes, whereas β pyridinium species lead to a classical pyridinium spectrum.


Experimental observation of spin delocalisation onto the aryl-alkynyl ligand in the complexes [Mo(C≡CAr)(Ph2PCH2CH2PPh2)(η-C7H7)]+ (Ar = C6H5, C6H4-4-F; C7H7 = cycloheptatrienyl): an EPR and ENDOR investigation. The paramagnetic aryl-alkynyl complexes [Mo(C≡CAr)(dppe)(η-C(7)H(7))](+) (dppe = Ph(2)PCH(2)CH(2)PPh(2); Ar = C(6)H(5), [1](+); C(6)D(5), [2](+); C(6)H(4)-4-F, [3](+); C(6)H(4)-4-Me, [5](+)) and [Mo(C≡CBu(t))(dppe)(η-C(7)H(7))](+) [4](+), have been investigated in a combined EPR and ENDOR study. Direct experimental evidence for the delocalisation of unpaired spin density over the framework of an aryl-alkynyl ligand has been obtained. The X-band solution EPR spectrum of the 4-fluoro derivative, [3](+), exhibits resolved hyperfine coupling to the remote para position of the aryl group [a(iso)((19)F) = 4.5 MHz, (1.6 G)] in addition to couplings attributable to (95/97)Mo, (31)P and (1)H of the C(7)H(7) ring. A full analysis of the (1)H ENDOR spectra is restricted by the low g anisotropy of the system which prevents the use of orientation selection. However, inter-comparison of the (1)H cw-ENDOR frozen solution spectra of [1](+), [2](+), [4](+) and [5](+), combined with spectral simulation informed by calculated values derived from DFT investigations, has facilitated estimation of the experimental a(iso)((1)H) hyperfine couplings of [1](+) including the ortho, ±3.7 MHz (±1.3 G) and para, ±3.9 MHz (±1.4 G) positions of the C(6)H(5) substituent of the aryl-alkynyl ligand.


Entrapping homogeneous catalysts by sol-gel methods: the bottom-up synthesis of catalysts that recycle and cascade. Homogeneous catalysts entrapped in silica matrices, including ionic liquid containing 'ionogels', exhibit high selectivity, unexpected activity and excellent recyclability.


Chlorometallate(III) ionic liquids as Lewis acidic catalysts--a quantitative study of acceptor properties. The Gutmann Acceptor Number (AN), which is a quantitative measure of Lewis acidity, has been estimated using the (31)P NMR chemical shift of a probe molecule, triethylphosphine oxide, for a range of chlorometallate(III) ionic liquids, based on Group 13 metals (aluminium(III), gallium(III) and indium(III)) and the 1-octyl-3-methylimidazolium cation, at different compositions. The results were interpreted in terms of extant speciation studies of chlorometallate(III) ionic liquids, and compared with a range of standard molecular solvents and acids. The value of these data were illustrated in terms of the selection of appropriate ionic liquids for specific applications.


Multi-chelation approach towards natural product-like skeletons: one-pot access to a nitrogen-containing tetracyclic framework from AlaAla dipeptide. Reductive transformation of the dipeptide BocAlaAlaOMe to a complex, internally charge-stabilized, natural product-like skeleton in one synthetic step is discussed. Stepwise replacement of the B-H bonds in borane by B-N or B-O resulted in incorporation of three boron atoms in a tetracyclic framework whereby one is stereogenic!


Ligand influence in the selective gold-mediated synthesis of allenes. The use of [(IPr)AuOH] permits the generation of gold(i)-amine complexes by a silver-free protocol. These in situ or well-defined complexes are used in a straightforward synthetic route to substituted allenes from propargylic acetates. The catalytic activity can be modulated as a function of the nature of the ligand bound to the gold-NHC moiety.


Efficacy of surface sampling methods for different types of beryllium compounds. The objective of the research work was to evaluate the efficiency of three different sampling methods (Ghost Wipe™, micro-vacuum, and ChemTest®) in the recovery of Be dust by assessing: (1) four Be compounds (beryllium acetate, beryllium chloride, beryllium oxide and beryllium aluminium), (2) three different surfaces (polystyrene, glass and aluminium) and (3) inter-operator variation. The three sampling methods were also tested on site in a laboratory of a dental school for validation purposes. The Ghost Wipe™ method showed recovery ranging from 43.3% to 85.8% for all four Be compounds and for all three quantities of Be spiked on Petri dishes, while recovery with the micro-vacuum method ranged from 0.1% to 12.4%. On polystyrene dishes with 0.4 µg Be, the recovery ranged from 48.3% to 81.7%, with an average recovery of 59.4% for Operator 1 and 68.4% for Operator 2. The ChemTest® wipe method with beryllium acetate, beryllium chloride, and AlBeMet® showed analogous results that are in line with the manufacturer's manual, but collection of beryllium oxide was negative. In the dental laboratory, Ghost Wipe™ samplings showed better recovery than the micro-vacuum method. The ratios between the recovered quantities of Be in each location where the Ghost Wipe™ was tested differed substantially, ranging from 1.45 to 64. In the dental laboratory, a faint blue color indicating the presence of Be was observed on the ChemTest® wipes used in two locations out of six. In summary, the Ghost Wipe™ method was more efficient than micro-vacuuming in collecting the Be dust from smooth, non-porous surfaces such as Petri dishes by a factor of approximately 18. The results obtained on site in a dental laboratory also showed better recovery with Ghost Wipes™. However, the ratio of Be recovered by Ghost Wipes™ versus micro-vacuuming was much lower for surfaces where a large amount of dust was present. Wet wiping is preferred over micro-vacuuming for beryllium forms, but this conclusion probably applies to the ultra-low particulate loading levels (0.4 micrograms or less) which was tested in this study.


Risk assessment of soils contaminated by mercury mining, Northern Spain. Analytical results of soil samples taken in three different mercury mining sites in Northern Spain are studied to assess the potential adverse health effects of the exposure to trace elements associated with the mining process. Doses contacted through ingestion and inhalation and the dose absorbed through the skin were calculated using USEPA's exposure parameters and the US Department of Energy's toxicity values. The results of the risk assessment indicate that the highest risk is associated with ingestion of soil particles and that the trace element of major concern is arsenic, the exposure to which results in a high cancer risk value for all the sites ranging from 3.3 × 10(-5) to 3.6 × 10(-3), well above the 1 × 10(-5) probability level deemed unacceptable by most regulatory agencies. Regarding non-cancer effects, exposure to polluted soils yields an aggregate hazard index above the threshold value of 1 for all three sites, with As and Hg as the main contributors. Risk assessment has proven to be a very useful tool to identify the contaminants and exposure pathways of most concern in the soils from metal mining sites, as well as to categorize them in terms of action priority to ensure fitness for use.


Synthesis of (±)-desethylrhazinal using a tandem radical addition-cyclization process. The indolizidine ring system present in (±)-rhazinal, was assembled using a xanthate-based sequential intermolecular radical addition-cyclization process. The novel (±)-desethylrhazinal was prepared in seven steps in approximately 12% overall yield from 2-formylpyrrole, using this strategy.


Synthesis and aggregation properties of dissymmetric phytanyl-gemini surfactants for use as improved DNA transfection vectors. Improvements in transfection efficiency are required in order to make the goal of cellular gene delivery by non-viral vectors realizable. Novel derivatives of gemini surfactants having dissymmetric tail groups have been designed specifically as a means to improve DNA transfection; the micelle and interfacial properties are reported herein. The effect of these substitutions on the aggregation properties of the gemini surfactants is discussed in the context of results for the m-3-m gemini series, previously reported in the literature. Phytanyl substitution results in lower cmc and higher micelle ionization. In addition, the phytanyl substituted gemini surfactants form vesicles at room temperature. Preliminary in vitro transfection assays showed the phytanyl substituted gemini surfactants to be more efficient transfection vectors as compared to symmetric gemini surfactants.


Structure and synthesis of 2-aminoimidazole alkaloids from Leucetta and Clathrina sponges. Marine sponges belonging to the Calcarea family have been studied for some time and have yielded a wide variety of structurally unique secondary metabolites. In particular, these sponges have produced a large number of bioactive alkaloids containing an imidazole heterocycle, typically substituted with two benzylic fragments at various locations around the azole nucleus and at various oxidation states. This review will describe the isolation, structural determination and synthetic studies towards this growing class of natural products.


Copper-catalyzed atom transfer radical addition (ATRA) and cyclization (ATRC) reactions in the presence of environmentally benign ascorbic acid as a reducing agent. In recent years, copper-catalyzed atom transfer radical addition (ATRA) has emerged as a viable organic procedure for the formation of carbon-carbon bonds starting from alkyl halides and alkenes. Studies have primarily focused on the use of free-radical initiators to regenerate the copper(I) complex or activator in situ. Although these initiators led to a significant decrease in the amount of metal catalyst, they were much less effective for highly active alkenes that readily undergo free-radical polymerization. In this study, the non-radical reducing agent ascorbic acid (commonly known as Vitamin C) was effectively employed resulting in TONs as high as 15,200 in the homogenous ATRA of polyhalogenated compounds to α-olefins, and enabling selective monoadduct formation for highly active alkenes such as acrylonitrile (TONs as high as 11,800). As low as 7-20 mol% of ascorbic acid relative to substrate was sufficient for all ATRA and ATRC reactions examined. Further, product isolations for all selected syntheses were quite facile and nearly quantitative, requiring only simple liquid-liquid extraction techniques. Reactions in the presence of ascorbic acid were also examined kinetically via (1)H NMR and UV/Vis spectroscopy. A half order rate dependence on reducing agent concentration was observed, but the first order kinetic plots became nonlinear as the concentration of ascorbic acid was increased. Finally, the use of ascorbic acid circumvented otherwise necessary purging techniques, successfully furthering the utility of these reactions in organic synthesis.


Infrared microspectroscopy of live cells in aqueous media. Fourier Transform Infrared (FTIR) spectroscopic measurements of individual, live HeLa cells in culture and buffer media are presented. Spectral data were acquired using a newly designed live cell chamber developed in the authors' laboratory. Data were processed using MATLAB-based routines that correct for the overcompensation of water encountered during live cell measurements in aqueous samples. Data presented are from live cells monitored over an extended period of time as well as a comparison of live cells exposed to perturbing conditions.


Iridium(III) molecular catalysts for water oxidation: the simpler the faster. We report on three Ir(iii) molecular catalysts for water oxidation: 1, [Cp*Ir(ppy)Cl]; 2, [Cp*Ir(bzpy)NO(3)]; 3, [Cp*Ir(H(2)O)(3)](NO(3))(2). 2 and 3 are water-soluble and show a long-term activity ca. 2 and 3 times higher than 1. It is remarkable that 3, having the simplest structure, is the catalyst with the highest activity.


Highly sensitive and selective turn-on fluorescent and chromogenic probe for Cu2+ and ClO- based on a N-picolinyl rhodamine B-hydrazide derivative. A new rhodamine B-based dual-function chromo- and fluorogenic probe for Cu(2+) and ClO(-) has been designed, synthesized, and characterized. The probe comprises a spectroscopic unit of rhodamine B and a Cu(2+)-specific chelating unit of pyridinecarboxamide as well as a ClO(-)-specific reactive moiety of diacylhydrazine, and is a highly selective and extremely sensitive fluorescent and colorimetric sensor for Cu(2+) and ClO(-) in different pH conditions. Compared with the reported probes for Cu(2+) or ClO(-), this is the first chemosensor based on a small molecule that can detect both Cu(2+) and ClO(-), respectively, at 1 nM level.


Fluorometric paired emitter detector diode (FPEDD). Integration of two light emitting diodes allows construction of a fluorometric paired emitter detector diode (FPEDD)--a compact optoelectronic device useful as a complete flow-through fluorescence detector.


Mobilization of very small embryonic-like stem cells in acute coronary syndromes and stroke. The bone marrow (BM) niche contains small heterogenous populations of cells which may contribute to cardiac and endothelial repair, including committed lineages [endothelial progenitor cells (EPCs), multipotent mesenchymal stromal cells (MSCs) and more primitive very small embryonic-like cells (VSELs) expressing pluripotent stem cell (PSC) markers (Oct-4, Nanog, SSEA-1)]. VSELs are present in BM, peripheral blood and some solid organs in mice and were recently identified in peripheral blood in patients with acute coronary syndromes and stroke. VSELs can be expanded in vitro and differentiated into cells from all three germ layers. This population of cells displays the morphology of primitive PSC (small size, open type chromatin, large nucleus, narrow rim of cytoplasm) and express PSC markers. The isolation of human VSELs is based on their size and presence of several surface markers (CXCR4, CD133, CD34) and lack of markers of hematopoietic lineage (lin, CD45). In acute myocardial infarction and ischemic stroke VSELs are rapidly mobilized into peripheral blood, and express increased levels of PSC markers as well as early cardiac (GATA-4, Nkx2.5/Csx), neural (GFAP, nestin, beta-III-tubulin, Olig1, Olig2, Sox2, Musashi) and endothelial lineage markers (VE-cadherin, von Willebrand factor). The number of VSELs mobilized in acute myocardial infarction is inversely correlated with left ventricular ejection fraction and the release of cardiac necrosis markers. Mobilization of these cells is also reduced in patients with diabetes and in the elderly. BM-derived VSELs were expanded and after cardiogenic pre-differentiation injected intramyocardially in mice models of myocardial infarction leading to improved left ventricular contractility. VSELs are probably progeny of epiblast cells which migrated to the BM and developing organs during embryonic development. The cells are present in a quiescent state in the adult BM and solid organs and might serve as a reserve pool of resident stem cells. VSELs are promising candidates for further pre-clinical and clinical studies on cellular cardiovascular therapy.


Cardiac allograft vasculopathy : complications and imaging studies. Cardiac allograft vasculopathy (CAV) is an accelerated form of coronary artery disease affecting both intramyocardial and epicardial coronary arteries and is observed in patients during long-term survival after cardiac transplantation. We report a case of CAV complicated with silent transmural myocardial infarction and massive left ventricular thrombus formation associated with silent pericarditis and with ischemic and non-ischemic scar tissue, as detected by cardiac magnetic resonance imaging (CMRI). The authors suggest CMRI as an additional technique along with echocardiography during follow-up of heart transplant recipients. CMRI may contribute to the early identification of areas of myocardial wall abnormalities suggestive of CAV, thus guiding diagnosis and prompt percutaneous treatment.


Evaluation of salinity tolerance and analysis of allelic function of HvHKT1 and HvHKT2 in Tibetan wild barley. Tibetan wild barley is rich in genetic diversity with potential allelic variation useful for salinity-tolerant improvement of the crop. The objectives of this study were to evaluate salinity tolerance and analysis of the allelic function of HvHKT1 and HvHKT2 in Tibetan wild barley. Salinity tolerance of 189 Tibetan wild barley accessions was evaluated in terms of reduced dry biomass under salinity stress. In addition, Na(+) and K(+) concentrations of 48 representative accessions differing in salinity tolerance were determined. Furthermore, the allelic and functional diversity of HvHKT1 and HvHKT2 was determined by association analysis as well as gene expression assay. There was a wide variation among wild barley genotypes in salt tolerance, with some accessions being higher in tolerance than cultivated barley CM 72, and salinity tolerance was significantly associated with K(+)/Na(+) ratio. Association analysis revealed that HvHKT1 and HvHKT2 mainly control Na(+) and K(+) transporting under salinity stress, respectively, which was validated by further analysis of gene expression. The present results indicated that Tibetan wild barley offers elite alleles of HvHKT1 and HvHKT2 conferring salinity tolerance.


Variation of GmIRCHS (Glycine max inverted-repeat CHS pseudogene) is related to tolerance of low temperature-induced seed coat discoloration in yellow soybean. In yellow soybean, seed coat pigmentation is inhibited by post-transcriptional gene silencing (PTGS) of chalcone synthase (CHS) genes. A CHS cluster named GmIRCHS (Glycine max inverted-repeat CHS pseudogene) is suggested to cause PTGS in yellow-hilum cultivars. Cold-induced seed coat discoloration (CD), a commercially serious deterioration of seed appearance, is caused by an inhibition of this PTGS upon exposure to low temperatures. In the highly CD-tolerant cultivar Toyoharuka, the GmIRCHS structure differs from that of other cultivars. The aim of this study was to determine whether the variation of GmIRCHS structure among cultivars is related to variations in CD tolerance. Using two sets of recombinant inbred lines between Toyoharuka and CD-susceptible cultivars, we compared the GmIRCHS genotype and CD tolerance phenotype during low temperature treatment. The GmIRCHS genotype was related to the phenotype of CD tolerance. A QTL analysis around GmIRCHS showed that GmIRCHS itself or a region located very close to it was responsible for CD tolerance. The variation in GmIRCHS can serve as a useful DNA marker for marker-assisted selection for breeding CD tolerance. In addition, QTL analysis of the whole genome revealed a minor QTL that also affected CD tolerance.


Identification of QTLs for morphological traits influencing waterlogging tolerance in perennial ryegrass (Lolium perenne L.). Perennial ryegrass is a globally cultivated obligate outbreeding diploid species (2n = 2x = 14) which is subjected to periods of waterlogging stress due to flood irrigation during winter and the lead-up to summer. Reduction of oxygen supply to root systems due to waterlogging produces consequent deleterious effects on plant performance. Framework genetic maps for a large-scale genetic mapping family [F₁(NA(x) × AU₆)] were constructed containing 91 simple sequence repeat and 24 single nucleotide polymorphism genetic markers. Genetic trait dissection using both control and waterlogging treatments was performed in the glasshouse, a total of 143 maximally recombinant genotypes being selected from the overall sib-ship and replicated threefold in the trial. Analysis was performed for nine quantitative morphological traits measured 8 weeks after stress treatments were applied. A total of 37 quantitative trait loci (QTLs) were identified; 19 on the NA(x) parental genetic map, and 18 on the AU₆ parental genetic map. Regions of particular interest were identified on linkage groups (LGs) 4 and 3 of the respective maps, which have been targeted for further analysis by selection of critical recombinants. This first study of genetic control of waterlogging tolerance in ryegrasses has important implications for breeding improvement of abiotic stress adaptation.


Mapping quantitative trait loci for seed size traits in soybean (Glycine max L. Merr.). Seed size traits in soybean--length, width and thickness--and their corresponding ratios--length-to-width, length-to-thickness and width-to-thickness--play a crucial role in determining seed appearance, quality and yield. In this study, an attempt was made to detect quantitative trait loci (QTL) for the aforementioned seed size traits in F(2:3), F(2:4) and F(2:5) populations from the direct and reciprocal crosses of Lishuizhongzihuang with Nannong 493-1, using multi-QTL joint analysis (MJA) along with composite interval mapping (CIM). A total of 121 main-effect QTL (M-QTL), six environmental effects, eight environment-by-QTL interactions, five cytoplasmic effects and 92 cytoplasm-by-QTL interactions were detected. Fifty-two common M-QTL across MJA and CIM, 21 common M-QTL in more than two populations and 5 M-QTL in all three populations showed the stability of the results. Five M-QTL had higher heritability, greater than 20%. In addition, 28 cytoplasm-by-QTL and 4 environment-by-QTL interactions were confirmed by CIM. Most M-QTL were clustered in eight chromosomal regions. Our results provide a good foundation for fine mapping, cloning and designed molecular breeding of favorable genes related to soybean seed size traits.


Fine mapping and analyses of R ( SC8 ) resistance candidate genes to soybean mosaic virus in soybean. Soybean mosaic virus (SMV) in soybean [Glycine max (L.) Merr.] is a destructive foliar disease in soybean-producing countries worldwide. In this study, F(2), F(2:3), and F(7:11) recombinant inbred lines populations derived from Kefeng No.1 × Nannong 1138-2 were used to study inheritance and linkage mapping of the SMV strain SC8 resistance gene in Kefeng No.1. Results indicated that a single dominant gene (designated R(SC8)) controls resistance, which is located on chromosome 2 (MLG D1b). A mixed segregating population was developed by selfing two heterozygous plants (RHL153-1 and RHL153-2) at four markers adjacent to the locus and used in fine mapping R(SC8). In addition, two genomic-simple sequence repeats (SSR) markers BARCSOYSSR_02_0610 and BARCSOYSSR_02_0616 were identified that flank the two sides of R(SC8). Sequence analysis of the soybean genome indicated that the interval between the two genomic-SSR markers is 200 kb. QRT-PCR analysis of the candidate genes determined that five genes (Glyma02g13310, 13320, 13400, 13460, and 13470) are likely involved in soybean SMV resistance. These results will have utility in cloning, transferring, and pyramiding of the R(SC8) through marker-assisted selection in soybean breeding programs.


BK channels affect glucose homeostasis and cell viability of murine pancreatic beta cells. Evidence is accumulating that Ca(2+)-regulated K(+) (K(Ca)) channels are important for beta cell function. We used BK channel knockout (BK-KO) mice to examine the role of these K(Ca) channels for glucose homeostasis, beta cell function and viability. Glucose and insulin tolerance were tested with male wild-type and BK-KO mice. BK channels were detected by single-cell RT-PCR, cytosolic Ca(2+) concentration ([Ca(2+)](c)) by fura-2 fluorescence, and insulin secretion by radioimmunoassay. Electrophysiology was performed with the patch-clamp technique. Apoptosis was detected via caspase 3 or TUNEL assay. BK channels were expressed in murine pancreatic beta cells. BK-KO mice were normoglycaemic but displayed markedly impaired glucose tolerance. Genetic or pharmacological deletion of the BK channel reduced glucose-induced insulin secretion from isolated islets. BK-KO and BK channel inhibition (with iberiotoxin, 100 nmol/l) broadened action potentials and abolished the after-hyperpolarisation in glucose-stimulated beta cells. However, BK-KO did not affect action potential frequency, the plateau potential at which action potentials start or glucose-induced elevation of [Ca(2+)](c). BK-KO had no direct influence on exocytosis. Importantly, in BK-KO islet cells the fraction of apoptotic cells and the rate of cell death induced by oxidative stress (H(2)O(2), 10-100 μmol/l) were significantly increased compared with wild-type controls. Similar effects were obtained with iberiotoxin. Determination of H(2)O(2)-induced K(+) currents revealed that BK channels contribute to the hyperpolarising K(+) current activated under conditions of oxidative stress. Ablation or inhibition of BK channels impairs glucose homeostasis and insulin secretion by interfering with beta cell stimulus-secretion coupling. In addition, BK channels are part of a defence mechanism against apoptosis and oxidative stress.


Indocyanine green plasma disappearance rate for monitoring hepatosplanchnic blood flow.


The diagnostic future for bloodstream infections?


Swept under the carpet? The role of mucociliary clearance in ventilator-induced lung injury.


Effects of different mechanical ventilation strategies on the mucociliary system. To evaluate the effects of different mechanical ventilation (MV) strategies on the mucociliary system. Experimental study. Twenty-seven male New Zealand rabbits. After anesthesia, animals were tracheotomized and ventilated with standard ventilation [tidal volume (Vt) 8 ml/kg, positive end expiratory pressure (PEEP) 5 cmH(2)O, flow 3 L/min, FiO(2) 0.4] for 30 min. Next, animals were randomized into three groups and ventilated for 3 h with low volume (LV): Vt 8 ml/kg, PEEP 5 cmH(2)O, flow 3 L/min (n = 6); high volume (HV): Vt 16 ml/kg, PEEP 5 cmH(2)O, flow 5 L/min (n = 7); or high pressure (HP): Ppeak 30 cmH(2)O, PEEP 12 cmH(2)O (n = 8). Six animals (controls) were ventilated for 10 min with standard ventilation. Vital signals, blood lactate, and respiratory system mechanics were verified. Tracheal tissue was collected before and after MV. Lung and tracheal tissue sections were stained to analyze inflammation and mucosubstances by the point-counting method. Electron microscopy verified tracheal cell ultrastructure. In situ tracheal ciliary beating frequency (CBF), determined using a videoscopic technique, and tracheal mucociliary transport (TMCT), assessed by stereoscopic microscope, were evaluated before and after MV. Respiratory compliance decreased in the HP group. The HV and HP groups showed higher lactate levels after MV. Macroscopy showed areas of atelectasis and congestion on HV and HP lungs. Lung inflammatory infiltrate increased in all ventilated groups. Compared to the control, ventilated animals also showed a reduction of total and acid mucus on tracheal epithelium. Under electron microscopy, injury was observed in the ciliated cells of the HP group. CBF decreased significantly after MV only in the HP group. TMCT did not change significantly in the ventilated groups. Different MV strategies induce not only distal lung alterations but also morphological and physiological tracheal alterations leading to mucociliary system dysfunction.


Production of liver preneoplasia and gallbladder agenesis in turkey fetuses administered diethylnitrosamine. The in ovo carcinogenicity assessing (IOCA) assay was used to examine the morphological changes in fetal turkey livers caused by the DNA-reactive carcinogen diethylnitrosamine (DEN). Fertilized turkey eggs were allocated into 3 groups: nondosed control (NDC), vehicle (water) control (VC) and DEN-dosed. At day 0, the fertilized eggs of the dosed groups were injected with 1 (LD) or 4 (HD) mg/egg (about 12.5 or 50 mg/kg egg) of DEN and the VC were injected with water. All eggs were allowed to incubate at 37°C and 60% humidity for 24 days. The fetal livers were collected and processed for histopathological evaluation (H&E staining). Typical survival rates were 82% for the NDC, 50% for the VC and 16-65% for the DEN-dosed fetuses. No difference in histology was found between NDC and VC control groups. Both DEN concentrations produced dose-related liver findings consisting of foci of altered hepatocytes (FAH), which had assumed a tubular cord (glandular) pattern, and in HD DEN group the FAH assumed a tumor-like morphology. In addition, the high DEN dose produced gallbladder agenesis. Thus, DEN produced both hepatocellular transformation (FAH) similar to preneoplastic microscopic changes in adult rodents, reflecting disruption of the fetal processes of differentiation and proliferation, and also teratogenicity (gallbladder agenesis).


The antidepressant-like effect of the 3β-hydroxysteroid dehydrogenase inhibitor trilostane involves a regulation of β-type estrogen receptors. Trilostane is a competitive inhibitor of 3β-hydroxysteroid dehydrogenase (3β-HSD), which notably converts pregnenolone into progesterone or dehydroepiandrosterone into androstenedione. Trilostane shows antidepressant-like properties in the forced swimming test (FST). The compound, however, induced only moderate effects on neuroactive steroid levels that could be related to its behavioral efficacy. We compared the behavioral effect of trilostane with the other 3β-HSD inhibitor, cyanoketone, and analyzed the putative involvement of the β-type estrogen receptor (ERβ) in its antidepressant effect. Trilostane reduced immobility in the FST significantly at 12.5 and 25 mg/kg subcutaneously (s.c.), whereas cyanoketone (0-100 mg/kg s.c.) was ineffective. The negative ER modulator fulvestrant (ICI 182780) dose-dependently blocked the effect of trilostane (25 mg/kg). Trilostane increased circulating estradiol levels in the 12.5-50 mg/kg dose-range, and this effect was unaffected by stress and not shared by cyanoketone (25 mg/kg). The trilostane (25 mg/kg) treatment increased the ERβ mRNA expression in adrenals (+100%) and centrally, in the hippocampus (+330%). Stress and cyanoketone failed to affect ERβ mRNA levels in periphery or in the brain. These data demonstrate that the antidepressant-like potential of trilostane is not due to its 3β-HSD inhibiting activity, since it is not shared by cyanoketone, but rather to its estrogenic activity. The compound, which releases estradiol and up-regulates ERβ receptors, could be used as a therapeutic tool to allow an estrogenic facilitation of antidepressant efficacy.


Prefrontal stimulation of GABAA receptors counteracts the corticolimbic hyperactivity produced by NMDA antagonists in the prefrontal cortex of the rat. The hypofunction of NMDA receptors in the prefrontal cortex (PFC) has been suggested to produce corticolimbic hyperactivity through the reduction of cortical GABA transmission. The present study investigates the effects of injections of the NMDA antagonist 3-[(R)-2-carboxypiperazin-4-yl]-propyl-1-phosphonic acid (CPP) into the PFC on (1) the release of dopamine and/or acetylcholine in the amygdala and hippocampus, (2) the levels of corticosterone in the hippocampus and (3) spontaneous motor activity. Also, the stimulation of GABA(A) receptors, by prefrontal injections of muscimol, on the effects produced by NMDA antagonists on these same neurochemical, hormonal and behavioural parameters was evaluated. Male Wistar rats were implanted with guide cannulae to perform bilateral microinjections into the PFC and microdialysis experiments in the amygdala and/or ventral hippocampus, simultaneously. Spontaneous motor activity was monitored in the open field. Injections of CPP (1 μg/0.5 μl) into the PFC increased dialysate concentrations of dopamine and acetylcholine in the amygdala, acetylcholine and free corticosterone in the hippocampus and also motor activity. Simultaneous injections of muscimol (0.5 μg/0.5 μl) into the PFC counteracted the increases of dopamine and acetylcholine in the amygdala and hippocampus and also significantly reduced the peak increase of corticosterone in the hippocampus. Injections of muscimol (0.05 and 0.5 μg/0.5 μl) reduced the increases of motor activity produced by prefrontal NMDA antagonists. These results suggest that the hypofunction of NMDA receptors in the PFC produces corticolimbic hyperactivity through the activation of prefrontal efferent projections to subcortical/limbic areas.


Cellular correlates of anxiety in CA1 hippocampal pyramidal cells of 5-HT1A receptor knockout mice. 5-HT(1A) receptor knockout (1AKO) mice have a robust anxiety phenotype. Tissue-specific "rescue" strategies and electrophysiology have implicated a critical role for postsynaptic 5-HT(1A) receptors, particularly in the CA1 region of the hippocampus. In this study, we evaluated differences in membrane properties and synaptic activity in CA1 hippocampal pyramidal cells between 1AKOs and wild-type (WT) controls to better understand the cellular correlates of anxiety in this mouse model. Whole-cell patch-clamp recordings were conducted in CA1 pyramidal cells in hippocampal brain slices from 1AKOs and WTs that had previously been screened for anxiety with the elevated-plus maze. Spontaneous miniature inhibitory and excitatory postsynaptic currents (IPSCs and EPSCs) and stimulus-evoked eIPSCs and eEPSCs were recorded in addition to the effect of the benzodiazepine agonist diazepam or the inverse agonist FG 7142 on γ-aminobutyric acid (GABA)ergic eIPSCs. Evoked EPSC amplitude was greater in 1AKOs than WTs. When subjects were pooled across genotypes, anxiety measures correlated with eEPSC amplitude, indicating enhanced postsynaptic glutamate synaptic activity under conditions of synaptic activation in anxious subjects. While GABA synaptic activity and sensitivity to diazepam were not affected by genotype or correlated with anxiety, sensitivity to the anxiogenic FG 7142 was smaller in anxious subjects. These data indicate enhanced postsynaptic glutamate receptor sensitivity and decreased GABAergic inhibition by a benzodiazepine inverse agonist in CA1 hippocampal neurons of anxious mice are produced by deletion of the 5-HT(1A) receptor. These data provide new information about interactions between 5-HT, GABA, and glutamate systems during the expression of chronic anxiety.


An in vitro study of silk stent morphology. Morphology of the Silk stent (Balt, Montmorency, France) after deployment is not fully understood, especially in tortuous vessels. An in vitro study was conducted to study morphology and flow-diverting parameters of this stent. Two sets of different-sized and curved polytetrafluoroethylene tubes were studied. To simulate the aneurysm neck, a small hole was created in a tube. A stent was placed in each of the different tubes. Angiographic computerized tomography and macroscopic photography were then obtained. The images were analyzed to calculate a Percentage of Area Coverage (PAC). Good stent conformability was observed. The PAC was 21% in the straight model with matched stent and vessel diameter. In the straight model with an oversized stent, the PAC was increased. In the curved models, dynamic wire repositioning occurred. The repositioning was affected by the size of the stent and the angle of the vessel curve. Compared to the straight model, this increased the PAC in two instances: on the convexity (oversized stent), and on the concavity (matched stent and vessel diameter). The PAC did not significantly change at the sides of the curve. By design, the wires of the silk stent move relative to each other. In a curved model, the PAC is different at the convexity, concavity, and lateral walls. The stent diameter affects the PAC. These results are clinically relevant because it is desirable to maximize and minimize the PAC across the aneurysm neck and branch vessel orifice, respectively.


Development of laminar organization of the fetal cerebrum at 3.0T and 7.0T: a postmortem MRI study. The purpose of this study is to show the condition of laminar organization on 3.0T and 7.0T postmortem magnetic resonance imaging (MRI) and analyze developmental changes. Heads of 131 fetal specimens of 14-40 weeks gestational age (GA) were scanned by 3.0T MRI. Eleven fetal specimens of 14-27 weeks GA were scanned by 7.0T MRI. Clear images were chosen for analysis. On T₁-weighted 3.0T MRI, layers could be visualized at 14 weeks GA and appeared clearer after 18 weeks GA. On 7.0T MRI, four zones could be recognized at 14 weeks GA. During 15-22 weeks GA, when laminar organization appeared typical, seven layers including the periventricular zone and external capsule fibers could be differentiated, which corresponded to seven zones in histological stained sections. At 23-28 weeks GA, laminar organization appeared less typical, and borderlines among them appeared obscured. After 30 weeks GA, it disappeared and turned into mature-like structures. The developing lamination appeared the most distinguishable at the parieto-occipital part of brain and peripheral regions of the hippocampus. The migrating thalamocortical afferents were probably delineated as a high signal layer located at the lower, middle, and upper part of the subplate zone at 16-28 weeks GA on T₁-weighted 3.0T MRI. T₁-weighted 3.0T MRI and T₂-weighted 7.0T MRI can well demonstrate the laminar organization. Development of the lamination follows a specific spatio-temporal regularity, and postmortem MRI of the parieto-occipital part of brain obtained with 3.0T or 7.0T is an effective way to show developmental changes.


Evolution of conserved non-coding sequences within the vertebrate Hox clusters through the two-round whole genome duplications revealed by phylogenetic footprinting analysis. As a result of two-round whole genome duplications, four or more paralogous Hox clusters exist in vertebrate genomes. The paralogous genes in the Hox clusters show similar expression patterns, implying shared regulatory mechanisms for expression of these genes. Previous studies partly revealed the expression mechanisms of Hox genes. However, cis-regulatory elements that control these paralogous gene expression are still poorly understood. Toward solving this problem, the authors searched conserved non-coding sequences (CNSs), which are candidates of cis-regulatory elements. When comparing orthologous Hox clusters of 19 vertebrate species, 208 intergenic conserved regions were found. The authors then searched for CNSs that were conserved not only between orthologous clusters but also among the four paralogous Hox clusters. The authors found three regions that are conserved among all the four clusters and eight regions that are conserved between intergenic regions of two paralogous Hox clusters. In total, 28 CNSs were identified in the paralogous Hox clusters, and nine of them were newly found in this study. One of these novel regions bears a RARE motif. These CNSs are candidates for gene expression regulatory regions among paralogous Hox clusters. The authors also compared vertebrate CNSs with amphioxus CNSs within the Hox cluster, and found that two CNSs in the HoxA and HoxB clusters retain homology with amphioxus CNSs through the two-round whole genome duplications.


Biochemistry of lactone formation in yeast and fungi and its utilisation for the production of flavour and fragrance compounds. The consumers' demand for natural flavour and fragrances rises. To be natural, compounds have to result from the extraction of natural materials and/or to be transformed by natural means such as the use of enzymes or whole cells. Fungi are able to transform some fatty acids into lactones that can thus be natural. Although some parts of this subject have been reviewed several times, the present article proposes to review the different pathways utilised, the metabolic engineering strategies and some current concerns on the reactor application of the transformation including scaling up data. The main enzymatic steps are hydroxylation and β-oxidation in the traditional way, and lactone desaturation or Baeyer-Villiger oxidation. Although the pathway to produce γ-decalactone is rather well known, metabolic engineering strategies may result in significant improvements in the productivity. For the production of other lactones, a key step is the hydroxylation of fatty acids. Beside the biotransformation, increasing the production of the various lactones requires from biotechnologists to solve two main problems which are the toxicity of lactones toward the producing cell and the aeration of the emulsified reactor as the biochemical pathway is very sensitive to the level of available oxygen. The strategies employed to resolve these problems will be presented.


Understanding the effect of foreign gene dosage on the physiology of Pichia pastoris by transcriptional analysis of key genes. Increased copy number of foreign gene can result in the alteration of normal metabolism in Pichia pastoris. To better understand the effect of foreign gene dosage on the cellular physiology of P. pastoris cells, comparative transcriptional analysis was performed among three P. pastoris strains carrying 0, 6, and 18 copies of porcine insulin precursor (PIP) expression cassettes, respectively. mRNA levels of 13 selected genes involved in methanol metabolic pathway, central metabolic pathway, protein folding, and oxidative stress were determined by real-time PCR. Results showed that enhanced PIP copy number resulted in an increase in PIP mRNA and also in folding stress on the yeast cells' endoplasmic reticulum. The metabolism of 6-copy P. pastoris strain was not significantly changed as compared to 0-copy strain (control). In contrast, physiology of 18-copy strain was remarkably affected, characterized by the upregulation of antioxidative genes and readjusted expression level of methanol metabolic pathway genes. These data suggested that high copy P. pastoris strain might be suffering from protein folding-related oxidative stress and insufficient supply of carbon and energy sources.


The accuracy of 64-slice MDCT for determining the perforation site of the gastrointestinal tract: ROC analysis. This study was performed to evaluate the diagnostic performance of 64-slice multidetector-row computed tomography (MDCT) for preoperatively detecting the perforation site in patients with gastrointestinal (GI) tract perforations. A total of 49 patients with pathologically proven GI tract perforations, who had undergone MDCT were included in this study. The contrast-enhanced axial images (3 mm thick) and multiplanar reformation (MPR) images (3 mm thick) were generated for all the patients. Two radiologists independently reviewed the two sets of MDCT images (axial set: the axial images alone, and combined set: the axial and MPR images) for the detection of the perforation site. The perforation site was considered to be positive according to the direct and indirect findings. The diagnostic accuracy was assessed with a receiver operating characteristic (ROC) analysis. Weighted kappa statistics were used to evaluate the interobserver agreement. The corresponding values in respect of the first and the second observers for the areas under the ROC curve were 0.984 and 0.966 for the axial set; and 0.998 and 0.973 for the combined set. The differences were not statistically significant between the two data sets for each observer (P > 0.05). Both the observers detected the perforation site in 43 (87.8%) and 40 (81.6%) patients on the axial set, and in 46 (93.9%) and 41 (83.7%) patients on the combined set, respectively. The kappa values between the two observers showed excellent agreement with the two data sets. 64-slice MDCT showed a consistently excellent diagnostic performance for preoperatively determining the perforation site in patients with GI tract perforations, irrespective of the availability of the MPR images.


Biocatalytic properties of a recombinant aldo-keto reductase with broad substrate spectrum and excellent stereoselectivity. In the screening of 11 E. coli strains overexpressing recombinant oxidoreductases from Bacillus sp. ECU0013, an NADPH-dependent aldo-keto reductase (YtbE) was identified with capability of producing chiral alcohols. The protein (YtbE) was overexpressed, purified to homogeneity, and characterized of biocatalytic properties. The purified enzyme exhibited the highest activity at 50°C and optimal pH at 6.5. YtbE served as a versatile reductase showing a broad substrate spectrum towards different aromatic ketones and keto esters. Furthermore, a variety of carbonyl substrates were asymmetrically reduced by the purified enzyme with an additionally coupled NADPH regeneration system. The reduction system exhibited excellent enantioselectivity (>99% ee) in the reduction of all the aromatic ketones and high to moderate enantioselectivity in the reduction of α- and β-keto esters. Among the ketones tested, ethyl 4,4,4-trifluoroacetoacetate was found to be reduced to ethyl (R)-4,4,4-trifluoro-3-hydroxy butanoate, an important pharmaceutical intermediate, in excellent optical purity. To the best of our knowledge, this is the first report of ytbE gene-encoding recombinant aldo-keto reductase from Bacillus sp. used as biocatalyst for stereoselective reduction of carbonyl compounds. This study provides a useful guidance for further application of this enzyme in the asymmetric synthesis of chiral alcohol enantiomers.


Primary intraluminal leiomyosarcoma of the inferior vena cava: value of MRI with contrast-enhanced MR venography in diagnosis and treatment. Primary intraluminal leiomyosarcoma of the inferior vena cava (IVC) is extremely rare. Diagnostic imaging plays an important role in the diagnosis and conducting treatment strategy. MRI with contrast-enhanced MR venography was performed in six patients with primary intraluminal leiomyosarcoma of the IVC. In the six patients, three had leiomyosarcoma of the middle IVC, and three the lower IVC. The mean axial diameter of tumor was 4.3 cm. MRI with contrast-enhanced MR venography not only demonstrated the tumor's location, morphology, extent, and collateral vessels but also distinguished tumor from thrombus of the IVC. Three patients underwent surgery and three did not. Four patients (three with surgery and one without surgery) were alive during the following periods, but one presented with local recurrence and all with metastases at a median time of 23 months. One patient died at 15 months after the diagnosis with liver and subcutaneous metastases, one lost to follow up. MR image with contrast-enhanced MR venography is a noninvasive and accurate technique for diagnosis of primary intraluminal leiomyosarcoma of IVC. Its providing information is very helpful for pre- and post-surgery. It can be used as one of the first choice examinations.


Symptomatic spontaneous celiac artery dissection treated by conservative management: serial imaging findings. The aim of this study was to evaluate the correlation of clinical characteristics with serial imaging findings of symptomatic spontaneous celiac artery dissection treated by conservative management. Eight consecutive, hemodynamically stable patients with symptomatic spontaneous celiac artery dissection without associated aortic dissection that received non-operative treatments were included in this study. Their clinical characteristics, treatment methods, serial imaging findings and outcomes were analyzed retrospectively. Acute left flank pain related to splenic infarction was the most common clinical manifestation. Initial contrast-enhanced dynamic computed tomography scan showed celiac artery dissection with partial thrombosis in all eight patients and involvement of branch vessels in 7. Full anticoagulation was carried out immediately after the diagnosis in seven patients. All patients, except one with endovascular stent placement, were asymptomatic after successful conservative management and follow-up computed tomography scan showed preservation of distal perfusion with ongoing regression of false lumen in five patients. After a mean follow-up of 16 months, there was no mortality or morbidity related to the dissection. Serial imaging findings showed that conservative management of celiac artery dissection can be performed successfully in selective patients with stable hemodynamics.


CT virtual endoscopy of the ampulla of Vater: preliminary report. To explore multi-slice spiral CT (MSCT) virtual endoscopy (CTVE) in the detection of Vater's ampulla lesions. In addition to 30 healthy volunteers, 18 cases of common bile duct stones, and 7 cases of ampullary carcinoma were scanned with MSCT including virtual endoscopy (VE) reconstruction. Patterns of the duodenal papilla were then observed, and its size was measured. Reconstructed images of CTVE in the volunteers showed that the normal type of the duodenal papilla was nodular in 16 cases, V-shaped in 8 cases, and Y-shaped in 6 cases. Its mean diameter was 0.84 ± 0.17 cm in the healthy volunteers; in patients with common bile duct stones of nodular type, mean diameter was 1.72 ± 0.32 cm. In ampullary cancer patients with an irregular protruded type, its diameter was 2.30 ± 0.85 cm, Overall the mean differences between the groups were statistically significant (P < 0.001). CTVE is a convenience, no-wound, and precise clinical examination mode utilizing which the shape of duodenal papilla can be observed, and size of the latter can be measured.


Identification of a cyclin B1-derived CTL epitope eliciting spontaneous responses in both cancer patients and healthy donors. With the aim to identify cyclin B1-derived peptides with high affinity for HLA-A2, we used three in silico prediction algorithms to screen the protein sequence for possible HLA-A2 binders. One peptide scored highest in all three algorithms, and the high HLA-A2-binding affinity of this peptide was verified in an HLA stabilization assay. By stimulation with peptide-loaded dendritic cells a CTL clone was established, which was able to kill two breast cancer cell lines in an HLA-A2-dependent and peptide-specific manner, demonstrating presentation of the peptide on the surface of cancer cells. Furthermore, blood from cancer patients and healthy donors was screened for spontaneous T-cell reactivity against the peptide in IFN-γ ELISPOT assays. Patients with breast cancer, malignant melanoma, or renal cell carcinoma hosted powerful and high-frequency T-cell responses against the peptide. In addition, when blood from healthy donors was tested, similar responses were observed. Ultimately, serum from cancer patients and healthy donors was analyzed for anti-cyclin B1 antibodies. Humoral responses against cyclin B1 were frequently detected in both cancer patients and healthy donors. In conclusion, a high-affinity cyclin B1-derived HLA-A2-restricted CTL epitope was identified, which was presented on the cell surface of cancer cells, and elicited spontaneous T-cell responses in cancer patients and healthy donors.


CIRSE vascular closure device registry.

CIRSE vascular closure device registry. Vascular closure devices are routinely used after many vascular interventional radiology procedures. However, there have been no major multicenter studies to assess the safety and effectiveness of the routine use of closure devices in interventional radiology. The CIRSE registry of closure devices with an anchor and a plug started in January 2009 and ended in August 2009. A total of 1,107 patients were included in the registry. Deployment success was 97.2%. Deployment failure specified to access type was 8.8% [95% confidence interval (95% CI) 5.0-14.5] for antegrade access and 1.8% (95% CI 1.1-2.9) for retrograde access (P = 0.001). There was no difference in deployment failure related to local PVD at the access site. Calcification was a reason for deployment failure in only <0.5% of patients. Postdeployment bleeding occurred in 6.4%, and most these (51.5%) could be managed with light manual compression. During follow-up, other device-related complications were reported in 1.3%: seven false aneurysms, three hematoma >5.9 cm, and two vessel occlusions. The conclusion of this registry of closure devices with an anchor and a plug is that the use of this device in interventional radiology procedures is safe, with a low incidence of serious access site complications. There seems to be no difference in complications between antegrade and retrograde access and other parameters.


Circulating procoagulant microparticles in cancer patients. Accumulating evidence indicates that microparticles (MPs) are important mediators of the interaction between cancer and the hemostatic system. We conducted a large prospective cohort study to determine whether the number of circulating procoagulant MPs is elevated in cancer patients and whether the elevated MP levels are predictive of occurrence of venous thrombembolism (VTE). We analyzed plasma samples of 728 cancer patients from the ongoing prospective observational Vienna Cancer and Thrombosis Study. Study endpoint was the occurrence of symptomatic VTE. Sixty-five age- and sex-matched healthy controls were recruited for defining the cut-off point for elevated MPs (4.62 nanomolar phosphatidylserine [nM PS]), which was set at the 95th percentile of MP levels in healthy controls. The measurement of MPs was performed after capture onto immobilized annexin V, and determination of their procoagulant activity was quantified with a prothrombinase assay. During a median observation period of 710 days, 53 patients developed VTE. MP levels (nM PS) were significantly higher in cancer patients than in healthy controls (median [25th-75th percentile], 3.95 [1.74-7.96] vs. 1.19 [0.81-1.67], p<0.001). Multivariate analysis including age, sex, surgery, chemo- and radiotherapy showed no statistically significant association of the hazard ratio of elevated MPs with VTE (0.95 [95% CI, 0.55-1.64], p=0.856). In conclusion, MP levels were elevated in cancer patients compared to healthy individuals in this study. However, elevated MP levels were not predictive of VTE.


Household epidemic models with varying infection response. This paper is concerned with SIR (susceptible → infected → removed) household epidemic models in which the infection response may be either mild or severe, with the type of response also affecting the infectiousness of an individual. Two different models are analysed. In the first model, the infection status of an individual is predetermined, perhaps due to partial immunity, and in the second, the infection status of an individual depends on the infection status of its infector and on whether the individual was infected by a within- or between-household contact. The first scenario may be modelled using a multitype household epidemic model, and the second scenario by a model we denote by the infector-dependent-severity household epidemic model. Large population results of the two models are derived, with the focus being on the distribution of the total numbers of mild and severe cases in a typical household, of any given size, in the event that the epidemic becomes established. The aim of the paper is to investigate whether it is possible to determine which of the two underlying explanations is causing the varying response when given final size household outbreak data containing mild and severe cases. We conduct numerical studies which show that, given data on sufficiently many households, it is generally possible to discriminate between the two models by comparing the Kullback-Leibler divergence for the two fitted models to these data.


Investigation of the veins in patients with Behçet's disease with no known vascular event by Doppler ultrasonography. In Behçet's disease, deep venous thrombosis occurs primarily in the lower extremities. Total recanalization rate is low, so thrombotic segment could be detected by imaging afterward. For disclosing vein involvement, leg swelling is commonly queried in the history taking in those patients. However, there are no data about the presence of "silent" thrombosis in patients with BD. We aimed at investigating the integrity of venous vessels in BD, without any known vascular event by using Doppler ultrasonography (DU). Patients having past events revealed in the vascular questionnaire or physical findings attributable to vascular disease were excluded. Various degree of venous insufficiency was detected in 74 patients in BD (74%), 24 out of 33 patients (72%) in AS and in 8 out of 34 (25%) in HC group. All were at the lower extremities, and there is no difference in the frequency between BD and AS, while both were significantly higher than in HC (P = 0.001, and 0.004, respectively). Six patients with BD (6%) have chronic venous thrombi at the lower extremities and none in either AS and HC. As a non-invasive method, DU of lower extremities may disclose "silent" thrombosis. Venous insufficiency in those patients should be considered cautiously as an indicator of vein involvement.


Ficus deltoidea (Mas cotek) extract exerted anti-melanogenic activity by preventing tyrosinase activity in vitro and by suppressing tyrosinase gene expression in B16F1 melanoma cells. Ficus deltoidea (Mas cotek) water extract has been widely used for woman health in Malaysia. Our investigation focused to identify anti-melanogenic efficacy of F. deltoidea since it has been known to have strong anti-oxidant activities. Anti-melanogenic effect of F. deltoidea extract was analyzed using cultured B16F1 melanoma cells. Cytotoxicity of the extract was measured using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and determined the highest concentration of the extract that did not affect cell viability as 0.1% (w/v). α-MSH-induced melanin synthesis was significantly inhibited with dose-dependent manner by treatment of F. deltoidea leave extract, which was comparable to that of kojic acid. The extract directly inhibited mushroom tyrosinase activity and intracellular tyrosinase activity of B16F1 as well. The inhibition of intracellular tyrosinase activity was found to be exerted at the protein expression level when analyzed by immunoblot and tyrosinase zymography. The expression of microphthalmia-associated transcription factor (MITF) was also reduced by the F. deltoidea extract. In conclusion, F. deltoidea extract has strong anti-melanogenic activity that is exerted by direct inhibition of tyrosinase enzyme activity and by down-regulation of the expression of genes involved in the melanogenesis pathways. Collectively, data shown in this study strongly suggest that F. deltoidea extract has potential to be used as a novel depigmenting agent for cosmetics.


Right ventricular function in grown-up patients after correction of congenital right heart disease. We investigated whether a correlation exists between biomarkers of the neurohumoral system and clinical markers in grown-up patients with congenital heart disease (GUCH) and right ventricular function. Prospective, cross-sectional, multicenter study of 104 GUCH patients (median) 16 years (range 6-43 years) after corrective surgery with RV pressure and/or volume overload and 54 healthy controls. Clinical, functional, and laboratory parameters were assessed. Natriuretic peptide levels were significantly increased in GUCH patients (NTproBNP 101 vs. 25 pg/ml, p < 0.001), but we observed no differences in norepinephrine, aldosterone, angiotensin II and Endothelin-1 levels. NTproBNP correlated significantly with clinical markers such as NYHA classification, prolonged QRS duration and reduced exercise capacity (VO(2) peak) (all p < 0.001), as well as self-reported quality of life (p < 0.001). MRI and echocardiography derived RV volumes were elevated and ejection fraction reduced in the patients (both p < 0.001). Tissue Doppler parameter showed significantly restricted ventricular longitudinal systolic function (longitudinal tricuspid valve movement, 1.7 vs. 2.3 cm, p < 0.001), suggesting stiffness and reduced RV compliance. In conclusion, grown-up patients with congenital right heart disease NTproBNP correlates well with various clinical markers of RV failure, such as prolongation of QRS duration, exercise capacity, echocardiography and MRI parameters, and quality of life.


Iron status parameters in preeclamptic women. Evidence of increased oxidative stress due to endothelial dysfunction in preeclampsia has been well established. Increase in the oxidative stress is catalyzed in the presence of free transitional metals. Therefore, the relationship of iron status with preeclampsia was under investigation. The objective of the study was to compare red blood cell (RBC) count, hemoglobin (Hb) concentration, hematocrit (Hct), RBC indices, and iron status parameters in preeclamptic and healthy pregnant women. Blood samples were collected from 40 pregnant females diagnosed as preeclampsia and 80 normal pregnant females at the Department of Obstetrics and Gynecology at King Abdulaziz Medical City, Riyadh, Saudi Arabia between February 2009 and January 2010. We recorded RBC count, Hb concentration, Hct, RBC indices, serum iron and ferritin levels in both the groups. Mean serum iron in preeclampsia group was 23.48 ± 9.05, while 12.2 ± 5.21 in normal group (p <0.05). Similarly, mean serum ferritin concentration in preeclamptic and normal pregnant women were 32.56 ± 11.72 and 19.89 ± 8.86, respectively (p < 0.05). No significant differences were found among RBC count, Hb concentration, Hct, and RBC indices in both the groups. We recommend that any pregnant female with higher serum iron and ferritin concentrations should be further investigated for preeclampsia.


Repeatability of intra-ocular pressure and central corneal thickness measurements provided by a non-contact method of tonometry and pachymetry. To examine the repeatability of intra-ocular pressure (IOP) and central corneal thickness (CCT) measurements provided by the Tono-Pachymeter NT530P (Nidek, Japan), and to assess agreement of the device with Goldmann applanation tonometry (GAT) and ultrasound pachymetry (UP). Sixty-two normal eyes of 62 subjects were included in the study. Three sessions of measurements, each consisting of three sets of measurements, were completed with each device. Repeatability was determined with the coefficient of variation (CoV) and the coefficient of repeatability (CoR) values. Agreement between devices was examined by Bland-Altman analysis and intraclass correlation coefficient (ICC) analyses. The CoV and CoR for IOP values were 18.4% and 5.5 mmHg with the NT530P and 16.6% and 4.3 mmHg with the GAT respectively. On average, NT530P overestimated the IOP compared with GAT by 1.3 mmHg. The 95% limits of agreement between the methods ranged from -5.9 to +3.3 mmHg, and the ICC for average IOP measures between devices was 0.64 (P < 0.001). The CoV and CoR for CCT measurements were 5.5% and 59.8 μm with the NT530P and 5.5% and 60.5 μm with UP. NT530P CCT readings were on average 13 μm thinner than those obtained with UP. The 95% limits of agreement (LoA) ranged from -7.4 to +33.1 μm, and the ICC for average CCT measures between devices was 0.93 (P < 0.001). The NT530P demonstrated high IOP and CCT measurement repeatability in the normal population studied. The device tended to slightly overestimate IOP compared to GAT. CCT values provided by NT530P were interchangeable with those of UP.


Intraobserver and interobserver repeatability of ocular components measurement in cataract eyes using a new optical low coherence reflectometer. The purpose of the study was to assess intraobserver and interobserver repeatability of eight ocular components measurement in cataract eyes using the optical low-coherence reflectometer Lenstar LS 900®. Five consecutive measurements of ocular components were taken by two examiners using the Lenstar. Components analyzed were: central corneal thickness, lens thickness, anterior chamber depth, axial length, retinal thickness, keratometry, white-to-white distance, and pupillometry. Within-subject standard deviation and the coefficient of variation were calculated for evaluation of intraobserver repeatability. Bland-Altman analysis was used for assessment of interobserver repeatability. Thirty-two eyes of 22 patients were included. For both observers, the smallest intraobserver coefficient of variation was obtained for axial length, while the largest was found for corneal steepest meridian position. Interobserver repeatability demonstrated less repeatable results for white-to-white distance and corneal steepest meridian position. Considering axial length and anterior chamber depth values, predicted refractive error was 0 ± 0.05 D and 0.02 ± 0.19 D respectively in 95% of observations. The Lenstar LS 900® evidenced excellent repeatability and observers´ independent results of all components analyzed except white-to-white distance and corneal steepest meridian position measurements. To the best of our knowledge, this is the first study on interobserver repeatability of optical low-coherence reflectometry in cataract eyes.


Predictors of maximal short-term power outputs in basketball players 14-16 years. Relationships between growth, maturation and maximal short-term power outputs were investigated in 94 youth basketball players aged 14-16 years. Data included chronological age (CA), skeletal age (SA), years of training; body dimensions, estimated thigh volume, a running based short-term exercise assessed by the line drill test (LDT), the Bangsbo sprint test (BST) and short-term muscle power outputs with the Wingate anaerobic test (WAnT). Multiple linear regression analyses were used to estimate the effects of CA, skeletal maturity (SA/CA), years of training experience, body size and lower-limb volume on short-term performance in the LDT, BST and WAnT, respectively. Explained variances differed between cycle-ergometry outputs (52-54%) and running test performances (23-46%). The independent effects of predictors were small in the fatigue scores of the WAnT (4%) and the BST (11%). Skeletal maturity, body mass and leg length were primary predictors for all maximal short-term power output measures. Leg length was more relevant as a predictor than stature in the WAnT outputs, while stature and body mass appeared in the model with the running tests as dependent variable. Maximal short-term running abilities were also sensitive to years of training. In summary, skeletal maturation, body size and thigh muscle mass explained moderate to large proportions of the variance on maximal short-term performances of adolescent basketball players. The results highlight the importance of considering maturity status in evaluating the maximal short-term power outputs of adolescent athletes.


Lidocaine partially depolarizes the S4 segment in domain IV of the sodium channel. Previous studies have shown that lidocaine and other local anesthetic drugs (LAs) cause use-dependent block of sodium current (I (Na)), i.e., block that increases with membrane depolarization by allosteric coupling between drug binding in the inner pore and the S4s in domains III and IV. MTSET protection experiments have established that LAs stabilize DIIIS4 in an outward, depolarized position. Similar tests have not been reported for the DIVS4, although LAs have been shown to reduce DIV's contribution to total gating charge by about one third and to alter its movement such that it contributes more gating charge at negative potentials around -100 mV compared to non-drug-bound sodium (Na) channels. To investigate whether lidocaine reduces the gating charge of DIVS4 by causing it to adopt either a depolarized position at rest or by restricting its outward movement upon depolarization, we performed MTSET protection experiments on I (Na) of the mutant Na channel, R1628C (R3C-DIV), in the presence and absence of 10 mM lidocaine. The results indicate that lidocaine causes the DIVS4 to assume a more depolarized position, which facilitates its movement upon depolarization leading to the excess gating charge at potentials near -100 mV.


Perceiving performer identity and intended expression intensity in point-light displays of dance. This study investigated agent and expression intensity recognition in point-light displays depicting dancing performances. In a first session, participants danced with two different expression intensities to music, solo or in dyads. In a subsequent session, they watched point-light displays of 1-5-s duration, depicting their own, their partner's or another participant's recorded actions, and were asked to identify the agent (self vs. partner vs. stranger) and the intended expression intensity (expressive vs. inexpressive) of the performer. The results indicate that performer identity and expression intensity could be discerned reliably from displays as short as 1 s. The accuracy in judgment increased with exposure duration and, for performer identification, with higher expression intensity. Judgment accuracy in agent and expression intensity recognition tasks correlated with self-report empathy indices. Accuracy correlated also with confidence in judgment, but only in the intensity recognition task. The results are discussed in relation to perceptual and neural mechanisms underlying action and intention recognition.


Chromosome 3p alterations in pancreatic endocrine neoplasia. Pancreatic endocrine tumors (PET) are rare neoplasms classified as functioning (F-PET) or non-functioning (NF-PET) according to the presence of a clinical syndrome due to hormonal hypersecretion. PETs show variable degrees of clinical aggressiveness and loss of chromosome 3p has been suggested to be associated with an advanced stage of disease. We assessed chromosome 3p copy number in 113 primary PETs and 32 metastases by fluorescence in situ hybridization (FISH) using tissue microarrays. The series included 56 well-differentiated endocrine tumors (WDET), 62 well-differentiated endocrine carcinomas (WDEC), and 6 poorly differentiated endocrine carcinomas (PDEC). Chromosome 3p alterations were found in 23/113 (20%) primary tumors, with losses being predominant over gains (14% vs. 6%). Loss of 3p was found in 5/55 (9%) WDET, 11/52 (21%) WDEC, and never in PDEC. Gains of 3p were detected in 4/55 (7%) WDET, no WDEC, but notably in 3/6 (50%) PDEC (OR 23.6; P = 0.003). Metastases were more frequently monosomic for 3p compared to primary tumors (OR 3.6; P = 0.005). Monosomy was significantly associated with larger tumor size, more advanced tumor stage, and metastasis. No association was found with survival. Chromosome 3p copy number alterations are frequent events in advanced stage PET, with gains prevailing in PDEC while losses are more frequent in WDEC, supporting the view that a specific pattern of alterations are involved in these diverse disease subtypes.


Clinical characteristics of children with group A streptococcal toxic shock syndrome admitted to pediatric intensive care units. Streptococcal toxic shock syndrome (STSS) is a very rare and severe form of group A streptococcal infection whose clinical characteristics, therapy, morbidity, and mortality in children are not well known. Our objective was to describe the clinical characteristics of STSS in a series of children admitted to pediatric intensive care units (PICU). A multicenter, retrospective study of children with STSS admitted to 14 PICUs between January 1998 and December 2009 was conducted. Clinical information was obtained retrospectively by chart review. Data from 41 children were collected, 90% corresponding to the second half of the study period. Initial symptoms and signs were nonspecific. All patients developed shock and organ dysfunction, 78.0% developed coagulopathy, 70.7% neurologic dysfunction, and 68.3% respiratory failure. Rapid pharyngeal test for Streptococcus was positive in 78.0%. Initial leukocyte count was quite variable, with leukopenia present in 51.2% of patients and leukocytosis in 31.7%. Children were treated with antibiotics against group A Streptococcus (GAS), usually G penicillin or cephalosporin plus clindamycin. After a median PICU stay of 7 days (range 0-41), 65.8% of patients survived, 26.8% with sequelae. The cause of death of the 11 non-survivors was refractory shock and multi-organ failure. STSS is a very severe condition secondary to invasive GAS infection. It can occur at any age, but especially in young children. Due to the lack of specific symptoms and signs and its very rapid progression to shock and organ dysfunction, pediatricians and emergency physicians must be aware of this possibility and immediately initiate aggressive treatment when suspected.


Maternal active or passive smoking causes oxidative stress in placental tissue. The aim of this study was to assess the influence of active and passive maternal smoking on placenta total oxidant/antioxidant status in term infants. The levels of cord blood total antioxidant capacity (TAC), total oxidant status (TOS), and oxidative stress index (OSI) were measured in samples of fetal placental tissue, cord blood, and the maternal peripheral blood serum and from 19 mothers who were active smokers, 19 who were passive smokers, and 22 who were nonsmokers (not exposed to active or passive smoking). The pregnancies were between 37 and 40 weeks' gestation, were uncomplicated, and the infants were delivered vaginally. Birth weight and head circumference in the active smokers were significantly (P < 0.001) lower than those in the controls. Placenta, cord blood, and the maternal peripheral TAC levels were significantly lower in the active smokers compared with the controls (P < 0.001), while TOS and OSI levels were significantly higher in the active and passive smokers than in the controls (P < 0.001). A positive significant correlation was found between active maternal smoking and placenta TOS and OSI levels (P < 0.016), and a significant negative correlation was found between number of cigarettes exposed to and birthweight and head circumference (P < 0.05). In conclusion, active or passive maternal smoking is associated with important alterations in oxidant and antioxidant balance in fetal placental tissue and causes potent oxidative stress.


Comparative karyological analysis of four diplozoid species (Monogenea, Diplozoidae), gill parasites of cyprinid fishes. The present study has revealed new data on chromosome complements of diplozoid parasites, namely Diplozoon paradoxum from freshwater bream Abramis brama, Paradiplozoon bliccae from white bream Blicca bjoerkna, Paradiplozoon sapae from white-eye bream Ballerus sapa, and Paradiplozoon nagibinae from zope Ballerus ballerus. Particularly, D. paradoxum is characterized by four pairs (2n=8) of long (up to 22.1 μm) chromosomes: pairs 1, 2, and 3 are metacentric and pair 4 acrocentric. Karyotypes of three Paradiplozoon species are nearly identical in number and morphological classification of chromosomes, each comprising diploid number of 14 one-armed chromosomes of very similar length ranging up to 12.5 μm in P. bliccae, 9.2 μm in P. sapae, and 9.9 μm in P. nagibinae. All four species are similar in their total complement length, ranging from 64.4 to 50.4 μm. Interspecific differences were found in location of secondary constriction: it is situated on short arm of the 1st chromosome pair in D. paradoxum, on long arm of the 7th pair in P. bliccae and on long arm of the 4th pairs in P. sapae and P. nagibinae. Phylogenetic interrelationship within the diplozoids and hypothetic karyotype evolution is here discussed.


Participation of metanauplii and juvenile individuals of Artemia parthenogenetica (Branchiopoda) in the circulation of avian cestodes. Adult crustaceans of the genus Artemia (brine shrimps) are intermediate hosts in the life cycle of cestode species parasitic in aquatic birds as their definitive hosts. However, there are no data on the role of larval and juvenile brine shrimps in the transmission of avian helminth parasites. In order to examine the possible role of early developmental stages (nauplii, metanauplii and juveniles) of Artemia for the circulation of avian cestodes, the natural cestode infection in the population of Artemia parthenogenetica from La Mata Lagoon, Mediterranean coast of Spain, was studied. Metacestodes (cysticercoids) of four cestode species were recorded in adult brine shrimps: Flamingolepis liguloides and Flamingolepis flamingo (hymenolepidids parasitic in flamingos), Confluaria podicipina (a hymenolepidid species parasitic in grebes) and Eurycestus avoceti (a dilepidid species parasitic in avocets, stilts, plovers and, to a lesser extent, in flamingos). No cysticercoids were found in nauplii. Two species, F. liguloides and F. flamingo, were found in metanauplii and juvenile brine shrimps. Only 36.3% of the cysticercoids of F. liguloides occurred in adult brine shrimps; the remaining 63.7% were parasitic in metanauplii (39.6%) and juveniles (24.1%). Similarly, the metacestodes of F. flamingo were also distributed among various age groups: in adults (44.4% of cysticercoids), juveniles (27.8%) and metanauplii (27.8%). These results indicate that the early developmental stages of Artemia have an important role for the circulation of certain parasite species. No cysticercoids of C. podicipina and E. avoceti were recorded in larval and juvenile brine shrimps. The selective infestation of larval brine shrimps with flamingo parasites is probably associated with the feeding behaviour of definitive hosts, which are filtering predators; in contrast, grebes and waders pick brine shrimps individually one by one. The possible underlying mechanism for selective infestation of metanauplii and adults by certain cestode species is associated with the size of parasite eggs, allowing only cestode species with small eggs to be ingested by larval brine shrimps.